Health Meaning

The legislation proposed by the Bush administration to stimulate the production of medicines and vaccines antibioterrorism is running into opposition in Congress. Although project "BioShield" was approved by a Senate committee last week, members of the House expressed strong reservations about its potentially astronomical costs and the negative impact on competition between pharmaceutical and biotechnology companies to design new treatments.

President George W. Bush first announced BioShield in his State of the Union in February. BioShield aims to accelerate research efforts and development base of the National Institute of Allergy and Infectious Diseases (NIAID), which was allocated a record $ 1.7 billion to research bioterrorism during exercise 03. It also includes a provision to distribute drugs and vaccines to fight against potential bioterrorist attacks without the usual clinical tests mandated by the Food and drug Administration.

But it was third provision BioShield that caused widespread concern among members of the two subcommittees, one of the House Committee on Energy and Commerce and one of the commission of Homeland security, which organized jointly today for their first discussion of the law. Representatives have doubts about the administration's plan to enter into multi-year contracts with companies that produce products antibioterror and provide guaranteed financial support of products once they reach fruit. This is necessary "to create a market" for products that would not have another one, said Tommy Thompson, secretary of the Department of Health and Human Services. Without BioShield, "it will not be a lot of companies are lining up to do."

But members of the House have pointed out potential flaws in this strategy. For example, if the government contracted with a production company, for example, a vaccine against the plague, then a second company developed a superior vaccine, the first contract was nevertheless held, and the government would be stuck paying for a potentially inferior product. "You can indeed stifle innovation" by discouraging competition, said Jim Turner (D-TX), and waste money. Bush tentatively proposed to spend $ 6 billion over 10 years on BioShield, but Thompson said during today's hearing that the amount is actually "indefinitely" without limit in a year. In addition, because the Project BioShield Act installs the current bill, a future administration would be bound to support it, even if displaced national security priorities, noted Christopher Cox (R-CA).

The Energy and Commerce and Homeland Security committees will now determine how, if necessary, modify the existing draft BioShield Act before voting on it.

Related Sites
information from the White House on BioShield
Senate Bill BioShield

Shooting millions of tiny RNA molecules in the blood of mice can protect the liver against the ravages of hepatitis. This is apparently the first time that this technique, called RNA interference (RNAi) was used to fight against the disease in an animal. But biologists warn that the therapy has a long way to go before it can be safely applied to humans.

RNAi uses thumbnails RNA molecules to silence specific genes ( Science NOW, December 19, 02). Normally, large RNA molecules convert genetic information into protein; but in the late 190s, researchers found that the truncated RNA could be induced to turn off genes. Hepatitis has become a center RNAi studies, because the liver easily absorbs molecules.

Harvard University immunologist Judy Lieberman and Premlata Shankar and colleagues wanted to see whether RNAi could prevent liver damage. They gave mice three injections massive high pressure - equivalent to about half the volume of blood "animals - a solution that forced the molecules in the liver. The molecules are designed to stop a gene called Fas , which when overactive, induces liver cells to self-destruction; Fas is also involved in human liver diseases.

The next day, the animals received an antibody that sends Fas in hyperdrive, causing liver failure. Control mice died within a few days, but 82% of the treated mice survived. About 80% to 0% of liver cells incorporated RNA molecules. In addition, RNA molecules hung around for 3 weeks, about three times longer than previous studies, the authors report online today in Nature Medicine

During this time, other mice face a distinct challenge :. Over six weeks, they received weekly injections of cells called Con, which Goad the immune system to attack the liver, producing the kind of scars seen in viral hepatitis. Some animals also received an RNA infusion during this time, and this group developed any damage to the liver. Despite the traumatic delivery method, the mouse does not seem to suffer any side effects.

"It is amazing how it worked," marvels Charles Rice of the Rockefeller University in New York City Still, he added, the delivery method is clearly problematic. In humans, the "hydrodynamic shock ... is not the way to go." Researchers have yet to determine if a more gentle approach might prove fruitful.

Related Sites
The homepage of Judy Lieberman
General Hepatitis Foundation International
Hepatitis C Information from NIH

Shooting millions of tiny RNA molecules in the blood of mice can protect the liver against the ravages of hepatitis. This is apparently the first time that this technique, called RNA interference (RNAi) was used to fight against the disease in an animal. But biologists warn that the therapy has a long way to go before it can be safely applied to humans.

RNAi uses thumbnails RNA molecules to silence specific genes ( Science NOW, December 19, 02). Normally, large RNA molecules convert genetic information into protein; but in the late 190s, researchers found that the truncated RNA could be induced to turn off genes. Hepatitis has become a center RNAi studies, because the liver easily absorbs molecules.

