Health Meaning

In the race for current weapons against microbes, vancomycin has long been a weapon of last resort. Unfortunately, more and more bacteria become resistant to the antibiotic. Now, a study hints at a way to extend the life of vancomycin.

Vancomycin works by bonding to a peptide, D-ala-D-ala, that the bacteria use to build their cell wall. This causes the bacteria to absorb much water they burst. But in bacteria resistant to vancomycin, part of this peptide was replaced with D-Ala-D-lac, making the drug ineffective. Gabriela Chiosis chemist at Columbia University and colleague Ivo Gomperts Boneca of Rockefeller University, both in New York, thought they could overcome this problem by splitting D-Ala-D-lac, which would cut leakage cells.

They screened about 300,000 peptides and found one that selectively chopped apart D-Ala-D-Lac. Because peptides are easily chewed by the bacteria, the researchers studied its chemical characteristics and designed a non-peptide compound, SProC5, which mimics the effects of the peptide. SProC5 had no effect on a strain resistant to vancomycin Enterococcus alone, but reduced the amount of vancomycin needed to kill bacteria 8 times, the team reports in the edition 24 August of Science.

SProC5 does not solve the problem of resistance to vancomycin, because even the reduced amount of vancomycin required to kill resistant bacteria would still be toxic to patients, says infectious disease physician Louis Rice Cleveland Veterans Affairs Medical Center in Ohio. Still, "I think it is a very interesting strategy," he said.

Related Sites

US the Food and Drug Administration site on antibiotic resistance
Laboratory Alexander Tomasz
Alliance working for education of antibiotic resistance

Women who have a baby before they are 35 tend to have a lower risk of breast cancer. This has been clear for years now, researchers have found finally found out why. The effects of the fight against cancer in pregnancy may be due to an inhibitor of tumor famous, p53.

The p53 protein helps keep the cancer in check by controlling a cell raking in response to DNA damage. One strategy is to stop a cell from dividing until it destroys itself, or its DNA can be repaired. In rats, the researchers found that treatment with pregnancy hormones estrogen and progesterone protects against breast cancer. Pregnancy hormones also cause a spike in the levels of p53. However, the rats are protected against breast cancer long after the hormone levels return to normal. Molecular biologist Bert O'Malley and colleagues at Baylor College of Medicine in Houston, Texas, wanted to understand why.

When the team of O'Malley exposed female rats to estrogen and progesterone to mimic pregnancy, the animals maintained high levels of p53 in mammary cells long after the hormone treatment ended. Pregnancy induced the same effect: During 35 days after the rats had given birth, p53 levels were significantly higher than in virgin rats. When rats were then exposed to a carcinogen, rats treated with hormones showed high levels of p53 and cell proliferation reduced compared to untreated rats, blank controls. The researchers report their findings in the October issue of the early edition of Proceedings of the National Academy of Sciences 16.

The group from O'Malley showed for the first time the additional protection afforded by p53 lasts well beyond the initial hormonal explosion, said D. Joseph Jerry, a cancer researcher at the University of Amherst, Massachusetts. He speculates that this new understanding may lead to preventive treatments that target p53 - and avoid the side effects associated with hormones. Jerry warns, however, that other molecular players can play a central role in keeping cancer at bay.

Related Sites

More on p53
bracing p53 to the war on cancer ( science NOW, December 23, 1999)

cholesterol-lowering drugs, at least in laboratory experiments, can foul the ability of HIV to copy itself and infect new cells. Although the new work is primarily intended to shed light on the specific steps that HIV uses to replicate the anti-cholesterol link opens a new way for future medications.

When HIV hijacks the genetic machinery of a cell, it causes the cell to produce many copies of viral building blocks. A type, a protein called gag, fixed within the outer membrane of the cell. Then, gag gets cut into various internal proteins that make new viruses. Building on the work earlier by the laboratory of James Hildreth at Johns Hopkins University in Baltimore, Maryland, molecular virologists Akira Ono and Eric Freed of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, sought to clarify how HIV is new viruses. Because HIV itself carries a layer of fat, the concentrated pair on areas rich in cholesterol in the plasma membrane called

When the researchers treated cells infected with HIV with drugs that deplete the cholesterol "rafts." - By withdrawing from the plasma membrane or by blocking its production - until they found a 80% reduction in the release of new viruses. In addition, they report in November 20 Proceedings of the National Academy of Sciences, new viruses that have managed to get out of the cells with disrupted rafts were found to be much less infectious. The researchers conclude that the newly formed molecules gag specifically associated with rafts.

Freed said he hopes the work helps uncover the complex interaction between the virus and the cell it infects. "We can not look the virus in a vacuum," said Freed, noting that cellular factors such as cholesterol-rich rafts play an essential role in the HIV life cycle. Although Freed calls for caution to present complaints about the clinical import of his laboratory studies, he and other researchers argue that a better understanding of the cellular factors that HIV exploits can lead to surprising - and badly needed - new lines of attack against the virus.

