Biology, Health and Medicine for the Third World

Suggestions please!

2007-02-09T23:46:00.000+05:45

Biology, Health and Medicine for the Third World is our motto!

You know it.

What we expect from you people is suggestions regarding uplift of the health sector in the third world, development of Scientific community and of course your write-ups, if you can contribute to us.

Thanks

Hypertension, alcohol OK in small doses

2007-01-03T00:55:00.000+05:45

A drink or two a day shouldn't increase the risk of heart attack for men with high blood pressure, U.S. and Dutch researchers said.
"We could not find any increased risk of heart disease or death due to heart disease for moderate drinkers. Moderate drinkers may even have a reduced risk for heart attack," Joline Beulens, University Medical Center Utrecht in the Netherlands.
Beulens said the study is the first to examine whether men who drink moderately and have high blood pressure are more prone to heart attacks than non-drinkers, USA Today reported.
Researchers analyzed data from 11,711 men with hypertension in the Health Professionals Study, begun in 1986. Participants completed surveys noting how often they consumed alcohol.
From 1986 to 2002, subjects reported 653 heart attacks, of which 279 were fatal, researchers said in the Annals of Internal Medicine. Men who drank up to two drinks a day reduced their heart attack risk by about a third.
"Moderate consumption of alcohol seems to be associated with a lower risk of heart attack, similar to the association seen in healthy men in general," says co-author Dr. Kenneth Mukamal, Beth Israel Deaconess Medical Center, Boston.
Copyright 2007 by United Press International. All Rights Reserved.
UTRECHT, Netherlands
via Sciencedaily

Newly Identified Strains Of Chlamydia Trachomatis Could Produce New Diseases

2007-01-03T00:52:00.000+05:45

A new study led by a scientist at Children's Hospital Oakland Research Institute (CHORI) is the first to conclude that Chlamydia trachomatis is evolving at a rate faster than scientists first thought or imagined. Chlamydia trachomatis is a bacterium that is the leading cause of sexually transmitted diseases and the second leading cause of blindness worldwide. Scientists believe the bacterium is evolving through a process called recombination where genes from one or more strains combine to create new strains and -- theoretically -- new diseases. The study is featured in the November issue of Genome Research and was led by Dr. Deborah Dean MD, MPH, senior scientist at Children's Hospital Oakland Research Institute (CHORI). Her research suggests that since Chlamydia trachomatis evolves through recombination where one or more strains combine, the traditional method of studying a single gene to track the transmission of the bacterium is wrong. "What we found is an organism that not only evolves rapidly, but in ways that we thought were rare. We also discovered that this organism can customize its attack," said Dr. Dean. "Consequently, the constant flux of the bacterium could serve as a gateway for new emerging diseases, but more research needs to be conducted to understand if and how this is happening."
600 million people are infected across the globe with Chlamydia trachomatis and 8 million are already blind or severely visually impaired. In some parts of third-world countries, more than 90% of the population is infected. Chlamydia trachomatis has a variety of strains; different strains are responsible for different diseases. Some strains cause sexually transmitted diseases while others cause eye infections. Blinding trachoma is caused by repeated eye infections that cause scarring, which result in the eyelashes turning in-wards. Bacterial infection develops as the eyelashes scratch the surface of the eye, which eventually heals by scarring, resulting in blindness.
Previously, the organism was identified using a single gene, ompA, and the protein encoded by that gene, MOMP. In this study, the clinical strains, which are samples of Chlamydia trachomatis currently responsible for human disease today, were compared to standard reference strains that have been laboratory adapted over the last few decades. By studying multiple strains, the researchers discovered that the strains that were identified as the same strain were actually different.
The next step will be to study clinical strains in comparison with laboratory reference strains to decipher exactly how different strains cause disease and whether new diseases are emerging as a result of the emergence of new strains. "Large-scale comparative genomics will be necessary to understand the precise mechanisms underlying Chlamydia trachomatis recombination and how other species of chamydiae may evolve and transfer from animals to humans."

Note: This story has been adapted from a news release issued by Children's Hospital & Research Center at Oakland. via Science Daily

Regulatory Pathway In Brain Development Possible Basis For Malformations

2007-01-03T00:47:00.000+05:45

Researchers at the University of California, San Diego (UCSD) School of Medicine have identified a genetic regulator of brain development that sheds new light on how immature neural cells choose between proliferation and differentiation. Defects in regulating this choice result in brain malformations. Their research will be published on line the week of December 4, in advance of publication in the Proceedings of the National Academy of Sciences (PNAS.)

Animals that lack the Zfp423 gene (right) have a malformed cerebellum (cbm), including a complete loss of the midline structure (vermis). This structure is important for postural control and coordinated movement. The protein encoded by Zfp423 regulates the expression of other genes and is required for normal levels of proliferation by neural precursor cells in the cerebellum. (Credit: UCSD Medical Center)

Bruce Hamilton, Ph.D., associate professor in the Department Medicine, and his colleagues have identified a genetic regulatory pathway that controls a neural precursor cell's decision to self-renew as a dividing precursor or differentiate into a non-dividing neuron. Cells that are unable to differentiate appropriately and continue to proliferate may give rise to brain cancers. On the other hand, cells that differentiate too soon or make too few cells can result in malformations of critical brain structures.
"Development of the brain requires intricate coordination to control the proliferation, differentiation, and connections among different groups of cells," said Hamilton. "We have found a gene in mice, mutated in one kind of malformation, which appears both to promote proliferation and to help coordinate differentiation of immature precursor cells."
The work in Hamilton's lab, led by UCSD Biomedical Sciences graduate students Wendy Alcaraz and David Gold, discovered a specific transcription factor called Zfp423. When Zfp423 is mutated in mice, developmental defects in the cerebellum occur that resemble Dandy-Walker malformations seen in human patients.
Dandy-Walker malformations occur in about one in 25,000 human births. Patients have a congenital malformation in the cerebellum, an area of the brain that controls movement, which can significantly slow motor development and cause progressive enlargement of the skull. Dandy-Walker malformation is frequently associated with disorders of other areas of the central nervous system and malformations of the heart, face, limbs, fingers and toes. Study of the Zfp423 mouse model in Hamilton's lab provides an important genetic clue in Dandy-Walker malformations, whose causes are not well understood.
"Loss of Zfp423 in mice results in diminished proliferation by precursor cells at a key time in the development of the cerebellum, resulting in its malformation," said Alcaraz.
The protein encoded by Zfp423 regulates the expression of other genes and is required for normal levels of proliferation by neural precursor cells in the cerebellum. This gene had previously been identified as a co-factor in two distinct signaling or regulatory pathways that mediate neuronal differentiation. The new work proposes that Zfp423 actually acts as a bridge between the two pathways.
"This means that external signals used in cell-cell communication could affect the developing neurons in ways we hadn't previously realized," Hamilton said. "In particular, cell lineage pathways that are often thought of as independent of signaling once they are initiated may really be under tight regulation by signaling-dependent pathways that compete with them for access to factors like Zfp423." He added that development of this mouse could lead to targeted therapies for some genetic brain disorders.
Additional contributors to this paper include Eric Raponi and Dorothy Concepcion of the UCSD Department of Medicine and Peter M. Gent, of the UCSD Biomedical Sciences Graduate Program. The research was funded in part by grants from the National Institutes of Health.
Note: This story has been adapted from a news release issued by University of California - San Diego. via Science Daily

How Bacteria Can Escape Destruction: Scientists Discover Mechanism Used To Pump Out Drugs

2007-01-03T00:41:00.000+05:45

In a new study published online in the open access journal PLoS Biology, Gaby Sennhauser, Marcus Gruetter, and colleagues use structural biology techniques to probe the molecular mechanisms of the major drug efflux pump in E. coli AcrB.
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Bacterial resistance to antibiotics is a major challenge for the current treatment of infectious diseases. One way bacteria can escape destruction is by pumping out administered drugs through specific transporter proteins that span the cell membrane, such as AcrB.
Making use of designer proteins that bind to and stabilize proteins of interest, the researchers were able to obtain better resolution structural data for the AcrB complex. After selecting for designed ankyrin repeat proteins (DARPins) that inhibit this pump, Sennhauser and colleagues solved the crystal structure of the DARPin inhibitor in complex with AcrB. They were able to confirm that the AcrB pump is split into three subunits, each of which exhibit distinctly different conformations.
Each subunit has a differently shaped substrate transport channel; these variable channels provide unique snapshots of the different phases employed by AcrB during transport of a substrate. The structure also offers an explanation for how substrate export is structurally coupled to simultaneous proton import--thus significantly improving our understanding of the mechanism of AcrB. This is the first report of the selection and co-crystallization of a DARPin with a membrane protein, which demonstrates not only DARPins' potential as inhibitors, but also as tools for the structural investigation of integral membrane proteins.
Citation: Sennhauser G, Amstutz P, Briand C, Storchenegger O, Gruetter MG (2007) Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol 5(1): e7. doi:10.1371/journal.pbio.0050007.
Note: This story has been adapted from a news release issued by Public Library of Science.
via Science Daily

Brain chemical linked to alcohol desire

2006-12-26T23:38:00.000+05:45

Australian scientists have identified a brain system that could not only blunt an alcoholic's craving for booze, but also the addiction.

The BBC reported Monday researchers at Melbourne's Howard Florey Institute discovered how to block the action of the brain's orexin system, which can also stop the desire for alcohol in its tracks.

Orexin cells, also known as hypocretins, are a pair of highly excitatory neuropeptides found in the brain. The chemical is involved in the "high" felt after drinking alcohol or taking illicit drugs or even eating a great meal.

Dr. Andrew Lawrence used a drug that actually blocked orexin's euphoric effects in the brain. Test rats, in fact, turned their noses up when faced with the oportunity of swilling unlimited alcohol, even those that had gone through detox chose to not imbibe.

"Orexin reinforces the euphoria felt when drinking alcohol, so if a drug can be developed to block the orexin system in humans, we should be able to stop an alcoholic's craving for alcohol," Lawrence told the BBC.

Measuring Pandemic Preparedness: Vaccination Campaigns Need A Shot In The Arm

2006-12-26T23:36:00.000+05:45

A federal plan to vaccinate hospital healthcare workers against a threat of smallpox fell short on several levels, according to the first metric analysis of the prophylactic health program. Results of the Temple University study raise troubling questions about future preparedness against possible outbreaks of avian flu or SARS.

The study, "Preparedness for a smallpox outbreak: comparing metrics for assessing levels of vaccination among health-care workers by state," has been published online ahead of print in the journal Epidemiology and Infection.

In 2003, the Centers for Disease Control and Prevention asked each state to vaccinate at least 50 to100 healthcare workers per hospital, a number the government considered large enough to respond to a possible smallpox outbreak. These workers could then vaccinate and treat others.

Doses of smallpox vaccine were distributed nationally based on each state's requests, with a goal of vaccinating 500,000 workers in 30 days. Yet by mid-2005, only about 39,000 -- or 17 percent of the requested dosages -- had been used.

"Some states requested thousands of vaccines, while others only a few hundred," said lead researcher Sarah Bass, Ph.D., MPH, assistant professor of public health in Temple University's College of Health Professions.

To critically examine how well the program worked, researchers analyzed vaccination patterns based on a series of metrics: the absolute numbers of health care workers vaccinated compared to the percentage of doses distributed to each state, the rate of vaccination per capita population, and the percentage of healthcare workers vaccinated compared to the number recommended by the CDC. States were then ranked into four quartiles.

"We had to do a very careful analysis because some states appeared to have a very high vaccination rate if you only looked at the number of absolute vaccinations as a percentage of the number of vaccines requested," Bass said.

Oklahoma, for example, vaccinated 376 people with the 700 doses requested -- slightly more than 50 percent. However, the state would have needed an estimated 9,675 doses to meet the CDC's recommendations, which leaves Oklahoma's true vaccination rate only at 3.9 percent of the goal set by the CDC.

Overall, researchers found a generally low compliance rate along with a great variability among states. States most affected by 9/11-- New York, Pennsylvania and Virginia -- ranked in the bottom quartiles of most metrics, while several states perceived to be at a lower terror risk, such as Nebraska, ranked at the top.

While the lack of an impending smallpox crisis may account for the differences in state response, both the federal and state governments could have done a better job, Bass said.

"Some felt the CDC or state health departments sent ambivalent messages about the importance of the program, and many states did not fully support the effort," Bass said. "The result was a very inconsistent uptake of the vaccination program by states, where some states had very coordinated efforts and others did not."

Adding to the variability were many healthcare workers who didn't believe that the benefits of the vaccine outweighed the personal risks.

"Workers worried that the vaccine, which had not been given to middle-aged or older adults in the past, might have unanticipated dangers. Others wondered if the vaccine might be effective against newer forms of weaponized smallpox," said Bass.

To uncover why healthcare workers did not accept vaccines, Bass, along with colleagues Tom Gordon and Sheryl Ruzek, is working on a new study that employs perceptual mapping to evaluate how healthcare workers balance risks and benefits in deciding whether or not to take part in a vaccination program.

"To be prepared, we need to have health workers protected," Bass said. "But as long as it's a decentralized program without an immediate outbreak, it will be difficult."

Note: This story has been adapted from a news release issued by Temple University. via Science Daily

Abnormal Proteins Linked To Schizophrenia Found In Body Tissue

2006-12-26T23:22:00.002+05:45

A new study suggests biochemical changes associated with schizophrenia aren't limited to the central nervous system and that the disease could have more encompassing effects throughout the body than previously thought. The findings, scheduled for publication in the January 2007 issue of the American Chemical Society's Journal of Proteome Research, could lead to better diagnostic testing for the disease and could help explain why those afflicted with it are more prone to type II diabetes, cardiovascular diseases and other chronic health problems.

Researcher Sabine Bahn, M.D., Ph.D., and her colleagues at Cambridge University in England and the University of Cologne in Germany, detected abnormal proteins linked to schizophrenia in the liver and red blood cells of people who have the disorder. It is the first time the same altered proteins have been detected both within brain tissue as well as in non-brain tissue, according to Bahn.

In time, Bahn says, these protein "biomarkers" could be used to trace the progression of the disease throughout the body.

"If changes in the rest of the body can be observed, and if these changes reflect what is going wrong in the brain, we can use these (findings) to learn about the cellular dysfunction that causes schizophrenia and this will allow us to develop better drugs and diagnostics," Bahn says.

About 1 percent of the world's population -- including 2.4 million Americans -- has schizophrenia, a complex and puzzling mental illness that can lead to delusions, hallucinations and disordered thinking. It is one of the world's most common causes of psychosis, according to Bahn. Since it was first described more than 100 years ago, scientists have made little progress in unraveling the causes of the disease, and no definitive test is available to diagnosis it, she says.

"We desperately need a better understanding of this illness. It is, however, difficult to study the disease, as the brain can't easily be investigated. We can't take multiple biopsies from patients to look at the disease-related changes," Bahn says. "We need a new concept."

While most scientists investigating the disease believe it only affects the brain, Bahn notes that researchers have long known that people who have schizophrenia are at higher risk than the general population for a number of chronic diseases. Some evidence suggests these health problems might be somehow tied to schizophrenia, she adds, but most studies have been inconclusive. Bahn's latest discovery could help bridge this gap.

Recently, Bahn and her colleagues discovered a set of abnormal proteins in post-mortem brains of people who had schizophrenia. In this new study, they sought to detect similarly altered proteins in other organs and tissues of individuals living with the disease. After looking at thousands of proteins, they found that people with schizophrenia had 14 liver proteins and eight red blood cell proteins that were significantly altered compared to individuals who didn't have the disease. These altered proteins were strikingly like those found in the post-mortem brains.

Several of these abnormal proteins appear to promote oxidative stress and disrupt energy metabolism in cells, Bahn says. She theorizes that schizophrenia is caused, at least in part, by these two problems. In her earlier work, for instance, Bahn found evidence that schizophrenic brains might have difficulty producing or using energy properly and are more susceptible to cell-damaging free radicals than healthy brains. The new findings, she says, suggest that the same sort of energy starvation, increased free-radical damage cycle could be occurring in other tissue and, in addition to schizophrenia, possibly be contributing to the onset of other chronic diseases.

Note: This story has been adapted from a news release issued by American Chemical Society. via Science Daily

Five New Technologies That Promise To Transform Medicine

2006-12-26T23:22:00.001+05:45

Fat zapping to shed excess weight, miniature telescopes to restore vision, and smart nappies to detect common childhood infections: these are some of the new technologies that promise to transform medicine, according to this week's Christmas issue of the British Medical Journal.

The forecasts are made by Professor Donald Combs of the Eastern Virginia Medical School and are based on existing technologies that are in varying stages of development and on extensions of those technologies.

His vision for the future includes airport x-ray style devices that "fry" excess fat with a laser. An overweight patient simply walks through the device and emerges several pounds lighter. No side effects are seen apart from the resizing of his wardrobe.

Patients with chronic diseases who need regular medication will benefit from a miniature implant that monitors and transmits data on heart and breathing rates, blood pressure, and blood sugar levels. And further into the future are links smart pumps that, when signalled, instantly deliver the correct medication.

Another prediction is the use of miniature telescopes that restore vision for patients with degenerative eye disease. The telescopes are powered by sunlight passing through the pupils to microscopic solar battery panels attached to the retinas.

These scenarios illustrate potential clinical applications of technologies currently under development, says Professor Combs. For instance, devices that can sense and transmit heart and breathing rates already exist and implantable lenses are well-known.

Other emerging technologies include wave technology to isolate cancer cells, fabrication technology to manufacture customised body parts, and the use of miniature robots to track and destroy infections before they cause disease.

The individual and collective impact of these technologies is already present in some aspects of contemporary medicine and the rate of their impact is increasing, he concludes.

Note: This story has been adapted from a news release issued by BMJ-British Medical Journal. via Science Daily

New Neurons Could Act To Alleviate Epilepsy

2006-12-26T23:22:00.000+05:45

cience Daily — The new neurons generated as a result of neural damage due to epilepsy show a reduced excitability that could alleviate the disorder, researchers have found. The researchers said their results suggest that therapies for epilepsy aimed at inducing neurogenesis could prove effective in alleviating the disorder.

In an article in the December 21, 2006, issue of the journal Neuron, published by Cell Press, Olle Lindvall and colleagues at Lund University Hospital and Stem Cell Center described studies in rats examining neurons generated after an epileptic event has been triggered in the animals.

In their experiments, the researchers compared the properties of new neurons generated in rats allowed to exercise by running on a wheel with those in rats in which epileptic seizures were induced by electrical brain stimulation. Specifically, the researchers analyzed the electrical properties of a type of new cells, called granule cells, in the structure called the dentate gyrus of the hippocampus. This structure is known to be a "gate" for propagation of seizures in the hippocampus, a center for learning and memory.

The scientists' analysis showed that the new neurons in both the runners and the epileptic animals had all the characteristics of mature dentate gyrus cells. However, they found that neurons born into an epileptic environment, compared to the physiological running environment, showed reduced excitatory connectivity to other neurons, as well as increased inhibitory connectivity. Such differences could mean the newly generated neurons "could have significant beneficial effect on the epileptic syndrome," concluded the researchers.

"Our study demonstrates that both a physiological stimulus and an insult to the adult brain trigger the formation of new dentate granule cells, which are functionally integrated into hippocampal neural circuitry," concluded Lindvall and colleagues. They wrote that "following insult, the functional connectivity of new neurons seems to develop in order to mitigate the dysfunction in the epileptic brain. These data provide further evidence for a therapeutic potential of endogenous neurogenesis."

The researchers include Katherine Jakubs, Avtandil Nanobashvili, Sara Bonde, Christine T. Ekdahl, Zaal Kokaia, Merab Kokaia, and Olle Lindvall of Lund University Hospital and Stem Cell Center in Lund, Sweden.

This work was supported by Swedish Research Council, EU project LSHBCT-2003-503005 (EUROSTEMCELL), and Söderberg, Crafoord, and Kock Foundations. Lund Stem Cell Center is supported by a Center of Excellence grant in Life Sciences from Swedish Foundation for Strategic Research.

Jakubs et al.: "Environment Matters: Synaptic Properties of Neurons Born in the Epileptic Adult Brain Develop to Reduce Excitability." Publishing in Neuron 52, 1047--1059, December 21, 2006 DOI 10.1016/j.neuron.2006.11.004. http://www.neuron.org

Note: This story has been adapted from a news release issued by Cell Press.

Blood test could show transplant rejection

2006-12-24T22:56:00.000+05:45

A blood test may replace invasive biopsies that heart transplant patients in the United States and elsewhere undergo to check for rejection, heart experts say.

The international team evaluated the blood test that analyzes a patient's genes and said it can accurately detect the absence of heart transplant rejection, according to data reported in an editorial the team wrote. The editorial was posted in the online edition of the Journal of Heart and Lung Transplantation.

The genetic-expression profiling test not only is less invasive and less risky than a biopsy, "it also monitors the absence of organ rejection and raises suspicion of damage before any damage to the heart happens. Biopsy records damage that has already occurred," said senior author Mario Deng, director of cardiac transplantation research and associate professor of clinical medicine at Columbia University College of Physicians and Surgeons.

About 30 percent of heart transplant patients reject their new heart at least once in the first year post-transplant. When testing reveals rejection, a patient's immunosuppressive regimen is adjusted.

The new data, however, showed that in more than 99 percent of cases, the GEP test predicted heart muscle biopsies that showed an absence of acute cellular rejection.

Protection Against Cancer May Begin During Pregnancy, Nursing

2006-12-24T22:44:00.003+05:45

There may be another reason for pregnant and nursing women to eat a nutritious diet that includes generous amounts of cruciferous vegetables like broccoli and cabbage -- it could help protect their children from cancer, both as infants and later in life.

A new study by scientists from the Linus Pauling Institute at Oregon State University, done with laboratory mice, found that supplements of a key phytochemical found in certain vegetables provided a very high level of protection against leukemia and lymphoma in young animals, and also significantly protected against lung cancer during the rodent's equivalent of middle age.

The research, published in the journal Carcinogenesis, is one of the first of its type to demonstrate that diet may play a protective role in a fight against cancer that may begin -- and could be won or lost -- well before a person is ever born. And some of the protective benefits may last into adulthood.

"Research of this type is still in its infancy, but it's pretty exciting," said David Williams, an LPI researcher and director of the Marine and Freshwater Biomedical Sciences Center at OSU.

"There's strong epidemiologic evidence that infant cancers can be caused by exposure of the fetus to carcinogens, either during pregnancy or by nursing," Williams said. "Among all childhood deaths in the U.S., cancer is second only to accidents as the leading cause, and the fetus and neonate are sensitive targets for toxic carcinogens. It would be important if we could affect this through maternal diet."

There are particular concerns about common environmental pollutants called polycyclic aromatic hydrocarbons, or PAHs, which can be produced by cigarette smoking or the combustion of organic materials such as wood, coal, cooking oil or diesel fuel. Exposure of a fetus to PAHs has been shown to cause DNA damage in newborns and is also associated with increased levels of childhood leukemia. It has also been shown that a significant portion of the total lifetime exposure to PAHs and other toxins, including PCBs and dioxins, is transmitted to the fetus across the placental barrier and during nursing.

In laboratory studies, researchers exposed pregnant mice to a single high dose of one PAH called dibenzopyrene, a potent carcinogen, and about 80 percent of their 100 offspring died early in life from an aggressive T-cell lymphoma. Of those that survived to the mouse-equivalent of middle age, 100 percent had lung tumors.

By comparison, in a group of pregnant mice given the same carcinogen but who also received the chemoprotective supplement Indole-3-carbinol, or I3C, deaths from lymphoma were cut in half, and the number of lung tumors later in life was significantly reduced.