Harvard University immunologist Judy Lieberman and Premlata Shankar and colleagues wanted to see whether RNAi could prevent liver damage. They gave mice three injections massive high pressure - equivalent to about half the volume of blood "animals - a solution that forced the molecules in the liver. The molecules are designed to stop a gene called Fas , which when overactive, induces liver cells to self-destruction; Fas is also involved in human liver diseases.

The next day, the animals received an antibody that sends Fas in hyperdrive, causing liver failure. Control mice died within a few days, but 82% of the treated mice survived. About 80% to 0% of liver cells incorporated RNA molecules. In addition, RNA molecules hung around for 3 weeks, about three times longer than previous studies, the authors report online today in Nature Medicine

During this time, other mice face a distinct challenge :. Over six weeks, they received weekly injections of cells called Con, which Goad the immune system to attack the liver, producing the kind of scars seen in viral hepatitis. Some animals also received an RNA infusion during this time, and this group developed any damage to the liver. Despite the traumatic delivery method, the mouse does not seem to suffer any side effects.

"It is amazing how it worked," marvels Charles Rice of the Rockefeller University in New York City Still, he added, the delivery method is clearly problematic. In humans, the "hydrodynamic shock ... is not the way to go." Researchers have yet to determine if a more gentle approach might prove fruitful.

Related Sites
The homepage of Judy Lieberman
General Hepatitis Foundation International
Hepatitis C Information from NIH

The inherited form of Lou Gehrig disease amyotrophic lateral sclerosis -familial (FALS) - causes disintegration of the motor neurons of the spinal cord and brain, a devastating loss of control the body, and death within 2 to 5 years. A study now shows that the molecular cause of FALS is similar to other neurological diseases such as Huntington's and Alzheimer's disease, offering new hope in the search for a cure.

Fals patients with mutations in a gene called superoxide dismutase ( SOD1 ), but it is a puzzle how these mutations lead to disease. Normally, the SOD1 protein binds zinc and copper atoms and uses them to break superoxide, a destruction of cellular respiration byproduct. So it would be logical if the mutations cripple the SOD1 protein, superoxide to build to toxic levels. But this idea was discarded when the researchers found that mice lacking the SOD1 gene remain healthy. Only one mutated copy causes paralysis, indicating that mutated SOD1 is itself toxic agent behind FALS.

Because the capacity of a protein is determined by its shape, a team led by John Hart at the University of Texas Health Science Center in San Antonio used x-ray crystallography to see how the mutation alters the structure of the protein of SOD1. Reporting in May 18 issue of Nature Structural Biology , Hart and colleagues show that the mutation may cause SOD1 proteins to lose their metals, exposing patches that have just the right shape and charge for proteins to lock onto each other. These new SOD1 link interfaces always growing fibrils that can overwhelm systems degrading proteins that cells use to keep themselves tidy, known pathology other neurodegenerative disorders. With this revealed mechanism, Hart hopes to identify drugs that inhibit the destructive link.

The quality of work is "breathtaking," said Mark Gurney, Vice President of Drug Discovery at deCODE Genetics in Reykjavik, Iceland. But before seeking the drug can begin in earnest, Gurney said, it will be important to demonstrate that this aggregation mechanism occurs "inside motor neurons not only in protein crystals."

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the homepage FALS at Imperial College London
Who was Lou Gehrig?

The AIDS virus dodges the ammunition dam immune system. researchers have now discovered one of his tricks: HIV disables a host protein that would otherwise break the virus into pieces. But the virus can not stop similar proteins in mice. The discovery, published in July 11 issue of Cell provides a new idea on why HIV only infects humans and may one day lead to better animal models of AIDS.

last year scientists discovered that a protein made by HIV, called Vif, protects the virus against the host attack. But they did not know how Vif ripped this feat. Now, AIDS researcher Nathaniel Landau of the Salk Institute for Biological Studies in San Diego, California, and colleagues report that Vif locks a human protein called APOBEC3G. In the absence of Vif in virus APOBEC3G slides and outputs the bits of its inactivating DNA. HIV Vif protects against death in human cells.

Curious how mice fight HIV so easily, Landau's group checked to see if rodents have their own version of the APOBEC3G gene. They did, but the mouse protein, the researchers found, is unrecognizable to HIV defense system. He circumvented the blockade Vif, moved into the virus, and hit it out of commission.

"It is a major breakthrough" to show that APOBEC3G plays a role in the unique sensitivity of humans to HIV, says Jeremy Luban, a virologist at Columbia University. For scientists studying drugs and vaccines against HIV, "it would be a huge technical advantage" if this information could help create laboratory mice that can support HIV infection, he said. Luban but warns that such a project is not likely to bear fruit immediately, as it is likely that many other barriers that prevent HIV from infecting other species.

