Health Meaning

A powerful protein that constricts blood vessels is four times more common in African Americans with high blood pressure than whites, according to a report this month Hypertension . The result suggests that genetic differences may help explain why more blacks than whites suffer from high blood pressure.

The finding is surprising because blacks and whites healthy approximately the same amount of endothelin-1, a chemical vasoconstrictor which is produced mainly by cells that line the inside of blood vessels. `` We were not expecting such a difference, '' said study leader Adviye Ergul, a molecular biologist at the University of Georgia, Athens.

The team used a new Ergul antibody test to measure levels of endothelin in 100 people, half of whom suffered from high blood pressure. In addition to racial differences, researchers found that hypertensive blacks are eight times more than black endothelin with normal blood pressure. `` elevated endothelin levels may be the reason why blacks develop hypertension earlier and develop complications of hypertension earlier '' than whites do, Ergul said.

The report was `` a good starting point, '' said John M. Flack cardiovascular epidemiologist Bowman Gray School of Medicine in Winston-Salem, North Carolina. However, he said, `` what we really need to know are the factors influencing endothelin [levels]. '' Flack predicts that larger studies will reveal a large variability in levels of endothelin in both black and white.

As if the inner cities of America are not troubled enough, now they have a newly recognized problem to deal with: leptospirosis. A report in Annals of Internal Medicine today showed that living in an inner city is a risk factor for the disease.

Leptospirosis is a disease with symptoms ranging from mild aches and pains to jaundice, meningitis, kidney failure, and in rare cases death. Caused by the bacterium Leptospira interrogans , which infects a range of animals, the disease is known and diagnosed mainly in tropical regions. An outbreak of leptospirosis in Nicaragua last fall sickened thousands of people, killing 20.

Cases in the United States are rare, although the disease is probably underestimated because its symptoms are often attributed to d other causes. Such was the case when a "very sick woman" showed at Johns Hopkins Medical Center in November 1993, says infectious disease specialist Joseph Vinetz Johns Hopkins. Its symptoms - severe jaundice and meningitis - baffled doctors. Then Vinetz recalls, "I literally woke up in the middle of the night and thought she had leptospirosis"

Vinetz team learned that the patient had walked barefoot in the streets of the center-. Baltimore city, where she had seen rats, and had cut his foot 10 days earlier. subsequent investigations revealed two other Baltimore patients with leptospirosis who had also been in infested alleys of rats

What particularly surprised Vinetz was none of the patients had been in the country. - most previous cases of leptospirosis in the United States have been associated with exposure to animals infected with activities such as camping or agriculture. Vinetz alleged that his patients had been infected by rats, and his suspicions were apparently confirmed when his team found L. interrogans in 19 of 21 rats caught in the alleys where patients were.

"leptospirosis in urban areas are not a new problem," said Richard Spiegel, epidemiologist at the Centers for Disease Control and Prevention. However, he said, "it is probably significantly underdiagnosed." Besides the confusion resulting in disease symptoms, there is no single laboratory test to confirm a diagnosis, but the disease is not going away, said Vinetz. ". Many inland cities are in a worse and worse "

heretical idea that prions - naked protein particles without a point of genetic material - may cause heritable disorders such as mad cow and Creutzfeldt-Jakob disease (CJD) in people has received a boost. In tomorrow's issue of Science , a team led by Glenn Telling and Stanley Prusiner of the University of California, San Francisco, provides compelling new evidence that may help explain how prions, that seem to exist in several strains, each with different characteristics, can transmit reproducible stress -. an apparent impossibility of an infectious agent that lack any genetic material

previous work of Prusiner team and others have shown that prions are made of a cellular protein that misfolded into a form abnormal. This can occur, for example, if the normal prion protein (PrP) in contact with an abnormal version, which then requires that misfold also. Over the past two years, other researchers, the study of prion disease called transmissible spongiform mink had provided evidence that different prion strains consist simply forms differently misfolded prion protein, each of which can transmit its own shape, or conformation, normal PrP. Now Telling, Prusiner and colleagues have extended the work to human prion in a mouse model.

They injected a special breed of transgenic mice with extracts of patients who died of brain or CJD or other prion disease, fatal familial insomnia. Prions responsible for both diseases have been known to bend differently because they produce fragments of different size when cut by an enzyme protein-splitting - an indication that the various amino acids are exposed on their surfaces. The team found that prion Prusiner produced in mice produce the same sized fragments that mothers molecules used for injections. The results are "a very powerful piece of support for the idea that abnormal protein can confer its abnormal configuration of the host prion protein," says neurologist Dennis Choi, of Washington University in St. Louis.