"It's clear that in mice this supplement provided significant protection against lymphoma and, later on, lung cancer," Williams said. "It's also worth noting that none of the infant mice received the protective supplement later in their life, at any stage beyond breast feeding. The protective effect of the compound came solely from maternal intake during pregnancy and nursing, but lasted into the animal's middle age. This is somewhat remarkable."

Although lung cancer is the leading cause of cancer death in both men and women, it's also true that only about one smoker in 10 gets lung cancer. It's possible, researchers say, that dietary and other factors in addition to smoking may predispose some smokers to get cancer while others don't. That this process may begin with carcinogens crossing the placental boundary -- and might be affected by diet -- is an area that has not been adequately studied, Williams said. In this study, both the exposure to carcinogens and the levels of Indole-3-carbinol given to pregnant mice through supplements were higher than those that would ordinarily be found in the environment or a normal diet, researchers said.

The scientists do not recommend that pregnant women take supplements of this compound, which is available in health food stores, because there have been questions about its possible role in causing birth defects when ingested at high levels in the first trimester of pregnancy. That topic needs further study, they said.

However, the amounts of this and other valuable phytochemicals that could be obtained in any normal diet rich in cruciferous vegetables should be safe and useful, they said. These vegetables include broccoli, cabbage, cauliflower, kale, radishes, turnips and other types of greens and cabbages.

Indole-3-carbinol is also being studied by scientists in other U.S. research programs for chemoprotection of women against breast cancer.

Cancer chemoprotection is one of the main research areas at the Linus Pauling Institute, a world leader in the study of vitamins, phytochemicals and other nutrients that may help prevent disease or provide optimum health.

This research was funded by the National Institutes of Health.

Note: This story has been adapted from a news release issued by Oregon State University.
via Science Daily

Researchers Find Stem-cell Therapy Effective In Targeting Metastatic Cancer

2006-12-24T22:44:00.002+05:45

Patients with advanced cancer that has spread to many different sites often do not have many treatment options, since they would be unable to tolerate the doses of treatment they would need to kill the tumors.

Researchers at City of Hope and St. Jude Children's Research Hospital may have found a way to treat cancers that have spread throughout the body more effectively. They used modified neural stem cells to activate and concentrate chemotherapeutic drugs predominately at tumor sites, so that normal tissue surrounding the tumor and throughout the body remain relatively unharmed.

"This approach could significantly improve future treatme nt options for patients with metastatic cancer," said Karen Aboody, M.D., assistant professor of Hematology/Hematopoietic Cell Transplantation and Neurosciences at City of Hope. "It not only has the potential to destroy residual tumor cells, but it should also improve patients' quality of life by minimizing toxic side effects such as nausea, diarrhea or bone marrow suppression."

Aboody is the lead investigator of the study done in collaboration with senior investigator Mary Danks, Ph.D., associate member of Molecular Pharmacology at St. Jude Children's Research Hospital in Memphis, Tenn. The study will be published Dec. 20 in PLoS ONE. A second paper with extended results from the study has been accepted for publication in Cancer Research in January.

Most chemotherapy drugs affect both normal and cancerous tissue, which is why they also are toxic to naturally fast-growing cells in the body such as hair follicles and intestinal cells. Aboody and her colleagues have developed a two-part system to infiltrate metastatic tumor sites, and then activate a chemotherapeutic drug, thereby localizing the drug's effects to the tumor cells.

The technique takes advantage of the tendency for invasive tumors to attract neural stem cells. The researchers injected modified neural stem/progenitor cells into immunosuppressed mice that had been given neuroblastoma cells, which then formed tumors. After waiting a few days to allow the stem cells to migrate to the tumors, researchers administered a precursor-drug. When it reached the stem cells, the drug interacted with an enzyme the stem cells expressed, and was converted into an active drug that kills surrounding tumor cells. The precursor-drugs were administered for two weeks, then after a two-week break, a second round of stem/progenitor cells and drugs were administered.

One hundred percent of the neuroblastoma mice appe ared healthy and tumor-free at six months. Without treatment, all the neuroblastoma mice died within two-and-a-half months.

The results hold promise for treating solid tumors that metastasize including neuroblastoma, which represents 6 percent to 10 percent of all childhood cancers worldwide, with higher proportions in children under 2 years of age.

"The results are especially important in the case of high-risk neuroblastoma, because treatment-resistant cancer returns in as many as 80 percent of children, and the majority die of their disease," said co-principal investigator Danks.

Aboody and her colleagues had previously published the efficacy of this technique in primary and metastatic tumors in the brain. This is the first research to demonstrate that it is also effective in a metastatic cancer model, targeting multiple solid tumor sites spread throughout the body. They speculate that the technique could also be applie d to other malignant solid tumors, including colon, brain, prostate and breast cancer, and are planning future preclinical trials using those tumors as well.

Citation: Aboody KS, Bush RA, Garcia E, Metz MZ, Najbauer J, et al (2006) Development of a Tumor-Selective Approach to Treat Metastatic Cancer. PLoS ONE 1(1): e23. doi:10.1371/journal.pone.0000023 (http://dx.doi.org/10.1371/journal.pone.0000023)

Note: This story has been adapted from a news release issued by Public Library of Science.
via Science Daily

Study On Accidental Introduction Of Invasive Snails With Parasitic Flatworms May Help Mitigate Spread Of Disease

2006-12-24T22:44:00.001+05:45

A paper that authors are calling a "home run" study on the spread of disease is published in this week's issue of the Proceedings of the National Academy of Sciences (PNAS).

The study traces -- through genetic analysis -- the accidental introduction of invasive snails with parasitic flatworms. The invaders were probably transported with Japanese seed oysters imported into the waters of the Pacific Northwest over a century ago. It is the first comprehensive genetic analysis of an invasive marine host and its parasites. The study points to broad implications for identifying and mitigating spreading disease in a globalized economy.

Understanding the invasion pathways of disease-causing organisms and their hosts is key in limiting future disease outbreaks -- in humans, in agriculture, and in wildlife.

Co-author Armand Kuris, professor of zoology in the Department of Ecology, Evolution and Marine Biology at the University of California, Santa Barbara, is one of a handful of experts who have been studying the ecology of parasites since the 1960s, an area of research that Kuris reports is understudied because parasites are so often invisible. He calls this PNAS paper a home run because it describes a complete picture of biological invasions. He explained that the imported snail has wiped out the native snails, changing the ecosystems of the Northwest.

"Little did the American oystermen of the early 1900s know that their activities could impact local fisheries one hundred years later," said Kuris. "Oyster aquaculture brought in many exotic species, including clams, worms, and snails. Importation was done in a crude and sloppy manner; there was little government regulation of these things at the time."

Invasive North American populations of Asian mud snails, Batillaria attramentaria, probably arrived with Pacific oysters, Crassostrea gigas, imported from northern Japan in the early 1900s, according to the scientists. Genetic research has now confirmed this. The team included first author Osamu Miura, a scientist with Tohoku University in Sendai, Japan; colleagues from the Smithsonian Tropical Research Institute in Panama (STRI); and, scientists from UC Santa Barbara.

"We saw a lot of genetic variation among snail populations in Japan but the North American snails are genetically most similar to those from northern Japan, the source of the imported oysters," Miura reports.

"Using genetics we have shown how the pest snail was introduced and that it came with a parasite that infects fishes and birds," said Mark Torchin, a biologist with STRI. Later, a second parasite came that was spread by migratory birds that ate the infected fish in Japan. The process shows that establishment of an invasive pest can lead to later establishment of disease organisms.

Ryan F. Hechinger, a doctoral student at UCSB, explained how the parasitic flatworm, or trematode, castrates the snail, replacing the gonads with its own mass. "The infected snail will never again make snail babies," said Hechinger. "It is now a parasite making machine. It's basically a robot driven by the parasite."

Hechinger explained that this is the first time that scientists have examined an invasion of a host and a parasite. Migrating birds are bringing one of the trematode parasites; they ingest them when they eat infected fish. The host is a particular snail --- only one species is vulnerable ---- and it is used as an intermediate host. The trematode moves on from the snail to burrow into fish. The trematode has permeated the ecosystem's fish.

Of the eight species of trematode parasites that plague the snails in Japan, only the most common, Cercaria batillariae, has arrived in America. Gene sequencing showed that this single species actually consisted of several cryptic, or similar looking but genetically distinct, species in its home range in Japan. In North America, they commonly found two of the species. One parasite shows much less genetic diversity in America than in Japan, whereas the other parasite is equally diverse in both regions.

"Genetic evidence suggests that while one cryptic parasite species experienced a bottleneck and probably came with the snails, the other was probably historically dispersed by migratory birds and could only establish in North America after the snail hosts arrived," added Torchin. "This is because these trematode parasites have complex life cycles, using snails as first intermediate hosts, fishes as second intermediate hosts and birds as final hosts. As we homogenize biotas as a result of repeated species invasions through global trade, we increase the chances of reuniting infectious agents with suitable hosts."

Parasites which may have historically gone unnoticed as "tourists" in some regions may become pervasive residents after invasion of their missing hosts.

Funding for this study was provided by the Japan Society for the Promotion of Science, the Ecology of Infectious Diseases program of the U.S. National Institutes of Health, and the National Science Foundation.

Note: This story has been adapted from a news release issued by University of California - Santa Barbara.
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Gene Chip Discovery May Lead To Individualized Treatment For 5 Hereditary Liver Diseases

2006-12-24T22:44:00.000+05:45

Gene Chip Discovery May Lead To

Researchers at Cincinnati Children's Hospital Medical Center have developed the first gene chip to use in the early diagnosis of at least five hereditary liver diseases, to detect genetic causes of jaundice in children and adults, and potentially to lead to personalized treatment options.

The chip, termed the "jaundice chip," is nearly 100 percent effective in the detection of the most common mutations in children with inherited causes of jaundice, according to a new Cincinnati Children's study in the January issue of the journal Gastroenterology.

"Other chips have been developed to assess drug metabolism," said Jorge Bezerra, MD, a pediatric gastroenterologist at Cincinnati Children's and the study's lead investigator. "This is the first chip in the world that has been customized to diagnose genetic mutations in patients with inherited types of liver diseases."

The chip uses a new technology that rapidly and accurately discloses the composition of several genes known to cause liver disease in children and adults. "The jaundice chip may also help us to discover whether subtle changes in these five genes that can cause devastating diseases in children may also modify the clinical course of other common liver diseases in adults,"said Mitchell Cohen, M.D., director of the division of gastroenterology hepatology and nutrition at Cincinnati Children's.

Jaundice is a yellowing of the eyes and skin caused by impairment in bile flow from the liver to the intestine. Impaired bile flow, or cholestasis, commonly known as jaundice, can lead to severe liver disease. In children, jaundice and cirrhosis are responsible for more than half of the need for liver transplantation.

Previous research on humans identified five genes responsible for inherited forms of jaundice, Until now, the broad array of causes of cholestasis including genetic, metabolic, inflammatory and drug- or toxin-induced disorders, created a challenge for physicians to diagnose a specific disease. Therefore, the treatment of affected children was not disease-specific and aimed at optimizing care to help reduce liver transplantation. With the jaundice chip, however, diagnosis can be simplified by surveying the genetic code for mutations in specific diseases.

The jaundice chip was designed as a "five-in-one" gene chip to screen mutations (a permanent change in the DNA sequence that makes up a gene) in five genes using only one milliliter, or less than a half of a teaspoon, of blood. Gene chips contain several thousand small fragments of DNA on a small piece of glass. Incubation of these chips with the patient's DNA sample produce chemical signals that "glow" and allow for the detection of the normal gene sequence, or of mutations if they are present in the patient.

"The jaundice chip is an extraordinary advance for our patients with liver diseases. It will improve diagnostic accuracy for perplexing diseases in infants and children, potentially decrease the need for invasive and costly studies, and allow us to develop specific treatment plans based on the correct genetic diagnosis," said Dr. Cohen.

"With further genetic testing of liver disease, there is the potential that medications can be tailored to meet the needs of individual patients taking into account the patient's genetic make-up," adds Dr. Bezerra. "For now, the use of the gene chip gives families piece of mind, knowing what their child is living with. The next focus of advances will be the development of medication that may block progression of their disease.

Today, detection of liver diseases with the jaundice chip is continuing, using samples from children worldwide through a research protocol in the division of gastroenterology, hepatology and nutrition at Cincinnati Children's. Once approved by the Food and Drug Administration, the potential for wider use is limitless, according to Dr. Bezerra.

The discovery of the jaundice chip was made possible through a grant from the Research Foundation at Cincinnati Children's with additional support by the National Institutes of Health (NIH).

Note: This story has been adapted from a news release issued by Cincinnati Children's Hospital Medical Center.

Treatments For Urinary Infections Leave Bacteria Bald, Happy And Vulnerable

2006-12-24T22:42:00.000+05:45

A different approach to treating urinary tract infections (UTIs) could defeat the bacteria that cause the infections without directly killing them, a strategy that could help slow the growth of antibiotic-resistant infections.

Instead of trying to wipe out bacteria, researchers in the laboratory of Scott Hultgren, Ph.D., the Helen L. Stoever Professor of Molecular Microbiology at Washington University School of Medicine in St. Louis, have been working to create pharmaceuticals that essentially "defang" the bacteria by preventing them from assembling pili, microscopic hairs that both enable the invasion of host cells and allow the bacteria to mount a cooperative defense against the host's immune system.

"We're leaving the bacteria bald but healthy and happy," says Jerome S. Pinkner, lab manager for Hultgren. "Rather than trying to kill them, we're working to make them non-pathogenic, so that they will be unable to adhere to or invade the bladder tissues and are readily eliminated from the body."

Pinkner and his colleagues think the bacteria will find it harder to evolve resistance to a treatment that does not directly impact their survival. According to an April 2006 National Institute of Allergy and Infectious Diseases fact sheet, resistance to at least one antibiotic has been detected in more than 70 percent of the bacteria that cause hospital-acquired infections.

In a recent paper in the Proceedings of the National Academy of Sciences, the Hultgren group and its collaborators reported on the successful development of a second generation of anti-pilus treatments or pilicides. A third generation is already undergoing tests now, and researchers are hoping to begin tests of their most potent pilicides in animal models in about a year.

UTIs mainly occur in women and are one of the most common infections, causing around $1.6 billion in medical expenses every year in the United States. Scientists believe 90 percent of all UTIs, which have been linked to poor hygiene, sexual behavior, and migration of intestinal flora, are caused by the bacterium Escherichia coli (E. coli).

Half of all women will experience a UTI at some point in their lives, and additional recurrent UTIs will affect 20 to 40 percent of these patients. Scientists previously thought repeat infections were primarily attributable to new infections from the intestine, where E. coli normally resides. But Hultgren's lab produced evidence showing that E. coli can enter a dormant state in the bladder where it causes no symptoms and is invisible to the immune system. Months or years later, the same bacteria can reactivate and start a new infection.

Hultgren's lab characterized in great detail the process E. coli uses to assemble its pili, which are capped by an adhesive compound that lets them attach to and invade host cells.

"E. coli is a Gram-negative bacterium, so it has an inner and an outer membrane, and many of its most important tools for interacting with the outside world are assembled in the space between the membranes," Pinkner explains.

A molecule known as the chaperone protein takes the parts of the pili from the inner membrane to their assembly site on the outer membrane. Hultgren's group determined the crystal structure of this protein and analyzed it to learn which regions of the protein needed to be blocked off by a pharmaceutical to prevent the chaperone from doing its job.

To synthesize an appropriate drug, Hultgren has been collaborating with chemists including Fredrik Almqvist, Ph.D., associate professor of bioorganic chemistry at Umeå University in Sweden.

Scientists hope that the pilicide approach will significantly diminish the bacteria's ability to find ways of evading the new treatments.

"For bacteria to develop resistance to a new antibiotic, which by definition kills bacteria, all you need is for one bacterium among trillions to acquire a genetic mutation that allows it to survive," Pinkner explains. "We think that pilicides will greatly reduce the pressure to develop resistance and have already shown in the lab that they have no effect on E. coli's growth or metabolic state."

Pinkner notes that all Gram-negative bacteria, including Yersinia pesitis (plague), Salmonella, and Klebsiella pneumoniae (pneumonia and burn and urinary tract infections) make pili and may be susceptible to the same treatments. Keeping the target of the drug specifically aimed at a virulence factor not essential for growth reduces the chances for general resistance to spread, Pinkner asserts. He also notes that such drugs will have fewer effects on bacteria that benefit the host by contributing to healthy human physiology.

"For example, there are bacteria in the intestinal tract that aid in metabolism and the normal function of the intestine, which also helps prevent this niche from being occupied by pathogenic bacteria," he explains. "Given the rise in antibiotic resistance, it is critical to design antimicrobials for the future that target the bad bacteria but leave the good ones alone."

Pinkner JS, Remaut H, Buelens F, Miller E, Åberg V, Pemberton N, Hedenström M, Larsson A, Seed P, Waksman P, Hultgren SJ, Almqvist F. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proceedings of the National Academy of Sciences, 2006 Nov 21;103(47):17897-17902.

Funding from the National Institutes of Health, the Swedish Natural Science Research Council, the Knut and Alice Wallenberg Foundation and the Medical Research Council supported this research.

Note: This story has been adapted from a news release issued by Washington University School Of Medicine.
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Researchers Use Stem Cells To Regenerate Parts Of Teeth

2006-12-24T22:37:00.001+05:45

A multi-national research team headed by USC School of Dentistry researcher Songtao Shi, DDS, PhD, has successfully regenerated tooth root and supporting periodontal ligaments to restore tooth function in an animal model. The breakthrough holds significant promise for clinical application in human patients.

The study appears December 20 in the inaugural issue of PLoS ONE.

Utilizing stem cells harvested from the extracted wisdom teeth of 18- to 20-year olds, Shi and colleagues have created sufficient root and ligament structure to support a crown restoration in their animal model. The resulting tooth restoration closely resembled the original tooth in function and strength.

The technique relies on stem cells harvested from the root apical papilla, which is responsible for the development of a tooth's root and periodontal ligament. Previous studies conducted by Shi and collaborator Stan Gronthos at the National Institutes of Health had utilized dental pulp stem cells. Shi found the new technique to be superior.

"The apical papilla provides better stem cells for root structure regeneration. With this technique, the strength of the tooth restoration is not quite as strong as the original tooth, but we believe it is sufficient to withstand normal wear and tear," says Shi.

He hopes to move the technique to clinical trials within the next several years, a potential boon for dental patients who are not appropriate candidates for dental implant therapy or would prefer living tissue derived from their own teeth.

"Implant patients must have sufficient bone in the jaw to support the implant. For those who don't, this therapy would be a great alternative," says Shi.

According to Shi, the not-so-distant future may be one in which not only wisdom teeth, but those baby teeth once left to the tooth fairy for a pittance, will become valuable therapeutic tools.

"We will be able to provide not only this technique, but other new therapies utilizing a patient's own stem cells harvested from their preserved teeth. This is a very exciting discovery and one that I hope to see in wide-spread clinical use in the near future," says Shi.

Funding for this study came from the National Natural Science Foundation of China, the Beijing Major Scientific Program grant and the National Institute of Dental and Craniofacial Research.

Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine. Wataru Sonoyama, Yi Liu, Dianji Fang, Takayoshi Yamaza, Byoung-Moo Seo, Chunmei Zhang, Liu He, Stan Gronthos, Cun-Yu Wang, Songlin Wang, Songtao Shi. PLoS ONE, 10.1371/journal.pone.0000079, Dec. 20, 2006.

Note: This story has been adapted from a news release issued by University of Southern California. via Science Daily

Risk Of Spina Bifida Associated With Choline Metabolism Genes, But Unrelated To Choline Intake

2006-12-24T22:37:00.000+05:45

A new study finds an association between two genes involved in choline metabolism and the risk of spina bifida. The study, published in the open access journal BMC Medicine, also shows that this association is independent of dietary choline intake by the mother during pregnancy.

Choline is a nutrient, essential for cardiovascular and brain function, and for cellular membrane composition and repair. Often taken as a lecithin supplement, choline is found in beef liver, egg yolk, peanuts, sunflower seeds, cauliflower and soy. Recent studies had suggested that choline intake during pregnancy might decrease the risk of spina bifida.

James Enaw, from the Texas A&M University System Health Science Center in Houston, Texas and colleagues from the California Birth Defects Monitoring Program, analyzed the presence of two specific variants of the genes encoding the enzymes human choline esterase A (CHKA) and CTP:Phosphocholine cytidylytransferase(PCYT1A) in 103 infants suffering from spina bifida and 338 unaffected infants, who served as controls.

Although the study had limited statistical power, Enaw et al.'s results show that one variant of CHKA is associated with a reduced risk of spina bifida and one variant of PCYTA1A is associated with a two-fold increased risk of spina bifida. Interestingly, these associations are not modified by intake of choline by the mother during pregnancy.

The authors conclude: "The results indicate that dietary choline and choline metabolism genes may affect the risk of spina bifida independently or through some other unknown mechanisms."

Note: This story has been adapted from a news release issued by BioMed Central.

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Structure Of Iron Regulatory Protein-RNA Complex Solved

2006-12-24T22:27:00.005+05:45

The surprising structure and properties of a protein responsible for regulating the transport, storage and use of iron -- as it binds its target RNA -- are described by researchers from the University of Illinois at Chicago in the Dec. 22 issue of Science.

Iron is an essential nutrient, and defects in uptake and metabolism that result in either deficiencies or overload of iron cause a variety of diseases and disorders, including heart disease, arthritis and cancer.

The iron regulating protein, called IRP1, has two structural forms, each with important functions within the cell.

When serving as one of two regulators of cellular iron metabolism through its control of gene expression, the tightly coiled IRP1 opens up to expose sites that bind messenger RNA at sites on the RNA called iron responsive elements, or IREs, that are common in genes involved in iron metabolism.

In its alternate form, IRP1 binds a cluster of iron and sulfur atoms to act as an important metabolic enzyme called aconitase. The assembly and disassembly of the iron/sulfur cluster in the aconitase form appears to be an effective mechanism for regulating IRP1 activity.

"We found that when IRP1 releases the iron/sulfur cluster and opens up to bind RNA, it undergoes an extraordinary, unexpected rearrangement," said William Walden, professor of microbiology and immunology at UIC and lead author of the study.

"This is the crucial step in understanding the specialized cellular processes that have evolved to maintain internal iron concentrations at the appropriate safe and useful levels and is important to the future design of therapeutic targets," Walden said.

IRP1 is a very large protein, composed of about 900 amino acids arranged into four major domains.

"We expected that IRP1 would open up the two major domains facing each other along a hinge, rather like a clam shell, to accommodate the RNA binding," Walden said. "What we didn't expect was that that opening up would also involve extensive movement within the domains."

The researchers also found two widely separated contact sites between IRP1 and the iron responsive element, said Karl Volz, associate professor in of microbiology and immunology at UIC and principle investigator of the study.

"This is one of the highest affinity bindings we have ever seen. The effect of binding a single iron responsive element, through interactions at two separate binding sites, essentially eliminates the possibility of non-specific binding," Volz said.

According to coauthor Elizabeth Theil, senior scientist at the Children's Hospital Oakland Research Institute in Oakland, Calif., just as drugs targeted to the three-dimensional protein structure emerged in the last century, "knowing how the iron response element RNA is folded in the IRP1 complex is a gift to drug design targeted to 3-D RNA structure -- a developing goal in this century."

