Binge drinking ‘can increase pancreatic cancer risk’

May 20, 2010 By Leave a Comment

Washington, May 20 (ANI): A new research from UT Southwestern Medical Center suggests that heavy alcohol use and binge drinking can increase the risk of pancreatic cancer in men.

Researchers found that men who consumed alcohol increased their risk of pancreatic cancer by 1.5 to 6 times compared with those who didn”t consume alcohol or who had less than one drink per month.

Also, men who engaged in binge drinking had a 3.5 times greater likelihood of developing pancreatic cancer.

“If this relationship continues to be confirmed, reducing heavy and binge drinking may be more important than we already know,” said Dr. Samir Gupta, assistant professor of internal medicine at UT Southwestern and lead author of the study, which was conducted at the University of California, San Francisco.

Researchers defined one drink as a can, bottle or 12 ounces of beer; a 4-ounce glass of wine; or one shot of liquor – each serving contains about 14 grams of alcohol.

The heaviest drinkers consumed 21 to 35 drinks per week. Binge drinking was defined as consuming five or more drinks during one drinking session.

However, because women don’t consume as much alcohol as men, researchers did not find the same association amongst them.

This study about the relation between pancreatic cancer and alcohol is different and more detailed because the researchers considered other multiple factors which weren’t taken into account earlier.

In the current study, researchers used structured questionnaires to interview pancreatic cancer patients in the San Francisco area diagnosed between 1995 and 1999 and compared those results with those of control participants matched by sex, age and county of residence.

The 532 cancer patients ranged in age from 21 to 85, with the majority between 60 and 80 years of age. Fifty-five percent of study participants were men; 83 percent of them were Caucasian; and most of them were of normal weight with some college education. The 1,701 control participants were of similar demographics.

Cancer of the pancreas, an organ important for digestion and production of hormones, has the lowest overall five-year survival rate of all specific cancers. Early signs of pancreatic cancer are difficult to diagnose, partly because the organ is located deep in the upper abdomen. Mortality rates have changed little in the past three decades, according to the National Cancer Institute.

This study is available online in Cancer Causes and Control. (ANI)

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Mood and anxiety disorders remain common in older adults

May 4, 2010 By Leave a Comment

Washington, May 4 (ANI): A study has found that many older adults, especially women, may still suffer from mood and anxiety disorders, which appear to decline with age.

“Knowledge of the prevalence of mood and anxiety disorders and co-existing mood-anxiety disorder in older community-dwelling adults is important; these are hidden and under treated but treatable disorders associated with poor health outcomes,” the authors write as background information in the article.

Amy L. Byers, Ph.D., M.P.H., of the University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, and colleagues determined nationally representative estimates of mood, anxiety and combined mood and anxiety disorders using a sample of 2,575 survey participants age 55 and older.

Of these, 43 percent were ages 55 to 64; 32 percent, 65 to 74 years; 20 percent, 75 to 84 years; and 5 percent, 85 years or older.

A total of 5 percent of participants had a mood disorder, including major depressive disorder or bipolar disorder, within the previous year.

Rates of anxiety disorders-such as panic disorder, agoraphobia, other phobias, generalized anxiety disorder and posttraumatic stress disorder-were 12 percent overall.

About 3 percent had co-occurring mood and anxiety disorders.

Prevalence of all the conditions declined with age. When comparing persons age 55 to 64 with those age 85 and older, 7.6 percent vs. 2.4 percent had mood disorders, 16.6 percent vs. 8.1 percent had anxiety disorders, and 4.8 percent vs. 0 percent had both conditions.

Women were more likely to have any of the disorders than men; 6.4 percent of women and 3 percent of men had mood disorders, 14.7 percent of women and 7.6 percent of men had anxiety disorders, and 3.7 of women and 1.6 percent of men had both.

“The study of nationally representative samples provides evidence for research and policy planning that helps to define community-based priorities for future psychiatric research,” the authors wrote.

“The findings of this study emphasize the importance of individual and co-existing mood and anxiety disorders when studying older adults, even the oldest cohorts.

“Further study of risk factors, course and severity is needed to target intervention, prevention and health care needs.

“Given the rapid aging of the U.S. population, the potential public health burden of late-life mental health disorders will likely grow as well, suggesting the importance of continued epidemiologic monitoring of the mental health status of the young-old, mid-old, old-old and oldest-old cohorts,” they concluded.

The findings have been published in the May issue of Archives of General Psychiatry, one of the JAMA/Archives journals. (ANI)

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First transgenic mouse created to mimic Parkinson’s earliest symptoms

May 4, 2010 By Leave a Comment

Washington, May 4 (ANI): Researchers have created the first transgenic mouse to display the earliest signs of Parkinson’s disease using the genetic mutation that is characteristic of human forms of the disease.