Not everyone is convinced by the results, however, mainly because of the difficulty to eliminate the possibility that a more conventional pathogen such as a virus could be lurking in the injected material. "The group took a [brain] extract relatively crude," said Michael Harrington, who studies diseases of the nervous system in Calfornia Institute of Technology in Pasadena. Therefore, it concludes that the work "does not confirm" that protein folding differences amounts to different strains. But Prusiner and his colleagues, the failure of years of research to the finger of a virus in prion diseases is proof that person is involved. "There is nothing to tell [people who think viruses cause the diseases] except that the evidence is overwhelming, "Prusiner maintains.

Tomorrow is the 73rd anniversary of one of the founders of Neuroendocrinology, Roger Guillemin. He and a group led by Andrew Schally competitor showed that the hypothalamus, an area of ​​the brain, regulates the pituitary gland by secreting chemicals called hormones into the blood. Make this discovery was 99% perspiration: Guillemin and his colleagues had to travel 500 tonnes of sheep brains to isolate 5 million hypothalamic slices. Finally, they caught their prey, releasing hormone thyrotropin (TRH). In 1969, they reported the TRH structure that Guillemin said later marked the beginning of a major new science. In 1977, the American of French origin endocrinologist shared the Nobel Prize in Physiology or Medicine for this work with Schally

[Source:EmilyMcMurrayEd Notable Twentieth Century scientists . Gale Research Inc., ITP 1995].

WASHINGTON, D.C. .-- There may be a magic bullet after all. Scientists at a small biotech company in California announced at a conference here press today that they have developed a drug that cures the flu by stopping the spread of influenza viruses among cells in the mucous membranes of the nose and lungs.

So far, the drug was tested in animals. If successful in clinical trials scheduled to begin this spring, it could have a huge impact: Some 20,000 Americans die each year from influenza, and the costs of the disease as much as $ 12 billion a year in health care and lost productivity. The new compound "is very exciting," says Robert Sidwell, a virologist at the State University of Utah in Logan, because unlike current vaccines against influenza, it seems to stop all influenza strains dead in their tracks.

the new compound, developed by scientists at Gilead Sciences in Foster City, California, blocks the activity of a key viral enzyme, known as neuraminidase name. the enzyme releases newly formed viral particles from cells in which they are produced, allowing the virus to infect other cells. Animals and test tube studies reported in the number of tomorrow Journal of the American Chemical Society show that the new compound puts a stop to all strains of influenza. This success stems from the fact that the active region of neurominidase "is almost identical for all strains of the virus," said Gilead medical chemist Choung Kim. The drug is also rapidly eliminated the symptoms of the flu, such as fever and cough, ferrets, the best animal model of the disease. The compound, tentatively named GS 4104, does not seem to have side effects, Kim said.

Gilead drug is actually the second of its kind. The first blocker neuraminidase was developed by researchers in Australia and the UK in 1993 and is now in clinical trials led by British pharmaceutical giant Glaxo Wellcome. The two compounds have similar chemical structure - both are small, sugarlike molecules - and the same mode of action, Kim said. Glaxo compound can not be absorbed by the intestine, so it must be given as a nasal spray, nasal drops, or by means of an inhaler.

In contrast, Gilead compound has an additional lipophilic, or grease-loving chemical group that allows him to easily cross the fatty membranes of intestinal cells and thus pass into the bloodstream. "This suggests that the drug may be stable for oral administration" as a pill, said Catherine Laughlin, head of the virology branch of the National Institute of Allergy and division of microbiology and infectious diseases Infectious diseases Bethesda, Maryland. Gilead plans to begin clinical trials this spring with the help of the pharmaceutical company Hoffmann-La Roche.

PHILADELPHIA - Last year, David Berd, oncologist at Thomas Jefferson University here has found that melanoma patients are injected with modified versions of their own tumor cells after surgery were almost twice as likely to remain without tumor as patients who received surgery alone. Now EBRD has shown that its new formulation appears to trigger an enhanced immune response. The finding, reported in the current issue of Journal of Clinical Investigation , is the first evidence that this pioneering cancer therapy acts as a vaccine at the cellular level.