The researchers believe the details of the IRP1:IRE interaction are likely also to apply to the other important iron regulatory molecule, IRP2, they wrote in their conclusion. "What remains to be determined is the evolutionary origin and selective advantage of such dramatic conformational plasticity and dual functionality as found in IRP1."

Anna Selezneva, of UIC, and Jerome Dupuy, Anne Volbeda and Juan Fontecilla-Camps of the Université Joseph Fourier in Grenoble, France, also contributed to the study. The study was funded by grants for the National Institutes of Health, and data were collected at the Southeast Regional Collaborative Access Team (SER-CAT) at the Advanced Photon Source at the U.S. Department of Energy's Argonne National Laboratory.

Note: This story has been adapted from a news release issued by University of Illinois at Chicago.
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Buildup Of Damaged DNA In Cells Drives Aging

2006-12-24T22:27:00.004+05:45

The accumulation of genetic damage in our cells is a major contributor to how we age, according to a study published in the journal Nature by an international group of researchers. The study found that mice completely lacking a critical gene for repairing damaged DNA grow old rapidly and have physical, genetic and hormonal profiles very similar to mice that grow old naturally. Furthermore, the premature aging symptoms of the mice led to the discovery of a new type of human progeria, a rare inherited disease in which affected individuals age rapidly and die prematurely.These progeroid mice, even though they do not live very long, have remarkably similar characteristics to normal old mice, from their physical symptoms, to their metabolic and hormonal changes and pathology, right down to the level of similar changes in gene expression," said corresponding author Jan Hoeijmakers, Ph.D., head of the department of genetics at the Erasmus Medical Center in Rotterdam, Netherlands. "This provides strong evidence that failure to repair DNA damage promotes aging-- a finding that was not entirely unexpected since DNA damage was already known to cause cancer. However, it shows how important it is to repair damage that is constantly inflicted upon our genes, even through the simple act of breathing."

The study found that a key similarity between the progeria-like, or progeroid, mice and naturally old mice is the suppression of genes that control metabolic pathways promoting growth, including those controlled by growth hormone. How growth hormone pathways are suppressed is not known, but this response appears to have evolved to protect against stress caused by DNA damage or the wear-and-tear of normal living. The authors speculate that this stress response allows each of us to live as long and as healthy a life as possible despite the accumulation of genetic damage as we age.

Findings from this study help to reconcile two conflicting hypotheses currently favored in the field of aging research about why we get old, according to the authors. The first is that our lifespan and how well we age is determined by the genes inherited from our parents. The second is that lifespan and fitness in old age is determined by how much damage we incur over our lifetime.

"Our study suggests that both of these hypotheses are correct. Damage, including DNA damage, drives the functional decline we all experience as we age. But how we respond to that damage is determined genetically, in particular by genes that regulate the growth hormone and insulin pathways," said Laura Niedernhofer, M.D., Ph.D., assistant professor of molecular genetics and biochemistry, University of Pittsburgh School of Medicine, and first author of the study.

How the researchers came to study the relationship between DNA damage and aging began almost serendipitously in the late 1990s while Dr. Niedernhofer was a post-doctoral fellow in Dr. Hoeijmakers' laboratory at Erasmus Medical Center, a well-known European center for medical genetics, including the diagnosis of people with unusual sensitivity to sunlight.

A German physician had contacted the center about a 15-year old Afghan boy who was highly sensitive to the sun and had other debilitating symptoms including weight loss, muscle wasting, hearing loss, visual impairment, anemia, hypertension and kidney failure. The boy's family had immigrated to Germany to seek better medical treatment for his condition.

Extreme sensitivity to ultraviolet (UV) radiation from sunlight is a hallmark of diseases caused by defective DNA repair--an important mechanism by which skin and other cell types normally cut out, or excise, damage to their DNA caused by UV light. Defects in one DNA repair mechanism, nucleotide excision repair (NER), causes xeroderma pigmentosum, a rare disease in which people have a 2,000-fold increased risk of skin cancer from sun exposure.

When the investigators obtained cells from the boy and tested them for NER activity, they found almost none. Further analysis of the boy's DNA revealed a mutation in a gene known as XPF, which codes for part of a key enzyme required for the removal of DNA damage. The XPF portion of the enzyme harbors the DNA-cutting activity; whereas a second portion, known as ERCC1, is essential for the enzyme to bind to the damaged DNA. Mutations in either XPF or ERCC1 lead to reduced activity of this key DNA repair enzyme.

"We were completely surprised by the finding that the patient had a mutation in XPF, because mutations in this gene typically cause xeroderma pigmentosum, which is a disease characterized primarily by skin and other cancers rather than accelerated aging," said Dr. Hoeijmakers. "This patient, therefore, has a unique disease, which we named XPF-ERCC1, or XFE-progeroid syndrome."

To understand why this XPF mutation caused accelerated aging, the investigators compared the expression pattern of all of the genes (approximately 30,000) in the liver of 15-day-old mice that had been generated in the laboratory to harbor a defect in their XPF-ERCC1 enzyme and that had symptoms of rapidly accelerated aging to the genes expressed by normal mice of the same age. This comparison revealed a profound suppression of genes in several important metabolic pathways in the progeroid mice. Most notably, the progeroid mice had a profoundly suppressed somatotroph (growth hormone) axis--a key pathway involved in the promotion of growth and development--compared to normal mice.

The investigators also found low levels of growth hormones in the progeroid mice and ruled out the possibility that this suppression was due to problems with their hypothalamus or pituitary glands, which regulate growth hormone secretion. Furthermore, they demonstrated that if normal adult mice were exposed to a drug that causes DNA damage, such as a cancer chemotherapy agent, the growth hormone axis was similarly suppressed. In other words, DNA damage somehow triggered hormonal changes that halted growth, while also boosting maintenance and repair.

Because growth hormone levels go down as we get older, contributing to loss of muscle mass and bone density, the investigators systematically compared the gene expression pattern of their progeroid mice to normal old mice to look for other similarities. What they found was a striking similarity pattern between the progeroid and normal-aged mice in several key pathways.

Indeed, for genes that influence the growth hormone pathway, there was a greater than 95 percent correlation in changes in gene expression between the DNA repair-deficient mice and old mice. And, remarkably, there was a near 90 percent correlation between all other pathways affected in the progeroid mice and the older mice.

"Because there were such high correlations between these pathways in progeroid and normal older mice, we are quite confident that DNA damage plays a significant role in promoting the aging process. The bottom line is that avoiding or reducing DNA damage caused by sources such as sunlight and cigarette smoke, as well as by our own metabolism, also could delay aging," explained Dr. Niedernhofer.

This research was supported by the National Institute of Aging, the National Institute of Environmental Health Sciences, the National Cancer Institute, the American Cancer Society, the Dutch Cancer Society, the Dutch Science Foundation and the Ellison Medical Foundation.

In addition to Drs. Hoeijmakers and Niedernhofer, others involved in this study include Andria Rasile Robinson and Anwaar Ahmad, University of Pittsburgh Cancer Institute; George Garinis, Anja Raams, Astrid Lalai, Esther Appeldoorn, Hanny Odijk, Roos Oostendorp, Arjan Theil, Wibeke van Leeuwen, Wim Kleijer, Wim Vermeulen, Bert van der Horst and Koos Jaspers, Erasmus Medical Center, Rotterdam, Netherlands; Peter Meinecke, Altonaer Kinder- Krankenhaus, Hamburg, Germany; and Jan Vijg, The Buck Institute for Aging Research, Novato, Ca.

Note: This story has been adapted from a news release issued by University of Pittsburgh Medical Center.

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Key Antibody Links Cells' Capture And Disposal Of Germs

2006-12-24T22:27:00.003+05:45

Scientists have found a new task managed by the antibody that's the workhorse of the human immune system: Inside cells, Immunoglobulin G (IgG) helps bring together the phagosomes that corral invading pathogens and the potent lysosomes that eventually kill off the germs.

The research, by Axel Nohturfft at Harvard University and colleagues at Harvard, Massachusetts General Hospital, and the Massachusetts Institute of Technology, appears this week in the Proceedings of the National Academy of Sciences.

"The IgG class of antibodies is a critical part of the human immune system, guarding us against infection by an endless array of microorganisms," says Nohturfft, associate professor of molecular and cellular biology in Harvard's Faculty of Arts and Sciences. "Our findings add yet another immunological task to the list of those handled by IgG."

While just one of several broad classes of human antibodies, IgG is by far the most important -- so much so that patients incapable of making their own antibodies to fight off infections are routinely treated with IgG alone. Broadly speaking, the immunological powerhouse manages the processes by which cells isolate and then kill invading microbes, viruses, and other antigens.

In a process called phagocytosis, intruding germs are first swallowed up by amoeba-like white blood cells and stored in membrane pouches called phagosomes. These compartments then fuse with lysosomes, toxic cellular reservoirs that kill and degrade the sequestered antigens by flooding the phagosomes with acid and destructive proteins.

IgG, Nohturfft and his colleagues report, plays a key role in this merger of phagosomes and lysosomes into the so-called phagolysosomes that finally do in most invading microbes. Specifically, the antibody prompts phagosomes and lysosomes to dock and bind to each other with actin filaments, the first step in the unification of the two vesicles.

Among the antibody's other known roles, Nohturfft's group has now shown that IgG serves to accelerate the creation of phagolysosomes. Under physiological conditions, the scientists found that latex beads coated with IgG formed phagolysosomes in just a third the time it took the cellular machinery to process uncoated beads, 15 minutes versus 45 minutes.

"This process is central to the human immune response," Nohturfft says. "But some of the most destructive microbial pathogens, such as those responsible for tuberculosis and salmonellosis, are able to hijack cells and use them as a breeding ground precisely because they block the merger of phagosomes and lysosomes. It had long been known that coating these germs with IgG can restore their destruction and our recent results reveal a new branch of this IgG-led counterattack."

Nohturfft's co-authors on the PNAS paper are Vishal Trivedi, Shao C. Zhang, Adam B. Castoreno, Walter Stockinger, and Eugenie C. Shieh of Harvard's Department of Molecular and Cellular Biology; Jatin M. Vyas of MIT's Whitehead Institute for Biomedical Research and Massachusetts General Hospital; and Eva M. Frickel of the Whitehead Institute for Biomedical Research. Their research was funded by the National Institutes of Health.

Note: This story has been adapted from a news release issued by Harvard University.
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More Common Associations Found Between BRCA1 And BRCA2 Mutations And Cancer

2006-12-24T22:27:00.002+05:45

BRCA1 and BRCA2 mutations may be more common in the general population than previously reported and may be associated with ovarian, breast, testicular, and pancreatic cancers, according to a study in the December 6 issue of the Journal of the National Cancer Institute.

Mutations in the BRCA1 and BRCA2 genes are known to lead to breast and ovarian cancer. However, the frequency of these mutations in the general population has not been well-characterized.

Harvey A. Risch, M.D., Ph.D., of the Yale University School of Medicine in New Haven, Conn., and colleagues looked for BRCA1 and BRCA2 mutations in 1,171 ovarian cancer patients from Ontario who were diagnosed between 1995 and 1999. They examined cancer outcomes in the patients' 8,680 first-degree relatives.

The authors found that 13.2% of the ovarian cancer patients had BRCA1 or BRCA2 mutations compared with 0.32% for BRCA1 mutations and 0.69% for BRCA2 mutations in the general Ontario population. BRCA1 mutations in the general Ontario population were associated with higher risk of ovarian, female breast, and testicular cancers. BRCA2 mutations in the general Ontario population were associated with higher risks of male and female breast, ovarian, and pancreatic cancer. They estimated that about 1% of people in the general Ontario population carried these mutations, which is much higher than had been previously thought.

"BRCA1 and BRCA2 mutations should be suspected in families with breast, ovarian, and various other cancers in male relatives as well as female," the authors write.

In an accompanying editorial, Kenneth Offit, M.D., of Memorial Sloan-Kettering Cancer Center, writes that the implications for doctors and patients remain unchanged. The prevalence of BRCA2 mutations associated with ovarian cancer "still warrants consideration of risk-reducing surgery, albeit at a somewhat older age than that recommended for BRCA1 mutation carriers. ...BRCA mutation status remains one of the strongest markers for risk of this disease, warranting increased surveillance with such modalities as magnetic resonance imaging, hormonal and other chemoprevention, and, in selected circumstances, preventive surgery."

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

Note: This story has been adapted from a news release issued by Journal of the National Cancer Institute.
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Study Identifies Characteristics Of Fast-growing Skin Cancers

2006-12-24T22:27:00.001+05:45

Melanomas (skin cancers) are more likely to grow rapidly if they are thicker, symmetrical, elevated, have regular borders or have symptoms, according to a report in the December issue of Archives of Dermatology, one of the JAMA/Archives journals. In addition, rapidly progressing melanoma is more likely to occur in elderly men and individuals with fewer moles and freckles, and its cells tend to divide more quickly and have fewer pigments than those of slower-growing cancers.Anecdotal experience suggests that there is a form of rapidly growing melanoma, but little is known about its frequency, rate of growth, or associations," the authors write as background information in the article. One previous study suggested that how quickly a melanoma grew predicted how likely the patient was to relapse at one year or to survive without relapsing. Other research indicates that different types of melanoma grow at different rates; for instance, an aggressive type known as nodular melanoma grows more quickly than any other kind.

Wendy Liu, M.B.Ch.B., Ph.D., Peter MacCallum Cancer Center, East Melbourne, Australia, and colleagues investigated melanoma growth rate in 404 consecutive patients (222 male, 182 female, average age 54.2) with invasive melanoma. Participants' skin was examined by a dermatologist and information about such characteristics as the number of typical and atypical moles was recorded. In addition, the patients were interviewed as soon as possible after diagnosis and preferably with a friend or family present. The researchers gathered information about demographics, skin cancer risk factors, the characteristics of the tumor and who first detected the cancer--the patient, a family member or friend, or a physician.

In addition, all patients and their families were asked to recall the date at which they first noticed a spot on their skin from which the melanoma later developed and then the date at which they noticed the marking had changed or become suspicious. The researchers used these two dates, the date that the melanoma was removed as obtained from medical records, and the thickness of the tumor at the time of removal to estimate the approximate rate of growth. This method was doubled-checked by comparing the rate of growth with the tumor mitotic rate, or the rate at which the cancer cells multiply. Those tumors with a faster mitotic rate also had a faster rate of growth as determined by the researchers' formula.

Approximately one-third of all the melanomas (141) grew less than .1 millimeters per month, another one-third (136) grew between .1 millimeters and .49 millimeters per month, and one-third grew by .5 millimeters or more per month. A high rate of growth was associated with tumor thickness, ulceration (formation of a break or sore on the skin), amelanosis (lack of pigment in the tumor), regular borders, elevation and symptoms. Faster-growing melanomas were more likely to occur in individuals 70 years or older, in men and in those with fewer moles and freckles. Factors that were not associated with the rate of growth were the number of atypical moles or solar lentigines (age spots or liver spots), history of sun damage or blistering sunburns, skin type, eye color, family or personal history of melanoma, and current or childhood sun exposure.

"In summary, this study provides descriptive data on the spectrum of melanoma rates of growth and insights into subgroups of patients with melanoma that are associated with rapid growth," the authors conclude. "We propose that this information on melanoma rate of growth be incorporated into education programs for patients and health professionals." Awareness of the clinical features of faster-growing melanomas could help ensure that aggressive cancers are diagnosed and treated quickly.

Note: This story has been adapted from a news release issued by JAMA and Archives Journals.

via Science Daily

Olive Oil Emulsion Helps With Problem Heart Arteries

2006-12-24T22:27:00.000+05:45

An emulsion of olive oil, egg yolk and glycerine might be just the recipe to keep heart patients away from the operating room and cardiac bypass surgery.

That's the finding of a study to be published in the January issue of the journal Catheterization and Cardiovascular Interventions led by Michael Savage, M.D., director, Cardiac Catheterization Laboratory at Thomas Jefferson University Hospital, Philadelphia.

The mixture is not swallowed, Dr. Savage explains. Rather, it is used in the Cardiac Catheterization Laboratory to bathe surgical stents before they are inserted into problem heart arteries.

Since being introduced in 1994, stents--the metal mesh tubes placed in a coronary artery to keep it open after an interventional procedure--have worked in the majority of patients.

Coated or drug-eluting stents, which prevented restenosis (the re-closing of the artery a short time after stent insertion) were the next advance in this field.

"There are still a small number of patients with arteries that cannot be stented because of anatomic obstacles," said Dr. Savage, who is also associate professor of Medicine, Jefferson Medical College of Thomas Jefferson University.

Tortuosity is one such obstacle. It occurs when there are extreme bends in the vessels leading to or from the heart artery which taxes the limited flexibility of stainless steel stents. Dr. Savage likens attempting to place a stent through a tortuous vessel to "trying to move a couch around a narrow stairwell." Other obstacles are calcification, which hardens bones, and diffuse plaque, which can make the vessels too rigid for effective stent delivery.

"Patients in whom stents cannot be placed are at high risk of abrupt re-closure of the artery which could lead to life-threatening complications such as heart attack of emergency bypass surgery," Dr. Savage says.

The cardiologists tested the emulsion in a group of 15 men and five women between the ages of 60 and 80. These patients had abnormal arteries that were oddly shaped or winding or had particularly tight blockages--and could not be stented. After failed conventional attempts to insert stents, the Jefferson physicians were able to place the lubricated stents successfully in 17 (85 percent) of these patients with no negative effects months after the procedure.

The lubrication used was RotaGlide, an emulsion originally designed to reduce catheter friction during other cardiovascular procedures.

Composed primarily of olive oil, egg yolk phospholipids, glycerin, sodium hydroxide and water, it is commercially available as a sterile solution. The only contraindication to use of the product is known allergy to any of the ingredients.

To address unresolved issues about biocompatibility with the often-used drug-eluting stents, the researchers studied additional patients for a longer follow-up period. None of the patients who received the drug-eluting stents developed blood clots or restenosis.

"We found that this emulsion is a safe, simple and effective aid for stent delivery in the rare cases where stents could not previously be inserted," Dr. Savage said. "It would be a worthwhile addition to the interventionalists' bag of tricks."

Members of the Jefferson University team who conducted this study are: Alok Singh, M.D., Mark Awar, M.D., Adeeb Ahmed, M.D., Paul Walinsky, M.D., David L. Fischman, M.D. and Michael P. Savage, M.D.

For information about innovative treatment for cardiac disease or to make an appointment with a Jefferson cardiologist, call 1-800-JEFF-NOW.

Note: This story has been adapted from a news release issued by Thomas Jefferson University Hospital.
via Science Daily

Relative Abundance Of Common Microbes Living In The Gut May Contribute To Obesity

2006-12-21T22:56:00.001+05:45

Science Daily — A link between obesity and the microbial communities living in our guts is suggested by new research at Washington University School of Medicine in St. Louis. The findings indicate that our gut microbes are biomarkers, mediators and potential therapeutic targets in the war against the worldwide obesity epide

A link between obesity and the microbial communities living in our guts is suggested by new research at Washington University School of Medicine in St. Louis. The findings indicate that our gut microbes are biomarkers, mediators and potential therapeutic targets in the war against the worldwide obesity epidemic.

In two studies published this week in the journal Nature, the scientists report that the relative abundance of two of the most common groups of gut bacteria is altered in both obese humans and mice. By sequencing the genes present in gut microbial communities of obese and lean mice, and by observing the effects of transplanting these communities into germ-free mice, the researchers showed that the obese microbial community has an increased capacity to harvest calories from the diet.

"The amount of calories you consume by eating, and the amount of calories you expend by exercising are key determinants of your tendency to be obese or lean," says lead investigator Jeffrey Gordon, M.D., director of the Center for Genome Sciences and the Dr. Robert J. Glaser Distinguished University Professor. "Our studies imply that differences in our gut microbial ecology may determine how many calories we are able to extract and absorb from our diet and deposit in our fat cells."

That is, not every bowl of cereal may yield the same number calories for each person. People could extract slightly more or slightly less energy from a serving depending upon their collection of gut microbes. "The differences don't have to be great, but over the course of a year the effects can add up," Gordon says.

Trillions of friendly microbes reside in the intestine, where they help to digest food that the body can't on its own, such as the complex sugars found in grains, fruits and vegetables. As part of the digestive process, the microbes break down nutrients to extract calories that can be stored as fat.

The researchers focused on two major groups of bacteria - the Bacteroidetes and the Firmicutes - that together make up more than 90 percent of microbes found in the intestines of mice and humans. In an earlier study, they compared genetically obese mice and their lean littermates. The obese mice had 50 percent fewer Bacteroidetes and proportionately more Firmicutes. Moreover, the differences were not due to a bloom of one species in the Firmicutes or a diminution of a single or a few species of Bacteroidetes: virtually all members of each group were altered.

In one of this week's Nature articles, Ruth Ley, Ph.D., a microbial ecologist in Gordon's group, reports on her investigation into whether these findings also held true among obese humans. She followed 12 obese patients at a Washington University weight loss clinic over a one-year period. Half the patients were on a low-calorie, low-fat diet and half were on a low-calorie, low carbohydrate diet.

At the outset of the study, the obese patients had the same type of depletion of Bacteroidetes and relative enhancement of Firmicutes as the obese mice. As the patients lost weight, the abundance of the Bacteroidetes increased and the abundance of Firmicutes decreased, irrespective of the diet they were on. Moreover, not one particular species of Bacteroidetes but the entire group increased as patients lost weight.

In a companion paper in the same journal, Peter Turnbaugh, a Ph.D. student in Gordon's lab, compared the genes present in the gut microbial communities of the obese and lean mice using the newest generation of massively parallel DNA sequencers.

The results of these so-called comparative metagenomic studies revealed that the obese animals' microbial community genome (microbiome) had a greater capacity to digest polysaccharides, or complex carbohydrates. By transferring the gut microbial communities of obese and lean mice to mice that had been raised in a sterile environment (germ-free animals), he confirmed that the obese microbial community prompted a significantly greater gain in fat in the recipients.

Gordon notes that these findings represent steps in a long journey designed to understand the contributions of our microbial self to our health. "Our microbial cells outnumber our human cells by as much as 10 fold and, and they may contain 100 times more genes than our own human genome," Gordon says.

These studies raise a number of questions, according to Gordon. "Are some adults predisposed to obesity because they 'start out' with fewer Bacteroidetes and more Firmicutes in their guts?" he asks. "Can features of a reduced Bacteroidetes-Firmicutes enriched microbial community become part of our definition of an obese state or a diagnostic marker for an increased risk for obesity? And can we intentionally manipulate our gut microbial communities in safe and beneficial ways to regulate energy balance?"

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, Dec. 21, 2006.

Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Human gut microbes associated with obesity. Nature, Dec. 21, 2006.

Funding from the National Institutes of Health and the W.M. Keck Foundation supported this research.

Note: This story has been adapted from a news release issued by Washington University School of Medicine.

Source: Washington University School of Medicine

Drug Shown To Be Clinically Active Against Multiple Target Mutations In Two Types Of Leukemia And Myeloproliferative Disorders

2006-12-21T22:56:00.000+05:45

Science Daily — Researchers at The University of Texas M. D. Anderson Cancer Center report that MK-0457 (VX-680), a novel multi-kinase inhibitor, is clinically active against multiple target mutations in two types of leukemia and myeloproliferative disorders, and produces few side effects for patients.

Francis J. Giles, M.D., professor in the Department of Leukemia at M. D. Anderson Cancer Center, presented the Phase I / II trial data at the annual meeting of the American Society of Hematology.

