Health Meaning

For many viruses, infiltrating cell replication and is only half the battle. Copies of the virus must then escape to infect other cells. Some viruses explode outside a host cell, destroy; others, like the influenza virus, taking a softer way. Now, a report in the latest EMBO Journal shows how the flu virus slips the bounds of his cell -. Prisoner and how, by knocking out parts of two key viral genes, it can be held

After the influenza virus invades a cell, it commandeers the cell genetic mechanism to multiply the viral RNA. The viral proteins assemble new virus particles that migrate to the cell wall, where they wrap themselves in the membrane. The bud, as it is called, clamp off and escapes. "It's almost like bubbles," said Robert Lamb, a virologist at Northwestern University.

The virus escape tools were thought to be two proteins, hemagglutinin and neuraminidase, which jab like grappling hooks in the cell membrane, leaving "tails" dangling for viral particles to enter on to test the importance of these protein "spike" to Houdini act of the virus, Lamb and his colleagues performed a simple experiment.: they disabled one, then two, portions of genes from influenza viruses encoding the tail proteins. viruses can manufacture one full spike protein had a time a little harder bud formation in cultured cells. But the effect on viruses without two tails protein was superb. the number of viral particles escaping from each cell has dropped by 0%, and the escapees were severely deformed instead of balloons, Lamb said, they looked like a "sausage chain with big bulges coming out the side -. As something of science fiction "

The deformed virus, not surprisingly, had a much harder time to infect new cells that made their spherical brothers. This could make the tails of a protein spikes tempting target for new drugs, says virologist John Rose of the medical School of Yale University, who called the research "an important work."

SAN FRANCISCO - As light a miniature oven in the body, scientists have created a compound that stimulates some of the fat cells to burn calories without forcing them to bear jogging, swimming or cycling. Chemical, described here today at the annual meeting of the American Chemical Society, took up the metabolic rate of rats by 30% - equivalent to a weight loss of nearly 3 kilograms per month among people. But it may take several years before the potential drug comes on the market, and even when it does, the researchers caution that this is not a "magic pill" for slenderness.

The compound mimics adrenaline, the hormone messenger of the "fight or flight" response to danger. A type of adrenaline receptor starts the heart beat faster, and a second dilates blood vessels and lowers blood pressure. In 1989, a third receiver - the so-called -adrenergic receptors - was discovered on brown fat cells, which convert fat into heat. Adrenalinelike a potential drug for weight control should target only fat cells receptors to avoid dangerous side effects in the cardiovascular system.

A team led by Robert Dow Pfizer in Groton, Connecticut, studied receiver to see what makes it unique. After homing in on a region carboxylic acid, they tinkered with adrenaline to get a version that only binds to the receptor. They added the modified adrenaline compound called CP-331,679, in cultured cells of human fat, and as the receptors were activated and were trigger a cascade biochemical within the cell. Then, they are fed the compound to rats and followed by the oxygen animals, an indirect measure of metabolic rate of fat cells. For several hours, the rats consumed 30% more oxygen than the control rats; the experiment was not designed to test the weight loss.

obesity experts are encouraged that so powerfully composed stokes the furnaces of brown fat cells. "This is a big step forward," said Xavier PiSunyer Columbia University Medical School. However, he noted, many obstacles remain, including the fact that human adipose tissue a few brown fat cells. To work in people, normal fat cells will respond to the drug, too.

If the drug was to be conducted in clinical trials, it would probably be prescribed as part of a plan, including regime change food and exercise, said Dow, who stressed that the drug is unlikely to be a magic bullet. "the idea of ​​a pill to cure obesity is probably not going to come to be," he said .

WASHINGTON, DC - National Science Foundation director Neal Lane yesterday announced the winners 1997 the National Medal of science, the highest scientific honor of the nation. Also announced were the winners of the National Medal of Technology. Medalists will be honored at a ceremony at the White House later this year.

A winner of the Medal of Science, Princeton astronomer Martin Schwarzschild, died April 10 and so is being honored posthumously. The others are:

• William K. Estes, scientist and professor emeritus of cognitive psychology at Harvard University
• Darleane C. Hoffman, nuclear chemist and director of the Institute Glenn T. Seaborg to Transactinium science at Lawrence Berkeley National Laboratory, University of California (UC), Berkeley
• Harold S. Johnston, professor emeritus of chemistry at UC Berkeley
• N Marshall . Rosenbluth, a physicist at UC San Diego
• James D. Watson, a molecular biologist and president of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York
• Robert A. Weinberg, geneticist cancer at the Whitehead Institute at the Massachusetts Institute of Technology
• George W. Wetherill, planetary dynamicist Carnegie Institution in Washington, DC
• Tung Yau Shing-mathematician to Harvard University.

The medalists of the technology are:

• Norman R. Augustine, CEO of Lockheed Martin in Bethesda, Maryland
• Ray M. Dolby , founder of Dolby Laboratories Inc. in San Francisco
• Robert S. Ledley, professor of radiology at Georgetown University Medical School
• Vinton Cerf gray MCI and Robert E. Kahn, Chairman of the Corporation for National Research initiatives. Both are honored as a team for the development of Internet protocols.

Today Spotlighted of minorities is the 67th anniversary of LaSalle Leffall Jr., an oncologist who has drawn attention to the problem of the high mortality rate of cancer among minorities especially African Americans. Leffall published research in 1973 showing the increase of cancer mortality in the black population of the United States. When he became the first African-American president of the American Cancer Society in 1978, Leffall helped organize the first conference on cancer in the black community. In addition to clinical research on breast cancer, colorectal, and head and neck Leffall served as an educator at Howard University in Washington, DC

[Source:EmilyMcMurrayEd notable scientific Twentieth Century (Gale Research Inc., ITP, 1995)]

The most common cause of blindness is the explosive growth of blood vessels near the retina, and scientists may have a finger key culprit in this process: growth hormone. The findings, reported in today's issue of Science * could lead to an alternative to drug-based laser surgery, the current treatment of this form of blindness that often strikes people with diabetes and children born prematurely.