The mouse model, which expresses the same mutant proteins as human Parkinson’s patients, also displays early signs of constipation and other gastrointestinal problems that are a common harbinger of the disease in humans.

Thus, researchers at University of California, San Francisco (UCSF) have said that these animals could serve as a means of investigating therapies for reversing the neurological dysfunction of the disease at its earliest stages.

For a long time, researchers have suspected that the neurological component of Parkinson’s, which causes tremors and stiffness among other symptoms, is actually a late-stage effect of a larger, systemic problem, says Dr. Robert L. Nussbaum, senior author on the paper.

“This new model validates that theory by mimicking what we know to be the genetic pathway leading to Parkinson’s, while also displaying the earliest symptoms that occur in humans. This will give us an important tool in identifying an early intervention for this devastating disease,” said Nussbaum.

The UCSF mouse model is the first to display the full gastrointestinal symptoms as well, and is consistent with the progression of the disease in humans.

The study has been published in the latest issue of the journal, ‘Human Molecular Genetics’. (ANI)

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Breakthrough in predicting invasive breast cancer risk

April 29, 2010 By Leave a Comment

Washington, April 29 (ANI): Scientists have found a novel way to predict whether women with ductal carcinoma in situ (DCIS) – the most common form of non-invasive breast cancer – are at risk of developing more invasive tumours in later years.

According to the scientists, the discovery would give women with DCIS the opportunity to be more selective about their treatment.

“Women will have much more information, so they can better know their risk of developing invasive cancer. It will lead to a more personalized approach to treatment. As many as 44 percent of patients with DCIS may not require any further treatment, and can rely instead on surveillance,”” said lead author Karla Kerlikowske.

Researchers at the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center followed the medical histories of 1,162 women aged 40 years and older who were diagnosed with DCIS and treated with lumpectomy.

They found that two factors were predictors of risk of developing invasive cancer within eight years after a diagnosis of DCIS: the method by which it was detected and expression of several biomarkers.

Findings showed that a breast lump that is diagnosed as DCIS was more predictive of a high risk of subsequent invasive cancer than DCIS diagnosis by mammography.

The study also found that different combinations of biomarkers measured on the initial DCIS tissue were associated with varying levels of risk of invasive cancer or DCIS.

These biomarkers include estrogen receptor, progesterone receptor, Ki67 antigen, p53, p16, epidermal growth factor receptor-2, and cyclooxygenase-2. Women who express high levels of p16, cyclooxygenase-2 and Ki67 were more likely to develop invasive cancer after their initial DCIS diagnosis.

According to Kerlikowske, because of the research, physicians will now be able to predict whether a DCIS patient treated by lumpectomy only will subsequently develop invasive cancer, DCIS, or be at very low risk of developing further tumours.

The study has been reported online by the Journal of the National Cancer Institute. (ANI)

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How sex hormones control ‘masculinization’ of the brain

April 29, 2010 By Leave a Comment

Washington, Apr 29 (ANI): A new study has uncovered some information about how sex hormones control masculinization of the brain during development and drive gender related behaviors in adult males.

Published by Cell Press in the April 29 issue of the journal Neuron, the study demonstrates that direct action of testosterone, the prototypical male hormone, is unnecessary for masculinizing the brain and behavior.

Testosterone and estrogen are thought to play an essential role in organizing and activating gender-specific patterns of behavior in sexually reproducing animals.

Testosterone is produced by the testes and directly activates the androgen receptor (AR) in target tissues such as muscle. Estrogen is produced by the ovaries and is nearly undetectable in the circulation of males of most species. However, circulating testosterone in males can be converted into estrogen in the brain, and this testosterone-derived estrogen has been shown to control many male behaviors.

“It was known that testosterone and estrogen are essential for typical male behaviors in many vertebrate species,” explains the study”s senior author, Dr. Nirao M. Shah from the Department of Anatomy at the University of California, San Francisco. “However, how these two hormones interact to control masculinization of the brain and behavior remained to be established.”

Dr. Shah and colleagues found that during the neonatal testosterone surge there is very little AR expressed in the developing brain, making it unlikely that testosterone signaling via AR plays a major role in masculinizing neural pathways. Importantly, they went on to show that the male pattern of AR expression in the brain was dependent on testosterone-derived estrogen signaling.

The researchers then used a genetic approach to knock out the AR in the mouse nervous system and observed that these mutants still exhibited male type mating, fighting, and territorial marking behaviors. However, these mutant males had striking reductions in specific components of these masculine behaviors. These results show that testosterone signaling via AR does not control masculine differentiation of the brain and behavior but regulates the frequency and extent of male typical behaviors.

“Our findings in conjunction with previous work suggest a model for the control of male pattern behaviors in which estrogen masculinizes the neural circuits for mating, fighting, and territory marking, and testosterone and estrogen signaling generate the male typical levels of these behaviors,” concludes Dr. Shah. “It will be interesting in future studies to identify the molecular and circuit level mechanisms that are controlled by these hormones.” (ANI)

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Gene variant could protect memory and thinking skills in older people

April 20, 2010 By Leave a Comment

Washington, Apr 20 (ANI): A gene variant could help protect the memory and thinking skills of older people, according to a new research.