According to Giles, the study of 44 patients, conducted at M. D. Anderson Cancer Center and Duke University Medical Center, showed the first clinical activity of a kinase inhibitor against the T315I BCR-ABL mutation found in chronic myeloid leukemia (CML) and acute lymphocytic leukemia (ALL). In addition, the trial showed the first activity against the JAK-2 mutation found in myeloproliferative disorders (MPD), a group of blood diseases that can evolve into leukemia. MK-0457 has also been found in previous studies to inhibit Aurora kinases A, B, C and FLT3 in leukemias.

Giles reported that patients on the study experienced minimal side effects, such that no maximum tolerated dose was defined. Mild side effects included lowering of white blood cells, hair loss, nausea and inflammation of the mouth.

"MK-0457 is a drug that produces clinical and biologic activity where we have not seen it before - in T315I-positive CML and ALL and JAK-2-positive MPD. This is a very active biologic agent for patients with advanced leukemia, and has very few side effects, all of which are quite manageable," Giles said. "With the data from this trial, we have a strong rationale to take this agent forward to more definitive and larger studies."

Though CML, ALL and MPD are relatively rare cancers, they are very aggressive and often fatal after failing standard therapy, said Giles. For the subset of leukemia patients who have the T315I mutation or for MPD patients with the JAK-2 mutation - about 10 percent of patients with the respective diagnoses - there are no therapies available to specifically attack these key mutations.

"This is a relatively small population that can potentially benefit from the drug, but for those who have these mutations, this research opens the door to a tremendous option for them," said Giles. "At present, there is nothing to offer them."

According to the American Cancer Society, there are about 4,000 new cases of ALL, about 4,500 new cases of CML and about 10,000 new cases of MPD diagnosed each year.

The T315I mutation is known to be responsible for the aggressive biological growth cycle and resistance to imatinib (Gleevec), nilotinib (Tasigna) and dasatinib (Sprycel) in CML and ALL. These kinase inhibitors have been found to be effective treating patients with leukemias who carry different mutations.

According to the study, the 35 leukemia patients on the study had at least four prior types of therapy, many of who received at least one of the three standard chemotherapies. The nine MPD patients' treatments ranged from one to seven prior lines of therapy.

But because of the mutations associated with resistance to these treatments, the patients did not respond until they were given the intravenous MK-0457 for five consecutive days. Of the patients with the T315I mutation, eight of nine patients with CML responded as did both of the T315I-positive ALL patients who had a partial response after the second cycle and complete response after the third cycle of treatment respectively.

"While we went into this trial to determine the safety and dosage of the drug, it became apparent quite quickly that the drug was very well tolerated and showing clinical response not only in patients but in terms of pharmacodynamics," said Giles. "As a result, we ended the Phase I aspect of the trial earlier than anticipated and moved into Phase II with a range of different doses to safely prescribe, depending on the patient's condition and outlook. We are quite hopeful that this drug will be beneficial for this segment of patients, but additional research will be needed."

Giles and his team are planning to begin later this month an international Phase II study of MK-0457 in patients with the T315I mutation.

Merck and Co. is currently conducting clinical trials of MK-0457 in various cancer types as part of a collaboration with Vertex Pharmaceuticals Incorporated. Merck and Co. holds worldwide and commercialization rights to MK-0457. MK-0457 (VX-680) was discovered by Vertex Pharmaceuticals.

Note: This story has been adapted from a news release issued by University of Texas M. D. Anderson Cancer Center.

Source: University of Texas M. D. Anderson Cancer Center

Blame Our Evolutionary Risk Of Cancer On Body Mass

2006-12-21T01:30:00.000+05:45

Science Daily — A key enzyme that cuts short our cellular lifespan in an effort to thwart cancer has now been linked to body mass
Until now, scientists believed that our relatively long lifespans controlled the expression of telomerase—an enzyme that can lengthen the lives of cells, but can also increase the rate of cancer.
Vera Gorbunova, assistant professor of biology at the University of Rochester, conducted a first-of-its-kind study to discover why some animals express telomerase while others, like humans, don't. The findings are reported in today's issue of Aging Cell.
"Mice express telomerase in all their cells, which helps them heal dramatically fast," says Gorbunova. "Skin lesions heal much faster in mice, and after surgery a mouse's recovery time is far shorter than a human's. It would be nice to have that healing power, but the flip side of it is runaway cell reproduction—cancer."
Up until now, scientists assumed that mice could afford to express telomerase, and thereby benefit from its curative powers, because their natural risk of developing cancer is low—they simply die before there's much likelihood of one of their cells becoming cancerous.
"Most people don't know that if you put mice in a cage so the cat can't eat them, 90 percent of them will die of cancer," says Gorbunova.
Evolution, it seems, has determined which species are allowed to express telomerase in their somatic cells in order to maintain a delicate balance between cells that live long, and cells that become cancerous. But while most scientists believed an organism's lifespan determined whether it was at a higher risk of cancer, Gorbunova has revealed evidence that it is not our long lifespan that puts us at risk, but our much-heavier-than-a-mouse body mass.
The tips of chromosomes, called telomeres, shorten every time a cell divides. After about 60 divisions, the telomeres are eroded away to the point that the cell stops dividing. Telomerase rebuilds those tips, so animals that express it, like mice, have cells that can reproduce more extensively and thus heal better.
Cancer cells, however, are those cells that constantly reproduce unchecked, and so evolution has shut off the expression of telomerase in human somatic cells, presumably because the threat of cancer outweighs the benefits of quick-healing.
But no one has looked into why mice express telomerase and humans don't. In fact, telomerase activity has been barely catalogued in the animal kingdom.
Gorbunova decided to take on the question by creating a unique test. She investigated 15 rodents from across the globe to determine what level of telomerase activity each species expressed, to see if there were some correlation she could find.
The species ranged from tiny field mice to the 100-pound capybara from Brazil. Lifespans ranged from three years for the mice, to 23 or more for common backyard squirrels.
Acquiring specimens of these animals from around the world proved to be an unusual task.
"At one point I was woken up at two in the morning by a guy on a cell phone hunting pest beavers in Montezuma," says Gorbunova. "I'm still trying to wake up and this voice says, 'I hear you're looking for beavers.' "
For over a year, Gorbunova collected deceased rodents from around the world and had them shipped to her lab in chilled containers. She analyzed their tissues to determine if the telomerase was fully active in them, as it was in mice, or suppressed, as it is in humans. Rodents are close to each other on the evolutionary tree and so if there were a pattern to the telomerase expression, she should be able to spot it there.
To her surprise, she found no correlation between telomerase and longevity. The great monkey wrench in that theory was the common gray squirrel, which lives an amazing two decades, yet also expresses telomerase in great quantity. Evolution clearly didn't see long life in a squirrel to be an increased risk for cancer.
Body mass, however, showed a clear correlation across the 15 species. The capybara, nearly the size of a grown human, was not expressing telomerase, suggesting evolution was willing to forgo the benefits in order to reign in cancer.
The results cannot be directly related to humans, but Gorbunova set up the study to produce very strong across-the-board indicators. It's clear that evolution has found that the length of time an organism is alive has little effect on how likely some of its cells might mutate into cancer. Instead, simply having more cells in your body does raise the specter of cancer—and does so enough that the benefits of telomerase expression, such as fast healing, weren't worth the cancer risk.
Gorbunova points out that these findings raise another, perhaps far more important question: What, then, does this mean for animals that are far larger than humans? If a 160-pound human must give up telomerase to thwart cancer, then what does a 250,000-pound whale have to do to keep its risk of cancer at bay?
"It may be that whales have a cancer suppressant that we've never considered," says Gorbunova. "I'd like to find out what kind of telomerase expression they have, and find out what else they use to combat cancer."
As for the tiny mice: "They don't have to worry about cancer," she says. "They're probably all praying for an anti-cat gene."
Note: This story has been adapted from a news release issued by University of Rochester.
Source:University of Rochester

Pioneers In Field Of Functional Genomics Work Toward Gene Therapy For Vision Defects

2006-12-21T01:28:00.000+05:45

Science Daily — For millennia anglers have wondered how fish see colors, and the rainbow of lures in every bait shop reveal that we're still guessing. But, in fish, reptiles and birds, that's all we can do for now, according to husband and wife vision researchers, Drs. Jay and Maureen Neitz at the Medical College of Wisconsin in Milwaukee.
Primates and humans have three photoreceptors and can only see four basic colors, red, green, blue and yellow," says Jay Neitz, Ph.D. "Birds, fish and reptiles have four photoreceptors, allowing them to see things we cannot. They must see an entire dimension of color, including ultraviolet, infrared and all the combinations thereof, which we miss."
He is the R.D. and Linda Peters Professor in Ophthalmology at the Medical College. Maureen E. Neitz, Ph.D., is the Richard O. Schultz/Ruth Works Professor in Ophthalmology Research.
Two of the world's leading color vision researchers, the Neitzes are also pioneers in the field of functional genomics. Their studies of human color vision have not only identified the genes responsible for colorblindness, but also defined one of the first examples of a nervous system defect for which a person's DNA can predict both the occurrence and the severity of the disorder.
"This has been an important breakthrough, because as scientists strive to understand the genetic basis of human disease, more than merely revealing the presence of a genetic defect, it is also important to forecast the severity of the impairment," says Dr. Maureen Neitz.
They are currently studying gene therapy at the Froedtert & The Medical College of Wisconsin Eye Institute to evaluate the plasticity of the adult human visual system. Gene therapy has been demonstrated to correct deficits in the retina, but the major unanswered question is whether the brain can interpret new information it receives from the therapeutically-treated retina to restore vision. For humans to migrate around objects in their world requires that information about objects be transmitted from the retina to the brain, and that the brain recreate an image of the world.
Their color vision research has also provided them with unique opportunities to discover the steps in the causal chain from the gene, to protein function, to neural signal. They are applying these lessons to other genetic defects that cause visual impairment.
"We anticipate that our studies of the basic mechanisms controlling gene expression in the retina, and the structure/functional relationships among proteins involved in signal transduction, may lead to development of new methods for early diagnosis of retinal disorders, and ultimately extend our knowledge of the role genes play in construction of the nervous system," she says.
The Neitzes are currently conducting several research studies involving human subjects including a study of color vision and a study of how eye growth is controlled to cause nearsightedness. To learn more about these studies, interested participants can call (414) 456 2056.
Note: This story has been adapted from a news release issued by Medical College of Wisconsin.
Source:Medical College of Wisconsin

Bacterial infection ID method created

2006-12-21T01:11:00.004+05:45

UPI-- US scientists say they've developed a method of identifying specific sites of localized bacterial infections in living animals.
Bradley Smith of the University of Notre Dame and colleagues previously developed fluorescent molecular probes containing zinc that could be used to discriminate between common pathogenic bacteria, such as E. coli and Staphylococcus aureus, and mammalian cells.
In the new study, the scientists used the probes to pinpoint the sites of staph infections in laboratory mice. The scientists say physicians might have difficulty distinguishing localized bacterial infections from sites of sterile inflammation.
"Bacterial imaging is an emerging technology that has many health and environmental applications," the researchers said. "For example, there is an obvious need to develop highly sensitive assays that can detect very small numbers of pathogenic bacterial cells in food, drinking water or biomedical samples. In other situations, the goal is to study, in vivo, the temporal and spatial distribution of bacteria in live animals."
The study is described in a report scheduled for the Jan. 10 issue of the Journal of the American Chemical Society.
Copyright 2006 by United Press International. All Rights Reserved.
via ScienceDaily

Testosterone Therapy May Prevent Alzheimer's Disease

2006-12-21T01:11:00.003+05:45

Science Daily — Researchers at the University of Southern California have discovered a direct link between loss of testosterone and the development of an Alzheimer's-like disease in mice. They also discovered that testosterone treatment slows progression of the disease.
The study, published in the December 20 issue of The Journal of Neuroscience, predicts that testosterone-based hormone therapy may be useful in the treatment and prevention of Alzheimer's disease in aging men.
"We've known that low testosterone is a risk factor for Alzheimer's disease but now we know why," said Christian Pike, senior author and associate professor at the Leonard Davis School of Gerontology at USC. "The implication for humans is that testosterone therapy might one day be able to block the development of the disease."
In order to investigate testosterone's role in the development of Alzheimer's disease, the team took away the ability of male mice to produce testosterone. Some mice were then given a form of testosterone while others were given none.
The mice with lowered testosterone showed increases in levels of the protein beta-amyloid, which has been widely implicated as playing a role in the development of Alzheimer's disease. They also showed signs of behavioral impairment.
The mice that were given testosterone showed reduced accumulation of beta-amyloid and less behavioral impairment.
"These results are exciting because they tell us that we are on to something that is worth pursuing," said Pike. "The next step is to look at what the long term effects of testosterone therapy are in aging men."
This study adds valuable new information to understanding the role of hormones in aging and disease. Recent evidence has suggested that testosterone may be useful in other neurological conditions. In a presentation at the Society of Neuroscience's annual meeting this fall, Chien-Ping Ko, professor of biological sciences at USC reported that testosterone therapy improved muscle coordination in mice suffering from a form of Amyotrophic Lateral Sclerosis, Lou Gehrigs Disease.
Pike's co-authors on the Journal of Neuroscience study were Emily R. Rosario and Jenna Carroll of the USC Neuroscience Graduate Program and Salvatore Oddo and Frank M. LaFerla of the University of California, Irvine. The Alzheimer's Association and the National Institutes of Health provided funding.
Note: This story has been adapted from a news release issued by University of Southern California.
Source:
University of Southern California

Testosterone Therapy May Prevent Alzheimer's Disease

2006-12-21T01:11:00.002+05:45

Researchers at the University of Southern California have discovered a direct link between loss of testosterone and the development of an Alzheimer's-like disease in mice. They also discovered that testosterone treatment slows progression of the disease.
The study, published in the December 20 issue of The Journal of Neuroscience, predicts that testosterone-based hormone therapy may be useful in the treatment and prevention of Alzheimer's disease in aging men.
"We've known that low testosterone is a risk factor for Alzheimer's disease but now we know why," said Christian Pike, senior author and associate professor at the Leonard Davis School of Gerontology at USC. "The implication for humans is that testosterone therapy might one day be able to block the development of the disease."
In order to investigate testosterone's role in the development of Alzheimer's disease, the team took away the ability of male mice to produce testosterone. Some mice were then given a form of testosterone while others were given none.
The mice with lowered testosterone showed increases in levels of the protein beta-amyloid, which has been widely implicated as playing a role in the development of Alzheimer's disease. They also showed signs of behavioral impairment.
The mice that were given testosterone showed reduced accumulation of beta-amyloid and less behavioral impairment.
"These results are exciting because they tell us that we are on to something that is worth pursuing," said Pike. "The next step is to look at what the long term effects of testosterone therapy are in aging men."
This study adds valuable new information to understanding the role of hormones in aging and disease. Recent evidence has suggested that testosterone may be useful in other neurological conditions. In a presentation at the Society of Neuroscience's annual meeting this fall, Chien-Ping Ko, professor of biological sciences at USC reported that testosterone therapy improved muscle coordination in mice suffering from a form of Amyotrophic Lateral Sclerosis, Lou Gehrigs Disease.
Pike's co-authors on the Journal of Neuroscience study were Emily R. Rosario and Jenna Carroll of the USC Neuroscience Graduate Program and Salvatore Oddo and Frank M. LaFerla of the University of California, Irvine. The Alzheimer's Association and the National Institutes of Health provided funding.
Note: This story has been adapted from a news release issued by University of Southern California.
Source:University of Southern California via Science Daily

Blood Transfusions Raise Heart Patients' Infection And Death Risk -- Especially Women

2006-12-21T01:11:00.001+05:45

Science Daily — Blood transfusions save the lives of millions of heart surgery patients and others each year. But a new study suggests that patients who receive transfusions during heart bypass surgery have a higher risk of developing potentially dangerous infections, and dying, after their operation.
In fact, this increased risk may help explain a longstanding medical mystery: why women bypass patients are more likely than men to die in the first few months after surgery. Women are more likely to receive blood during heart bypass operations, which are performed on more than 465,000 Americans each year.
The findings, from the Patient Safety Enhancement Program (PSEP) at the University of Michigan Health System, are based on data from 9,218 Michigan bypass patients. After adjusting for factors such as the urgency of the operation, those who received blood transfusions from donors were five times more likely to die within 100 days of their operation than those who did not.
The paper is published in the December issue of the American Heart Journal. It builds on a previous U-M analysis that found that a difference in infection rates accounted for the difference in death risk between men and women bypass patients.
The U-M team, with the help of Neil Blumberg, M.D., of the University of Rochester Medical Center, focused on blood transfusions as a contributing factor. Prior research has shown that recipients of stored donor blood have more post-surgical infections, and that women receive more transfusions because they tend to have lower hemoglobin concentrations.
This new study connects the dots. "To the best of our knowledge, this is the first study to state that allogeneic transfusions may be the reason why women have a greater post-bypass surgery mortality risk than men," says author Mary A.M. Rogers, Ph.D., M.S., PSEP, research director and research assistant professor of internal medicine. Allogeneic is the term for blood from another person.
The authors strongly note that blood transfusions can be life-saving, and that the infections observed in this study are not likely due to contamination of the blood. Rather, they may be due to other factors, including the patient's immune response to substances such as white blood cells that are present in stored donor blood. These findings may help guide hospitals and blood banks in deciding whether to filter donated blood to reduce the levels of white blood cells. This practice is increasingly common, but not yet universal, in the United States.
The study is based on analysis of data from all Medicare beneficiaries ages 65 and older who had coronary artery bypass operations in Michigan in a single year.
The researchers performed statistical analyses that took into account the patients' blood transfusion status, their co-existing diseases, age, race, sex, and whether the bypass operation was done on an elective, urgent or emergency basis. They looked at infections and deaths that were reported during the 100 days after surgery.
In all, about 88 percent of women received an allogeneic blood transfusion during bypass surgery, compared with nearly 67 percent of men. When the researchers adjusted for other factors, women were 3.4 times as likely as men to receive blood. This gender difference was evident regardless of whether the operation was elective, urgent or emergency.
The odds of having an infection of any kind were about three times greater in patients who received allogeneic blood than in patients who did not. The more blood they received, the higher their infection risk. This "dose dependent" relationship strengthens the evidence that transfusions may be related to infections.
No single type of infection stood out as more common among blood recipients, which suggests a body-wide immune response issue rather than a problem, for example, at the site of the incision.
The analyses revealed that women were more likely to experience an infection than men after bypass surgery, which appeared to be due to the increased number of transfusions in women. This resulted in an increased mortality rate in women. Overall, 9 percent of women and 6 percent of the men died within 100 days of their operation.
For patients who had banked their own blood ahead of the operation and who received only their own blood, the infection risk was similar to that of patients who received no blood transfusions. Rogers notes that patients should ask their doctors regarding banking their own blood if possible, when scheduled for a bypass operation or other kind of surgery.
In addition, physicians are increasing their use of transfusion alternatives such as blood "expanders," blood substitutes and blood-conserving procedures during bypass surgeries.
The results also highlight the importance of the proper use of antibiotics and infection control practices in patients hospitalized for a surgical procedure, says Rogers.
The U-M team is investigating the issue further, including a new study funded by Blue Cross Blue Shield of Michigan Foundation to extend the research into elderly patients who recently underwent bypass surgeries in Michigan.
In addition to Rogers and Blumberg, the study authors included PSEP director Sanjay Saint, M.D., MPH; Catherine Kim, M.D., MPH; Brahmajee Nallamothu, M.D., MPH; and Kenneth Langa, M.D., Ph.D. It was funded by the Agency for Healthcare Research and Quality, the National Institutes of Health, the Department of Veterans Affairs, the John A. Hartford Foundation and a Paul B. Beeson Physician Faculty Scholars in Aging Research award.
Reference: American Heart Journal, Volume 152, Issue 6, Pages 1028-1034 (December 2006).
Note: This story has been adapted from a news release issued by University of Michigan Health System.
Source: University of Michigan Health System
via Sciencedaily

Study Explores Link Between Nanoparticles And Kidney Stones

2006-12-21T01:11:00.000+05:45

Science Daily — Researchers at Mayo Clinic have successfully isolated nanoparticles from human kidney stones in cell cultures and have isolated proteins, RNA and DNA that appear to be associated with nanoparticles. The findings, which appear in the December issue of the Journal of Investigative Medicine, are significant because it is one step closer in solving the mystery of whether nanoparticles are viable living forms that can lead to disease -- in this case, kidney stones.
Kidney stones are associated with pathologic calcification, the process in which organs and blood vessels become clogged with calcium deposits that can damage major organs like the heart and kidneys. What causes calcium deposits to build up is not entirely known. Medical scientists at Mayo Clinic are studying calcification at the molecular level in an effort to determine how this phenomenon occurs.
There is a growing body of scientific evidence that links calcification to the presence of nanosized particles, particles so small that some scientists question whether a nanoparticle can live and if so, play a viable role in the development of kidney stones.
The presence of proteins, RNA and DNA does not prove that nanoparticles are viable living forms because a genetic signature has not been identified, says the study's author John Lieske, M.D., a nephrologist with Mayo Clinic. A genetic signature would prove that nanoparticles are indeed living forms that replicate and can cause disease.
"We are looking at how kidney stones start as very small calcifications inside the kidney and then eventually grow into stones," says Dr. Lieske. "In the laboratory, we have isolated nanoparticles from kidney tissue and kidney stones, and have successfully propagated them in culture. This does not clearly confirm the role of nanoparticles in the formation of kidney stones, but it offers insight not otherwise known."
Approximately 12 percent of men and 5 percent of women will develop kidney stones by the time they reach 70 years old. Some $5 billion is spent in the United States each year to treat patients with kidney stones, but exactly how kidney stones form is not known. Scientists theorize that if nanoparticles become localized in the kidney, they can become the focus of subsequent growth into larger stones over months to years. Other factors, such as physical chemistry and protein inhibitors of crystal growth, also play a role. But what scientists don't quite understand is why, where and how they start growing, Dr. Lieske says.
The study cites evidence that indicates the unlikelihood that events linked to the calcification process are driven solely by physical chemistry, but instead are influenced by specific proteins and cellular responses. Understanding these events will provide clues to develop new therapy to treat kidney stones, the authors say.
"There are at least two novel hypotheses here in terms of how stones might actually form. One: an infectious agent. If that was the case, that would point us in the direction of using different kinds of treatments specific to an infectious agent. Two: the idea that cells drive calcification. That would suggest other alternative therapies," according to Virginia Miller, Ph.D., a specialist in vascular research at Mayo Clinic and a study author.
In addition, researchers examined how urine proteins alter the way crystals and cells interact in binding to cells -- the way in which cells respond to the crystals and assume more of a bone-like morphology and drive calcification over time.
In a second study, due to appear in the December issue of the Journal of Investigative Medicine, Drs. Lieske, Miller, and Karim Benzerara, Ph.D., of the Institut de Physique du Globe de Paris, attempted to identify a DNA chemical marker in nanoparticles. The preliminary study suggests that nanoparticles from human samples share spectroscopic characteristics with calcified bacteria that exist in freshwater lakes. However, studies could not confirm whether the nanoparticles are calcified bacteria or hydroxyapatite crystals that precipitated upon proteins present in the culture medium used to replicate the nanoparticles. Researchers did, however, identify chemical bonds between proteins and calcium in nanoparticles that were similar to those found in the bacteria that calcified in the environment.
"Right now the results are inconclusive. In some of the segments we saw a characteristic signal that might suggest DNA, but in others we did not," Dr. Miller says.
This is a relatively new area of science, so the tools and processes used in this research have yet to be perfected. "Many of these tools haven't been applied to these systems in a consistent, rigorous way. So we are still in the learning process of how to handle the material. For example, what are the ideal conditions in the laboratory in which we should study nanoparticles?
"It was disappointing that we did not find any consistent DNA information. We think the findings were inconclusive, in part, because of the inability to apply these techniques in conditions suitable to nanoparticles," Dr. Miller says.
The Lieske study was supported by grants from the National Institutes of Health, the Ralph C. Wilson Sr. and Ralph C. Wilson Jr. Medical Research Foundation, the Oxalosis and Hyperoxaluria Foundation, and Mayo Clinic.
The Benzerara study was supported by a National Science Foundation grant, the Stanford Institute for the Environment, the France-Stanford Center for Interdisciplinary Studies, the U.S. Department of Energy at Lawrence Berkeley National Laboratory, the National Institutes of Health, the Ralph C. Wilson Sr. and Ralph C. Wilson Jr. Medical Research Foundation, and Mayo Clinic.
Note: This story has been adapted from a news release issued by Mayo Clinic.
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Mayo Clinic
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New Technologies For Heart Disease: Are Drug-eluting Stents Worth The Cost?