There are fifty years, doctors have found that removal of the pituitary gland could restore vision in some blind diabetics. But the loss of the plant hormone - which produced a number of chemicals essential for metabolism, including growth hormone - makes people tired, intolerant of stress, and susceptible to infections. Today, the treatment of choice is laser surgery, but it can partially destroy the retina and decrease peripheral vision, and not always successful in restoring sight.

The search for a less risky treatment, a team led by Lois Smith, a pediatric ophthalmologist at Harvard Medical School and Children's Hospital Boston, hungry mice of oxygen, which induces growth of blood vessels near the retina, the layer of cells that captures light for forming images. Blood leaking from blocks light of new vessels from reaching the retina. "Even more devastating, leaking vessels form scar tissue, which pulls the retina at the back of the eye and leads to total blindness," says Smith.

team induced by the blood of the Smith growth of vessels in normal mice and mice genetically to express a gene for a protein that inhibits the growth hormone. the dwarf transgenic mice had 34% less growth of new blood vessels that checks had. the team Smith then injected normal mice with MK678, a hormone drug growth suppression, and found that reduced blood vessel growth up to 44%. Smith suspect that growth hormone triggers the growth of blood vessels by stimulating another hormone, insulin-like growth factor-I, and indeed, infusing the mice with IGF-I washed the beneficial effects of the drug.

experts applaud the results . "Before, it was only an assumption that hormones did the damage," said David Clemmons, an endocrinologist at the University of North Carolina, Chapel Hill. Now, he says, the study "proves unequivocally" that growth hormone is involved. But Smith and others warn that the development of a drug to fight against this form of blindness will not be easy: the growth of blood vessels is required for processes such as wound healing and repair heart tissue after a heart attack . Thus, any new drug must seek growth in the retina and allow growth hormone to work in peace elsewhere in the body.

* For details, Science Online subscribers can link to the full report.

Claude Bernard, a French researcher founder of the field of experimental medicine, was born July 12, 1813. While conducting experiments on a animal fed a sugar-free diet, Bernard discovered that the liver stores sugar as glycogen. In other animal studies, it was observed that pancreatic juices break down fats and starches, and some blood flow nerve control by triggering veins constrict or dilate. Bernard also found that red blood cells to carry oxygen throughout the body. The most important theoretical contribution of Bernard was his observation that life requires a stable internal environment, or "within the medium."

Scientists have discovered a new way for genetic mutations lead to cancer - making the DNA adjacent sections most likely to be mutated. The chance discovery, reported in the September issue of Nature Genetics could explain the unexplained cases of colon cancer and helps in the early detection of these cancers, especially among Ashkenazi Jews.

Inheritance seems to play a role in somewhere between 15% and 50% of colon cancers and benign polyps which are often precursors. However, the genes of colon cancer found up to now have been linked to less than 5% of the total cases. A hint of what could explain the discrepancy came to light when a social visitor Bert Vogelstein laboratory at the School of Medicine at Johns Hopkins University mentioned that he had multiple colorectal polyps and mild family history of colon cancer. As a courtesy, Vogelstein, whose lab had already discovered a handful of genes involved in the disease, proposed to test the 39-year-old man for known mutations.

Vogelstein, Kenneth Kinzler, and other colleagues found a minor change in the CPA gene that normally keeps cell growth in check and can cause colon cancers when mutated. At first glance, the change appears to be harmless - a simple switch from a thymine (T) to adenine (A). Such changes of genes, called polymorphisms, are common. But curiously, the tumor suppressor protein made by the gene began to pick up additional mutations in and around the area that contains the T-to-A switch. Does it seem to come Kinzler said, because the mutation creates a stretch of eight straight As, which can get rid of the enzyme that transcribes DNA and completely garble the resulting protein.

The team guessed that the A chain could also confuse the enzyme that copies DNA when cells replicates, creating new - and more damaging - mutations. Indeed, all the tumors of patients who have worn this particular T mutation also had additional mutations that inactivate the CPA gene. But the blood cells from the same patients had only to change A T - suggesting that patients have inherited the basis for change and develop other changes later, but only in colon cells that have become cancerous

". This could be a historical study of a new mechanism," says molecular biologist Jeffrey Trent of the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland. Trent and others say that the same mechanism could be at work in the genes linked to other cancers, such as breast cancer and prostate cancer, which were found to contain similar variations "harmless" sequence

Strokes inflict 80% less brain damage in mice lacking a DNA repair enzyme, according to a report in the issue of this month Nature Medicine . In normal mice, the enzyme zealous deprives brain cells of energy - trying to repair damaged DNA - for hours after a stroke. The discovery suggests that an enzyme inhibitor may prevent damage in humans after existing drugs have restored blood flow

During a stroke, blood flow to part of the brain is cut off. - So that supply oxygen and nutrients such as sugar. Most stroke research has focused on restoring oxygen to the brain, says Valina Dawson, a neuroscientist at Johns Hopkins University. But research has shown that brain cells continue to die after blood flow is restored, since the renewed metabolism generates free radicals that damage DNA and other cell parts. In response, the cells activate an enzyme called poly (ADP-ribose) polymerase (PARP) to repair DNA damage. Dawson said that to try to repair the DNA of the cell, PARP could seriously deplete energy resources and perhaps even kill the cell.

Dawson and his team first have to mice brain cell cultures that have been bred not to produce PARP. Even when the cells were starved of oxygen and sugar, or exposed to chemicals which release neurotoxins such as nitric oxide, they are not damaged - that up to 65% of the cells from normal mice death when subjected to similar treatment. When the researchers then induced stroke in mice with or without the PARP gene, they found that tissue damage resulting from the mice without the enzyme was 80% less than in normal mice. "The protection was phenomenal and beyond our best expectations," said Dawson. Most tests of drug animal stood between 10% to 30% less damage, and sometimes up to 50%, she added.