For the study, researchers followed 2,858 African-American and Caucasian people between the ages of 70 and 79 for eight years.

Participants” DNA was analysed for the catechol-O-methyltransferase (COMT) gene, a gene shown in studies to affect thinking skills.

The allelic variants associated with this gene are the Val and Met variants.

“This is the first study to identify a protective relationship between this gene variant and cognitive function,” said study author Dr. Alexandra Fiocco, with the University of California, San Francisco.

The group was also given two types of thinking tests. One test measured skills such as language, concentration and memory.

The other test measured response time, attention and judging sights and objects.

The study found that the Met variant of the COMT gene was linked to a greater decline in thinking skills over the years, while the Val variant had a protective effect on thinking skills, with lower declines over the years.

In Caucasians, those with the Val variant scored 33 percent better over time than those without the variant. Among African-Americans, people with the Val allele gene variant scored 45 percent better over time than those who did not have the variant.

“This finding is interesting because in younger people, the Val genotype has been shown to have a detrimental effect. But in our study of older people, the reverse was true. Finding connections between this gene, its variants and cognitive function may help scientists find new treatments for the prevention of cognitive decline,” said Fiocco.

However, he added that the results need to be replicated by others before the field can be confident that the Met variant of the COMT gene plays a role in late life cognitive decline.

The research will be published in the latest issue of Neurology, the medical journal of the American Academy of Neurology. (ANI)

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Promising new approach for Parkinson’s disease treatment

March 26, 2010 By Leave a Comment

Washington, March 26 (ANI): Scientists at the University of California, San Francisco have found a promising new approach for the treatment of symptoms of Parkinson’s disease and other neurodegenerative diseases and disorders, including epilepsy.

They used a novel cell-based strategy to treat motor symptoms in rats with a disease designed to mimic Parkinson’s disease.

The scientists transplanted embryonic neurons from foetal rats into an area of the adult rat brain known as the striatum, which integrates excitatory and inhibitory neurotransmitter signals to control movement.

In Parkinson’s disease, cells that produce the neurotransmitter dopamine are damaged, and thus unable to project their communication wires, or axons, to the region.

As a result, the balance of excitation and inhibition in the striatum is lost, causing the motor deficits that are a primary symptom of the disease.

In the study, the transplanted embryonic neurons migrated and integrated into the correct neural circuitry of the striatum, matured into so-called GABAergic inhibitory interneurons, and dampened the over-excitation in the region.

The rats had improved motor function, as seen in their balance, speed, and length of stride during walking. Moreover, the healthy “control” rats in which the cells had been transplanted took longer strides and ran faster on a runway test.

The researchers say that the results demonstrate that the transplanted cells, known as embryonic medial ganglionic eminence (MGE) cells, can very precisely modify the balance of excitation and inhibition in neural circuits to influence behavior.

As overactive neural circuits are associated with other neurodegenerative diseases – a result of nonfunctioning or missing cells or abnormal synaptic transmission—the finding may have broad implications.

“This strategy represents a whole new approach to treating nervous system disorders,” says neurologist Arnold Kriegstein, the senior author of the study and director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

The study appears in the journal Cell Stem Cell. (ANI)

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Inability to ignore distractions behind memory decline in old age

March 26, 2010 By Leave a Comment

Washington, Mar 26 (ANI): Older adults fail to retain information because they cannot ignore irrelevant information when forming memories, according to a new study at the University of California San Francisco.

Research has shown that in older adults there is an increase in brain activity at the time of suppressing responses to distractions.

In the new study, researchers have shown that even prior knowledge of an impending distraction does not help to improve the working memory performance of older adults.

Drs. Theodore Zanto and Adam Gazzaley studied 21 adults aged between 60 and 80 years while they performed a working memory task in which they were shown random sequences of pictures containing faces and scenes.

From a given sequence, participants were asked to remember either only the faces (ignoring scenes) or only the scenes (ignoring faces). In a second round of testing, the participants were given prior information about which specific pictures in the sequence would be relevant and which to ignore.

The participants” brain activity during the tasks was recorded using electroencephalograms (EEGs).

In earlier study, the researchers have shown that the increase in brain activity in response to distractions occurs very soon (within 200 milliseconds) after the distraction appears.

Since there is only a very short amount of time allotted for the brain to identify an item as irrelevant and suppress any further neural processing, it was suggested that older adults might benefit from prior knowledge of the impending distraction.

However, results from the new study have proved that this is not the case.

Interestingly, the researchers found that later stages of neural processing (500-650 milliseconds after item presentation) do show signs of suppression, confirming that the “suppression deficit” is related to early stages of neural processing.