2006-12-21T01:05:00.000+05:45

Over the past 3 decades, percutaneous coronary intervention (PCI, or balloon angioplasty) has significantly changed the treatment of coronary artery disease (narrowing of the arteries supplying the heart muscle).
Unlike the more invasive coronary artery bypass graft (CABG) surgery, angioplasty is a nonsurgical procedure in which a tiny catheter with a balloon is inserted into the coronary artery. The balloon is then inflated to push aside the plaque causing the narrowing. Often a stent (wire mesh tube) is left in place to help keep the treated artery open; however, restenosis, or repeat narrowing, of the artery can occur over time.
Drug-eluting stents were recently introduced to lower this risk of restenosis and have become an attractive alternative to bare-metal stents. However, they are much more expensive than bare-metal stents, and studies have shown no significant differences in rates of death or heart attack between patient groups receiving either type of stent.
Two articles that will appear in the Jan. 16, 2007, issue of CMAJ provide new insights into the use of drug-eluting stents.
The first is a research article by Grilli and colleagues in which they compare the use of drug-eluting stents for PCI in public versus private sectors of the Italian medical community. They also evaluate the effect PCI with drug-eluting stents has had on the volume of cardiac surgery, including traditional CABG surgery. They found that drug-eluting stents were used more frequently in private hospitals, with public hospitals using them more sparingly and selectively in patients with high-risk coronary artery disease. Overall cardiac surgery volumes decreased significantly in the public hospitals but remained stable in the private hospitals.
The authors note that future assessments of the impact of drug-eluting stents need to consider the influence of system-wide financial and organizational incentives for adoption of their use.
In the second article, Ligthart and colleagues systematically review all published cost-effectiveness analyses comparing drug-eluting stents and bare-metal stents for PCI. They comment on how the conclusions of these analyses have differed despite using a relatively constant measure of the efficacy of drug-eluting stents. The factors they found to be associated with these different conclusions were study quality, funding source and country of origin.
In a related commentary, Knudtson examines the ongoing debates that surround the cost-effectiveness of drug-eluting stents and the clinical indications for their use. Knudtson notes that even the clinical indications for PCI have been questioned by the findings of a recent trial that has successfully challenged the long-held belief that an open artery is always worth striving for, even late in a heart attack.
Note: This story has been adapted from a news release issued by Canadian Medical Association Journal.
Source:Canadian Medical Association Journal
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Kidney Transplantation Linked With Increased Risk Of Various Cancers

2006-12-21T00:44:00.002+05:45

Science Daily — Following kidney transplantation, some recipients may face a 3-fold increased risk of certain cancer types, according to a study in the December 20 issue of JAMA.
Immune suppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer, non-Hodgkin lymphoma, and Kaposi sarcoma. Whether other cancers occur at increased rates is uncertain, because there have been few long-term population-based studies, according to background information in the article.
Claire M. Vajdic, Ph.D., of the University of New South Wales, Sydney, Australia, and colleagues compared the incidence of cancer in 28,855 patients with end-stage kidney disease (ESKD) who received renal (kidney) replacement therapy (RRT). Data were collected for three separate time periods: the 5 years before RRT, during dialysis, and after transplantation. New cancers (1982-2003) were determined by record linkage between the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Cancer Statistics Clearing House.
The researchers found that the overall incidence of cancer, excluding nonmelanoma skin cancer and those cancers known to frequently cause end-stage kidney disease, was markedly increased (3.27 times) after transplantation. In contrast, cancer incidence was only slightly increased (1.35 times) during dialysis and before RRT (1.16 times). After transplantation, cancer occurred at significantly increased incidence at 25 sites, and risk exceeded 3-fold at 18 of these sites.
"Although the incidence of some cancers was increased during dialysis, and the incidence of a few was increased before RRT, the magnitude and breadth of the increased risk after transplantation suggests that immune suppression causes a substantial and broad-ranging increase in cancer risk," the authors write.
"After kidney transplantation, a wide variety of cancers across a number of organ systems occur with substantially increased incidence. Most, but not all, of these cancers are those with known or suspected viral causes. In contrast, cancer incidence was only slightly increased before kidney transplantation. Our findings point to an important role of the interaction between common viral infections and the immune system in the etiology [cause] of cancers at a broad range of sites," the researchers conclude.
Note: This story has been adapted from a news release issued by JAMA and Archives Journals.
Source:
JAMA and Archives Journals

Allergy Drug Slows Pancreatic Tumor Growth In Preclinical Studies

2006-12-21T00:44:00.001+05:45

An anti-allergy drug in use for more than 40 years significantly reduced tumor growth in animal models of human pancreatic cancer and also increased the effectiveness of standard chemotherapy, say researchers at The University of Texas M. D. Anderson Cancer Center.
In the Dec. 20 issue of the Journal of the National Cancer Institute, the investigators report that combining the drug, cromolyn, with chemotherapy was nearly three times better at retarding growth of pancreatic tumors in mice compared to the chemotherapy agent gemcitabine alone.
The finding may lead to a treatment advance for patients with pancreatic cancer, believed to be the most lethal of all cancers. More than 95 percent of patients diagnosed with the disease die from it, and half of those deaths occur in the first six months after diagnosis.
"Our goal is to offer longer life to these patients, and the combination of these two agents may well do that," says the study's lead author, Craig Logsdon, Ph.D., a professor in the Department of Cancer Biology.
Logsdon is working with physicians at M. D. Anderson to prepare for a clinical trial. Although cromolyn is off patent and widely available, it has been used only as a topical agent (through an inhaler, nasal spray and eye drops), so the research team is studying how to deliver the drug internally.
"Cromolyn seems to reduce survival mechanisms in pancreatic cancer cells enough that when gemcitabine is added, the chemotherapy is more effective," Logsdon says. "This is good, because chemotherapy normally has very little effect in patients."
The JNCI study demonstrates in mouse models of human pancreatic cancer that the cromolyn-gemcitabine combination reduced cancer growth by 85 percent compared to control animals, Logsdon says. "Cromolyn used alone actually had a good effect on reduction of tumors compared to control animals, which surprised us," he adds. It reduced tumor growth by 70 percent, compared to growth reduction of 50 percent when gemcitabine was used as a single agent, compared to control animals.
No one knows exactly how cromolyn works to control allergies. However, Dr. Logsdon has found that cromolyn can bind a specific protein produced by cancer cells and block that protein's ability to interact with a receptor that stimulates cancer cell growth, survival, and spreading. The relationship between how the drug controls allergies and its anti-tumor effect in pancreatic cancer remains unclear. "It may be possible that cromolyn has more than one target that influences cancer," he says.
Logsdon discovered the cancer-stimulating protein, determined how it triggers tumor growth and spread, and identified cromolyn as an inhibitor. "Through serendipity and basic science sleuthing we may now have something that helps patients," he says.
The study culminates Logsdon's five-year search for an agent to treat pancreatic cancer.
Logsdon searched for genes that produced proteins secreted only by cancer cells, which would then loop around and act on the cancer cell through a receptor on the cell surface. "That way, we could have two potential drug targets - the secreted protein and the receptor," he said.
Out of a long list of such genes, Logsdon and his research team selected one called "S100P" because it is a member of the large S100 gene family, some of which produce secreted proteins and some of which are associated with other cancers. Further work showed that S100P over-expression was very specific to pancreatic cancer; the protein was not found in normal pancreatic cells. "It is important to embryonic development, but no one knows its physiological role in adult biology," he says.
By using gene-silencing techniques, Logsdon found that when the protein is disabled, cancer growth is slowed. "S100P plays a role in tumor development because it causes cancer cells to grow faster, survive better, and be more invasive," he says.
Logsdon found that S100P interacts with a receptor known as "RAGE" which also plays a role in diabetes, arthritis and Alzheimer's disease. If RAGE is blocked in pancreatic cancer cells, addition of synthetic S100P to the tumor does not accelerate growth.
While Logsdon was defining S100P in pancreatic cancer, a Japanese research team working on allergies ran an experiment to see which proteins "stuck" to anti-allergy drugs, including cromolyn. Several members of the S100 family did. Logsdon then discovered that the drug also bound to S100P. He applied cromolyn to laboratory pancreatic cancer cells, and found that tumor growth was slowed. A larger effect was seen when the chemotherapy agent gemcitabine was combined with cromolyn.
Logsdon suspects that cromolyn may have other anti-tumor effects, a theory which he is currently testing. "For me this is pretty thrilling," he says. "In a relatively short time, we have gone all the way from discovering a molecule to preparations for a clinical trial."
The study was funded by the Lockton Endowment and the M. D. Anderson Cancer Center Pancreatic SPORE grant from the National Cancer Institute. Working with Logsdon were M. D. Anderson researchers Thiruvengadam Arumugam Ph.D. and Vijaya Ramachandran, Ph.D.
Note: This story has been adapted from a news release issued by University of Texas M. D. Anderson Cancer Center.

Source:
University of Texas M. D. Anderson Cancer Center
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High Levels Of Vitamin D In Body May Decrease Risk Of Multiple Sclerosis

2006-12-21T00:44:00.000+05:45

The possibility that vitamin D could help protect people from developing multiple sclerosis (MS) has been posited by researchers in recent decades, but evidence to support that link has been scant. In the first large-scale, prospective study to investigate the relationship between vitamin D levels and MS, researchers at the Harvard School of Public Health (HSPH) have found an association between higher levels of vitamin D in the body and a lower risk of MS. The study appears in the December 20, 2006, issue of the Journal of the American Medical Association.

If confirmed, this finding suggests that many cases of MS could be prevented by increasing vitamin D levels. Although these levels could be increased by taking supplements, before any recommendation is made it is important to establish whether we are seeing a true causal association or whether vitamin D levels are only a marker of MS risk," said Alberto Ascherio, senior author of the study and associate professor of nutrition and epidemiology at HSPH.
MS is a chronic degenerative disease of the central nervous system. It affects some 350,000 people in the U.S. and 2 million worldwide, and occurs most commonly in young adults. Women, who are affected more than men, have a lifetime risk of about 1 in 200 in the U.S. Vitamin D is a hormone manufactured naturally in the body, and its levels can be increased with exposure to sunlight, consumption of foods rich in vitamin D, such as fatty fish, and by taking supplements.
The researchers, led by Ascherio, worked in collaboration with colleagues in the U.S. Army and Navy to determine whether vitamin D levels measured in healthy young adults predict their future risk of developing MS. The investigation relied on a study population of more than 7 million individuals, whose serum samples are stored in the Department of Defense Serum Repository. Between 1992 and 2004, 257 U.S. Army and Navy personnel with at least two serum samples stored in the repository were diagnosed with MS. A control group, consisting of participants who did not develop MS, was randomly selected from the study population. Serum samples were analyzed for levels of 25-hydroxyvitamin D, a good indicator of vitamin D availability to tissues, and individuals were divided into five groups of equal size according to their average levels. Because vitamin D levels are strongly influenced by skin color, separate analyses were conducted among whites, blacks, and Hispanics.
The results showed that, among whites, MS risk declined with increasing vitamin D levels--the risk was 62% lower among individuals in the top fifth of vitamin D concentration (corresponding approximately to levels above 100 nmol/L or 40 ng/mL) than among those in the bottom fifth (approximately below 63 nmol/L or 25 ng/mL). The association was strongest among individuals who were younger than 20 when they first entered the study. No significant association was found among blacks and Hispanics, possibly because of a smaller sample size and the lower levels of vitamin D found in those groups. The average age of onset of MS cases was 28.5 years old; there was no significant difference in the results between men and women.
"The results of this study converge with a growing body of experimental evidence supporting the importance of vitamin D in regulating the immune system and suppressing autoimmune reactions, which are thought by most experts to play a key role in the development of MS," said Ascherio. Kassandra Munger, first author and a doctoral candidate in nutrition at HSPH, added, "The amount of vitamin D that is needed to reach levels associated with MS protection is largely considered safe, and in fact higher vitamin D levels could be beneficial to prevent osteoporosis and other chronic diseases."
The researchers note that there could be other possible explanations for the protective role of vitamin D. For example, it's possible that exposure to UV light from the sun--the major determinant of serum levels of 25-hydroxyvitamin D--could protect people in other ways than increased vitamin D production.
The authors suggest further studies exploring how vitamin D may protect individuals from developing MS. "Although the results of this study are quite encouraging, reasonable certainty of a protective effect of vitamin D supplements requires direct experimental evidence in a large trial. Meanwhile, we are planning to expand our study to obtain more accurate data on the importance of age and of the vitamin D levels that need to be achieved for optimal protection," said Ascherio.
The work was supported by grants from the National Institute of Neurological Disease and Stroke and by a pilot grant from the National Multiple Sclerosis Society.
Note: This story has been adapted from a news release issued by Harvard School of Public Health.
Via: Sciencedaily

Older Men Treated For Early Prostate Cancer Live Longer Than Those Who Are Not

2006-12-20T02:11:00.001+05:45

Recent findings from an observational study by researchers at the University of Pennsylvania School of Medicine suggest that men between 65 and 80 years of age who received treatment for early stage, localized prostate cancer lived significantly longer than men who did not receive treatment. The study is published in the December 13th issue of the Journal of the American Medical Association.
Thanks to better cancer prevention education and the resulting wide-spread increase in using prostate-specific antigen (PSA) screenings, more men are being diagnosed with early-stage and low-or intermediate-grade prostate cancer. Studies have shown that the slow-developing nature of prostate cancer during its earliest stages makes treatment options, such as a radical prostatectomy (surgical removal of the prostate) and radiation therapy, controversial with unpredictable outcomes. Often, recently diagnosed men of this group were advised to just "watch and wait" to see how their situation progressed.
"For this study we looked back over the existing data of a large population of prostate cancer patients, aged 65 to 80, with small tumors that were at a low or intermediate risk of spreading," said senior author Katrina Armstrong, MD, MSCE, who worked on the study with colleagues from Penn's Abramson Cancer Center, Center for Clinical Epidemiology and Biostatistics, Leonard Davis Institute of Health and Economics, and Division of Internal Medicine, and Fox Chase Cancer Center. "After accounting for all their differences, we discovered that the men -- who within six months of diagnosis underwent surgery or radiation therapy -- were 31 percent less likely to die than those who did not undergo treatment during that time."
Researchers acquired the necessary data for this study from the Surveillance, Epidemiology, and End Results (SEER) Medicare database, a population-based cancer registry which encompasses approximately 14 percent of the US population. Data was included on 44,630 men, aged 65 to 80, who were diagnosed between 1991-1999, with prostate cancer and had survived more than a year after diagnosis. All patients were followed-up until death or December 31st, 2002, the end of the study. Of the 44,630 men, 32,022 (71.8 percent) were actively treated with either surgery or radiation therapy during the first six months after diagnosis. The remaining group of 12,608 (28.3 percent) were classified as having received "observation" and did not undergo surgery, radiation or hormonal therapy.
During the 12-years of follow-up, researchers found that the patients who received treatment had a 31 percent lower risk of death. In the observation-only group, 37 percent of the patients died whereas only 23.8 percent of those in the treatment group died.
Since this was not a randomized, controlled study but a retrospective analysis of existing data, the researches had to perform extensive statistical adjustments to account for study participants differences. Even with all these differences taken into account, there was still a significant improvement in the overall survival of those men who received active treatment. "This benefit was also seen across the board in all subgroups examined, including African-American men and older men aged 75-80 at diagnosis," added Armstrong. "However, as we summarized in the study, because observational data can never completely adjust for potential selection bias and confounding, our results must be validated by rigorous randomized controlled trials of elderly men with localized prostate cancer before the findings can be used to influence treatment decisions."
This study was funded by the Center for Population Health and Health Disparities at the University of Pennsylvania, Public Health Services Grant P50-CA105641.

Note: This story has been adapted from a news release issued by University of Pennsylvania School of Medicine.
Source: University of Pennsylvania School of Medicine
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Phototherapy For Neonatal Jaundice Associated With Increased Risk Of Skin Moles In Childhood

2006-12-20T02:11:00.000+05:45

Children who received light therapy (phototherapy) for jaundice as infants appear to have an increased risk of developing skin moles in childhood, according to a report in the December issue of Archives of Dermatology, one of the JAMA/Archives journals. Some types of moles are risk factors for developing the skin cancer melanoma.
Jaundice or hyperbilirubinemia occurs when bilirubin, a yellow pigment created as a byproduct of the normal breakdown of red blood cells, cannot yet be processed by a newborn's liver and builds up in the blood, turning the skin, whites of the eyes and mucous membranes yellow. The condition affects between 45 percent and 60 percent of healthy babies and as many as 80 percent of infants born prematurely, according to background information in the article. During phototherapy, the treatment of choice for jaundice, babies are placed under blue lights (bili lights) that convert the bilirubin into compounds that can be eliminated from the body. Studies have been performed to assess the safety of this therapy, but many have not focused on its effects on the skin, the authors write.
Emmanuelle Matichard, M.D., Bichat-Claude Bernard Hospital, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, and colleagues assessed the presence of melanocytic nevi (moles) in 58 French children who were 8 or 9 years old at the time of the study. Eighteen children had phototherapy as newborns; 40 who were the same age but did not have phototherapy were recruited from a public school and served as controls. All the children and their parents were interviewed about the use of phototherapy, history of sun exposure and sunscreen use. A dermatologist performed physical examinations on the children and recorded their skin color, eye color, hair color, skin type and the number and size of moles.
Thirty-seven children (63 percent) had moles that were 2 millimeters or larger, and there was an average of 2.09 moles per child. Those who were exposed to phototherapy had significantly more moles of this size than those who did not--an average of 3.5 vs. 1.45 per child. When the analysis was limited to moles between 2 millimeters and 5 millimeters, the association was stronger. "Lentigo simplex [moles smaller than 2 millimeters in diameter] may represent more recent nevi, whereas those nevi due to early events should be larger," the authors write. "Nevi larger than 5 millimeters probably are congenital nevi and are most probably associated with genetic predisposition." These associations did not change when other risk factors for the frequency of moles, including skin type and light hair, were considered. Sun exposure, particularly during vacations, was also associated with the number of moles of all sizes, and light hair color was correlated with the number of moles smaller than 2 millimeters.
The study did not examine whether phototherapy increases the risk for melanoma in adults, and it is possible that the small difference in the number of moles between the two groups would not change their risk of developing cancer. However, further study could help illuminate the association. "Higher numbers of acquired benign nevi are associated with increased risk of melanoma," they conclude. "A detailed evaluation of the factors responsible for the development of nevi in children would be useful to identify high-risk groups to be targeted for prevention. The link between melanoma and phototherapy should be the focus of such a study."

Note: This story has been adapted from a news release issued by JAMA and Archives Journals.
Source: University of Pennsylvania School of Medicine

Low To Moderate Blood Alcohol Level Linked To Reduced Mortality Following Traumatic Head Injury

2006-12-20T02:09:00.000+05:45

Patients who have low to moderate blood alcohol levels may be less likely to die after arriving at the hospital with a traumatic brain injury than those with no alcohol in their bloodstream, according to a report in the December issue of Archives of Surgery, one of the JAMA/Archives journals. However, those with the highest alcohol levels appear to have an increased risk of dying in the hospital.
Alcohol use is a major risk factor for trauma, according to background information in the article. About one-third to one-half of all patients hospitalized with trauma are intoxicated at the time of injury. However, the effect of alcohol on how patients fare after a traumatic brain injury--a leading cause of disability and death among young people--is unclear. Some human and animal studies suggest that alcohol may be neuroprotective, keeping the injury from worsening once it has occurred.
Homer C. N. Tien, M.D., F.R.C.S.C., Sunnybrook Health Sciences Centre, University of Toronto, and colleagues studied 1,158 consecutive patients who were evaluated at an academic level I trauma center for severe brain injury caused by blunt trauma between 1988 and 2003. Tests done when the patients were admitted determined blood alcohol concentration (BAC). This information, as well as data on demographics, type of injury, severity of the injury, length of hospital stay and whether the patient died or left the hospital, was gathered from the hospital's trauma registry. The researchers also assessed a group of 528 patients with severe torso injuries, but no or mild head injuries, as a comparison.
Of the 1,158 traumatic brain injury patients, 740 had a BAC of zero, 315 had low to moderate BAC (0 to 230 milligrams per deciliter) and 103 had high BAC (230 milligrams per deciliter or higher); 403 died in the hospital. Those with a low to moderate BAC were less likely to die than those with no BAC (27.9 percent died vs. 36.3 percent). After adjusting for other factors that could influence the risk of death--including injury severity, blood transfusions and whether the trauma occurred in a motor vehicle crash--BAC was still associated with the risk of death. Those with a low to moderate BAC had 24 percent lower odds of dying in the hospital than those with no BAC. In contrast, those with a high BAC had 73 percent higher odds of dying than those with no BAC. Among patients with torso injuries, BAC was not related to the risk of death.
The authors mention that low to moderate doses of alcohol may protect the brain by stopping the mechanisms that contribute to secondary brain injury, which occurs when traumatized brain cells continue to be deprived of oxygen and worsens the damage caused by the initial event.
"There are major sociologic implications from implying that intoxicated patients with severe traumatic brain injury have better outcomes than non-intoxicated patients," the authors write. "We stress that our study only examined the role of alcohol on outcome in the post-injury phase because we examined only in-hospital deaths." About half of all individuals who die from trauma do so before they arrive at the hospital, they continue. Because alcohol use increases the likelihood of a severe injury, alcohol-related deaths comprise a large percentage of those who die before they have a chance to get to the hospital.
"Overall, people are still at much greater risk of dying if they drive while intoxicated," the authors conclude. "What our study implies is that there may be a role for an alcohol-based resuscitation fluid in improving outcomes in adequately resuscitated patients with severe head injury."
Note: This story has been adapted from a news release issued by JAMA and Archives Journals.