"It is a beautiful paper," says Eric Hunter, a virologist at the University of Alabama, Birmingham, who studies how copies of HIV. Hunter added that it remains possible that HIV actually interacts with cholesterol outside of rafts, which Freed and experiences of Ono has not excluded.

Related Sites

homepage Eric Freed
homepage James Hildreth

GENEVA - the Board of the World Organization of Health Administration (WHO) yesterday decided to delay the destruction of the last known samples of smallpox now kept on ice in two high-security facilities in Russia and the United States. The decision reflects a new consensus that stocks may be needed to defend humanity against the possible use of smallpox as a biological weapon.

Smallpox was eradicated in 1980, and stocks were doomed to destruction in 1993, but two developments helped persuade WHO to delay this order. A well-placed defector revealed that the Soviet Union had amassed tons of smallpox as a weapon. And in the wake of the Gulf War, UN inspectors reported that Iraq may have sought to weaponize smallpox through research on camel pox, a close cousin that is not harmful to humans.

The board acted on the recommendation of the Director-General Gro Harlem Brundtland, who based his decision on a report last month from a scientific advisory committee. Staying an execution scheduled for this December, the board delivered a spectacular victory researchers hope to design drugs and a better vaccine. One interesting development is a potential animal model of smallpox developed by virologist Peter Jahrling of the Medical Research Institute of Infectious Diseases US Army at Fort Detrick, Maryland, and colleagues. The model could be important to test drugs and vaccines.

But some countries are troubled by an open research effort. China, Cuba, and several other countries are expected to pressure hard for a period of fear that an open program increases the risk that terrorists might steal the virus or the virus could escape in a laboratory accident. Observers believe that the World Health Assembly could set a deadline of 05 or 06 for destroying stockpiles when it meets in May.

The growing concern about bioterrorism has led some health experts to question the central principle that stocks of all microbial killer must be destroyed once it is eradicated in the wild. This reaction relates Jonathan Tucker, director of the nonproliferation program chemical and biological weapons at the Monterey Institute of International Studies in Washington, DC "The situation of smallpox sets a worrying precedent for other infectious diseases, such as polio and measles, "he said.

It warms the heart of a mother to see her child has inherited his nose, hair, or smile. But could it also have transmitted a trigger for diabetes? Researchers working with mice now suggest that insulin antibodies transferred from mother to child during pregnancy and breastfeeding may trigger type 1 diabetes in some children.

Type 1 diabetes develops when the body's immune system mistakenly kills insulin-producing beta cells of the pancreas. Insulin is a hormone that allows cells to absorb blood sugar. Without enough insulin, sugar levels in the blood increases unchecked and eventually damage every system in the body - resulting in kidney failure, heart disease, poor circulation, and blindness. symptoms of diabetes are brought out after 60% to 80% of beta cells have been destroyed. full blown diabetes is marked by quantities of antibodies specific for insulin in the blood increases. Such antibodies are proteins created by the immune system in response to the destruction of beta cells, but until now, they were considered as secondary effects of the disease.

Surgeon Ali Naji and his team at the University of Pennsylvania School of Medicine in Philadelphia asked whether specific insulin antibodies passed from mother to child could revive the autoimmune response causes diabetes. The team implanted two days old embryos of diabetes mouse strain prone in either normal home moms or prone diabetes. Only 15% of pups birthed and nursed by normal adoptive mothers eventually developed diabetes compared with 73% of pups birthed and nursed by adoptive mothers prone diabetes, the researchers report in the April issue of Nature Medicine .

to study the potential role of antibodies passed from mother to offspring, the team then developed diabetes-prone mice that did not make antibodies against insulin. When females mated with males prone diabetes, their young were much less likely to develop diabetes than are puppies prone diabetic mothers who pass on antibodies.

This research brings a new controversy in the study of diabetes, says diabetologist Mark Atkinson of the University of Florida College of Medicine in Gainesville. previous human studies have shown that fathers genes can predispose their children to diabetes, while this study clearly demonstrates a maternal influence as well. In addition, these results suggest that, in some cases, but not all, antibodies play a pathogenic role in the development of diabetes. "It is simply a fantastic study," said Atkinson.

Related Sites
American Diabetes Association
Diabetes Dictionary

The first signs of the disease Huntington's disease occurs in middle age: Jerks and muscle spasms are followed over the years by the worsening of memory and loss muscle control. Although a mutated gene is to blame, it is not clear how it causes symptoms. Now scientists studying mice and human cells affected by Huntington's disease have shown that chronic damage to mitochondria, cells of the plants plays an important role.