The findings suggest that a working memory decline in older adults is indeed due to an inability to ignore distracting information, which furthermore cannot be improved with preparedness.

The study has been published in the latest issue of Elsevier”s Cortex. (ANI)

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Kidney disease ‘hiding in people with undiagnosed diabetes’

March 26, 2010 By Leave a Comment

Washington, Mar 26 (ANI): People with prediabetes and undiagnosed diabetes may already be suffering kidney damage, claims a new study.

According to the study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN), millions of Americans may have chronic kidney disease (CKD) and not know it.

“Our research indicates that much of the CKD burden in the United States is in persons with prediabetes and undiagnosed diabetes, who are not being screened for CKD,” comments Laura C. Plantinga, ScM (University of California, San Francisco). The researchers believe that broader screening may be needed to detect patients with these two “relatively silent yet harmful diseases.”

In a study funded by the Centers for Disease Control and Prevention, Plantinga and colleagues analyzed a nationally representative sample of about 8,200 Americans from the National Health and Nutrition Examination Survey. Standard laboratory tests were used to assess the rate of CKD, focusing on people with undiagnosed diabetes or prediabetes (sometimes called “borderline” diabetes).

Based on lab tests, 42 percent of subjects with undiagnosed diabetes had CKD—similar to the 40 percent rate in those with diagnosed diabetes. “Only a small percentage of participants were aware of the diagnosis of CKD,” says Plantinga.

In addition, CKD was present in nearly 18 percent of subjects with prediabetes. Among participants without diabetes or prediabetes, the rate of CKD was about 11 percent.

“Based on these results, there may be a substantial number of individuals in the United States—up to 13 million—who have undiagnosed diabetes or prediabetes and who already have signs of kidney damage and/or reduced kidney function,” says Plantinga. Such patients would be at high risk for worsening kidney disease and diabetes, and for the poor outcomes associated with both conditions—including cardiovascular disease and death.

Diabetes is the most important risk factor for kidney disease, but the new results suggest that harmful effects on the kidneys may be occurring even before diabetes is diagnosed. “Persons at risk for diabetes and their health care providers should be aware that earlier screening for both diabetes and kidney disease may be warranted,” says Plantinga. “Earlier screening would allow for appropriate, timely medical care to prevent further progression and poor outcomes.” (ANI)

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Clinic-based HIV prevention effective in reducing sexual risk behaviors

March 25, 2010 By Leave a Comment

Washington, March 25 (ANI): Clinic-based HIV prevention is effective in reducing sexual risk behaviours, a new American study has revealed.

The study, conducted by researchers at the University of California, San Francisco (UCSF), has appeared in the online edition of the journal “AIDS and Behavior”.

Lead author Janet J. Myers, assistant professor of medicine at the UCSF Center for AIDS Prevention Studies and co-principal investigator of the project, said: “We found the greatest and most sustained reductions in sexual risk took place when the prevention interventions were delivered by medical care providers during HIV patients” routine visits. An important feature of this research is that it was conducted in actual clinical settings and not in the somewhat artificial setting of a clinical trial.”

On receiving risk assessment prevention counselling from their clinical providers, HIV patients showed a consistent decline in risky behaviour over the 12-month study period.

The researchers found HIV patients cut almost by 50 per cent their sexual risk behaviours: unprotected anal or vaginal intercourse with either a HIV-negative partner or one whose status was unknown.

HIV patients receiving services from health educators, social workers or peer educators also significantly reduced risk behaviours at 6 months, but not at 12 months.

Steve Morin, professor of medicine and director of the UCSF Center for AIDS Prevention Studies and the study”s principal investigator, said: “Other studies testing behavioral prevention interventions have demonstrated that boosters delivered at periodic intervals assist in sustaining behavior changes. Since patients see their medical providers regularly to monitor disease and therapeutic regimens, delivering prevention services during these visits is not only exceedingly effective in reducing risk behaviors, but is likely to be highly cost-effective.”

The roughly 3500 HIV-positive trial participants were diverse – half of the sample was homosexual men, 30 per cent was women and 20 percent was heterosexual men. The study was carried out at 13 demonstration sites in 12 states and included sites in major urban centres and sites in smaller cities.

Morin said: “These findings are very robust given the number of participants and their diversity and the variety of sites where the research was conducted. This intervention, especially when delivered by medical care providers, should be considered for inclusion in emerging ”test and treat” and ”test, treat and link to care” models that seek to dramatically increase the number of HIV-infected patients receiving care. The expected prevention benefits from increasing the number of people who know their HIV status and from successfully achieving some viral control amongst those infected could be effectively and efficiently increased if these behavioral interventions are included as part of a combination HIV prevention effort.” (ANI)

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Clinic-based HIV prevention effective in reducing sexual risk behaviors

March 25, 2010 By Leave a Comment

Washington, March 25 (ANI): Clinic-based HIV prevention is effective in reducing sexual risk behaviours, a new American study has revealed.