Source: JAMA and Archives Journals
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High Levels Of Blindness In Southern Sudan Following Years Of War

2006-12-20T01:54:00.001+05:45

Surveys conducted in southern Sudan, after conflict there ended in 2004, found much higher levels of blindness than anticipated. The results, published in PLoS Medicine, have major implications for the provision of health services in the region.
Sudan is the largest country in Africa and one of the poorest in the world. The southern region of the country is very remote and was devastated by a civil war that went on for nearly half a century, with only short intervals of peace.
An international team of researchers conducted a survey in May 2005 in Mankien--a district of Sudan with a total population estimated to be around 50,000. Their aim was to estimate how many people were blind or had ''low vision'' and to find out the main causes. Working under very difficult conditions, the researchers selected villages to be visited at random. A house in each village visited was selected by spinning a pen in the middle of the village. The people in this house were examined and then other houses were chosen, also at random. Around 2500 people were examined. Children under five years were not included in survey. A very high rate of blindness was found--4%. This is more than twice the level that would be expected, given what is known about the prevalence of blindness in other parts of rural Africa. The two most common causes of blindness and low vision were cataract and trachoma, each accounting for over one-third of cases. Trachoma, which is caused by an infection, was responsible for a greater proportion of the cases of blindness than has been found in studies in other parts of rural Africa.
In a second survey in the same district, the researchers looked specifically for cases of trachoma, both in its early stages and later when it has led to blindness. Some 3500 people were examined, of whom 2000 were children aged less than 15 years. The earliest stages of infection were very common indeed, particularly in children aged 1--9, over half of whom had some sign of infection. In adults, one in five had trichiasis caused by trachoma.
Trachoma can be passed from one person to another through contact with hands and clothes, and by flies. The disease develops gradually--while children are most susceptible to infection, they may not note its effects until adulthood, when scarring from repeated infections causes the eyelashes to turn inward (''trichiasis''). The cornea--the transparent front part of the eye--becomes damaged by the eyelashes and develops ulcers, and eventually blindness results.
The situation revealed by the researchers is particularly tragic as improved living conditions, better hygiene, and early treatment of the infection with antibiotics can prevent trachoma. Surgery for trichiasis is also very effective. The World Health Organization recommends a strategy for trachoma control known as 'SAFE': surgery, antibiotics, facial cleanliness, and environmental change. The authors call for its urgent implementation in southern Sudan.
The surveys are also discussed in two 'Perspective' articles in the same issue of PLoS Medicine. One article discusses the possibility that the methods used in these (and other) health surveys could over-estimate the level of blindness.
Citation: Ngondi J, Ole-Sempele F, Onsarigo A, Matende I, Baba S, et al. (2006) Prevalence and causes of blindness and low vision in southern Sudan. PLoS Med 3(12): e477. (http://dx.doi.org/10.1371/journal.pmed.0030477)
Note: This story has been adapted from a news release issued by Public Library of Science.
Source: Public Library of Science

High Levels Of Blindness In Southern Sudan Following Years Of War

2006-12-20T01:54:00.000+05:45

Surveys conducted in southern Sudan, after conflict there ended in 2004, found much higher levels of blindness than anticipated. The results, published in PLoS Medicine, have major implications for the provision of health services in the region.Sudan is the largest country in Africa and one of the poorest in the world. The southern region of the country is very remote and was devastated by a civil war that went on for nearly half a century, with only short intervals of peace.
An international team of researchers conducted a survey in May 2005 in Mankien--a district of Sudan with a total population estimated to be around 50,000. Their aim was to estimate how many people were blind or had ''low vision'' and to find out the main causes. Working under very difficult conditions, the researchers selected villages to be visited at random. A house in each village visited was selected by spinning a pen in the middle of the village. The people in this house were examined and then other houses were chosen, also at random. Around 2500 people were examined. Children under five years were not included in survey. A very high rate of blindness was found--4%. This is more than twice the level that would be expected, given what is known about the prevalence of blindness in other parts of rural Africa. The two most common causes of blindness and low vision were cataract and trachoma, each accounting for over one-third of cases. Trachoma, which is caused by an infection, was responsible for a greater proportion of the cases of blindness than has been found in studies in other parts of rural Africa.
In a second survey in the same district, the researchers looked specifically for cases of trachoma, both in its early stages and later when it has led to blindness. Some 3500 people were examined, of whom 2000 were children aged less than 15 years. The earliest stages of infection were very common indeed, particularly in children aged 1--9, over half of whom had some sign of infection. In adults, one in five had trichiasis caused by trachoma.
Trachoma can be passed from one person to another through contact with hands and clothes, and by flies. The disease develops gradually--while children are most susceptible to infection, they may not note its effects until adulthood, when scarring from repeated infections causes the eyelashes to turn inward (''trichiasis''). The cornea--the transparent front part of the eye--becomes damaged by the eyelashes and develops ulcers, and eventually blindness results.
The situation revealed by the researchers is particularly tragic as improved living conditions, better hygiene, and early treatment of the infection with antibiotics can prevent trachoma. Surgery for trichiasis is also very effective. The World Health Organization recommends a strategy for trachoma control known as 'SAFE': surgery, antibiotics, facial cleanliness, and environmental change. The authors call for its urgent implementation in southern Sudan.
The surveys are also discussed in two 'Perspective' articles in the same issue of PLoS Medicine. One article discusses the possibility that the methods used in these (and other) health surveys could over-estimate the level of blindness.
Citation: Ngondi J, Ole-Sempele F, Onsarigo A, Matende I, Baba S, et al. (2006) Prevalence and causes of blindness and low vision in southern Sudan. PLoS Med 3(12): e477. (http://dx.doi.org/10.1371/journal.pmed.0030477)
Note: This story has been adapted from a news release issued b
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Public Library of Science
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Low To Moderate Blood Alcohol Level Linked To Reduced Mortality Following Traumatic Head Injury

2006-12-20T01:51:00.000+05:45

Patients who have low to moderate blood alcohol levels may be less likely to die after arriving at the hospital with a traumatic brain injury than those with no alcohol in their bloodstream, according to a report in the December issue of Archives of Surgery, one of the JAMA/Archives journals. However, those with the highest alcohol levels appear to have an increased risk of dying in the hospital.Alcohol use is a major risk factor for trauma, according to background information in the article. About one-third to one-half of all patients hospitalized with trauma are intoxicated at the time of injury. However, the effect of alcohol on how patients fare after a traumatic brain injury--a leading cause of disability and death among young people--is unclear. Some human and animal studies suggest that alcohol may be neuroprotective, keeping the injury from worsening once it has occurred.
Homer C. N. Tien, M.D., F.R.C.S.C., Sunnybrook Health Sciences Centre, University of Toronto, and colleagues studied 1,158 consecutive patients who were evaluated at an academic level I trauma center for severe brain injury caused by blunt trauma between 1988 and 2003. Tests done when the patients were admitted determined blood alcohol concentration (BAC). This information, as well as data on demographics, type of injury, severity of the injury, length of hospital stay and whether the patient died or left the hospital, was gathered from the hospital's trauma registry. The researchers also assessed a group of 528 patients with severe torso injuries, but no or mild head injuries, as a comparison.
Of the 1,158 traumatic brain injury patients, 740 had a BAC of zero, 315 had low to moderate BAC (0 to 230 milligrams per deciliter) and 103 had high BAC (230 milligrams per deciliter or higher); 403 died in the hospital. Those with a low to moderate BAC were less likely to die than those with no BAC (27.9 percent died vs. 36.3 percent). After adjusting for other factors that could influence the risk of death--including injury severity, blood transfusions and whether the trauma occurred in a motor vehicle crash--BAC was still associated with the risk of death. Those with a low to moderate BAC had 24 percent lower odds of dying in the hospital than those with no BAC. In contrast, those with a high BAC had 73 percent higher odds of dying than those with no BAC. Among patients with torso injuries, BAC was not related to the risk of death.
The authors mention that low to moderate doses of alcohol may protect the brain by stopping the mechanisms that contribute to secondary brain injury, which occurs when traumatized brain cells continue to be deprived of oxygen and worsens the damage caused by the initial event.
"There are major sociologic implications from implying that intoxicated patients with severe traumatic brain injury have better outcomes than non-intoxicated patients," the authors write. "We stress that our study only examined the role of alcohol on outcome in the post-injury phase because we examined only in-hospital deaths." About half of all individuals who die from trauma do so before they arrive at the hospital, they continue. Because alcohol use increases the likelihood of a severe injury, alcohol-related deaths comprise a large percentage of those who die before they have a chance to get to the hospital.
"Overall, people are still at much greater risk of dying if they drive while intoxicated," the authors conclude. "What our study implies is that there may be a role for an alcohol-based resuscitation fluid in improving outcomes in adequately resuscitated patients with severe head injury."
Note: This story has been adapted from a news release issued by JAMA and Archives Journals.

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JAMA and Archives Journals
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Male Circumcision Reduces HIV Risk, Study Stopped Early

2006-12-19T22:17:00.003+05:45

A University of Illinois at Chicago study has been stopped early due to preliminary results indicating that medical circumcision of men reduces their risk of acquiring HIV during heterosexual intercourse by 53 percent.
The study’s independent Data Safety and Monitoring Board met Dec. 12 to review the interim data. Based on the board’s review, the National Institutes of Health halted the trial and recommended that all men enrolled in the study who remain uncircumcised be offered circumcision.
“Circumcision is now a proven, effective prevention strategy to reduce HIV infections in men,” said Robert Bailey, professor of epidemiology in the UIC School of Public Health and principal investigator of the study.
The clinical trial, funded by the National Institute of Allergy and Infectious Diseases and the Canadian Institute of Health Research, enrolled 2,784 HIV negative, uncircumcised men between 18 and 24 years old in Kisumu, Kenya.
Half the men were randomly assigned to circumcision, half remained uncircumcised. All men enrolled in the study received free HIV testing and counseling, medical care, tests and treatment for sexually transmitted infections, condoms and behavioral risk counseling for 24 months.
Study results show that 22 of the 1,393 circumcised men in the study contracted HIV, compared to 47 of the 1,391 uncircumcised men. In other words, circumcised men had 53 percent fewer HIV infections than uncircumcised men.
Until now, public health organizations have not supported circumcision as a method of HIV prevention due to a lack of randomized controlled trials.
“With these findings, the evidence is now available for donor and normative agencies, like WHO and UNAIDS, to actively promote circumcision in a safe context and along with other HIV prevention strategies,” Bailey said.
“Circumcision cannot be a stand-alone intervention. It has to be integrated with all the other things that we do to prevent new HIV infections, such as treating sexual transmitted diseases and providing condoms and behavioral counseling,” Bailey said. “We can’t expect to just cut off a foreskin and have the guy go on his merry way without additional tools to fight against getting infected.”
Opponents of circumcision have speculated that circumcised men may feel they are not at risk of contracting HIV and may be more likely to engage in risky behavior. The Kenya study suggests that circumcision did not increase risky behavior among circumcised or uncircumcised men, according to Bailey.
“Both uncircumcised and circumcised men are reducing their sexual risk behavior,” he said, “which indicates that our counseling is doing some good.”
The study also evaluated the safety of circumcision in a community health clinic with specially trained practitioners. There were no severe or lasting complications from circumcision. However, 1.7 percent of surgeries resulted in mild complications, such as bleeding or infection.
Bailey said that promoting circumcision in Africa must be done in conjunction with proper technical training and medical tools, equipment and supplies necessary to perform large numbers of circumcisions safely.
“Already, there are large numbers of boys and young men who are seeking circumcision in areas of Africa where men are not traditionally circumcised,” he said. “The danger is that unqualified practitioners will fill a niche by providing circumcision, but with much higher complication rates.”
An estimated 30 million people in Africa are infected with HIV/AIDS and more than 90 percent of HIV infections in adults result from heterosexual intercourse. In Kisumu, the third-largest city in Kenya, an estimated 26 percent of uncircumcised men are HIV infected by age 25.
“This study will likely not have a large impact on the incidence of HIV/AIDS in the United States or Europe where heterosexual transmission of HIV is low compared with areas like sub-Saharan Africa and parts of Asia,” Bailey said. “However, there are other proven health benefits of circumcision, including better hygiene, fewer urinary tract infections, and less risk of cervical cancer in the partners of circumcised men.”
The armamentarium of HIV prevention strategies is very small, according to Bailey. The only other strategy proven effective is the use of antiretroviral drugs to reduce transmission from mother to child.
If a significant proportion of men in a population get circumcised, it will have an enormous impact on preventing HIV infection in men, as well as reducing infections in women, Bailey said.
Co-investigators of the study include Stephen Moses and Ian Maclean at the University of Manitoba, Jekoniah Ndinya-Achola at the University of Nairobi, Corette Parker at Research Triangle International, Kawango Agot at UNIM Project, John Krieger at University of Washington, and Richard Campbell at UIC.
During the past two decades, more than 40 observational epidemiological studies and one previous clinical trial have reported an association between male circumcision and a reduced risk of HIV infection.
On Dec. 12, the NIH stopped another clinical trial of male circumcision undertaken by investigators in Uganda and at Johns Hopkins University, after the study’s Data Safety Monitoring Board reviewed the preliminary results and found a protective effect similar to that found in Bailey’s study.

Source: University of Illinois at Chicago

Painkillers May Threaten Power Of Vaccines

2006-12-19T22:17:00.002+05:45

With flu-shot season in full swing and widespread anticipation of the HPV vaccine to prevent cervical cancer, a new University of Rochester study suggests that using common painkillers around the time of vaccination might not be a good ideaResearchers showed that certain nonsteroidal anti-inflammatory drugs (NSAIDs), also known as cyclooxygenase inhibitors, react with the immune system in such a way that might reduce the effectiveness of vaccines.
The research has widespread implications: study authors report that an estimated 50 to 70 percent of Americans use NSAIDs for relief from pain and inflammation, even though NSAIDs blunt the body’s natural response to infection and may prolong it.
“For years we have known that elderly people are poor responders to the influenza vaccine and vaccines in general,” said principal investigator Richard P. Phipps, Ph.D., a professor of Environmental Medicine, and of Microbiology and Immunology, Oncology and Pediatrics. “And we also know that elderly people tend to be heavy users of inhibitors of cyclooxygenase such as Advil, aspirin, or Celebrex. This study could help explain the immune response problem.”
The study is available online in the Dec. 1, 2006, Journal of Immunology, and was funded in part by the National Institutes of Health.
When a person is vaccinated, the goal is to produce as many antibodies as possible to effectively neutralize the infection. To do this, white blood cells called B-lymphocytes, or B cells, spring into action to produce those antibodies. B cells also serve as the immune system’s memory for future protection against the illness.
But Phipps and colleagues discovered that human B cells also highly express the cyclooxygenase-2 (cox-2) enzyme, which is not intrinsically bad unless it is overproduced, causing pain and fever. So, when a person takes a drug to block the cox-2 enzyme — and thereby reduce pain and fever — the drug also reduces the ability of B cells to make antibodies.
“The next step is to figure out the worst time to take drugs that inhibit cox-2 in the context of getting vaccinated. Is it the day before, the day of, or the day after” The timing is likely to be very important,” Phipps said. “But meanwhile, we believe that when you reach for the medicine cabinet to reduce pain at the injection site, that is probably the wrong thing to do.”
The findings are based on laboratory studies of blood samples from people who participated in early clinical trials for the HPV vaccine, and on studies of mice.
For the animal portion of the study, researchers vaccinated normal mice and mice engineered to be cox-2 deficient with a component form of the HPV vaccine. They analyzed the amount of antibodies the animals produced, focusing on the critical virus-neutralizing antibodies. The cox-2 deficient mice made 50 to 70 percent less of these key antibodies.
The same experiment was done on preserved blood samples from people who had been vaccinated against HPV-16, the strain linked to cervical cancer. Scientists reactivated the B cells in the blood samples and watched them churn out antibodies, as expected. But when researchers treated the B cells with a cox-2 inhibiting drug, the cells significantly diminished their production of antibodies — showing that cox-2 is essential for an optimal immune response against HPV 16.
This study is not questioning the effectiveness of the newly marketed HPV vaccine, the Rochester scientists said. They pointed out that in many clinical trials involving thousands of women, the vaccine offered complete protection against the development of cervical cancer. And presumably some of these women were taking NSAIDs at the time.
“There’s no doubt the HPV vaccine showed 100 percent efficacy. Still, our data does suggest that it might be wise to limit the use of NSAIDs when you receive any vaccine,” said co-author Robert Rose, Ph.D., associate professor of Medicine and Microbiology and Immunology at the University of Rochester, and one of the virologists whose work led to the development of the new cancer vaccine.
Scientists do not completely understand the mechanism by which cox-2 influences the immune response in humans. They do believe the response may depend upon the dose and frequency of NSAID use.
The negative effects of blocking cox-2 could be more pronounced in people with compromised immune systems, such as AIDS or cancer patients, the study noted. Moreover, if a vaccine is in short supply and needs to be given in lower-than-optimal doses, taking an NSAID could hamper the immune response even more.
In addition to Phipps and Rose, graduate student Elizabeth Ryan was a co-author on the study, with assistance from students Matt Bernard and Christine Malboef.

Source: University of Rochester Medical Center

New Protective Action For Powerful Anti-HIV Factor Identified

2006-12-19T22:17:00.001+05:45

Scientists at the Gladstone Institute of Virology and Immunology (GIVI) have identified a previously unknown function of APOBEC3G (A3G), a protein that acts against HIV, a finding that may lead to new approaches for controlling HIV infection.
The work is published today, Oct. 2, 2006, in Proceedings of the National Academy of Sciences, USA.
The research, conducted by scientists in the laboratory of GIVI Director Warner C. Greene, MD, PhD, explains why CD4 T cells — the immune system cells targeted by HIV — are sometimes so susceptible to HIV infection and at other times are highly resistant.
Scientists have known that resistant CD4 T cells, called “resting cells,” are made up predominantly of CD4+ T cells that are in an inactive state, awaiting a stimulus to move into action. In these cells, A3G blocks HIV at an early step in its life cycle. However, when resting CD4 T cells are stimulated by a foreign protein or other signal, A3G is rapidly recruited into large RNA protein complexes within the cells. This change neutralizes the anti-HIV properties of A3G, opening the door to HIV infection.
In the current study, the researchers set out to decipher the protein and RNA components of the A3G RNA protein complexes. In so doing, Ya-Lin Chiu, PhD, a postdoctoral fellow in Greene’s laboratory, determined that the complexes help to prevent a threat within cells posed by a class of “jumping genes,” or retro-elements, which are sequences of DNA that change position within the genome, causing mutations, activating or inactivating other genes, or duplicating themselves, thereby increasing the quantity of DNA in each cell.
As with HIV, the replication and movement of these retro-elements to new chromosomal sites with potentially damaging effect involves copying DNA into RNA and then back into DNA again. The A3G RNA protein complex, Chiu determined, interrupts this retro-element replication cycle by binding the retro-element RNAs and sequestering them in the cytoplasm away from the nuclear machinery required for copying the RNA back into DNA and inserting the retro-element at a new chromosomal site.
Understanding A3G’s role in activated CD4 T cells could lead to a new strategy against HIV.
“If we can find a way to partially block A3G assembly into the large complexes during CD4 T cell activation, we could both preserve the potent anti-HIV effect of the small form of A3G and the protective function of the large A3G complex against select mobile genetic elements,” Greene said. Gladstone scientists are now exploring various ways to achieve this desired balance.
Other authors on the study were Gladstone postdoctoral fellows Mario Santiago PhD, and Vanessa B. Soros, PhD, and H. Ewa Witkowska and Steven C. Hall of the University of California, San Francisco, and Cécile Esnault and Thierry Heidmann from the Institut Gustave Roussy in Villejuif, France. Funding for the study came from the National Institutes of Health, San Francisco Women’s HIV Interdisciplinary Network, the American Foundation for AIDS Research, UCSF-GIVI Center for AIDS Research, Ligue Nationale Contre le Cancer, Sandler Family Foundation and the J. David Gladstone Institutes. The Gladstone Institute of Virology and Immunology is one of three research institutes of The J. David Gladstone Institutes, a private, nonprofit biomedical research institution. It is affiliated with UCSF, a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the health professions and life sciences, and providing complex patient care.

Source: University of California - San Francisco

Causes Of Global Death And Disease In The Next 25 Years

2006-12-19T22:17:00.000+05:45

In 1993, the World Bank sponsored the 1990 Global Burden of Disease study carried out by researchers at Harvard University and the World Health Organization (WHO). This study provided the first comprehensive global estimates of death and illness by age, sex, and region. It also provided projections of the global burden of disease and mortality up to 2020. The study and its projections have been crucial in national and international health policy planning. Colin Mathers and Dejan Locar (from the World Health Organization, Geneva) have now updated the projections based on 2002 data on mortality and burden of disease and published their results in the international open-access journal PLoS Medicine.
As for the earlier report, the researchers used projections of socio-economic development to model future patterns of mortality and illness for three different scenarios: a baseline scenario, a pessimistic scenario that assumes a slower rate of socio-economic development, and an optimistic scenario that assumes a faster rate of growth.
They predict that between 2002 and 2030 under all three scenarios life expectancy will increase around the world, fewer children under the age of 5 years will die, and the proportion of people dying from non-communicable diseases such as heart disease and cancer will increase. Although deaths from infectious diseases will decrease overall, HIV/AIDS deaths will continue to increase. Despite this increase, 50% more people are predicted to die of tobacco-related disease than of HIV/AIDS in 2015. By 2030, the three leading causes of illness will be HIV/AIDS, depression, and ischemic heart disease in the baseline and pessimistic scenarios. In the optimistic scenario, road-traffic accidents (which increase with socioeconomic development) will replace heart disease as the number 3 killer.

In an accompanying editorial, the PLoS Medicine editors ask whether they are publishing “the right stuff”, i.e. research and commentary whose goal it is to reduce mortality and suffering from the most relevant conditions–and whether research funding and health expenditure are consistent with these results.

Citation: Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3(11): e442. (http://dx.doi.org/10.1371/journal.pmed.0030442)
Source: Public Library of Science

Effective HIV Control May Depend On Viral Protein Targeted By Immune Cells

2006-12-19T00:49:00.004+05:45

An effective response of the immune system's 'killer' T cells against infection with HIV may depend on exactly which viral protein is targeted, according to an international group of researchers. A new study finds that HIV-infected individuals in whom virus-specific CD8 T cells are targeted against the Gag protein have lower viral levels than do those with CD8 responses directed against other viral proteins. The report from the Partners AIDS Research Center at Massachusetts General Hospital (PARC-MGH), the University of Oxford and University of KwaZulu-Natal in South Africa is receiving early online release in Nature Medicine.

Understanding which immune responses are effective in control of HIV is of critical importance in vaccine development," says Philip Goulder, MD, PhD, of PARC-MGH and Oxford, the senior author of the study. "Previous approaches have focused on a 'more is better' approach, seeking to generate responses against a broad range of viral proteins, but these results challenge that dogma."

While many strategies for developing a vaccine to control HIV focus on the activity of the CD8 T lymphocytes that recognize and destroy virus-infected CD4 T cells, the fact that even patients in the last stages of AIDS can have measurable CD8 responses indicates that those responses are not always effective. To investigate how variations in CD8 response alter the ability to control HIV, the research team enrolled almost 600 South African patients who had not yet been treated for their HIV infections.

The researchers comprehensively mapped the CD8 responses against all viral proteins and also investigated whether the versions of HLA Class I molecules involved in the immune system's recognition of HIV protein fragments made a difference. When new viruses are produced within an infected cell, Class I molecules grab viral fragments and display them at the cell surface, thereby alerting CD8 cells that the cell has been infected and should be destroyed. Earlier studies, including a 2004 Nature report from the same group, showed that the genetically determined version of an individual's HLA Class I molecules could strongly influence immune control of HIV.

The current study found that only CD8 responses against the Gag protein were associated with significantly reduced viral levels and that individuals with responses against several different Gag fragments had even lower viral loads. In contrast, those with stronger responses against other HIV proteins -- including Env, a protein that is the focus of several vaccine studies -- had higher viral levels indicating poorer control of HIV.

In people receiving no antiretroviral treatment, the improved HIV control associated with Gag-specific CD8 response would probably translate into asymptomatic infection for more than a decade, compared with progression to AIDS within two to three years of infection in those with no Gag responses. The reason why patients' particular HLA Class I molecules are linked to different HIV disease outcomes now appears to be related to the number of Gag fragments displayed by different versions of the Class I molecule.