Huntington's disease is inherited by a person over 10 000 in the United States. The mutated gene adds unusually long chains of glutamine, an amino acid in a protein huntingtin (htt), and in general, the more glutamine chains corresponding to an earlier onset and more severe neurological symptoms. But scientists still do not know for sure what normal htt made or how the abnormal version of throws a wrench in the works.

neurologist and biochemist Timothy Greenamyre Alexander Panov from Emory University School of Medicine in Atlanta and his colleagues believe that mitochondria are an important factor in Huntington's disease. Mitochondria of the team examined are from mouse and human cells affected by Huntington's disease. They found that the long chains of glutamine in the stick abnormally htt protein in the outer membrane of mitochondria and allow ions to flow freely in and out. Accordingly, mitochondria "run" like a battery exploited, reports the team in the July 1st issue of Nature Neuroscience . In addition, Greenamyre and Panov found that pepper mitochondria with too much glutamine can not properly regulate calcium, which can reach toxic levels and kill the cell

But all body tissues htt -. So why the abnormal protein hit the cells of the nervous system so hard? Probably because neurons live so long, said Panov. As cells age, their mitochondria become less efficient. This problem is particularly acute for neurons because they are not often replaced as cells elsewhere. The subtle mitochondrial damage caused by mutant htt can exacerbate the wear and tear of natural aging, said Panov. This could explain why the disease remains at rest until the Middle Ages.

The debate on the role of mitochondrial damage in Huntington's disease fluctuated for years between scientists, says neurologist Kenneth Fischbeck of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. "But this research should help resolve the issue and to focus the research."

Related Sites
The site of Timothy Greenamyre
The site Kenneth Fischbeck
Information about Huntington's Disease from the National Institute of Neurological Disorders and Stroke
Disease Huntington Society of America

People with the disease Parkinson's struggle with progressive worsening tremors, stiffness, poor balance, and abnormally slow movement. The drugs relieve these symptoms, but there is still no cure for the disease. Now researchers say it might be possible to slow its progression with a compound called coenzyme Q ₁₀ .

called coenzyme because it improves the performance of other enzymes, Q ₁₀ is also a powerful antioxidant. Antioxidants help protect cells against the harmful oxidation - the biological equivalent of rust. Q ₁₀ is also known to play a critical role in the normal functioning of the energy generators of cells, the mitochondria. Previous studies have found that people with Parkinson's disease have mitochondrial dysfunction and low levels of Q ₁₀ . And over the last decade, neurologists Clifford Shults of the University of California, San Diego, and Flint Beal of Cornell University in Ithaca, New York, showed that rodents with symptoms like sickness Parkinson were able to control their movements much longer when given Q ₁₀ .

To determine if Q ₁₀ could help people with Parkinson's disease, Shults and Beal have teamed up with researchers from 10 research centers across the country. They recruited 80 people in the early stages of Parkinson's disease to be one of three doses of Q ₁₀ or placebo. The researchers then followed the progress of each patient for 16 months, monitoring symptoms each with a battery of standardized tests. The progression of Parkinson's disease was slowed by 44% in the group taking the higher dose of Q ₁₀ , reports the team in the October 15 issue of the Archive of Neurology . Blood tests taken before and after the Q ₁₀ The treatment showed an increase of mitochondrial activity, indicating an improvement in mitochondrial function. Encouragingly, none of the patients experienced serious side effects.

The results clearly show that mitochondrial dysfunction plays a role in the progression of Parkinson's disease, said neurobiologist Virginia Lee of the University of Pennsylvania in Philadelphia. Although it needed more research before the drug can be approved as a treatment for Parkinson's disease, the study provides "clear and convincing support" for the hope that Q ₁₀ can slow the disease, she said.

related sites
site Clifford Shults
site Flint Beal
the site of Virginia Lee
basic information on Parkinson's disease NINDS

Checking clogged arteries could someday be as simple as a blood test. Researchers report that a relatively quick and inexpensive analysis of chemicals in the blood can reliably detect the disease and indicate its seriousness.

coronary artery disease, the leading cause of death in the United States, results when fats clog the arteries that supply blood to the heart. Currently, patients doctors screen for the disease by checking a laundry list of risk factors, including high cholesterol, smoking and obesity. But they can not be sure until they donned a catheter into the coronary arteries and to take X-ray films that reveal their status. This procedure, called angiography is invasive time-consuming, and expensive. Biochemist David Grainger of Addenbrooke's Hospital in Cambridge, UK, and his team say they have found an effective alternative to a powerful technique borrowed from analytical chemistry.