The study, conducted by researchers at the University of California, San Francisco (UCSF), has appeared in the online edition of the journal “AIDS and Behavior”.

Lead author Janet J. Myers, assistant professor of medicine at the UCSF Center for AIDS Prevention Studies and co-principal investigator of the project, said: “We found the greatest and most sustained reductions in sexual risk took place when the prevention interventions were delivered by medical care providers during HIV patients” routine visits. An important feature of this research is that it was conducted in actual clinical settings and not in the somewhat artificial setting of a clinical trial.”

On receiving risk assessment prevention counselling from their clinical providers, HIV patients showed a consistent decline in risky behaviour over the 12-month study period.

The researchers found HIV patients cut almost by 50 per cent their sexual risk behaviours: unprotected anal or vaginal intercourse with either a HIV-negative partner or one whose status was unknown.

HIV patients receiving services from health educators, social workers or peer educators also significantly reduced risk behaviours at 6 months, but not at 12 months.

Steve Morin, professor of medicine and director of the UCSF Center for AIDS Prevention Studies and the study”s principal investigator, said: “Other studies testing behavioral prevention interventions have demonstrated that boosters delivered at periodic intervals assist in sustaining behavior changes. Since patients see their medical providers regularly to monitor disease and therapeutic regimens, delivering prevention services during these visits is not only exceedingly effective in reducing risk behaviors, but is likely to be highly cost-effective.”

The roughly 3500 HIV-positive trial participants were diverse – half of the sample was homosexual men, 30 per cent was women and 20 percent was heterosexual men. The study was carried out at 13 demonstration sites in 12 states and included sites in major urban centres and sites in smaller cities.

Morin said: “These findings are very robust given the number of participants and their diversity and the variety of sites where the research was conducted. This intervention, especially when delivered by medical care providers, should be considered for inclusion in emerging ”test and treat” and ”test, treat and link to care” models that seek to dramatically increase the number of HIV-infected patients receiving care. The expected prevention benefits from increasing the number of people who know their HIV status and from successfully achieving some viral control amongst those infected could be effectively and efficiently increased if these behavioral interventions are included as part of a combination HIV prevention effort.” (ANI)

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Cellular defect that leads to cancer discovered

March 17, 2010 By Leave a Comment

Washington, March 17 (ANI): Scientists at the University of California, San Francisco researchers have found that a key cellular defect that disturbs the production of proteins in human cells can lead to cancer susceptibility.

They also discovered that a new generation of inhibitory drugs offers promise in correcting this defect.

According to researchers, their finding has broad clinical implications in the fight against cancer and could affect treatment of lymphoma and many other forms of the disease, including prostate cancer, breast cancer, colorectal cancer, brain cancer and multiple myeloma.

The discovery was made in the laboratory of UCSF faculty scientist Davide Ruggero, whose lab team is doing research in the burgeoning field of study on how defects in protein synthesis can lead to cancer susceptibility.

“Our work has the potential to create real, tangible benefits for the medical community,” said Ruggero.

The researchers focused on a multi-protein unit known as mTOR, which stands for the “mammalian target of rapamycin.” mTOR controls several important processes in mammalian cells, including cell survival and proliferation.

One of the most significant of these processes is the production of proteins within a cell, the control of which is known as translational control. mTOR integrates information about the cell’s nutritional and energy needs, and prompts the cell to manufacture key proteins for cell growth. Cancer cells exploit this signal for their own growth.

According to the researchers, when the cells in the body lose the ability to control mTOR activity, mTOR is considered “hyperactivated.”

This hyperactivation causes protein synthesis rates to climb. Cells begin to proliferate without limits and simultaneously become immortal, all of which leads to tumour formation.

The findings are featured as the cover story in the March 16, 2010 issue of the scientific journal Cancer Cell. (ANI)

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Soon, simple jab to prevent prostate cancer

September 8, 2009 By Leave a Comment

Washington, Sept 8 (ANI): A simple jab may soon help prevent prostate cancer, say researchers.

The research team from University of Utah and University of Columbia have identified a virus, known to trigger leukaemia, in malignant human prostate cancer cells.

The research team hopes that the virus, XMRV (Xenotropic murine leukemia virus-related virus), would open opportunities for developing diagnostic tests, vaccines, and therapies for treating the cancer.

“We found that XMRV was present in 27 percent of prostate cancers we examined and that it was associated with more aggressive tumours,” said Dr Ila R. Singh, associate professor of pathology at University of Utah and the study’s senior author.

“We still don’t know that this virus causes cancer in people, but that is an important question we’re going to investigate,” Singh added.

The study also makes it evident that XMRV is present in malignant cells, and that XMRV is a gammaretrovirus, a simple retrovirus first isolated from prostate cancers in 2006 by researchers at the University of California, San Francisco (UCSF), and the Cleveland Clinic, known to cause cancer in animals.

