Health Meaning

In the war against cancer vaccines designed to teach the immune cells to look for proteins on cancer cells and fuse to kill has been less sparkling results provided that. Now, researchers report in the March issue of Nature Biotechnology that inoculating mice with a protein fragment that mimics the shape of abnormal cancerous cells sugars attached to proteins seems to do the trick. The new therapy is currently being studied in clinical trials

The new work -. Directed by Vasso Apostolopoulos, Austin Research Institute, Heidelberg, Australia - target the sugar molecules on the surface of a protein called mucin (MUC1), which is secreted by the epithelial cells of the mucous membranes of the kidney, lung, breast and other tissues. MUC1 on cancer cells is strewn with sugar molecules that are shorter and less numerous than those of normal cells. Previous experiments had shown that these sugars Nabot themselves make good vaccines because they are poor to stimulate immune cells to attack.

Apostolopoulos and his colleagues got around this problem by using a short protein fragment that mimics the structure of aberrant sugar molecules and is able to trigger a stronger immune response. They tested the mimetic in mice that received human breast cancer cells transplanted expressing the modified MUC1 protein. The mice that received the vaccine injections fake sugar will not continue to develop cancer, while the control animals did.

In an accompanying review Olivera Finn, University of Pittsburgh School of Medicine and Sandra Gendler of the Mayo Clinic in Scottsdale, Arizona, called the new strategy an important approach that "could prove useful in a clinical context. "in fact, efforts are already underway to begin clinical trials, said member Ian McKenzie group." Initially, the test will be performed on cancer patients, "he said. "If this is successful, it will be done on patients in [high risk] groups."

The dangerous pathogen Staphylococcus aureus causes infections ranging from skin abscesses toxic shock syndrome. About a third of currently isolated strains from patients who acquire S. aureus then hospital infections are resistant to all antibiotics except one, vancomycin - and now the resistance to this antibiotic began cropping. But new research suggests an approach to the fight against S. aureus that can bypass the ability of the organism to develop resistance.

In Science tomorrow , the researchers say they can decresase the incidence and severity of S. aureus infections in mice by blocking the ativity of a protein called RAP, which controls the production of toxins and other proteins that make the pathogenic bacterium. The work suggests that disabling RAP - perhaps by vaccinating people with the protein so that the immune system takes out of commission, or by developing drugs that prevent it from doing its job - could keep microbe to spread in the body before the patient's immune system exhausts outside. These drugs do not directly kill the organism, and in the absence of such selective pressures, resistant strains may be less likely to develop.

Naomi Balaban, a researcher of infectious diseases at the University of California, Davis Medical Center in Sacramento discovered RAP and its role in the last few years. His previous work has suggested that S. aureus multiplies it secretes HBP. When the protein reaches a critical concentration, it sends a signal which activates genes for toxin production. This suggested, Balaban said, the protein could be a good target for prevention strategies. She and her colleagues inoculated mice with purified RAP from S. aureus cultures. Vaccinated animals developed antibodies to RAP, and when the researchers injected S. aureus under the skin of animals, only 28% developed skin lesions, against 70% of controls.

Because it takes weeks to mount an immune response, such a vaccine could benefit those whose risk could be expected, such as diabetics and kidney dialysis and surgery patients. But "it opens up a new strategy for treating or preventing one of the most serious nosocomial infections that we strongly support," said Julie Gerberding, an infectious disease specialist at the University of California, San Francisco. "The methods that prevent disease without selection for drug resistance could really help us. - And we're going to need help quickly"

Researchers have made a new compound aspirin that promises to provide the same pain relief as aspirin, but without stomach ache or the risk of kidney damage. The compound described in tomorrow Science , can also help reduce the risk of certain cancers and Alzheimer's disease.

This new "superaspirin" is one of a dozen new compounds under development that soothe joint pain by blocking the activity of an enzyme called COX-2, which promotes the inflammation, pain and fever. The problem with aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) is that they also interfere with the activity of the COX-1 enzyme, which protects the walls of the stomach and kidneys. Thus, pharmaceutical companies have been eager to find drugs that target only COX-2, especially since epidemiologic and laboratory studies now indicate the long-term use of these drugs may protect against cancer colon and Alzheimer's disease.

At least two companies, Monsanto Corp. in St. Louis, Missouri, and Merck and Co., based in Whitehouse Station, New Jersey, tested COX-2 inhibitors in people and hope to be marketing their new superaspirin next year. "Finally, all these [NSAID] marketing molecules become dinosaurs," predicts Philip Portoghese, a medicinal chemist at the University of Minnesota in Minneapolis.