Berd and his colleagues at the National Institute of tumors in Milan, Italy, treated melanoma cells from six patients dinitrophenyl, a chemical that binds to cells and serves as a red flag for immune system. The treated tumor cells deactivated by radiation, are designed to trigger the production of new T cells, which may be required to thwart recurrence of melanoma.

The group injected the modified cells back into the patients, who underwent surgery to remove the melanoma lesions. The preparation has in fact cause increased immune response: Blood samples from five of the six patients had increased levels of T cells, a type of white blood cells which attack tumor cells. "It is not only the old T cells, but specific clones of T cells that had been caused by the vaccine," said EBRD.

Part of what makes the vaccine so ingenious, said Pramod Srivastava, an immunologist at the University of Connecticut, Farmington, is that it is customized for each patient. Berd "is something very difficult, but something that is very appropriate."

For the second time in two months, scientists reported the discovery of a gene linked to childhood glaucoma. This time it is a primary congenital glaucoma gene, a condition that affects about 2,000 infants and young children in the United States each year. The results described in the next month number Human Molecular Genetics , could lead to a genetic test, resulting in earlier diagnosis and treatment for a disease that can cause blindness. There

Four years Sarfarazi Mansoor and his colleagues at the University of Connecticut Health Center in Farmington began looking for families with more than one diagnosis of the state member, which is associated with a recessive gene. binding studies have failed to find a candidate gene, so that the group "began to filter across the genome at random," says Sarfarazi finally installed on chromosome 2. After months of grunt work to power genes, the band nailed their careers. they linked mutations in a gene called CYP1B1 disease Because CYP genes code for metabolic enzymes, Sarfarazi speculates that CYP1B1 codes for an enzyme that removes excess steroids, operating essentially "as an antitoxin," he said.

the finding comes on the heels of a report last January of a gene linked to juvenile glaucoma, what is striking in the teenage years ( science NOW January 30). These versions together represent less than 2% of glaucoma cases in total, most of which grow to adulthood . the juvenile glaucoma gene should shed more light on the adult form, said Ellen Liberman of the National eye Institute, because the subtle pathological changes in the eye in these forms are similar, while congenital version is characterized by abnormalities gross structural.

Nevertheless, the discovery of the CYP1B1 gene could prevent thousands of cases of blindness each year in the US and abroad - in particular, said Liberman, in countries " very first -cousin marriages "that tend to keep recessive genes. "This is a very important step that will provide a new dimension to neonatal care," said Jay Wisnicki, chairman of ophthalmology at Beth Israel Medical Center in New York. In fact, a test for the defect could detect about 85% of new -nés with the disease in afflicted families, says Kumar Chandrasekaran, President of InSite Vision of Alameda, California, which owns the licensing rights to explore and develop a genetic test.

SAN FRANCISCO - A single injection of microscopic plastic capsules could someday eliminate the need for injections booster vaccination. The new technique, described here yesterday at the annual meeting of the American Chemical Society, could save money for health care by reducing the need for the doctor to repeat visits.

The vaccines against diseases such as polio and tetanus currently are given in several small doses spaced weeks or months apart. But this can pose logistical problems in developing countries and even in some urban areas of the United States, a significant proportion of children fail to return for repeat injections. It was five years ago, a team led by Jeffrey Cleland of the biotech company Genentech in San Francisco set out to simplify the procedure with microspheres, plastic ball a few tens of micrometers through that slowly release drugs as they dissolve into the muscles or other tissues.

to mimic a booster injection, the microspheres have been designed to survive for months in the body, then quickly release the vaccine. The key is found to be using a thicker crust of plastic - polylactidglycolide, the same substance used in medical sutures - to encapsulate small vaccine droplets. Researchers tested the thicker shell microspheres with an experimental vaccine against AIDS, called GP0, developed by Genentech. They injected a group of baboons with a normal dose as a first vaccination, combined with a booster shot nestled in microspheres that dissolve after 40 days. This group had an immune response much higher and more prolonged than those given traditional booster shot injection after 40 days had. Cleland speculates that the microspheres, which took several days to release the vaccine, have done a better job of stimulating the immune system. "The more you can keep antibody levels up, the better you are," he said.