During the study, the researchers examined more than 200 human prostate cancers, and compared them to more than 100 non-cancerous prostate tissues.

They found 27 percent of the cancers contained XMRV, compared to only 6 percent of the benign tissues.

The viral proteins were found almost exclusively in malignant prostatic cells, suggesting that XMRV infection may be directly linked to the formation of tumors.

The study is published in the Proceedings of the National Academy of Sciences. (ANI)

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Missing protein in rare genetic brain disorder restored

September 7, 2009 By Leave a Comment

Washington, Sep 7 (ANI): By using protease inhibitors, researchers at the University of California-San Francisco (UCSF) have restored to normal levels a key protein that is involved in early brain development, and causes the rare brain disorder lissencephaly.

Reduced levels of the protein called LIS1 have been shown to cause lissencephaly, which is characterized by brain malformations, seizures, severe mental retardation and very early death in human infants.

The findings in mice offer a proof-of-principle that the genetic equivalent to human lissencephaly, also known as “smooth brain” disease, can be treated during pregnancy and effectively reversed to produce more normal offspring.

The researchers are hoping that this approach could also be used to treat other defects in utero, or even those manifesting after birth, when caused by a partial deficiency in one gene, according to Dr. Anthony Wynshaw-Boris.

“Researchers have not considered it possible to treat such a pervasive, early developmental brain disorder as lissencephaly. Not only were we able to show a clear cellular effect from using these protease inhibitors, but also were able to treat the disorder in utero,” Nature quoted Wynshaw-Boris as saying.

The work is the culmination of 15 years of collaborative research into the cause and mechanisms of lissencephaly, which is caused by a deletion or loss of one copy of the LIS1 gene, and affects an estimated one in 50,000-100,000 infants.

In 1998, the researchers reported of producing a mouse with the same mutation that displayed defective brain development.

The current research used these mice, and found that the protein calpain degrades the LIS1 protein to less than half its normal levels near the surface of the cells.

The team then used a specific small-molecule protease inhibitor of calpain in these mice.

At a cellular level, the protease inhibitors enabled LIS1 protein to be expressed at near-normal levels.

The team then gave daily injections of a calpain inhibitor to pregnant mice whose foetuses had the mouse-model of this defect.

They observed that the resulting offspring had more normal brains and showed no sign of mental retardation.

“This study is really a proof-of-principle not only for treating complex developmental brain disorders, but also for any disorder with reduced protein levels where proteases normally play some role in breaking down that protein. This will be much more difficult to apply to humans, because of the safety issues involved, but it could lead to new therapies that might be effective for a wide range of developmental disorders,” said the researchers.

The findings have been published in the journal Nature Medicine. (ANI)

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Scientists move closer to realising better diagnoses, treatments for chronic ailments

August 15, 2009 By Leave a Comment

Washington, August 15 (ANI): Scientists from Brown University and other institutions have moved a step closer to realising quicker and more precise disease diagnoses, and more targeted treatments of many chronic ailments, by taking the first step towards mapping epigenetic variability in cells and tissues.

Mapping the human epigenome is similar to the human genome project in the 1990s.

A research article published in the online edition of PLoS Genetics describes epigenetics, a relatively new endeavour in science, as the control of the patterns of gene expression in cells, which gives rise to the necessary differences responsible for creating the complex and interacting tissues in the body.

Scientists globally have begun working on a Human Epigenome Project in a bid to compile detailed data documenting, within a person, the epigenetic changes in different types of cells and tissues, something that will complement the already-completed Human Genome Project.

The Brown University researchers say that they have completed a far-reaching study of more than 200 human tissue samples in a bid to map variations in epigenomic structure.

They have carried out this work in collaboration with researchers from the Harvard School of Public Health and Harvard Medical School, the University of California-San Francisco, University of Minnesota-Minneapolis, Dartmouth Medical School, Women and Infants Hospital in Providence, and Brigham and Women’s Hospital in Boston.

The researchers have found that human cells display wide epigenetic variation that appears related to aging and smoking, which may increase susceptibility to several diseases such as cancer.

While the scientists emphasize that more research is necessary, they say that taking a step to map epigenetic variability will help bring them closer to discovering important epigenetic differences in people, which in turn could help better diagnose disease and create more targeted treatments.

“Scientists have already found out it is critical to look at genetic variation to diagnose disease. What we are trying to do is complement that by looking at what is normal and how much variation in epigenetics exists,” said Brock Christensen, a postdoctoral research associate at Brown University’s Department of Pathology and Laboratory Medicine.

According to Christensen, more tissue samples and data are needed to allow for a thorough mapping of epigenetic variability in cells.