The protective effect of PARP inhibition is "striking" and made "a strong case" to examine the role of PARP in the human race, said Thomas Jacobs, a neuroscientist at the National Institute of neurological disorders and Stroke in Bethesda, Maryland.

A new therapy for pancreatic cancer reduced the tumor growth rate in patients in a pilot trial and in a separate study, kept the remote mouse tumors altogether. The treatment, reported in today's edition of Proceedings of the National Academy of Sciences , rallies "killer" immune cells to fight the devastating cancer.

Less than 1% of pancreatic cancer patients live more than 5 years after diagnosis. "There are no successful medical treatment," says Wolff Schmiegel, a gastroenterologist at the Ruhr University Bochum, Germany. In the hope of improving this grim statistic, the group moved to exploit the Schmiegel ability of the immune system to recognize certain cancer cells as enemies by the developer carpet proteins, such as the receptors for epidermal growth factor receptor (EGFR), which stud their surfaces. A cancer cell with a lot of EGFR antibody which attracts many lock onto receptors;. the antibodies, in turn, attract the killer cells that destroy tumor cells increasing the number of receptors on tumor cells, the researchers reasoned, would enhance the effectiveness of what is called the immunotherapy, in which antibodies are administered designed to attract killer cells.

Four years Schmiegel and colleagues found they could increase the levels of EGFR on the cell surface of pancreatic cancer by adding a protein of tumor necrosis Factor- a (TNF- a ) to cells in culture. In their latest work, the researchers injected human pancreatic cancer cells in mice, which quickly developed tumors. Treatment of these mice with TNF a and EGFR antibodies have kept tumors from growing larger, like those of control mice Eightfold inflated.

In a second study, the team Schmiegel treat 26 patients at similar stages of pancreatic cancer with TNF- a and a variable amount of the antibody. The tumors of patients receiving more antibodies increased by less than 10% on average, while those in patients receiving the lowest dose more than doubled in size. Patients receiving the high dose also lived more than twice as long on average as those in the lower dose, but this result was less reliable because of the small number of patients.

The therapy offers hope for pancreatic cancer patients, said immunologist Hilary Koprowski of Thomas Jefferson University in Philadelphia, who says he is "cautiously optimistic" that the treatment will prove a hit long term. "I wish there was no difference in survival rates" between the lower and higher dose groups, he said. Schmiegel now working towards the next stage -. A study with more patients who could provide more reliable information on the survival time

A toxin derived from the skin of a South American frog led to a potential new pain reliever that may lack some of the side effects of morphine. In tests on animals, the drug, which apparently is not opioid receptors but rather by a receptor for the neurotransmitter acetylcholine, has proved effective in blocking the acute and chronic pain. In addition, the researchers saw little evidence that the drug, reported in Science today is addictive or toxic.

The drug's design was based on a compound extracted from the skin of an Ecuadorian frog by chemist John Daly, of the National Institute of Diabetes and Digestive and Kidney Diseases. In 1976, he discovered that the compound, called epibatidine, is 0 times more potent than morphine in blocking pain in mice. Unfortunately, it also caused convulsions and even death. Approximately 10 years later, her lab used nuclear magnetic resonance spectroscopy to determine the structure that resembles epibatidine to that of nicotine. Other experiments have shown that the compound activates the nicotinic acetylcholine receptor.

The research has attracted the attention of a team from Abbott Laboratories Abbott Park, Illinois, who noticed that the epibatidine structure resembles that of the compounds they studied as therapies for Alzheimer ' Alzheimer. Neuropharmacologist Stephen Arneric and colleagues fiddled with their compounds, trying to create a derivative that only kills the pain.

They have now shown that a variant, called ABT-594 is as effective as morphine in acute and chronic pain wetting rats. By placing electrodes in the spinal cord of rats, the researchers also showed that the drug inhibits the ability of nerve cells to fire in response to noxious mechanical and thermal stimuli, but it does not affect the touch response or the gentle heat. The company also found Arneric said that ABT-594 depresses the respiratory system less than morphine does, and it makes the animals more alert instead of the sedative. In addition, in at least one test, ABT-594 appears to be nonaddictive.

Much more work will be needed to determine whether the drug is safe and effective in humans. For example, other researchers point out that ABT-594 mechanism of action raises the possibility that it will lead to other forms of addiction. Abbott has begun safety testing in Europe and hopes to conduct trials in this country as well. "If it works in people, it'll be a whole new kind of pain," said Howard Fields, professor of physiology and neurology at the University of California, San Francisco.

A potential treatment for Parkinson's disease can be in an unusual place: the body of the carotid artery, a small organ in the neck. In February the number of Neuron José López-Barneo and colleagues at the University of Seville in Spain reported that in rats, the carotid body cells-transplanted animals neck in their brains reverse symptoms of an experimental form of dementia.

normal work of the carotid body, nestled in the carotid artery, is to signal your brain to increase your breathing if your oxygen levels in the blood drop too low. The main interest of López-Barneo was in how the carotid body-cells captures the lower oxygen levels in the blood. But, he recalls, colleagues kept stressing that these cells could make excellent candidates for transplantation into the brains of Parkinson's patients to correct their shortcomings. Indeed, movement problems and other symptoms of the disease are caused by the death of neurons, in a part of the brain called the substantia nigra that produce the neurotransmitter dopamine. And because the carotid body-cells are much dopamine, they might be able to compensate for the loss of normal dopamine-producing neurons.