The technique, called proton nuclear magnetic resonance (1H NMR), the reflected light from a sample records placed in a magnetic field and zapped with radio waves. Any chemical has such a unique spectrum that digital emission footprint. The Grainger team sampled serum (blood with clotting cells) removed 36 people with coronary artery disease diagnosed by angiography and 30 healthy people. After analyzing the spectra with a statistics program, the team was able to diagnose the samples with an accuracy of 92%. Differences in the amount of lipoproteins - a type of fat - were the most significant indicators of the disease, they found

The team also demonstrated that 1 H NMR can indicate the severity of the disease: They attributed precisely 76 other patients. to one of three categories - benign (an affected artery), moderate (two arteries in difficulty), and large (all three coronary arteries blocked). These results, as well as the ease with which the technique can be done, make NMR suitable for clinical use, the team argues in the November 25 issue Nature Medicine .

"This study is a beautiful integration of analytical chemistry, clinical medicine and biostatistics" said chemist and toxicologist Mark Viant the University of California, Davis. The technique capture huge amounts of data that can be exploited for new ideas on how the diseases progress, says toxicologist Marion Miller, also at UC Davis.

Related Sites
Bio David Grainger
Marion Miller website

the benefits of exercise for the heart have long been touted, but we do not know how, for example, jogging protects the blood vessels against cardiovascular disease. Now scientists suggest that simply will get your blood is what helps. In experiments with cow arteries, they find that the fast-flowing blood has anti-inflammatory effect as powerful as that of certain steroid medications that protect the arteries.

Scientists have known for years that the hardened plates that are a big factor in heart disease tend to form in areas where the blood slows and inflammation in these areas contribute to the disease . Curiously, when the walls of the vessels experienced increased drag faster blood flow, the cells lining the walls of blood vessels are more certain molecules that protect the arteries. Link the evidence together, Scott Diamond, a biomedical engineer at the University of Pennsylvania in Philadelphia, has suggested that the trail itself could activate anti-inflammatory pathways as do many steroid medicines like dexamethasone.

Diamond and his colleagues have endothelial cells cow arteries in a special chamber that mimics the conditions of flow of arterial blood. They reported a steroid receptor in the cytoplasm of cells with green fluorescent protein. When they pumped fluid on the cells to create a shear stress, the receiver has looked into the cell nucleus - as if the cell was exposed to dexamethasone. Once inside the nucleus, the activated receptor a steroid-sensitive gene, reports the online team in January 24 Traffic . Finally, the team repeated the experiments in the segments of human arteries and found a similar effect.

The work is important because it really connects changes in blood flow with protection against heart disease, says Peter Davies, a vascular biologist at the University of Pennsylvania, which is not associated with the project. "This system can be the manifestation of [exercise's] protective effect." The next step, Diamond and Davies agree, is to see if the increased blood flow that triggers anti-inflammatory pathway in living animals.

Related Sites
Background information on atherosclerosis
Scott L. diamond site
Peter F. Davies site

A mysterious disease that causes flu-like symptoms and pneumonia rapidly around the world last week after sickening dozens Asia. More than 0 people in seven countries have fallen ill in recent weeks, according to the World Health Organization (WHO), and at least four died. These figures raise concerns about a new and uncontrollable pandemic.

Researchers are desperately trying to determine the cause of severe acute respiratory syndrome (SARS), WHO has called the disease. Hospital staff seem to be more at risk, suggesting that close contact with a patient is necessary for infection. But until now, scientists are not even sure that the infection is viral or bacterial - much less how it spreads, or the best way to treat and prevent. The researchers tried to "a wide range phenomenal" diagnostic tests on samples available, says Klaus Stöhr, an expert from the flu to WHO in Geneva, but they were all negative. "We really have to start from zero and put aside all our hypotheses "in the search for a culprit, he said.

Initial symptoms include high fever, muscle aches, sore throat and headache, sometimes followed by pneumonia and acute respiratory distress. "This kind of flu screams," said Brian Hjelle, a virologist at the University of New Mexico, Albuquerque. Indeed, some initially thought that the epidemic could be linked to a small outbreak of a virulent strain of bird flu, called H5N1, which has killed a man in Hong Kong last month and sickened her 9 year old son ( Science , 7 March, p. 1504). But such a link has been found, and most scientists say that if the disease was the flu, doctors have recognized now.

Other potential candidates include human parvovirus, or something that looks like Nipah, a paramyxovirus that triggered a deadly epidemic among pig farmers in Malaysia in 1999, said CJ Peters, director of the Center for biodefense at the University of Texas Medical Branch in Galveston. Having studied deadly epidemics in many parts of the world, Peters said. "I do not know who gave me such a feeling of danger"

At the same time, the new home puts public fears bioterrorism and biodefense bloated budgets perspective reaffirming the impact of naturally occurring diseases, said Marjorie Pollack, which monitors the epidemic ProMED, an electronic reporting system in the world. says Pollack :. ". Mother Nature is by far the worst bioterrorist there "

With Gretchen Vogel reportage in Berlin

Related Sites
World Health Organization
health updates on SARS of the US Centers for Disease Control and Prevention