Mechanisms underlying the different effects of the protein-specific immune responses are unknown and require further investigation. The researchers suggest that responses against proteins like Env might be inherently less effective or might only be generated in response to elevated viral loads. Therefore, the findings of this study, which reflect chronic HIV infection, might not apply in situations in which vaccination generates an immune response before infection occurs.

"The possibility that there may be fundamental differences between the impact of Gag and non-Gag CD8 responses on the ability to control HIV has clear relevance to vaccine development," says Goulder, who is an associate professor of Medicine at Harvard Medical School.

Co-authors of the Nature Medicine report from Doris Duke Medical Research Institute at the University of KwaZulu-Natal are first author Photini Kiepiela, Kholiswa Ngumbela, Christina Thobakgale, Dhanwanthie Ramduth, Eshia Moodley, Shabashini Reddy, Chantal de Pierres, Zenele Mncube, Nompumelelo Mkhwanazi, Karen Bishop, Mary van der Stok, Kriebashnie Nair, Nasreen Kahn, and Hoosen Coovadia. Other co-authors are Isobella Honeyborne, Hayley Crawford, Rebecca Payne, Alasdair Leslie, Julia Prado, Andrew Prendergast, John Frater, and Noel McCarthy, University of Oxford; Christian Brander and Bruce Walker, Partners AIDS Research Center at Massachusetts General Hospital; Gerald Learn, David Nickle, Christian Rousseau and James Mullins, University of Washington School of Medicine; and David Heckerman, Microsoft Research.

The study was supported by grants from the U.S. National Institutes of Health, the Wellcome Trust, and the Mark and Lisa Schwartz Foundation. Walker is a Howard Hughes Medical Institute investigator and a Doris Duke Distinguished Clinical Science Professor, and Goulder is an Elizabeth Glaser Pediatric AIDS Foundation Scientist.

Massachusetts General Hospital

Stem Cell Activity Deciphered In The Aging Brain

2006-12-19T00:49:00.003+05:45

Neurobiologists have discovered why the aging brain produces progressively fewer new nerve cells in its learning and memory center. The scientists said the finding, made in rodents, refutes current ideas on how long crucial "progenitor" stem cells persist in the aging brain.

The finding also suggests the possibility of treating various neurodegenerative disorders, including Alzheimer's disease, dementia and depression, by stimulating the brain's ability to produce new nerve cells, said senior study investigator Ashok K. Shetty, Ph.D., professor of neurosurgery at Duke University Medical Center and medical research scientist at Durham VA Medical Center.

Results of the study appear online in the journal Neurobiology of Aging. The research was funded by the National Institutes of Health and the U.S. Department of Veterans Affairs.

Previous studies by Shetty and others had demonstrated that as the brain ages, fewer new nerve cells, or neurons, are born in the hippocampus, the brain's learning and memory center. In one study, Shetty and colleagues showed that the production of new neurons in rats slows down dramatically by middle age -- the equivalent of 50 years in humans.

But scientists did not know what causes this decline.

The common assumption had been that the brain drain was due to a decreasing supply of neural stem cells in the aging hippocampus, said lead study investigator Bharathi Hattiangady, Ph.D., research associate in neurosurgery. Neural stem cells are immature cells that have the ability to give rise to all types of nerve cells in the brain.

In the current study, however, the researchers found that the stem cells in aging brains are not reduced in number, but instead they divide less frequently, resulting in dramatic reductions in the addition of new neurons in the hippocampus.

To conduct their census, the researchers attached easy-to-spot fluorescent tags to the neuronal stem cells in the hippocampus in young, middle-aged and old rats.

They found that in young rats, the hippocampus contained 50,000 stem cells -- and, significantly, this number did not diminish with aging. This finding, the researchers said, suggested that the decreased production of new neurons in the aged brain was not due to a lack of starting material.

The researchers then used another fluorescent molecule to tag all stem cells that were undergoing division in the process of staying "fresh" in case they were recruited to become mature nerve cells.

They found that in young rats, approximately 25 percent of the neural stem cells were actively dividing, but only 8 percent of the cells in middle-aged rats and 4 percent in old rats were dividing. This decreased division of stem cells is what causes the decreased neurogenesis, or birth of nerve cells, seen with aging, the scientists said.

"This discovery provides a new avenue to pursue in trying to combat the cognitive decline associated with conditions such as Alzheimer's disease and with aging in general," Hattiangady said.

The team now is searching for ways to stimulate the brain to replace its own cells in order to improve learning and memory function in the elderly.

One approach being explored is to treat older rats with drugs designed to mimic the action of compounds called neurogenic factors, which encourage stem cells in the brain to divide, Shetty said. The researchers also are grafting neural stem cells grown in culture dishes into the hippocampus, to stimulate those already present. Additional approaches include using behavioral modification techniques, such as physical exercise and exposure to an enriching environment, that are known to stimulate proliferation of stem cells.

Source:

Massachusetts General Hospital

&Sciencedaily

Eat To Live: Saving food traditions

2006-12-19T00:49:00.002+05:45

By JULIA WATSON for UPI

As environmentalists rush to save the earth fearful for the future of large swathes of it, foodies rush to save national cuisines whose traditions they think have already disappeared.

Italian Carlo Petrini founded Slow Food in 1986 to protect our food heritage. He was galvanized to do so by the affront of a McDonald's restaurant opening in Rome's historic Piazza di Spagna. He realized traditional dishes, produce, livestock were all vanishing, under the assault of fast food convenience, the power of supermarkets and the might of the industrial agribusiness.

Another Italian, Egeria di Nallo, head of political science at the University of Bologna, has made her own quiet and influential contribution to the preservation of food customs. She has created a network of women throughout Italy, proud home cooks every one, who will conjure up a meal of traditional dishes in their own kitchens for eight or so international members of Home Food, as the organization is called.

Once a month, these self-styled 'Cesarine' -- loosely 'empresses' of the kitchen, passionate about good cooking -- produce a meal for 8 or so paying guests who have registered in response to the monthly newsletter. They have been vetted for their cooking skills and divided, without apparently raising any hackles, into four social categories -- popular, middle class and two levels of the aristocracy. Whichever social spectrum the guests choose to dine in, each enables people to experience real Italian cooking in the homes of the cooks themselves.

Professor di Nallo, despondent at the lack of authentic Italian food in restaurants, launched the growing group two years ago. Now she has more than 50 Cesarine ready at their chopping boards. On different menus across Italy this coming January are regional specialties from the goose meat salami of Lombardy, to presnitz -- pasta filled with walnuts, almonds, sultanas and pine nuts -- from the Italy-Austria border, and Rome's aniseed dougnuts, all made with devotion and expertise by these proud amateurs.

It's not only in Europe that the call is out to protect food heritages. But it isn't working so effectively elsewhere. Last year, Mexico applied to UNESCO, the cultural arm of the U.N. for formal recognition of its food traditions. It wanted them acknowledged as part of their country's cultural heritage. But they were turned down.

Now the French are knocking at UNESCO's door with the same intent. L'Institut EuropÃ©en d'Histoire et des Cultures de l'Alimentation, an institute of food history and culture has joined with Tours University to gather up food professionals, writers, even the ex-minister of culture, to get behind a push to have France's gastronomic heritage recognized by UNESCO.

Perhaps they believe in a French kind of way that their classic cuisine stands a better chance to get the juices of those whose decision it will be flowing more readily than they did when Mexico's gastronomy was up for review.

At any rate, it is interesting that the movement to protect food as a cultural heritage is growing. And it's coming to a high end restaurant menu near you.

Increasingly, chefs are writing the provenance of their prime ingredients next to their dishes. At the Blue Duck Tavern in Washington D.C., there is even a separate column, with the name of each producer in capital letters. Nora Pouillon, at Restaurant Nora in the nation's capital, uses her menu "as a message board. If there is a campaign around a certain topic, such s fish that is nearly extinct, I note it on the menu so that the customers can learn."

It's almost impossible to order a plain ol' pork chop in an up-market eatery these days. The cut will be touted as coming from an acorn-fed Berkshire pig, a traditional breed with a better pedigree than you or me. And demand for a proper heritage turkey has been so great this year, it's far too late to think of ordering one now (though you could try at http://www.localharvest.org). Smaller than the supermarket balloon, it will have scampered around the thistly fields for between 24 and 30 weeks, instead of the 18 weeks it takes a flavorless White Breasted Tom to reach its requisite 32 pounds sale-weight.

These aspirations to save our food heritage shouldn't be sneered at as the stuff of the privileged classes. Our food is far too cheap. It prices hard-working small farmers around the globe out of the market. The pleasure in eating food that has been thoughtfully raised is immediate in the mouth. It's all about taste. And the well-being of the animal and the earth that raises the produce. Since we don't need to eat a lump of protein every day, it shouldn't necessarily make our weekly shopping a more expensive venture. We are paying a high price for convenience shopping and convenience eating.

Instead of satisfying that meat urge with a quick-to-throw-on-the-plate steak or chicken breast, take a little more time to put together this slow-braise casserole adapted from Nigel Slater. It will give you more than one meal with far cheaper meat.

--Italian-style slow-cooked aromatic lamb

--Serves 4 with left-overs

--1 pound dried cannellini or navy beans

--8 lamb shoulder or neck chops

--2 medium red onions, peeled and cut into eighths

--4 carrots, cut into thick chunks on the diagonal

--4 stalks of celery, cut on the diagonal into thick slices

--6 cloves garlic, peeled and bashed with the side of a knife

--2 small dried red chilies

--1 bottle quaffable red wine

--1 Â½ pints chicken stock

--2 oranges

--4 large portobello mushrooms

--2 tablespoons balsamic vinegar

--4 bay leaves and a small tied bunch of fresh thyme

--olive oil

--salt to taste

--Soak the beans overnight.

--Also overnight, marinade the lamb in a glass or china bowl with the next seven ingredients plus several long curls of scrubbed orange peel taken off with a potato peeler and then the oranges sliced into eighths.

--Next day, bring the beans to a boil covered with fresh water and boil for 10 minutes, then cover and turn off heat.

--Coat the bottom of a heavy bottomed pan with oil, dry off the chops and brown them both sides in batches and set aside in a heavy bottom lidded casserole.

--Drain off the marinade and fry everything left, together with the mushrooms, for around 10 minutes till softened. Add to the casserole.

--Bring the rest of the marinade to a boil in the pan, then add to the casserole with all remaining ingredients including the drained beans, cover with greaseproof parchment paper and the lid and leave to simmer gently for about 1 Â½ hours.

--If you allow 2 days for this, you can refrigerate it and spring off the fat. And the dish will develop more flavor.

CT scans used to analyze wood

2006-12-19T00:49:00.001+05:45

US government scientists say they are developing ways to use computerized tomography imaging to analyze various types of wood.

The U.S. Department of Energy researchers at the Oak Ridge National Laboratory say their findings might lead to important applications in the pulp, paper and nascent bioenergy industries.

Oak Ridge National Laboratory researcher Justin Baba is working to develop analytical tools to determine parameters such as fiber length and arrangement, cell wall thickness and density from CT scans. Those scans could replace more destructive, chemical-dependant, methods of analyzing wood samples that currently compromise the information collection process.

For bioenergy, after some basic measurement standards are established, Baba says the scans will be able to show the cellulosic content of wood to help create a cellulose-based biofuel supply.

Stem Cell Activity Deciphered In The Aging Brain

2006-12-19T00:49:00.000+05:45

Source:	Duke University Medical Center

Results of the study appear online in the journal Neurobiology of Aging. The research was funded by the National Institutes of Health and the U.S. Department of Veterans Affairs.

But scientists did not know what causes this decline.

To conduct their census, the researchers attached easy-to-spot fluorescent tags to the neuronal stem cells in the hippocampus in young, middle-aged and old rats.

The researchers then used another fluorescent molecule to tag all stem cells that were undergoing division in the process of staying "fresh" in case they were recruited to become mature nerve cells.

"This discovery provides a new avenue to pursue in trying to combat the cognitive decline associated with conditions such as Alzheimer's disease and with aging in general," Hattiangady said.

The team now is searching for ways to stimulate the brain to replace its own cells in order to improve learning and memory function in the elderly.

Anti-aging ingredient ready for market

2006-12-18T16:53:00.000+05:45

Source: UPI
A new anti-aging ingredient developed by university researchers in Australia may be available in skin products as soon as next year.
Known as GGC, the ingredient is a forerunner for the anti-oxidant glutathione and has a number of possible health benefits, the University of New South Wales researchers said. Glutathione is a defense for detoxifying harmful compounds implicated in cancer, diabetes, aging and other diseases and degenerative conditions in the body.
University researchers said after nine years they developed a new, cost-effective way to manufacture GGC, which has been licensed to Biospecialties Australia.
Researchers said they expected the ingredient would be used in foods, health and beauty products, dietary supplements and anti-aging creams.
Natural dietary sources of GGC are available, including milk whey protein and garlic in diluted concentrations, researchers said. The new GGC product could allow for more effective doses.

Copyright 2006 by United Press International. All Rights Reserved.

'Clumping' Protein Linked To Return Of Ovarian Cancer

2006-12-18T16:47:00.000+05:45

Johns Hopkins scientists have discovered that women treated for ovarian cancer are at increased risk of a rapid and potentially fatal recurrence if their tumor cells have high levels of a binding protein that triggers abnormal growth and slows down cell death, both hallmarks of malignancy.Now there's the possibility that testing for NAC-1 protein in cancer tissue removed during surgery might identify women most at risk for recurrence and guide doctors and patients to greater vigilance and extended therapy," said Ie-Ming Shih, M.D., Ph.D., associate professor of pathology at Johns Hopkins Kimmel Cancer Center. The research also suggests that drugs capable of blocking NAC-1 activity may be a useful strategy in preventing and treating recurrences as well.
A report on the research, the first to link NAC-1 to cancer, appears in the December 5 issue of the Proceedings of the National Academy of Sciences.
"Because recurrent cancers are often what really kill patients, and most ovarian cancer is diagnosed when it's already advanced, our findings offer women a better chance of catching or preventing recurrent disease early and increasing survival," says Shih.
An estimated at least 60 percent of advanced-stage ovarian cancer patients who appear to be disease-free after initial treatment develop recurrent disease, according to the researchers.
When the investigators compared levels of NAC-1 among primary and recurrent tumor samples taken from 338 ovarian cancer patients from two hospitals, they found that levels of NAC-1 were significantly higher in recurrent tumors compared with primary tumors taken from the same patient. Women whose primary cancers had high levels of NAC-1 were more likely to suffer a recurrence within one year.
Studying the functions of NAC-1, the researchers genetically modified cells so they made both NAC-1 and a component of the protein found at the ends of natural NAC-1 that is a binding site. In the modified cells, N130 capped off NAC-1 proteins disrupting their ability to bind with each other. This action can prevent tumor formation and kill cancer cells in experimental mice. Shih says that in the future, drugs that mimic N130 can be used to treat cancer.
This research was supported by the Department of Defense and the National Institutes of Health.
Co-authors of the published research include Kentaro Nakayama, Naomi Nakayama, Jim J.-C. Sheu, Antonio Santillan, Ritu Salani, Natini Jinawath, Robert E. Bristow, Robert J. Kurman, and Tian-Li Wang from Johns Hopkins; Ben Davidson from the Norwegian Radium Hospital, Oslo, Norway; and Patrice J. Morin from the National Institute on Aging, NIH.
Nakayama, K. "A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival." Proceeding of the National Academy of Science, Vol 103:49: pp18739-18744.
Source:
Johns Hopkins Medical Institutions and Sciencedaily

Boost For New Cancer Therapies

2006-12-18T16:43:00.001+05:45

Scientists have revealed the critical role a key enzyme plays in helping cells divide in what could prove an important breakthrough for new cancer therapies.
Cells divide to form two identical cells as part of the body's natural development and replenishment processes but when cells divide in an abnormal manner, tumours can develop.
Research has shown that an enzyme called 'Polo kinase' is involved in normal cell division but that it also goes into overdrive in cancer helping cells to multiply in an uncontrolled way.
Clinical trials on drugs that block the actions of Polo kinase started in the United States last year but the complete picture of how the enzyme assisted the cell-division process has not been clear until now.
Writing in the highly respected science journal, Nature, a team of researchers from the Universities of Manchester and Newcastle-upon-Tyne have described a new way in which the enzyme works.
"Enzymes are proteins that speed up or 'catalyse' the body's chemical reactions such as those required for normal cell division," explained Professor Andrew Sharrocks, lead researcher in Manchester's Faculty of Life Sciences.
"As its name suggests, the enzyme we have studied is from a group known as kinase enzymes which use a particular chemical -- a phosphate -- to catalyse the reactions that lead to cell division.
"Our study has identified a new target protein that uses these phosphate groups to switch on genes and alter the properties of cells.
"When the actions of enzymes like Polo kinase go unchecked, cells divide in an uncontrolled manner to form tumours. However, if we block their activity using chemical inhibitors the cells can no longer divide and the cancer cannot grow and spread."
The identification of a new key step in which Polo kinase functions confirms the choice of this enzyme as a target for anti-cancer drug development and will spur on efforts in this direction.
Indeed, as scientists now have a much greater understanding of the mechanisms involved, it might enable them to either develop more effective drugs or suggest different situations in which the drug can be used.
"Kinase inhibitors are proving to be very effective at killing off rogue cells and trials on patients elsewhere have been promising with fewer toxic effects than current cancer treatments," said Professor Sharrocks.
"Our research on Polo kinase will help with this line of drug development and hopefully produce more effective kinase-blocking chemicals that will one day treat patients with different types of cancer."

Source:
University of Manchester and Sciencedaily

Just How Useful Are Animal Studies To Human Health?

2006-12-18T16:43:00.000+05:45

Just How Useful Are Animal Studies To Human Health?
Animal studies are of limited usefulness to human health because they are of poor quality and their results often conflict with human trials, argue researchers in a study online in the British Medical Journal.

Before clinical trials are carried out, the safety and effectiveness of new drugs are usually tested in animal models. Some believe, however, that the results from animal trials are not applicable to humans because of biological differences between the species.
So researchers compared treatment effects in animal models with human clinical trials.
They used systematic reviews (impartial summaries of evidence from many different studies) of human and animal trials to analyse the effects of six drugs for conditions such as head injury, stroke and osteoporosis.
Agreement between human and animal studies varied. For example, corticosteroids did not show any benefit for treating head injury in clinical trials but did show a benefit in animal models. Results also differed for the drug tirilazad to treat stroke - data from animal studies suggested a benefit but the clinical trials showed no benefit and possible harm.
Some results did agree. For instance, bisphosphonates increased bone mineral density in both clinical trials and animal studies, while corticosteroids reduced neonatal respiratory distress syndrome in animal studies and in clinical trials, although the data were sparse.
Animal studies are generally of poor quality and lack agreement with clinical trials, which limits their usefulness to human health, say the authors. This discordance may be due to bias, random error, or the failure of animal models to adequately represent clinical disease.
Systematic reviews could help translate research findings from animals to humans. They could also promote closer collaboration between the research communities and encourage an interative approach to improving the relevance of animal models to clinical trial design, they conclude.

Source:
BMJ-British Medical Journal
and Sciencedaily

2006-12-18T16:39:00.000+05:45

'Clumping' Protein Linked To Return Of Ovarian Cancer
Johns Hopkins scientists have discovered that women treated for ovarian cancer are at increased risk of a rapid and potentially fatal recurrence if their tumor cells have high levels of a binding protein that triggers abnormal growth and slows down cell death, both hallmarks of malignancy.
"Now there's the possibility that testing for NAC-1 protein in cancer tissue removed during surgery might identify women most at risk for recurrence and guide doctors and patients to greater vigilance and extended therapy," said Ie-Ming Shih, M.D., Ph.D., associate professor of pathology at Johns Hopkins Kimmel Cancer Center. The research also suggests that drugs capable of blocking NAC-1 activity may be a useful strategy in preventing and treating recurrences as well.
A report on the research, the first to link NAC-1 to cancer, appears in the December 5 issue of the Proceedings of the National Academy of Sciences.
"Because recurrent cancers are often what really kill patients, and most ovarian cancer is diagnosed when it's already advanced, our findings offer women a better chance of catching or preventing recurrent disease early and increasing survival," says Shih.
An estimated at least 60 percent of advanced-stage ovarian cancer patients who appear to be disease-free after initial treatment develop recurrent disease, according to the researchers.
When the investigators compared levels of NAC-1 among primary and recurrent tumor samples taken from 338 ovarian cancer patients from two hospitals, they found that levels of NAC-1 were significantly higher in recurrent tumors compared with primary tumors taken from the same patient. Women whose primary cancers had high levels of NAC-1 were more likely to suffer a recurrence within one year.
Studying the functions of NAC-1, the researchers genetically modified cells so they made both NAC-1 and a component of the protein found at the ends of natural NAC-1 that is a binding site. In the modified cells, N130 capped off NAC-1 proteins disrupting their ability to bind with each other. This action can prevent tumor formation and kill cancer cells in experimental mice. Shih says that in the future, drugs that mimic N130 can be used to treat cancer.
This research was supported by the Department of Defense and the National Institutes of Health.
Co-authors of the published research include Kentaro Nakayama, Naomi Nakayama, Jim J.-C. Sheu, Antonio Santillan, Ritu Salani, Natini Jinawath, Robert E. Bristow, Robert J. Kurman, and Tian-Li Wang from Johns Hopkins; Ben Davidson from the Norwegian Radium Hospital, Oslo, Norway; and Patrice J. Morin from the National Institute on Aging, NIH.
Nakayama, K. "A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival." Proceeding of the National Academy of Science, Vol 103:49: pp18739-18744.
Source:
Johns Hopkins Medical Institutions