To find out, the Seville team turned to a common animal model for Parkinson screening potential therapies. This involves killing the neurons of the substantia nigra on one side of the rat brain, which then develop an imbalance of movement which causes them to turn around, and exhibiting other symptoms. When the researchers transplanted into the damaged side rats pieces of brain carotid body, they found that the grafts not only survived, but reversed the animals of symptoms, including the imbalance of the movement. There were even indications that the cells could be the production of growth factors that promote the substantia nigra cells remaining to sprout new connections.

These results are "quite fascinating, very promising," said neuroscientist Arnon Rosenthal, who works on Parkinson therapies in the biotechnology company Genentech Inc. in South San Francisco. Carotid-body cells will pass much more testing before researchers can even consider trying them on patients, however, Rosenthal said, they may have an advantage over therapeutic potential competitor. transplantation of fetal neurons Because the cells of the carotid produce so much dopamine. - up to 45 times the fetal neurons - and because they thrive in relatively low concentrations of oxygen in the brain, he says, they can do a better job to correct the symptoms of Parkinson that fetal cells make - and they raise fewer ethical issues

Much new research takes shape held in Kansas City, Missouri, that could one day compete with larger charities biomedical world. With $ 125 million in public funding, the Stowers Institute for Medical Research has begun to renovate a medical center of 55,000 square meters in Kansas City to accommodate an initial staff of 100 people, including 20 Ph.D.s. The institute plans to open five laboratories for basic science in January 00.

According to its co-founder, financier James Stowers Jr., the organization will focus on the genetics of development and growth, with a goal of fighting cancer. For scientific leadership, Stowers has relied heavily on geneticist Leroy Hood of the University of Washington, Seattle, and Eric Davidson of the California Institute of Technology in Pasadena, both members of the National Academy of Sciences.

Stowers, 74, and his wife Virginia, 68, are cancer survivors; according Stowers, "which is what motivated us" to consider funding medical research. "My wife and I wanted to give something more than money for people who have made our success possible." They launched the endowment of the Institute, with 327 million shares $ of the investment company, they founded, American Century funds the couple plans to leave the rest of their assets. - estimated at more than $ 1 billion. - the institute to death If these funds are also developing faster than he managed in Historically, Stowers said, staffing may be worth $ 30 billion in 25 years

Stowers said he has a clear scientific strategy, based partly on the advice of Hood .: "We wanted focus our efforts in one area and not be scatter-gun. " Davidson, who also serves on the advisory board, said, "You can not organize science, but we hope to find and recruit people" interested in "looking at the complex interactions of groups of molecules" using advanced technology. the key to success of the institute recognizes Stowers will be its ability to attract "top scientists" in Kansas City.

An enlarged heart increases the likelihood of death from heart disease in adults. Now it seems that 8% of children and adolescents with high blood pressure - perhaps in 1250 in the United States - also have a disturbing thickening of the heart muscle. The discovery, published in the latest issue of Traffic , suggests that testing for heart enlargement must indicate which children need a more aggressive treatment of risk factors for heart disease.

specifically enlargement-- heart's main pumping chamber of the heart, the left ventricle - was first linked to an increased risk of fatal heart disease in 190, as part of the Framingham study massif of heart disease. Since then, doctors have found that treatment of other risk factors for heart disease such as high blood pressure and obesity, can reduce the relative size of the left ventricle.

Wondering how early in life from this disease develops, cardiologist Stephen Daniels and colleagues from the University Hospital Medical Center of Cincinnati Children interviewed 130 children who had been admitted to the Clinical Hypertension hospital and thus may be more likely to have an enlarged left ventricle. To calculate the relative size of the heart of each child, the researchers scanned every heart with ultrasound. Eight percent of children aged 6 to 23 has reached or exceeded the threshold that defines a high-risk adults. "It is surprising because it suggests that this process is already underway, and these children can be directed to paths for future cardiovascular disease," says Daniels.

Other cardiologists say the test should help guide treatment as well. Samuel Gidding of Northwestern University says children with both high blood pressure and enlargement of the ventricle could be dealt with not only a weight loss program over diet healthy, but also with drugs that reduce blood pressure. "to this very small group of children who clearly detrimental to their heart, we need to be more aggressive in the treatment," he said.

There have been nearly a century since first Alois Alzheimer fibrous plaques found infesting the brains of people with dementia but scientists still do not know with certainty, however-or even if - the plaques cause Alzheimer's disease. Now a trio of studies in the July issue of Nature Medicine opens new avenues for research on the plate with a new animal model for the formation of plaque, a diagnostic tool for identify, and a possible way to break them.

scientists have long suspected that Alzheimer's patients lose their memories and minds when the beta amyloid proteins form aggregates that needle punch holes in the brain cells and kill them. Alzheimer mostly affect the elderly, but scientists have not been able to understand why because they lacked a good animal model of the disease; in previous mouse models, the amyloid plaques formed but brain cells survived. Now neurologists Changiz Geula and Bruce Yankner of Harvard Medical School found such a model: Rhesus monkeys. They injected tiny amounts of amyloid protein in the brains of monkeys and found that the old rhesus monkeys developed symptoms, but young Alzheimer's monkeys remained healthy.

Research on plates was also hampered by the lack of a good method for diagnosing Alzheimer's disease in living patients. A new diagnostic test, created by Detlev Riesner and colleagues at Heinrich-Heine-Universitat in Dusseldorf, Germany, can help identify the plates long before brain cells die. The test, which measures levels of beta-amyloid plaque in the spinal fluid, successfully diagnosed 15 Alzheimer's patients and was not triggered by 19 people with other neurological diseases.

If the plates show a crucial link in Alzheimer's disease, a treatment that breaks down can repair the damage. Claudio Soto and colleagues at New York University Medical Center may have found a protein fragment that does exactly that. In rats and human nerve cells in tissue cultures, these "beta sheet breakers" not only prevent amyloid plaques from forming, but also dissolve existing plaques.