So far, however, all new inhibitors COX-2 pain relief for only as long as they were attached to the COX-2. But now biochemist Lawrence Marnett at Vanderbilt University school of Medicine in Nashville, Tennessee, and colleagues describe one that works much like aspirin and chemically modifies COX-2, permanently blocking the production of hormones until the body makes more enzyme COX-2.

to build the next generation of these selective inhibitors, Amit and Kalgutkar Vanderbilt Marnett made a molecule which retains original side group acetylated aspirin, aspirin which transfers to the COX-2 enzyme to destroy it. This new molecule also has a carbon ring attached to a sulfur atom, and short chain of carbon atoms which hang sulfur. They found that it could reduce the activity of COX-2 by as much as temporary COX-2 inhibitors exist. Marnett, whose university has patented this class of COX-2 inhibitors permanent, hopes to partner with a pharmaceutical company to come up with a more efficient version of the new superaspirin.

A chemical in marijuana may protect against brain damage from a stroke, according to a report in The Acts of the future national Academy of Sciences . The compound known as cannabidiol in the test tube SOP damage by oxygen free radicals more effectively than vitamins C and E, the more potent known food antioxidants.

As every knows pothead, marijuana and its component psychoactive tetrahydrocannabinol (THC) inhibit the activity of certain brain areas. Aidan Hampson, in collaboration with colleagues from the National Institute of Mental Health and also undertook to check whether the inhibitory effects of THC may also prevent the toxic overstimulation of brain cells that occurs when brain cells become starved for oxygen and sugar, and are then unable to pump the neurotransmitter glutamate.

researchers simulated a stroke while bathing a Petri dish full of neurons in the neurotransmitter glutamate, which is toxic in high doses. When they added purified THC, half as many neurons died. First, the researchers speculated that THC binds to the cannabinoid receptor, but when they added another chemical that blocks the receptor, THC always protected the cells. "It should not have protected the neurons, but it also works well," says Hampson. Other tests have shown that THC was raking free radicals such as hydrogen peroxide, which are spewed from the excited neurons. They have also shown that cannabidiol, a component of marijuana similar to THC but its psychoactive effects, provided that the same antioxidant benefits.

Hampson is already at work simulating shots rats and try to prevent damage with cannabidiol. But pharmacologist Steve Childers, Wake Forest University Medical School in Winston-Salem, NC, is skeptical that cannabidiol would be effective in preventing strokes in people at safe doses. "They are not testing a very low concentration of the compound," he said.

L ONDRES - Since the first indication in 1995 that "mad cow" had crossed the species barrier in people, causing a deadly new form of brain disease, a key question remains unanswered: How many cases are likely to occur given the long period of illness latency? - perhaps 10 years or more. - It's hard to say whether Britain is facing a silent epidemic or just a handful of cases in excess of 27 diagnosed far

Late last week, the British government announced that it is about to launch a groundbreaking study to try to find. It will review hundreds of tonsils and appendices stored, removed during surgery in recent years, for traces of protein misshapen called "prion" that have been associated with brain disease known as new variant Creutzfeldt-Jakob disease (vCJD).

study was prompted by the case of Tony Barrett, a 45 year old coastguard southwest England, who died of vCJD in June. According to an article in August 29 issue of The Lancet , Barrett had his appendix removed in a local hospital eight months before he first showed symptoms of the disease. When doctors examined the tissue stored evidence misshapen prions, he tested positive. This was the first demonstration that vCJD can be detected before symptoms appear, said James Ironside of the National CJD Surveillance Unit, a co-author of Lancet paper.

The government now expects test more than 1,000 of the 800,000 samples of tonsils and 45,000 samples of the removed appendix and stored each year. Comparison of tissue removed before and up to the outbreak of mad cow in the late 1980s can provide a rough estimate of the extent to which the population harbors prion protein vCJD. The study is too small, however, provide something more than an indication of whether or not there is a widespread problem. "Interpretation of [data] require great caution," said Kenneth Calman, Chief Medical Officer of Great Britain, who announced the study last week.

Government officials and their advisors not yet worked on the ethical rules that will govern the testing program, however. One option is to remove all identifiers so that the fabric can be traced back to the patient. If this is not done, the researchers will face the question of whether to tell patients if prions are detected in their organs.