The experts are happy to see the progress. "I am very positive, very happy" with the work says chemical engineer Bob Langer of the Massachusetts Institute of Technology. "Ideally, you can use this method with any vaccine." Haro Hartounian, specialist drug delivery technologies to DepoTech in San Diego, provides that the microspheres will prove more effective than traditional booster shots and - by eliminating this second visit to the doctor - could reduce the cost. Cleland says the technology is ready to be allowed to vaccinemakers willing to give it a shot.

A consistant en vaccinia genes from HIV, the AIDS virus, HAS suppressed infection in two chimpanzees injected with the virus Itself. Experts aim bail que la vaccinia Described in next month's issue of Nature Medicine May not offer protection from more virulent HIV strains.

University of Pennsylvania Researchers Jean Boyer, David Weiner, and Their colleagues injected HIV genes into two chimpanzees, Then Several weeks later injected with high doses of Them HIV. The genes in the vaccinia Manufactured by the firm Apollo in Malvern, Pennsylvania, trigger the body to Produce proteins from the viral core and surface qui shoulds in theory result in a strong immune response. ALTHOUGH the chimps infected DID Become Briefly, neither harbored detectable virus 48 weeks partner after the virus injection. An unvaccinated control chimp injected with the Sami strain HAS Remained infected with high HIV levels ever since.

Other AIDS vaccines-have similar Successes Scored in chimps, purpose-have failed to stir much excitement. For one thing, Many Researchers matter whether the vaccines Would Produce a similar response in Human Beings. An additional concern with the Penn study is que la Researchers used an HIV strain called Expired SF-2. "Getting protection with SF-2 is so easy," says John Moore of the Aaron Diamond AIDS Research Center in New York City. Indeed, a similar DNA vaccine failed to protect monkeys from exposure to a notoriously virulent strain of the AIDS virus.

Weiner contends That SF-2 is a valid test to strain. "SF-2 Was lethal in the person it was taken from," he notes. Other AIDS-vaccine developers back him up. "SF-2 is not that wimpy," says Ronald Kennedy, an AIDS vaccine researcher at the University of Oklahoma. In a Nature Medicine editorial, Kennedy writes That he: has a "Relatively pessimistic view of new AIDS-vaccine Approaches," but is excited by the prospect That a DNA vaccine Could Be Produced much more cheaply than --other vaccines. The Apollo vaccinia, he says, "is as good - if not better -. Than anything out there before" The vaccine is now Being used in pilot safety studies with people.

Some pilferage in the basement of the University of Munich has transformed samples of brain first patient known to be correctly diagnosed with Alzheimer's disease. In this month's issue of Neurogenetics , German psychiatrists describe 0 years slides of brain tissue from a patient known as Johann F. They think it was the case that got the name of the German doctor Alois Alzheimer in medical textbooks.

Alzheimer had described a previous case of dementia, a patient called Auguste D. Last year, however, a team from the University of Frankfurt in Germany questioned whether she really suffered what is now known as Alzheimer's disease when they rediscovered his medical records. No tissue samples remained, but the autopsy report describes the hardening smaller cerebral arteries - a condition that now prevents a diagnosis of Alzheimer's disease. Later that same year, 107, Johann F. Alzheimer treaty, which also showed signs of dementia and died three years later. For decades, their records remain lost.

Now, an extensive search of the basement of the University of Munich has turned up what "beyond reasonable doubt" Johann F. brain sections, said Manuel Graeber the Max Planck Institute of psychiatry, who led the research. To verify their authenticity, Graeber had the Bavarian State Office of Criminal Investigation confirmed that the ink on the slides were more than 80 years. Book clinical autopsy, which was also found, listed the cause of death. "Alzheimer'sche Krankheit", or Alzheimer's disease

The analysis of tissue confirmed the diagnosis, but is that even this second patient did not have a typical case of the disease: Johann F. suffered from the "plate only" less common variant. It also lacks the susceptibility allele apo Alzheimer's, an established variant of apolipoprotein E gene carried by about two out of three patients.

Graeber also speculates that the case of Johann F. convinced the Alzheimer boss Emil Kraepelin to name the affliction "Alzheimer's disease" in 1910 - diagnosed by plaques in the brain - in the 8th edition his psychiatric manual. "Kraepelin and Alzheimer's were very close friends. This patient had Alzheimer staff cases, but it is very likely that he was seen by two of them," Graeber said. When Johann F. died shortly after the publication of the book, Alzheimer wrote the name of his disease in the autopsy book.