Taken together, the new studies create interesting new tools in the fight against Alzheimer's disease, says Robert Szarek, a pathologist at Queens University in Kingston, Ontario. early diagnosis could help doctors intervene and using a new therapy to preserve brain cells, he said. and if the beta sheet breakers are effective in monkeys and rats, they could also help treat Alzheimer's patients. But this should not be simple. for treating humans, the researchers must still find a way to deliver fragments of proteins past the blood-brain barrier, which prevents movement of proteins into the brain, and the site of the plates. Kisilevsky adds, "These are formidable problems."

A new drug can block the symptoms of schizophrenia as in rats without apparent side effects. The work, described in Science tomorrow , suggests a new approach to drugs for schizophrenia that may one day lead to better therapies for the disease, which affects 1% of the population of the United States only.

These drugs are sorely lacking. Current drugs against schizophrenia, known as neuroleptics, are designed to relieve the symptoms of the disease by blocking the action of a brain chemical signal, dopamine. But as patients who take the often see reductions of paranoia and hallucinations, medications provide little relief of other symptoms, such as poor attention spans, confused thoughts, and difficulty interacting with other people. In addition, neuroleptics often cause disturbing side effects, including uncontrollable tremors similar to Parkinson's patients

Phencyclidine of psychoactive substances, or PCP, offered tempting tips that a different approach could to work:. Blocking the activity of another neurotransmitter called glutamate. PCP induces symptoms of schizophrenia as in healthy people. Following these observations, neuroscientists Bita Moghaddam and Barbara Adams of Yale University School of Medicine and the Veterans Administration Medical Center in West Haven, Connecticut, PCP administered to rats who develop symptoms such as the frenzied race and turn his head thought parallel psychotic symptoms in humans, and examined what happens to the brain glutamate levels in animals. Although previous work has suggested that they should go down in response to the CFP, Yale workers found instead they jumped. Moghaddam then speculated, she recalls, that "if we block the activation of glutamate, maybe we can block these behavioral effects."

To avoid side effects, Moghaddam and Adams wanted to block the glutamate activity in the parts of the brain where it can be high. So, they turned to a drug called LY354740, which is under development at Eli Lilly & Co. in Indianapolis for other psychiatric disorders such as anxiety. By binding to metabotropic receptor called glutamate on nerve endings glutamatergic releasing LY354740 dampens the output of the transmitter, but only when the too high. when Moghaddam and Adams rats given the drug before Lilly administer the CFP, they found that glutamate levels went up in the prefrontal cortex, one of the regions of the brain that breaks down in schizophrenia. the six LY354740-treated rats also remained calm and showed little behavior nods, compared with controls who received only CFP.

Encouraging results in rats do not guarantee that the approach will work in humans. Yet, says Horvitz Jon schizophrenia researcher at Columbia University in New York, "it's an awesome job. This is a promising way to a drug that alleviates the symptoms of schizophrenia."

Association today presented Alzheimer's largest single research grant, he has never given to a husband and wife team at the University of Pennsylvania School of Medicine in Philadelphia. Neuropathologist John Trojanowski and Virginia Lee neurobiologist use the grant of $ 1 million over the next five years to develop new tests for the diagnosis of Alzheimer's disease in its early stages.

Since some cases of Alzheimer's disease resemble other neurodegenerative diseases such as Parkinson's disease, Trojanowski and Lee intends to look for ways to identify Alzheimer's disease true. "To get good treatment in drug trials you need to know what you are dealing with," says Trojanowski. He and Lee are the players in the field of Alzheimer's disease well known, having collectively published over 100 Articles on neurodegenerative diseases.

Association of Alzheimer's disease has designed the Pioneer award with the needs of innovative scientists in mind. Unlike many other subsidies, the price enables researchers to save unspent funds for unexpected opportunities that may arise. other scientists say the price is generous enough for academic researchers to pursue drug development projects that otherwise would not be possible without corporate financing. "Therapeutics was the field of biotechnology and pharmaceutical industry, and this could change that, "says Sam Sisodia, a molecular biologist at the University of Chicago. The Alzheimer's Association will award three more $ 1 million grant to Pioneer in June 1999.

W ASHINGTON , DC - Worried about an imminent new era of terrorism, a scientific committee urged the government today to redouble their efforts to protect civilians against emerging biological and chemical threats.

The report, published by the Institute of Medicine (IOM), asks the public health service to build local health surveillance systems and emergency services. It also aims to create a national stockpile of antidotes and vaccines that could be transported to the site of an attack across the United States. The panel, chaired by the specialist in Emergency Medicine Peter Rosen of the University of California, San Diego, also has a long list of research needs. Among other things, the report recommends studies on how to conduct medical triage large-scale, the development of new biohazard detection equipment, better vaccines against anthrax and smallpox, and more effective protective equipment.

While the Pentagon has invested billions of dollars to protect troops against biological and chemical attacks, the report notes, these "military traditional approaches" are not suitable to treat civilian settings, where attacks future may occur. Despite the "very low probability" of a terrorist attack on a particular site, IOM offers a 220 page program to remedy the absence of civil preparedness. Many of the proposals, according to the report, are intended to strengthen local networks of public health, which makes the "valid even if no attack never happens."

The IOM report was warmly welcomed at the Department of Health and Human Services (HHS), the home of the public health service. Margaret Hamburg, the assistant HHS secretary for planning, acknowledges that "we are very badly prepared" for the kind of panic that would result from a bioterrorist attack and HHS spokesman Campbell Gardett said. "We welcome the report" adding that "we are currently developing a plan that will detail how we will use" approximately $ 150 million Congress gave HHS for bioterrorism defense in a special 1999. appropriation

- E LIOT M ARSHALL

Eleven prominent AIDS researchers, primatologists and animal advocates urge vaccine developers not to inject chimpanzees with stem HIV that can cause diseases like AIDS in animals. In a letter published in Science tomorrow , they raise ethical and scientific objections to these experiences.