Karl Kelsey, corresponding author and a Brown professor of community health and pathology and laboratory medicine, says: The real importance of the work has to do with beginning to define what is normal in different tissues. And then you dig deeper to see what is the same and different about different people.”

The study involved analysis of 217 nonpathologic human tissue samples, including blood, lung, head and neck, and brain tissue.

It was funded by multiple grants through the National Institutes of Health. (ANI)

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‘Heart healthy’ diet, exercise ‘protects against cognitive decline’

July 15, 2009 By Leave a Comment

Washington, July 15 (ANI): A ‘heart healthy’ diet and taking moderate exercise can protect against cognitive decline, according to two new studies.

Researchers at Utah State University in the US found that over-65s on a diet full of green leafy vegetables, oily fish and the odd glass of red wine scored higher in mental tests.

A separate study at the University of California found that moderately physically active older adults might experience slower rates of mental decline.

In the first study, Heidi Wengreen, an assistant professor of nutrition at Utah State University, asked 3,831 adults, aged 65 and older, to complete a food survey. They then tested their cognitive skills over an 11-year period, beginning in 1995.

The researchers looked to see how well the participants followed the DASH diet, an eating regimen that protects against hypertension and heart trouble.

Those who followed the DASH diet more closely had higher scores on the cognitive tests at the start of the study and over time, Wengreen found.

In the second study, Deborah E. Barnes, of the University of California, San Francisco, followed more than 3,000 adults aged 70 to 79.

Those who were sedentary had the lowest level of cognitive function at the start and higher rates of decline over the course of the seven-year study.

The two studies were reported at the Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease in Vienna. (ANI)

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Gene key to maintaining embryonic stem cells’ pluripotent state identified

July 10, 2009 By Leave a Comment

London, July 9 (ANI): Scientists at the University of California, San Francisco claim to have identified a gene crucial to maintaining embryonic stem cells’ all-purpose, pluripotent state.

The researchers say that their finding may prove helpful in improving the scientific understanding of how cells acquire their specialized states, and provide a strategy to efficiently reprogram mature cells back into the pluripotent state, an elusive step in stem cell research but one crucial to a range of potential clinical treatments.

They conducted their research on mouse embryo cells, and found that a gene known as Chd1 loosens the packaging that normally protects DNA in the cell nucleus.

The research group say that this step, known as chromatin remodelling, allows the cell’s protein-making machinery to gain access to the DNA, and transform progenitor cells into specialized cells and tissue, such as neurons, muscle and bone.

A number of genes are known to trigger chromatin remodelling, allowing small sections of DNA to become accessible in order to make specific proteins.

The scientists say that Chd1 is the first gene found to regulate a “global” loosening of the DNA in embryonic stem cells. The global condition sets the stage for turning on many different genes to make a broad range of specialized cells.

“Embryonic stem cells are characterized by this open state, but, up to now, we didn’t know the mechanisms that maintain this state, or even if it is necessary for the full stem cell potential,” Nature magazine quoted Alexandre Gaspar-Maia, lead author of the paper, as saying.

“We found that Chd1 is critical for both, and for allowing an efficient reprogramming. Chd1 is important for allowing the normal differentiation process, and it is essential for playing the ‘differentiation tape’ backwards – bringing differentiated cells back to pluripotency,” he added.

The scientists discovered the pivotal role of Chd1 by using the powerful technique of RNA interference (RNAi) to screen this gene, and 40 other candidate genes.

When the researchers silenced the gene by using the technique, embryonic stem cells could not make the full range of specialized cells.

In a laboratory test used to simulate normal cell specialization, the scientists detected no differentiation of cardiac muscle, and also no formation of a tissue known as primitive endoderm, which is essential for the embryo to survive and develop.

The researchers also found Chd1 to be necessary for the reprogramming of specialized cells back to the pluripotent stem cell state.

They are planning to further study chromatin remodelling in more detail to clarify what other molecules work in concert with the Chd1 gene to direct the process, hoping that this would aid efforts to increase the efficiency and safety of reprogramming cells.

According to them, their research may also shed light on how cells transition from one type to another, a process that happens normally during embryonic development and goes astray in cancer.

“We now know that Chd1 is essential, and, so far, appears unique in its global effect, but we expect that there are major players yet to be discovered,” said senior author Ramalho-Santos, UCSF assistant professor of obstetrics, gynecology and reproductive sciences, and pathology.

“If we can understand how Chd1 works, that will also tell us more about how the cells regulate their precise specialization during development, and turn on their pluripotency program during reprogramming,” Ramalho-Santos added.

Based on their findings, the researchers came to the conclusion that embryonic stem cells exist in a dynamic state, poised between the open condition that may assure the cell’s full potential, and the more constrained state that allows only certain kinds of cells to progress.