A hospital's imaging magnetic resonance imaging (MRI) room has no space for credit cards. MRI magnets used to paint accurate pictures of your insides are strong enough to pull a screwdriver out of your hands from a meter away. , Portable devices can be cheaper more in store, however. The researchers report in the next week Physical Review Letters that high-quality images of at least some parts of the body like the lungs, can be made using a magnet to 10 times lower than that native art pin refrigerators.

With traditional MRI, someone slipped into the hole of a giant superconducting magnet that generates a field some 20,000 times stronger than the Earth. The field aligns the nuclei of hydrogen atoms within the body, leaving the spinning atoms as tiny synch bar magnets. Then a brief advice electromagnetic pulse nuclei so they flicker like quirky tops. The whirling atoms emit an electromagnetic wave of its own which can be detected. By adding a second weak magnetic field to change the frequency of the atoms in different places, researchers can map the density of water molecules and build a clear picture of the tissues and internal organs.

Ron Walsworth of Harvard-Smithsonian Center for Astrophysics in Cambridge, Massachusetts, and his colleagues took a slightly different approach. They used a pioneering technology several years ago by physicist from Princeton University William Happer: First align atomic nuclei in gas rubidium with a laser, and then allow them to mix with a helium gas -3 (helium least one neutron). When the atoms collide, a portion of the alignment is gradually transferred to the helium atoms. toxic rubidium atoms can then be removed. Because the helium atoms are an inert gas, they can stay lined up for a few minutes at a time, even without a magnetic field.

In one test, researchers have inflated the lungs of a rat with polarized helium gas and makes high quality photos cavities with a resolution of one millimeter. The magnetic field used to adjust the rotation rate them was only 40 times stronger than the Earth. "It is embarrassing simple," Walsworth said. "You and your brother can liquidate your own magnet and get an MRI as well as what you get in a hospital," he said, although Science NOW is not recommended.

Researchers had known that such a low field imaging with tissue could be done, but no one had bothered to put all the pieces together, says Walsworth. Still, others are impressed: "It's a beautiful piece of work," says Alex Pines, a Lawrence Berkeley National Laboratory physicist in California. "They are very sharp images."

traditional MRI magnets can cost a million dollars, says Pines. The technique could lead to MRI at low price Laptop for imaging the lungs, they say it. Happer added that the lungs are only the beginning. Replacing helium with xenon gas, which is absorbed like oxygen in the blood, also allow researchers to take small budget MRI arteries and brain he predicted.

clinical researchers received a bioethics kit for Christmas, and some may be afraid to open it. He arrived this month in the form of a draft report of the National Bioethics Advisory Commission (NBAC) President calls for tighter controls on research on stored samples of blood and tissue. NBAC says its goal is to protect donor privacy.

The "matter tissue", as bioethicist Robert Yale Levine called, has become a hot topic. Stored tissue may contain a goldmine of information for researchers tracking the spread of the disease, hunting, disease genes and the study of human genetic variation. And it is a huge resource: NBAC calculates that American institutions hold more than 282 million samples of archived human tissue. People who have donated the equipment probably gave general consent for its use, but ethicists argue that the more specific consent may be needed now

CCNB -. A group of 17 members, lawyers, ethicists and health professionals chaired by Princeton President Harold Shapiro of the University - suggests that, in many cases, the identity of the samples secretly encoded by a third party to make them truly anonymous . If a researcher does not want to do, NBAC said, research should go to a local ethics panel, or the Institutional Review Board for approval. NBAC also said that researchers may need to get a new donor consent, particularly for certain genetic studies that provide more than minimal risk to economic or psychological harm.

These are among the 16 recommendations in the draft report of CCNB, which is drawing mixed reactions from the research community. Pathologist John Trojanowski, a specialist in Alzheimer's disease at the University of Pennsylvania, objected that the proposed new notice and consent requirements are so onerous that they "bring research to the judgment." But others were more accepting. Judith Greenberg, who oversees the operations of a large collection of human tissue for the National Institute of General Medical Sciences, said the new report "appears to have reached a fairly reasonable balance." NBAC has set a deadline of 17 January for public comment and may vote on a final report early next year.

biomedical and scientific groups began an intense lobbying effort to convince Congress to resist conservative campaign to block federal support for research human stem cells. Both parties should encounter Capitol Hill in the coming weeks. The first skirmishes could take place as early as 23 and 24 February, when Donna Shalala, Secretary of Health and Human Services (HHS), and Harold Varmus, director of the National Institutes of Health (NIH), before committees of appropriations Congress to defend their 00 budget proposals.

row erupted this week as conservative members of the House and Senate, demanding a change in policy, sent angry letters to the Clinton administration. The Conservatives have attacked an HHS-NIH decision to fund research on human stem cells. These cells, which scientists hope to develop in a variety of transplantable tissues are derived from aborted fetuses and human "spare" embryos in fertility clinics. In a letter of 16 February to Shalala, eight Republican senators, including Sam Brownback of Texas and Jesse Helms of North Carolina, have expressed concern that this research could "give incentives for the killing of human embryos."