Until recently, chimpanzees have been considered poor models for testing vaccines, because HIV does not replicate well in animals or seem to make them sick. But that changed when researchers at the Yerkes Primate Research University Regional Centre Emory in Atlanta, Georgia, found a strain of HIV that causes a sharp decline in CD4 cells of animals and an increase of virus in their blood. In a study published in the June 19, 1998 Science , Norman Letvin Medical Center Beth Israel Deaconess Harvard in Boston noted that the strain might be useful for candidates Test vaccines, and many researchers on the AIDS agreed.

But not virologist Alfred Prince Of Blood Center of New York, who runs a chimpanzee colony in Liberia, and his colleague Linda Andrus. "The prospect of causing a rapidly progressive and fatal disease in this near-human species is abhorrent," they wrote in a letter to 18 December 1998 Science . A more acceptable to test vaccine candidates, they say, is whether it can prevent a virus to establish a chronic infection; where applicable, the disease does not occur. And several non-virulent strains seem to reproduce fairly well in chimpanzees to provide a realistic challenge, they wrote

In the new letter, Prince, Andrus, and nine others, including defender chimpanzees Jane Goodall, raise new objection .: the virulent strain of HIV may be too "hot". It destroys the immune system of a chimpanzee in a few weeks, while in men the same process generally takes years. This could "seriously compromise the vaccine effort against HIV" excluding vaccines do not protect against this strain, but but could be effective against wild-type HIV, they write.

But Patricia Fultz from the University of Alabama at Birmingham does not believe that the Emory HIV strains are too hot, noting that the infected animals have lived up to 4 years. and Letvin said that focusing only on the ability of a vaccine to ward off chronic infection rather than its effect on the disease process, may lead researchers to overlook a useful vaccine: "If we have a vaccine that can make people live decades longer, we need to know ".

A sometimes fatal heart enlargement can be inherited or acquired through infection. In this month's issue of Nature Medicine , the scientists show that the virus causes symptoms in the same way as genes are faulty, suggesting that a single therapy could work against the disease.

Dilated cardiomyopathy, which can cause shortness of breath and the result of heart failure and death, affects about 50,000 people in the United States each year. For several years, researchers know that up to a third of patients suffering from viral infections, most of them with the Coxsackie B virus infections swell and irritates the heart, sometimes leading to chronic inflammation which can lead to cardiomyopathy. Cardiomyopathy but can also be caused by genetic diseases such as muscular dystrophy, which causes abnormalities in a protein called dystrophin. Dystrophin is responsible for binding of the cell membrane to contractile proteins such as actin and allows the force of contraction in the cells to be transmitted outside.

Cardiologist Kirk Knowlton San Diego University and his colleagues wanted to know if the Coxsackie B virus also affected dystrophin. The researchers showed that in test tubes, proteins produced by the virus Coxsackie B virus separated dystrophin, but not to other proteins present in cardiac cells. After the rat heart cells in culture were infected with Coxsackie virus B virus, the amount of normal dystrophin decreased within 3 days. Finally, the researchers injected immunodeficient mice with Coxsackie B virus when they killed animals a week later, they found that the virus had broken dystrophin in their hearts and that the membranes of heart cells infected with Coxsackie virus B were more permeable to blue dye than uninfected cells. This implies that the distribution of dystrophin damaged cell membranes, said Knowlton; this weakening of cell membranes allows the virus to spread, but damages the heart, as it makes the cells less resistant and less able to contract effectively. In an attempt to keep pumping enough blood, the heart starts getting larger.

The study is the first to show that the damaged dystrophin underlies both genetic and acquired cardiomyopathy, said Jeffrey A. Towbin, a cardiologist with the Baylor College of Medicine and Children's Hospital of Texas in Houston. This similarity suggests that researchers should target the underlying process in different varieties of the disease, he says, for example by developing a drug to prevent the dystrophin breaking down.

A new artificial kidney consists of living kidney cells on a plastic scaffold restored the main functions of the organ during the test in dogs. If the device, described in the May issue of Nature Biotechnology , can replace kidneys in humans, it could save the lives of thousands of patients who suffer from sudden kidney failure each year.

More than half of those whose kidneys fail during or after major surgery die, usually within 2 weeks. Indeed, the standard treatment for kidney failure, pumping blood through a dialysis machine, do filter metabolic waste from the blood, says nephrologist David Humes of the University of Michigan, Ann Arbor. A kidney, in comparison, pumps hormones such as activated vitamin D can increase the capabilities against the body of the infection subsides and the salts and nutrients from the liquid become urine. To create a better replacement kidney, Humes and his colleagues enlisted the real experts -. Kidney cells themselves

First, the team extracted primitive kidney cells called renal tubular cells from adult pigs and inject them into plastic tubes. These tubes form a hemofiltration cartridge, a blood filtering device already used by a handful of patients with kidney failure. The cells can collect on the tubes with small holes to allow the dissolved molecules to slip through. The cells then come together to form a fabric sheet, as they do in a normal kidney. When the blood of dogs that had just had their kidneys removed was passed through the device, it filters the blood more effectively than standard dialysis machine. In addition, devices with better maintained cells control blood pH and actively secreted hormones to fight against infection and glutathione activated vitamin D in the blood of animals compared to devices without cells. The group is seeking regulatory approval to begin clinical trials for patients with acute renal failure later this year, said Humes. And a variant of the device for chronic renal failure is scheduled for tests on animals.