Chd1, they say, is central to maintaining the open, pluripotent stem cell state. (ANI)

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Genetic region linked with rare ability to recognize, name musical notes identified

July 3, 2009 By Leave a Comment

Washington, July 3 (ANI): Scientists at the University of California-San Francisco (UNSF) say that they have identified a particular region of genes on human chromosome eight that is linked to perfect pitch, the rare ability to recognize and name musical notes without any reference pitch for comparison, at least in people of European ancestry.

Reporting their work in American Journal of Human Genetics, the researchers say that their next step will be to identify a specific gene.

The finding, part of a larger examination of families of various ancestries – Europeans, Ashkenazi Jews, Indians and East Asians – is the first significant genetic evidence of a role of genes in perfect pitch.

The researchers say that it is likely that multiple genes are involved in all cases of perfect pitch, and that different genes could be associated with different ethnic backgrounds.

But despite that, they say, the finding is an important advance in their effort to move in on the relative roles of early musical training and genetic inheritance on perfect pitch.

Professor Jane Gitschier, the senior author of the study who is a singer herself, says that it is an advance in the team’s effort to explore the relative contributions of environmental factors and genes on learning and other behaviours.

“Perfect pitch is a window into the way in which multiple genes and environmental factors influence cognitive or behavioural traits,” she says.

The team has learnt over the last decade that both factors contribute to perfect pitch.

“What’s exciting now is that we now have made the first foray into teasing out the genes that may be involved,” she says.

Besides continuing to identify and collect data on families with multiple cases of perfect pitch, the researchers plan to analyse candidate genes for variations that might be associated with perfect pitch in participants of European ancestry.

For this purpose, the team plans to recruit and study individuals of European ancestry without perfect pitch, but with equivalent early musical training.

The ongoing effort is supported in part by a grant by the NAMM Foundation, which was established by the international music products industry association with the aim of promoting “active participation in music making across the lifespan,” in part by supporting scientific research. (ANI)

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Avoid selenium if you already have prostate cancer

June 27, 2009 By Leave a Comment

Washington, June 26 (ANI): An intake of selenium could worsen the conditions of people who are already suffering from prostate cancer, and have a variant of a gene called superoxide dismutase (SOD2), according to a study.

Researchers at Dana-Farber Cancer Institute the University of California, San Francisco, have observed a higher risk of more-aggressive prostate cancer in men with SOD2 genetic variant, found in about 75 percent of the prostate cancer patients in the study.

In such men, having a high level of selenium in the blood was linked with a two-fold greater risk of poorer outcomes than men with the lowest amounts of selenium.

On the other hand, the 25 percent of men with a different variant of the same gene, and who had high selenium levels, were at 40 percent lower risk of aggressive disease.

The variants are slightly different forms of a gene that instructs cells to make manganese superoxide dismutase (SOD2)-an enzyme that protects the body against harmful oxygen compounds.

Senior author Dr. Philip Kantoff, director of Dana-Farber’s Lank Center for Genitourinary Oncology, says that the findings of the study suggest that for those who already have prostate cancer, it may be a bad thing to take selenium.

The unexpected results are the first to raise concern about this potentially harmful consequence of taking supplemental selenium.

Kantoff said: “These findings are interesting particularly in light of the recent negative results from the SELECT prevention study, which asked if selenium could protect against prostate cancer.”

The new study reveals the strong interaction between selenium and SOD2 to influence the biology of prostate cancer-a finding that has earlier been shown.

The authors said that the current research demonstrated that variations in the make up of the SOD2 gene dramatically alter the effects of selenium on the risk of aggressive prostate cancer.

Selenium is a mineral found widely in rocks and dirt and small amounts of selenium are essential for health.

The study has been published in the Journal of Clinical Oncology. (ANI)

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Partner issues significantly influence women’s sexual activity

June 27, 2009 By Leave a Comment

Washington, June 26 (ANI): It’s not just age, partner’s health and interest in sex too have significant impact on sexual activity among middle-aged and elderly women, say researchers.

During the study, the team from University of California, San Francisco and Kaiser Permanente examined 2,000 women, aged 45 to 80 years old, 43 percent reported at least moderate sexual desire, and 60 percent had been sexually active in the previous three months.

Among sexually inactive women, the most common reason was lack of interest in sex with 39 percent of the respondents saying the same.

Thirty-six pct said lack of a partner, 23 pct agreed to physical problem of partner while 11 pct said lack of interest by partner.

Only nine percent were inactive from personal physical problems.

According to the researchers, sexual activity was defined as any activity that was arousing, including masturbation.

“Our findings indicate that a substantial portion of women are interested and engaged in sexual activity as they age,” said lead author Alison Huang, MD, assistant professor in internal medicine at the University of California, San Francisco.

“Clinicians should consider a woman’s overall health when addressing concerns about sexual inactivity.

However, treatment directed solely at improving women’s sexual functioning, such as medications, may not substantially affect their activity if partner issues also are not addressed,” Huang added.

The study appears in Journal of the American Geriatrics Society. (ANI)

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