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laboratory Nathaniel Landau Jeremy Luban laboratory

An outbreak of a mild respiratory disease in two nursing homes near Vancouver, in Canada, scientists and experts puzzled and worried public health. Tests suggest that a very similar to the agent that causes severe acute respiratory syndrome (SARS) is involved, but symptoms of SARS does not look full. The results suggest that the SARS coronavirus can cause mild disease that has not been known.

The health authorities in the province of British Columbia reported that 94 residents and 49 employees at a nursing home in Surrey have fallen ill since July 1. Most had mild, coldlike symptoms, although 11 elderly patients developed pneumonia and six died of pneumonia, often accompanied by other diseases. Nine cases occurred in a second home close

In studies at Canada's National Microbiology Laboratory in Winnipeg, nine of the 19 patients had traces of the RNA of the SARS coronavirus. four of seven patients also had antibodies against the virus. Researchers still have sequenced the genome of the virus involved in the disease, but the 750 base pairs sequenced so far closely resemble extracts in the genome of the SARS coronavirus, David Patrick of the Center for Disease Control BC said yesterday in an announcement on ProMED, a list of e-mail for emerging infectious diseases

So far, the SARS virus. - The transmission of the World Health Organization (WHO) was arrested around 5 July - has not been known to cause mild disease. In its report, Patrick offered three possible explanations: Perhaps the virus was originally a benign disease unnoticed throughout; a major mutation may have rendered the SARS virus less aggressive; or the virus may be a close relative of SARS.

The results are potentially worrisome, says virologist Albert Osterhaus of Erasmus University in Rotterdam, the Netherlands, "but right now we just do not have enough data to say anything useful ". But Henry Niman, a Harvard researcher, says the results suggest that the real virus SARS is still circulating in Canada and could mutate back into the deadliest form.

The WHO sent a virologist to Winnipeg to monitor studies- -but he does not judge a health emergency because the disease is so mild. "Right now, this is just a laboratory abnormality," said spokesman Dick Thompson of the WHO. Meanwhile, Canadian authorities have isolated patients and are looking for people who might have come into contact with them.

Related Sites
More information about the epidemic
WHO SARS information

WASHINGTON, DC - Scientists reported three new animal models that could provide relatively cheap and convenient means for testing drugs and vaccines against severe acute respiratory syndrome (SARS), the disease that broke out in southern China last spring

these are not the first animal models for SARS. that honor goes to a monkey. At the height of the SARS crisis last April, virologist Ab Osterhaus and colleagues at the Erasmus University Rotterdam, the Netherlands, cynomolgus monkeys inoculated with a newly discovered coronavirus. The monkeys have developed a lung infection resembling SARS in humans, providing evidence that the new virus was indeed the culprit, and the first animal model. In Rotterdam and elsewhere, researchers are studying SARS pathogenesis and to test drug candidates in infected monkeys

But the use of monkeys raises ethical questions. Moreover, they are heavy and expensive to experiment animals, especially under strict biocontainment standards. At a meeting here last week, organized by the Institute of Medicine Board on Global Health, Kanta Subbarao of the National Institute of Allergy and Infectious Diseases said she sprayed the SARS virus in the nose of mice and found that, although the animals didn 't get sick, the virus began to replicate inside their bodies - sufficient for an animal model. "Everyone calls us to test their pet vaccine," said Subbarao, who presented the results for publication.

In an article that has been accepted by Nature , meanwhile, Osterhaus says that his group has infected two other species of SARS and found that the virus is easily reply within two . Osterhaus declined to reveal the two species pending the release, but said they are more closely related to palm civets masked Melogale - two species in which the SARS virus was found in China ( Science NOW, May 23) - than they are to mice. The results suggest that the virus may have a remarkably wide host range, says Osterhaus.

The announcement of Subbarao was one of the few concrete measures before reported during the meeting last week. With drugs and vaccine studies in childhood and flu and cold season about to hit the northern hemisphere, many wondered if the overstretched public health systems will be able to cope if SARS reappears. Summing up his feelings after the meeting, National Center for Infectious Diseases director James Hughes said: "What I have heard does not make me sleep better"

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. paper the Lancet describing the SARS model in macaques (free registration required)
Ab Osterhaus laboratory
more on SARS

No, they are not designed as a tasty alternative low-calorie cat chow diets. But scientists have created a strain of mice that can not produce cholesterol. The animals are viable, the study shows because another fat molecule can pick up most cholesterol functions.