The new system "should provide much normal kidney function as possible with conventional dialysis," says biomedical engineer Barry Solomon Circe Biomedical Inc. in Lexington, Massachusetts, which produced similar devices fill for failing livers. the device also shows the promise of bioartificial organs plastic compounds and living tissue, said biomedical engineer Clark Colton Massachusetts Institute of Technology. "I think it is a big step forward for the field. "

American geneticist Barbara McClintock, who challenged the prevailing theory that genes are stable elements of chromosomes with his discovery of "jumping genes", was born in date 102. McClintock studied inheritance in corn, examining patterns of color appearing in the nuclei and leaves.

in 1931, McClintock and a graduate student Harriet Creighton proved that the physical mixing of chromosomes could lead to the exchange of genetic material. In 1944, McClintock observed that certain genes cell hopped cell developed as a core. Four years later, she discovered that the controlled breaking of chromosomes was that allowed genes to move. When McClintock published the surprising discovery in 1950, the scientific community was skeptical, but in 1983 she received the Nobel Prize in physiology or medicine. His work was then used to explain the inheritance patterns that follow the rules of Mendel based on dominant and recessive characters. McClintock died in 1992.

A potential AIDS drug called azodicarbonamide suppresses not only HIV, but also the human immune system, the scientists report in the August issue Nature Medicine . Although some scientists believe that the discovery casts doubt on the future of the drug in the treatment of AIDS, it points to its possible use to prevent the body from rejecting organ transplants.

In 1996, azodicarbonamide has been found to inhibit HIV replication in cell cultures by interfering with "zinc fingers" - elongated members comprising a zinc atom - a crucial viral protein. it has been shown to work in both the early and late stages of AIDS and is currently in clinical trials. researchers at the University of Brussels, Belgium, wonders, however, if the drug could also affect on the immune system -. More particularly, on CD4 cells, the class of white blood cells infected with HIV

the researchers used monoclonal antibodies to activate the human CD4 cells in test tubes They. then measured azodicarbonamide effect on the production of cytokines, proteins which signal other cells to mount defenses of cells. "We were surprised that this drug has a drastic effect," said a member of the Jamila Ismaili team. In most tested human samples, the drug reduced cytokine production by 80% to 0% within 72 hours

The result led the researchers to think about a completely different use for azodicarbonamide: . As a drug that could stop the immune system from attacking the transplanted organs. Thus, in a second experiment, they gave a daily dose to mice that received a skin graft rejection and controlled. Without the drug, the skin grafts survived only 12 days; on average, doubled it azodicarbonamide. This suggests that azodicarbonamide can be added to the arsenal of immunosuppressive drugs, said Ismaili.

But the study raises questions about the use of azodicarbonamide as anti-HIV agent. "You could worry additional immunosuppressive effects with AIDS," says Stephen Desiderio, a molecular biologist at the School of Medicine at Johns Hopkins University. He stressed that the drug could still be useful in the early stages of infection when it will be more important than maintaining the immune system in the form containing the replication. "This is really a first look at the issue," says Desiderio.

"Nobels of America," the annual awards - light on money, but heavy prestige - the Albert and Mary Lasker Foundation, will this year six biomedical researchers. They include neuroscientist Seymour Kety, 84, pioneer explorer in the biological roots of schizophrenia, who works at McLean Hospital in Belmont, Massachusetts.

The winners of the basic price of medical research, for work on the architecture of ion-channel proteins are physiology Clay Armstrong professors from the University of Pennsylvania, Philadelphia, and Bertil Hille, University of Washington, Seattle; and neurobiologist Roderick MacKinnon of Rockefeller University in New York City. The medical clinic Research Award goes to David W. Cushman and Miguel A. Ondetti two Bristol-Myers Squibb researchers have designed ACE inhibitors, cardiovascular drugs. The $ 10,000 awards will be presented in New York on October 1st.

Sometimes called the "genome guardian" protein known p53 responds to DNA damage or by halting cell division or causing the cell to commit suicide. Anyway, p53 action helps the formation of short-circuit preventing tumor cells that have undergone malignant mutations continue to grow. However, the p53 gene itself may be damaged, which is thought to contribute to the development of half of all cancers. In tomorrow Science , the researchers describe a drug that may be able to restore the normal function of certain mutated p53 proteins and could therefore open the way for a new type of cancer treatment.

To stop cell division or trigger cell suicide, p53 needs to regulate the activity of various genes, which requires that the first bind to DNA regulatory sequences of genes. The researchers found that many mutations that inactivate p53 cause the protein to misfold, producing a three-dimensional conformation without rigid molecule needed for this connection.

Before searching for a molecule capable of bracing aberrant p53 in the proper position to attach to DNA, biologists Farzan Rastinejad cancer and Barbara Foster Pfizer Central Research in Groton, Connecticut, needed to a quick way to tell if a compound worked. They hit on the idea of ​​using a known antibody that recognizes a part of p53 that is exposed only when the protein is in the right conformation. Ultimately, they examined more than 100,000 compounds with antibodies, initially to identify compounds that could increase its binding to p53 normal, then testing them successfully compounds on the mutant p53 in the tube test. Compounds that have taken this test then went to the next phase, in which the group Rastinejad looked to see who could correct a mutant p53 protein in tumor cells in culture. After winnowing the pack further, they showed that the drugs remaining candidates slowed cancer growth in mice.

The results are a first step on the long road to the manufacture of a drug that can be used in humans. Nevertheless, they represent "an exciting proof of principle of what promises to be a new form of therapy," says Bert Vogelstein, a cancer biologist at Johns Hopkins University School of Medicine in Baltimore, Maryland. In addition, Rastinejad adds, because misfolded proteins are involved in other diseases, including Alzheimer's disease, cystic fibrosis and diseases of the brain thought to be caused by infectious proteins called prions, "this approach may relate to a large number of diseases. "

Shining some light on the skin lesions and the extent of reflection can help dermatologist to identify the most dangerous form of cancer skin more easily, according to a new study. The technique could help pick up the cancer early and save patients from unnecessary biopsies.