Five days earlier, 70 House members led by abortion opponent Jay Dickey (R-AR) had written a letter to Shalala as severe, complaining that HHS misinterpreted a recent law that bans US funding for research that involves the destruction of human embryos. In January, HHS found that the law does not apply to embryonic stem cells because they can not grow naturally in embryos. Indeed, Varmus announced January 19 that researchers may soon be funded to study these cells ( Science , 22 January, p. 465). But members of Dickey group - which includes prominent conservative Republicans such as Henry Hyde (IL), Richard Armey (TX) and Tom DeLay (TX) - disagree vehemently. HHS has read the law too restrictive, they claim; Congress intended to block not only the destruction of the embryo, but also "looking after dependent or destruction or injury of a human embryo."

Neither Shalala nor Varmus yet responded to Conservative calls. But today, 70 scientific groups, academic, and patients sent a petition to Congress, prepared by the Association of American Medical Colleges (AAMC), which calls for research on stem cells. This field, communication AAMC said, holds "enormous potential for the treatment of many diseases" and should be allowed to go ahead.

H Ebden B RIDGE , UK - A recent sharp increase the number of deaths from variant Creutzfeldt-Jakob disease (vCJD) in Britain has caused concern that an epidemic long dreaded the fatal brain disease is imminent. But the numbers may be a statistical fluke, scientists write in tomorrow's issue of The Lancet .

Researchers agree that vCJD, to which some 39 Britons have died since 1995, can be caused by eating meat from cows with bovine spongiform encephalopathy (BSE), better known as disease mad cow. Millions of British people may have been exposed to meat from cows infected during a BSE epidemic that peaked in the late 1980s; but nobody knows how many are likely to be victims of vCJD, or how long the disease develop in the average patient

So far the figures have been reassuring. In each of the first three quarters of 1998, only two deaths were reported. But in the last quarter of '98, the number suddenly jumped to nine. This may be a coincidence, a team of scientists led by Robert Wills of the CJD Surveillance Unit in Edinburgh write in their analysis. But it could also signal the beginning of a larger increase, says one of the authors, Simon Cousens of the London School of Hygiene & Tropical Medicine. "I do not want to prejudge the issue," said Cousens, "but I would not be surprised if it was the beginning of an upward curve." It is unlikely that the apparent increase is due to increased vigilance among doctors, writing team, because vCJD is a high profile disease for years.

The scientists and the public are now eagerly awaiting the latest data. So far, there has only been one confirmed death vCJD in the first quarter of 1999, but that means little, because it usually takes months for cases confirmed to arrive. It will be 6 to 9 months before there is more certainty, Cousens said. "Certainly I'm concerned about the numbers," said John Collinge, head of the Neurogenetics department at Imperial College School of Medicine in London.

Microsoft CEO Bill Gates and his wife Melinda will announce a contribution of $ 25 million to the International AIDS Vaccine Initiative (IAVI), the largest single philanthropic gift ever made to the research against AIDS, science has learned. "Bill and Melinda Gates are very excited and pleased to work with organizations making such a difference in global health," says Trevor Neilson, a spokesman for the William H. Gates Foundation.

IAVI will receive 5 $ million per year for the next 5 years of the foundation, which last June gave the new York-based non-profit of $ 1.5 million. According to Neilson, $ 13.5 million will fund up to three new international teams of vaccine development against AIDS. another $ 3.5 million will support these two teams met last year to develop vaccines against HIV specifically for Kenya and South Africa. Between 2.5 million and $ 3.5 million will go to the program of applied research, advocacy and trial preparation IAVI in developing countries, and operational support. "This historic act of generosity will allow us to dramatically accelerate scientific endeavor, "said Seth Berkley, president of IAVI.

The new grant will be two chests of IAVI to nearly $ 50 million and is expected to significantly increase the capacity of the Institute to carry out development and human trials of these vaccines. The National Institutes of Health is by far the biggest player in the field, now spend $ 0 million annually in R & D vaccine against HIV. The iconoclastic IAVI, however, hopes to address the problem of a novel angle, marrying academics from both rich and poor countries with cash-strapped businesses.