Despite its bad reputation, cholesterol is an important part of our lives. Cell membranes are full, enzymes to alter sex steroid, and developing embryos rely on it to grow. In cells, two biochemical pathways convert sterols cholesterol, and disruption of one or the other leads to serious diseases of the human endocrine system. Researchers had already eliminated a route in mice and found that scurriers can not live without it. Now, another group of scientists, led by Elena Feinstein Quark Biotech in Cleveland, Ohio, arrested another generation cholesterol pathway, they report in the December issue 19 Science .

team has found the gene encoding a key enzyme, desmosterol reductase, which converts desmosterol to cholesterol, and created mice lacking both copies of the gene. Compared to normal mice, the modified mice had very low levels of cholesterol both in the blood and liver; they also had about 20% to 60% less total sterols. The team found that desmosterol was the predominant sterol, suggesting that this molecule can take over in the absence of cholesterol. They also found that embryos, transgenic mice had almost normal cholesterol concentrations, probably they received from their mother and that allowed them to develop normally until birth. As they grew up, however, they developed health problems, including infertility.

The novelty of the results is that "desmosterol seems to be able to perform for cholesterol," said clinical geneticist Forbes Porter of the National Institute of Child Health and Human Development in Bethesda. The work can help researchers understand why cells bother to cholesterol instead of using its precursors, he said. metabolic clinical geneticist Hans Andersson at Tulane University Medical School says the work might not be relevant to human disease because that humans with mutations in desmosterol reductase are sick and yet have high levels of cholesterol, unlike rodents. "mice can not be the best model for human disorders of sterol biosynthesis," he said.

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Quark biotech

Interferon a , a drug widely used to treat hepatitis C and several cancers, may also work against SARS, according to a study published online this week by Nature Medicine . Clinical studies with the drug should start as soon as possible if SARS reappears, said lead researcher Albert Osterhaus of Erasmus University in the Netherlands.

During the SARS epidemic last year, doctors have tried all kinds of treatments. A combination of an antiviral drug, ribavirin, and steroids - which attenuates the immune response and are often used in other lung infections - has quickly become the standard of care in many countries. Some studies have suggested that patients responded well, but they did, and the blind randomized controlled design that enables researchers to be sure, said Simon Mardel, a doctor working on SARS to the World Health Organization health (WHO) in Geneva. Indeed, some researchers now think the combo of drugs has done more harm than good.

Interferon a , which comes in more than a dozen varieties, is a double hammer. It blocks the replication of several viruses and also activates the immune system. It was first held in 30 of the first patients in the southern Chinese province of Guangdong, but seemed ineffective, a group of Chinese researchers reported recently. A small trial in Toronto, however, released in December, suggested some benefit.

In the new study, cynomolgus macaques received the form of interferon a chemically modified to last longer in the bloodstream. When injected 3 days before infection with the SARS virus, macaques excreted much less virus in their throat and lung damage was reduced by about 80%. When animals received compound 1 and 3 days after exposure, lung lesions was also reduced, but not as much.

This means that the compound would probably be more effective as a prophylactic for, say, family members or patients health care workers at high risk of infection, says Jindrich Cinatl Medical School of University of Frankfurt in Germany. Whether the drug might work in people with the whole SARS remains to be seen, he said.

The lead author of the small Canadian study, Eleanor Fish of Toronto General Research Institute, said she is encouraged by the new results. Already, Health Canada approved a protocol for a human trial with interferon alone, without steroids or ribavirin in SARS reappears. Several other Western countries consider the same course.

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has been shown in mice, fish and yeast; Now the first study of calorie restriction long term in humans suggest that if you really want to live longer, eat less.

Few people are willing to significantly reduce their caloric intake for years. But researchers from the University of Washington in St. Louis managed to locate 18 (15 of them men), aged 25-82, who spent an average of 6 years of balanced diets recommended by the Company calorie Restriction. The scientists compared 18 people with otherwise clean livers, on a "typical Western diet." On average, the subjects ate 1700 calories a day, compared to at least 2100 for controls, says lead investigator Luigi Fontana, who also works for the Italian Institute of health.

Dr. Atkins notwithstanding, the subjects lost a lot of weight while consuming 46% of their calories from complex carbohydrates. their "bad" cholesterol, blood lipids, and diabetes risk markers went down the blood pressure dropped to childhood levels the bodies of the subjects were 9% fat -.. compared to 24% for the controls and, surprisingly, with 12% for people who run 50 miles a week, said Fontana. And none of the dieters had plaque in their carotid arteries, scientists report online April 19 in Proceedings of the national Academy of science .

William Harlan, a nutrition expert and consultant clinical trials at the National Institute of Mental Health, called "provocative" study. He noted that while the study subjects were self-selected, "the differences that are present are striking. ... More studies like this [would] give us a better idea of ​​what a truly healthy diet look like. "

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