Melanoma, the most aggressive form of skin cancer, shows first as a dark pigmentation patches on the skin, but it is difficult to say such a malignancy a harmless mole or freckle . Dermatologists can have a computer compare the following images and search for mysterious reasons, they usually rely on signs, like irregular edges or more colors. Even specialists can have trouble detecting melanoma, however, and most would like to spare patients the stress of a biopsy when possible.

In 1991, an Italian team developed a new technique. When they shine a beam of light on the lesions of the skin, they found that the spectra of the reflected light are different for melanoma and benign skin lesions. Now, a research team from the Institute of Cancer and the Royal Marsden Hospital, UK, took this a step further technique.

Physicist Vincent Wallace and colleagues first measured the spectra of 121 "worrisome lesions," which were then removed and diagnosed in the laboratory. They found seven main differences between the spectra of benign lesions and melanomas, they used to develop software that analyzes the signal and determines whether the lesion is likely to be a melanoma or not. they integrated it in an experimental scanner, they tested of 47 lesions. As reports team in the March Physics in Medicine and Biology , they could change the system so that he can choose each malignant tumor, but produce few false alarms. the system has outperformed the analysis current computerized image, and as good as the visual inspection by most dermatologists, says physicist and member of the Jeffrey Bamber team. the process is also faster and can consider smaller lesions. And because it is fully automated, it could be used by nondermatologists such as GPs, said Bamber.

But Ronald Barr, a dermatologist at the University of California, Irvine, said he would be wary of using the technique to systematically screen patients - at least in the US - because he is afraid , it may not detect certain malignancies. "We have a litigious society," said Barr. Instead, he said the system could be helpful to detect many lesions on one patient known to have a melanoma, or for monitoring patients after treatment.

Smoking or inhaling secondhand smoke can increase the risk of breast cancer, according to a large study, published in the current number of Causes and control [cancer. The work may help explain why previous studies of the link between smoking and breast cancer has come up with conflicting results.

Researchers have long puzzled over the blurred relationship between cigarettes and breast cancer. Some studies have suggested that smoking may actually protect women, a finding the researchers attributed to the removal of nicotine from estrogen, often linked to breast cancer hormone. But most follow-up studies found no relationship between smoking and breast cancer; and others have shown that smoking and secondhand smoke in particular, increased the risk.

Kenneth Johnson and colleagues at the Laboratory of the Canadian government for Disease Control in Ottawa glean information on 2317 women with breast cancer and 2438 healthy women from a Canadian study monitoring Cancer. Participants answered questions about risk factors such as alcohol consumption, physical activity and age at menarche, and their lifetime exposure to tobacco smoke at home and at work. For premenopausal women, smoking or regular exposure to secondhand smoke doubled the risk of breast cancer; for postmenopausal women, these factors have increased the risk of 50% and 30% respectively

Johnson said the study may explain why studies consistently show that secondhand smoke increases the risk of breast cancer -. his is the seventh to do - while others that examined smokers have had mixed results. Maybe, he says, it is because smoking and passive smoking are almost the same risk. Most previous studies have compared active smokers to people who had never smoked; but most women in the latter group were exposed to passive smoke "so that you are really exposed to compare exposed," Johnson said. In fact, when smokers in the new study were compared to all non-smoking - regardless of whether they were exposed to secondhand smoke or not - the risk of breast cancer was equal, as in studies previous. The results suggest that some women develop breast cancer when they were exposed to a certain amount of smoke, Johnson said - no matter how it gets into their bodies

Support for this theory came in 1996, when Christine. Ambrosone, biologist at the National Center for Toxicological Research in Jefferson, Arkansas, reported that women with a slow form of an enzyme that metabolizes carcinogenic tobacco had an increased risk of breast cancer. Ambrosone Johnson said the study is solid, but cautions that researchers still need to work on many details about the link between smoking and breast cancer. "My feeling is that breast cancer is a very heterogeneous disease, so that this relationship will be complicated."

Chafing at the slow pace of commercial development of the drug, a disease advocacy group made last week to fund new drugs for his district . Last week, cystic fibrosis (CF) Foundation Bethesda, Maryland, has announced it will invest at least $ 30 million in a small biotech company, Aurora Biosciences of San Diego, to identify compounds that could be useful in treating CF. The project, initially fed by a gift of $ 20 million from the Bill and Melinda Gates Foundation, marks a new departure in the growing trend of patient groups that support biomedical research.

The plan calls for Aurora to several one hundred thousand molecules display in his library over the next five years and identify two or three that could be candidate drugs for CF. If this approach gives promising results "," CF Foundation plans to pay an additional amount of $ 16.9 million Aurora to prepare candidates for clinical trials. Carry drugs through the final approval, however, would require co-investment by a major pharmaceutical company. The benefits would be shared between the CF Foundation and its business partners, but the foundation would immediately plow all its own charges directly in research on new therapies.

President Robert Beall CF Foundation believes that this new society "virtual drug," a hybrid business, non-profit, is unique in the pharmaceutical industry. Her group decided to take the plunge into the drug R & D because he did not wait for drug manufacturers to small molecules to take an interest in the FC

Large pharmaceutical companies have not been drawn on the ground, Beall notes, because the number of cystic fibrosis patients that could buy a drug is relatively small - only about 30,000 in the United States. And he said that "when we tried to involve them" in the search for new compounds of interest, "they did not return our calls." Thus, the foundation has hired a consultant veterinarian for innovative small businesses; they have settled quickly Aurora, which maintains a library of 400,000 small molecules that can be screened at high speed for medical applications.

Francis Collins, director of the National Institute for Research on the human genome and co-discoverer of the CF gene, said, "This roll-up-your sleeves partnership" between an advocacy group for the disease and a drug discovery company's new "The CF Foundation is taking an interesting step. this obviously has a high risk, but could also have a strong gain if it works." By providing early support for drug discovery, Collins said, the foundation ensures that the disease "will get more attention and approaches more advanced than it would otherwise."