2006-12-18T16:36:00.000+05:45

In 2003, breast cancer incidence in the United States dropped sharply, and this decline may largely be due to the fact that millions of older women stopped using hormone replacement therapy (HRT) in 2002, according to a new analysis led by researchers at The University of Texas M. D. Anderson Cancer Center.At the 29th annual San Antonio Breast Cancer Symposium, the investigators report that there was an overall 7 percent relative decline in breast cancer incidence between 2002 and 2003, and that the steepest decline - 12 percent - occurred in women between ages 50-69 diagnosed with estrogen receptor positive (ER-positive) breast cancer. This is the kind of breast cancer that is dependent on hormones for tumor growth.
From this, the researchers conclude that as many as 14,000 fewer women were diagnosed with breast cancer in 2003 than in 2002, a year in which the American Cancer Society estimates 203,500 new cases of breast cancer were diagnosed.
"It is the largest single drop in breast cancer incidence within a single year I am aware of," says Peter Ravdin, M.D., Ph.D., a research professor in the Department of Biostatistics at M. D. Anderson.
"Something went right in 2003, and it seems that it was the decrease in the use of hormone therapy, but from the data we used we can only indirectly infer that is the case," he says.
"But if it is true, the tumor growth effect of stopping use of HRT is very dramatic over a short period of time, making the difference between whether a tumor is detected on a mammogram in 2003 or not," says Ravdin.
The study's senior investigator, Donald Berry, Ph.D., professor and head of the Division of Quantitative Sciences at M. D. Anderson, says he was, at first, very surprised by both the magnitude and the rapidity of the decline in incidence, but adds "it makes perfect sense" if you consider that use of HRT may be an important contributing factor to breast cancer development.
"Incidence of breast cancer had been increasing in the 20 or so years prior to July 2002, and this increase was over and above the known role of screening mammography," he says. "HRT had been proposed as a possible factor, although the magnitude of any HRT effect was not known. Now the possibility that the effect is much greater than originally thought all along is plausible, and that is a remarkable finding."
HRT provides both estrogen and sometimes also progestin hormones to women who are postmenopausal. The ongoing Women's Health Initiative study of 16,608 women 50-79 years old using HRT was prematurely stopped in July, 2002 when the combination of estrogen and progestin was found to significantly increase the risk of developing invasive breast cancer.
Ravdin said about 30% of women older than 50 had been taking HRT in the early years of this decade, that about half of these women stopped using HRT in late 2002 after the results of the large study were announced. "Research has shown that ER-positive tumors will stop growing if they are deprived of the hormones, so it is possible that a significant decrease in breast cancer can be seen if so many women stopped using HRT," he says.
"It takes breast cancer a long time to develop, but here we are primarily talking about existing cancers that are fueled by hormones and that slow or stop their growing when a source of fuel is cut," Berry adds. "These existing cancers are then more likely to make it under mammography's radar."
But the researchers stress that because the analysis is based solely on population statistics, they cannot know for certain the reasons why incidence declined. "We have to sound a cautionary note because epidemiology can never prove causation," he says. They considered whether other effects may be involved (such as decreased use of screening mammography and changes in the use of anti-inflammatory agents, SERMs or statins) but only the potential impact of HRT was strong enough to explain the effect."
To conduct the study, Ravdin, Berry, and researchers at the National Cancer Institute (NCI) and Harbor UCLA Medical Center analyzed data from nine regions across the country that contribute data to the NCI's Surveillance Epidemiology and End Results (SEER) database, from which national cancer incidence statistics are derived.
They examined rates of breast cancer in the United States from 1990 to the end of 2003 and found that while incidence increased at 1.7 percent per year from 1990 to 1998, it began to decrease, relative to other years, 1 percent each year from 1998 to 2002. When that 1 percent increase was adjusted for age in each of those years, incidence from 1998 to 2002 stayed about the same, Ravdin says. "There were more cases of breast cancer being diagnosed, but that was because women were getting older and entering the higher risk pool."
But by the end of 2003, there was a 7 percent, age-adjusted decrease in the number of breast cancer cases diagnosed. With further analysis, the researchers discovered that decline in incidence was far greater in ER-positive breast cancer (8 percent) compared to ER-negative breast cancer (4 percent). And when they looked at women 50-69 years old, the decline in ER-positive cancer was 12 percent, compared to 4 percent in ER-negative breast cancers. After adjusting for age, the researchers concluded that there was an absolute decline of about 14,000 fewer women diagnosed with breast cancer in 2003 than in 2002.
The study was funded by grants from the National Cancer Institute and from M. D. Anderson.
Coauthors also include Kathy Cronin, Ph.D., and Nadia Howlader from the National Cancer Institute, and Rowan Chlebowski, M.D., Ph.D., from Harbor UCLA Medical Center.
Source:
University of Texas M. D. Anderson Cancer Center

Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism

2006-12-18T16:32:00.000+05:45

Ricardo T. Gazzinelli and Eric Y. Denkers

Abstract
Toll-like receptors (TLRs) have emerged as a major receptor family involved in non-self recognition. They have a vital role in triggering innate immunity and orchestrate the acquired immune response during bacterial and viral infection. However, the role of TLRs during infection with protozoan pathogens is less clear. Nevertheless, our understanding of how these parasitic microorganisms engage the host TLR signalling system has now entered a phase of rapid expansion. This Review describes recent insights into how parasitic protozoans are sensed by TLR molecules, and how the TLR system itself can be targeted by these microbial pathogens for their own survival.

Source: Nature

Microbe Fixes Nitrogen At A Blistering 92 deg C, May Offer Clues To Evolution Of Nitrogen Fixation

2006-12-18T16:30:00.000+05:45

A heat-loving archaeon capable of fixing nitrogen at a surprisingly hot 92 degrees Celsius, or 198 Fahrenheit, may represent Earth's earliest lineages of organisms capable of nitrogen fixation, perhaps even preceding the kinds of bacteria today's plants and animals rely on to fix nitrogen. The genetic analysis reported in the Dec. 15 issue of Science supports the notion that the gene needed to produce nitrogenase -- an enzyme capable of converting nitrogen gas, that's unusable by life, to a form like ammonia that is useable -- arose before the three main branches of life -- bacteria, archaea and eukaryotes -- diverged some 3.5 billion years ago, according to oceanographer Mausmi Mehta, who recently received her doctorate from the UW, and John Baross, UW professor of oceanography. This is opposed to the theory that the nitrogenase system arose within archaea and was later transferred laterally to bacteria.
"There's been lots of evidence that point to high-temperature archaea as the first life on Earth but the question has been, 'So why can't we find archaea that fix nitrogen at high temperatures"'" says Baross, who's been on a 20-year quest to find just such a microbe. Archaea are single-celled organisms that live under extreme environmental conditions, such as the high temperatures and crushing pressures below the seafloor. If heat-loving archaea were the first life on the planet, they would have needed a usable source of nitrogen, Baross says.
Known as FS406-22 because of the fluid and culture samples it came from, the archaeon discovered by the UW researchers is the first from a deep-sea hydrothermal vent that can fix nitrogen, says Mehta, first author on the Science paper.
It was collected at Axial Volcano on the Juan de Fuca Ridge off the coast of Washington and Oregon. Fixing nitrogen at 92 C smashes the previous record by 28 C, a record held by Methanothermococcus thermolithotrophicus, an archaeon that was isolated from geothermally heated sand near an Italian beach and fixes nitrogen at temperatures up to 64 C.
Nitrogen is necessary for all life because it is an essential part of amino acids and proteins. To be used by organisms, gaseous nitrogen must be converted to other compounds, or "fixed," which can only be done by certain bacteria and specific archaea. Nitrogen can be fixed into ammonia, nitrate and other products that can be used by land and sea plants, which in turn are eaten by higher animals.
Today's oceans contain nitrogen both as a dissolved gas and as nitrate. Ocean water that percolates down into the seafloor can pick up enough heat from volcanism deep in the earth to cause the fixed nitrogen to revert to its gaseous form. Venting water hotter than 30 C contains very little nitrate so organisms in areas where the subseafloor temperatures are higher would lack nitrogen in a form they can use.
The discovery of FS406-22's nitrogen fixing capabilities at 92 C, therefore, widens the realm of where life can grow in the subseafloor biosphere and other nitrogen-limited ecosystems, perhaps even on other planets, Mehta says.
Scientists have speculated since 1981 that nitrogen fixation was occurring at hydrothermal vents because vent animals had completely different nitrogen isotope ratios than non-vent deep sea animals.
The work that led to FS406-22 was supported by Washington Sea Grant, based at the UW, and the NASA Astrobiology Institute. Mehta worked five years doing some 600 enrichments, with FS406-22 being the only one she was could wean off fixed nitrogen completely. An unimpressive looking sphere of a microbe, FS406-22 is able to grow with gaseous nitrogen as its sole source of nitrogen at temperatures ranging from 58 to 92 C, with the fastest growth at 90 C.
The genetic analysis shows FS406-22 as having one of the deepest-rooted genes and the most primordial characteristics in terms of gene sequence, Baross says.
"We propose that among diazotrophic archaea, the nitrogenase from FS406-22 might have retained the most ancient characteristics, possibly derived from a nitrogenase present in the last common ancestor of modern life," the co-authors conclude in their report.

Source:
University of Washington and Sciencedaily

Young Women Unfamiliar With Safety, Effectiveness Of IUD

2006-12-18T16:28:00.000+05:45

The IUD might be one of the best-kept birth control secrets for young women, according to researchers at the University of Rochester Medical Center.
Their study, published in this month's journal Obstetrics & Gynecology, revealed that most young women who sought birth control after a first pregnancy were unaware of the safety and effectiveness of modern intrauterine devices (IUD). An IUD is a small T-shaped device that is inserted into the uterus by a health care provider. It provides long-term birth control by preventing sperm from fertilizing eggs.
"Modern IUDs are safe, effective, and reversible, but only about 2 percent of U.S. women use them," said Nancy L. Stanwood, M.D., M.P.H., assistant professor of Obstetrics and Gynecology at the University of Rochester Medical Center. Suspecting the low use of IUDs was related to awareness, Stanwood's study aimed to estimate knowledge of IUDs among young pregnant women.
In the study, nearly 200 pregnant women, ages 14 to 25, were asked about their contraceptive history, plans, and knowledge. They were also asked if they had heard of IUDs, and if they knew anything about them. Half of the women in the study said they had heard of IUDs, but 71 percent were unaware of their safety and 58 percent did not know about their effectiveness in preventing pregnancy.
"Those results have significant implications, especially when you consider that only 9 percent of the women surveyed had planned their current pregnancy," Stanwood said. "More than half said they wanted to wait at least four years before becoming pregnant again, and more than a quarter said they never wanted to be pregnant again."
Though not widely used in the U.S., today's IUDs have been proven to be highly effective in preventing pregnancy and are also quite safe, Stanwood said. Modern IUDs have failure rates similar to tubal ligation, but are not permanent and do not require surgery.
Pregnancy rates for women using IUDs are 0.1% in the first year and are 2 percent over a total of 10 years. Compared to other more popular methods, pregnancy rates for condom users are 14 percent in the first year with typical use and 3 percent with perfect use. For birth control pills, the rate is 3 to 8 percent in the first year with typical use and 0.1 percent with perfect use.
"Young women choosing contraception after a pregnancy would benefit from counseling about the relative safety and effectiveness of IUDs, allowing them to make fully informed contraceptive decisions," Stanwood said.

Source: University of Rochester Medical Center and Sciencedaily

Researchers Barcode DNA Of Venice Museum's Vast Fungi Collection

2006-12-18T16:27:00.000+05:45

In the storerooms of a Venice, Italy, museum, a University of California, Berkeley, scholar and Italian experts are at work on a rare collection, but the objects aren't Renaissance paintings or the art of ancient glassblowers. Instead, the team is collecting samples from the largest and best preserved collection of fungi in Italy to create an unprecedented DNA database
These 28,000 samples of fungi that represent 6,000 species - many of which are quite rare - are housed at the Venice Museum of Natural History, a partner with UC Berkeley for this ambitious project. The collection also is one of the largest in Europe.
The project was publicly announced in Italy today (Wednesday, Dec. 13) at the prestigious Venetian Institute of Sciences, Letters and Arts.
"We are building up a huge molecular database that will be available to the entire scientific community," said Matteo Garbelotto, UC Berkeley adjunct associate professor of ecosystem sciences and principal investigator of the project. "In addition to aiding research on the productivity of forests and agricultural ecosystems, this database will greatly aid the diagnosis of plant diseases."
Fungi are a kingdom of organisms that include yeasts, mushrooms and mold. They are essential to most terrestrial ecosystems, channeling nutrients in the soil and making them available for the growth of plants, including trees and agricultural crops. "Without fungi, there would be no forests," Garbelotto pointed out.
A large number of fungi are also plant pathogens and cause serious diseases of crops and trees, especially when transported to new areas of the world through the global trade of goods and movement of people. In addition, some species of fungi can lead to human illness, including pneumonia, skin infections, allergies and asthma.
Garbelotto is perhaps best known for his work in the identification of Phytophthora ramorum, the fungus-like plant pathogen that made its way from Europe to the United States. The pathogen is responsible for sudden oak death, the disease that has caused widespread dieback of tanoaks and coast live oaks in California and southwest Oregon.
"In the case of exotic plant diseases, DNA information may be used, as it is in criminal forensics, to identify possible culprits and to understand how they were introduced," said Garbelotto. "This provides governments with pivotal information needed to avoid repeated introductions of pathogens."
Garbelotto is working with Italian mycologist Giovanni Robich and Luca Mizzan, curator of Marine Biology at the Venice Museum of Natural History, to sort through the samples in the museum, which are being sent to Garbelotto's lab at UC Berkeley for DNA sequencing and analysis.
The Venice Natural History Museum is part of the Musei Civici Veneziani, a network of 11 museums in Venice. It is housed in the Fontego dei Turchi, a Byzantine-style palace on the Grand Canal that dates back to the 12th century. Before it was established as a museum in 1923, it had served as a trading depot for Turkish merchants.
"Often museums are seen as places where people just go and see things," said Garbelotto, who is doing this work during a sabbatical leave from UC Berkeley. "This shows that museums are actually involved in cutting-edge research. Providing a database of this scope is pretty novel."
Museum curator Mizzan said the museum's vast collection of fungi got a kick start when the Venice Society of Mycology formed in the late 1980s to monitor the mycological flora in the Lagoon of Venice and surrounding areas. The collected samples represented over 1,200 species of fungi and formed the foundation of the museum's present collection.
Garbelotto noted that the relatively young age of the samples has been critical to obtaining good quality tissue for DNA analysis. The samples come from throughout Europe, with a significant number representing species found elsewhere in the world.
Rather than sequencing the entire genome of each species, the researchers are focusing on a non-coding region of the ribosomal DNA that is known to be unique in each species. The length of the region varies from around 450 base pairs to 900 base pairs, depending upon the taxa from which it is sampled.
"If you're going to cross-compare species, you've got to amplify the same region," said Sarah Bergemann, the post-doctoral researcher in ecosystem science who is heading the lab analysis work at UC Berkeley. Bergemann is working with Amy Smith, staff research associate at Garbelotto's lab, to process the samples Garbelotto sends from Italy.
"This will be important for people who study the evolutionary characteristics of fungi," said Bergemann. "They'll be able to use our database for cross comparisons. It's also useful for people who study species distribution. For example, if you want to figure out how some species are related to one another, and you know something about their taxonomy, you can go back to their DNA to see if the morphological characteristics match their molecular code."
Without the DNA fingerprint, researchers traditionally need to wait for fungi to fruit or mushroom to identify them. "This can be very limiting because mushrooms are only produced seasonally, with some species only fruiting once every several years," said Garbelotto. "The database we are creating will allow people to identify the fungi present in plants, in the soil and in the air at any time."
The project, which began in April, is expected to be completed by the end of 2007. "We do not know of any similar project in Europe, at least of this dimension," said Enrico Ratti, the museum's scientific director.
"The importance of this project is in the cooperation between different subjects, namely private collectors, a private association, a public municipal museum and a foreign university," said Giandomenico Romanelli, director of the Musei Civici Veneziani. "We think that this is an exemplar model, to be followed in subsequent projects. Furthermore, in our philosophy, natural science collections are public goods that everybody belonging to the scientific community should be able to take advantage of."

Source: University of California - Berkeley and Sciencedaily

Linchpin Discovered In Insulin Metabolism; Gene Might Contribute To Type II Diabetes

2006-12-18T16:25:00.000+05:45

Scientists from the new interdisciplinary LIMES (Life & Medical Sciences) Centre at the University of Bonn have identified a new gene which could play an important role in the development of diabetes. Flies in which this hereditary factor is defective are also significantly smaller than other members of their species and live appreciably longer. The gene seems to have such a crucial function that it has hardly changed in just under a billion years: it is found in flies, but in a similar form it is also found in mice and humans. In the current issue of the prestigious journal Nature the Bonn researchers have published two articles on this topic.
Sometimes science resembles a relay race: in 1996 the biochemist Professor Waldemar Kolanus discovered a group of cellular proteins, the cytohesins, and described their function in the immune system. Two of his colleagues at the LIMES Centre in Bonn have now found a totally new and completely unexpected function of these proteins which is very relevant to medicine. "We wanted to know whether there were also cytohesins in the fruit fly drosophila and what functions they have there," the evolutionary biologist Professor Michael Hoch reminisces. He and his team were in fact successful. They discovered a protein which is very similar to the cytohesins in mammals. Even more interestingly, fruit flies in which the genetic blueprint for this gene is defective are smaller in size. So the researchers nicknamed cytohesin 'Titch'. "The effect on the insect's growth showed us that 'Titch' could play a key role in the metabolism of insulin -- a completely new role for cytohesins," Professor Hoch says.
New drugs for diabetes
The maximum size of plants or animals is written into their genes. Yet whether they exploit this potential is influenced by a number of other factors. One of them is insulin. Mammals produce increased amounts of this hormone after eating as a reaction to the increasing blood sugar level. Via a complicated sequence of reactions it ensures that muscles and other organs absorb blood sugar. What is more, however, the cascade of insulin signals also determines size and number of the body cells during growth. Apparently, 'Titch' plays a key role in this shower of signals. "The fruit fly larvae increase their weight 200-fold in the first three days after hatching," Michael Hoch explains. "If their 'Titch gene' has mutated, they grow visibly more slowly." A series of additional observations support the thesis that 'Titch' is extremely important for the metabolism of insulin in drosophila. If there were a cytohesin with a similar function in mammals, this would, for instance, be of great interest for research into diabetes.
In parallel to Michael Hoch's research, Professor Michael Famulok produced an active substance that inhibits cytohesins, known as SecinH3. 'We fed this inhibitor to mice,' he explains. Unlike fruit flies, the rodents do not have just one cytohesin at their disposal, they have four. Professor Famulok wanted to find out whether they play a similar crucial role in the insulin metabolism of mice as 'Titch' does in the fly and discovered the following: "Liver cells of the animals treated with SecinH3 reacted to insulin not nearly as strongly as they should." Medical people know this effect: this insulin resistance is regarded as a warning signal for the onset of Type II diabetes.
Six million people suffer from this type of diabetes in Germany alone. It is triggered by an unhealthy diet and lack of exercise, and the tendency is rising. Michael Famulok now thinks new drugs are on the cards. "There is a class of switch molecules which are activated by cytohesins. This activation is apparently necessary to pass on the signals. If we manage to stimulate the switch molecules with a suitable active substance, we might possibly be able to thereby reverse the resistance to insulin." A new method described by Michael Famulok in the Nature paper could help in the search for this kind of drug. With its help his team has already found the inhibitor SecinH3.
A long life thanks to a genetic defect
The joint ancestor of the fruit fly and the mouse lived at least 900 million years ago. Nevertheless, 'Titch' and the corresponding cytohesin in mice are so similar that SecinH3 is effective with both. "We have fed the inhibitor to our fly larvae," Michael Hoch explains. "They then developed as if their 'Titch gene' were defective." This hereditary factor also has a completely different effect, which really sets the researchers' imagination going. Flies which have a 'Titch' defect live a lot longer than others of their species. "An exciting effect,' Michael Hoch thinks. 'We certainly must investigate this further."
Source: University of Bonn and Sciencedaily.

Microbe Fixes Nitrogen At A Blistering 92 C, May Offer Clues To Evolution Of Nitrogen Fixation

2006-12-18T16:07:00.000+05:45

A heat-loving archaeon capable of fixing nitrogen at a surprisingly hot 92 degrees Celsius, or 198 Fahrenheit, may represent Earth's earliest lineages of organisms capable of nitrogen fixation, perhaps even preceding the kinds of bacteria today's plants and animals rely on to fix nitrogenThe genetic analysis reported in the Dec. 15 issue of Science supports the notion that the gene needed to produce nitrogenase -- an enzyme capable of converting nitrogen gas, that's unusable by life, to a form like ammonia that is useable -- arose before the three main branches of life -- bacteria, archaea and eukaryotes -- diverged some 3.5 billion years ago, according to oceanographer Mausmi Mehta, who recently received her doctorate from the UW, and John Baross, UW professor of oceanography. This is opposed to the theory that the nitrogenase system arose within archaea and was later transferred laterally to bacteria.
"There's been lots of evidence that point to high-temperature archaea as the first life on Earth but the question has been, 'So why can't we find archaea that fix nitrogen at high temperatures"'" says Baross, who's been on a 20-year quest to find just such a microbe. Archaea are single-celled organisms that live under extreme environmental conditions, such as the high temperatures and crushing pressures below the seafloor. If heat-loving archaea were the first life on the planet, they would have needed a usable source of nitrogen, Baross says.
Known as FS406-22 because of the fluid and culture samples it came from, the archaeon discovered by the UW researchers is the first from a deep-sea hydrothermal vent that can fix nitrogen, says Mehta, first author on the Science paper.
It was collected at Axial Volcano on the Juan de Fuca Ridge off the coast of Washington and Oregon. Fixing nitrogen at 92 C smashes the previous record by 28 C, a record held by Methanothermococcus thermolithotrophicus, an archaeon that was isolated from geothermally heated sand near an Italian beach and fixes nitrogen at temperatures up to 64 C.
Nitrogen is necessary for all life because it is an essential part of amino acids and proteins. To be used by organisms, gaseous nitrogen must be converted to other compounds, or "fixed," which can only be done by certain bacteria and specific archaea. Nitrogen can be fixed into ammonia, nitrate and other products that can be used by land and sea plants, which in turn are eaten by higher animals.
Today's oceans contain nitrogen both as a dissolved gas and as nitrate. Ocean water that percolates down into the seafloor can pick up enough heat from volcanism deep in the earth to cause the fixed nitrogen to revert to its gaseous form. Venting water hotter than 30 C contains very little nitrate so organisms in areas where the subseafloor temperatures are higher would lack nitrogen in a form they can use.
The discovery of FS406-22's nitrogen fixing capabilities at 92 C, therefore, widens the realm of where life can grow in the subseafloor biosphere and other nitrogen-limited ecosystems, perhaps even on other planets, Mehta says.
Scientists have speculated since 1981 that nitrogen fixation was occurring at hydrothermal vents because vent animals had completely different nitrogen isotope ratios than non-vent deep sea animals.
The work that led to FS406-22 was supported by Washington Sea Grant, based at the UW, and the NASA Astrobiology Institute. Mehta worked five years doing some 600 enrichments, with FS406-22 being the only one she was could wean off fixed nitrogen completely. An unimpressive looking sphere of a microbe, FS406-22 is able to grow with gaseous nitrogen as its sole source of nitrogen at temperatures ranging from 58 to 92 C, with the fastest growth at 90 C.
The genetic analysis shows FS406-22 as having one of the deepest-rooted genes and the most primordial characteristics in terms of gene sequence, Baross says.
"We propose that among diazotrophic archaea, the nitrogenase from FS406-22 might have retained the most ancient characteristics, possibly derived from a nitrogenase present in the last common ancestor of modern life," the co-authors conclude in their report.

(Source: Sciencedaily)

Scientists Find Potential Weapon Against Tuberculosis Infection

2006-12-18T16:03:00.000+05:45

The discovery of a unique copper-repressing protein in the bacterium that causes tuberculosis in humans may pave the way toward new strategies for halting tuberculosis infection.
Scientists have known that when macrophages - the host’s immune cells - swallow an invading bacterium, they dump excessive amounts of copper onto the invader in an effort to kill it. While all cells need copper to function, too much of the metal ion causes cell death.
“But the invaders fight back with their own defense,” says Adel Talaat, a microbiologist at the University of Wisconsin-Madison School of Veterinary Medicine. “They block the excess copper.”
In a paper published in the January 2007 issue of Nature Chemical Biology, Talaat and colleagues from Texas A&M University and University of Saskatchewan in Saskatoon, Canada describe a unique protein repressor that they have identified as the mechanism used by invading bacterium cells to fight off the host’s copper attack.
Prior to the discovery of this repressor protein, scientists did not know exactly how invading bacterium protected themselves from copper ions used by the body as a defense against infection.
“With this discovery, we can now pursue ways to deactivate the repressor protein,” says Talaat. “Our goal is to disable the tuberculosis bacterium from fighting back against the host body’s defense mechanisms, so that we can stop tuberculosis.”

Source: University Of Wisconsin-Madison

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2006-12-18T15:56:00.000+05:45

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