Health Meaning

In the days following the death of Ludwig van Beethoven, friends and admirers came to see her body and cut her hair for the memories. Recent chemical analysis of one of these stolen locks has now led scientists to conclude that medical treatment may have accelerated Beethoven's death by his deteriorating lead poisoning.

Four months before his death in March 1827, Beethoven began to suffer from excessive abdominal swelling, perhaps due to cirrhosis. To drain fluid, his doctor, Andreas Wawruch, pierced her abdomen with a needle. Researchers have known since 05 that Beethoven had suffered from a severe lead poisoning. The most recent study of his hair, led by forensic pathologist Christian Reiter of the Medical University of Vienna in Austria, links the two problems.

As the hair grows, it absorbs substances, including lead, from the bloodstream. For his research, Reiter analyzed two hairs with a spectrograph and created a daily log of the internal chemistry of Beethoven in his last 4 months. The composer received abdominal punctures four times on his deathbed, draining between 7.7 and 14 liters of fluid from his body each time. The amount of lead in the hair spiked after each composer abdominal puncture. The correlation suggests that palliative measure worsened the lead poisoning, and Reiter accuses lead salts used to clean the wound as a likely culprit. Reiter speculates that lead has worsened cirrhosis of the composer and hastened his death. The English translation of his study appears in the latest issue of The Beethoven Journal .

"The fact doctor may have killed [Beethoven] with lead poisoning," says William Walsh, director of research at the Health Research Institute and Pfeiffer Treatment Center in Warrenville, Illinois . Walsh, who orchestrated an earlier chemical analysis of hair from Beethoven, spent 30 years conducting a forensic analysis of hair.

Reiter reported lower levels of lead to the end of Beethoven's life that made the Walsh studies. as a result, Walsh said, the two scientists will work together to reach consensus on possible levels of lead. "There are limits to what you can do with hair," he said . "There is a lot of data showing that chemical analysis is completely reliable when you get a few inches of the scalp."

Related Sites

• The Ira F. Brilliant Center for Beethoven studies
• The film "Hair Beethoven"
• health research Institute and Pfeiffer Treatment Center

Mention resistant staph bacteria, and most people think about the almost invincible strains - formally called methicillin-resistant Staphylococcus aureus (MRSA) --What infect immunocompromised individuals and patients in hospitals. But in recent years, MRSA strains that are more virulent began to spread outside hospitals and attack people in perfect health ( Science , 14 March 03, p. 1639) . Now, researchers say they have discovered how these bugs, which some see as a major threat to public health, do their damage.

Typically transmitted in prisons, schools and locker rooms, "community associated" MRSA (CA -MRSA) can cause serious infections of the skin and soft tissue, pneumonia and an infection of the blood known the bacteremia name, sometimes with fatal consequences. Why bacteria are so virulent is uncertain. Many believe it is because all CA-MRSA strains carry the gene for a toxin called (PVL) Panton-Valentine; A recent Science document suggests that this molecule plays an important role in CA-MRSA caused by pneumonia ( Science , 23 February, p. 1130).

But some scientists disagree. "We fight about PVL much," said Michael Otto, a researcher at the Rocky Mountain Laboratories, part of the National Institute of Allergy and Infectious Diseases in Hamilton, Montana. He was not convinced by the Science paper, and points out that pneumonia occurs in about 2% of CA-MRSA. PVL does not appear to play a role in skin infections and soft tissue or bacteremia, said Otto.

Now his team found another group of biochemical guilty. They found that CA-MRSA strains produce called phenol-soluble modulins peptides (PSM) in much larger quantities than do strains . hospital When the researchers knocked the genes for four of these peptides, the so-called PSMs of α-type, CA-MRSA bacteria have become much softer in mice: skin infections were less severe, and bacteremia was less often fatal. Apparently, the peptides are the most virulent microbe, the authors concluded

Learn why PSM-aS are destructive, the researchers added the peptides in human neutrophils -. A class of white blood cell that engulfs the bacteria --In the test tube. Neutrophils have started to collapse within 5 minutes, and less than an hour, many have been completely destroyed. So PSMs seem to strike a defense system, said Otto, giving vent MRSA.

"I have no doubt that these peptides contribute to the virulence of Staphylococcus aureus ," said Francois Vandenesch the University of Lyon in France, which has long defended the hypothesis and PVL co-author of science paper.. But he still believes PVL plays a major role as well

Henry Chambers, who is studying MRSA at the University of California, San Francisco, said PSMs that form "an attractive alternative explanation" for PVL - but both can be important. If the results of Otto maintain, Chambers said, they offer researchers a series of new drug targets.

Related site

• More CA-MRSA, the Centers for Disease Control and Prevention

BOSTON -. Two prominent researchers evaluated the downright depressing state of vaccine research against AIDS and urged the National Institutes of Health (NIH) to correct its course.

in the plenary discussions back-to-back at the 15th Conference on retroviruses and opportunistic infections today, Ronald Desrosiers, director of the New England Primate Research Center in around Southborough, said he thought the NIH - the largest funder of the research of vaccine against AIDS - had "lost its way," spending too much money on development and testing products and not enough on basic research. Virologist Neal Nathanson, professor emeritus at the University of Pennsylvania who formerly headed the Office of the NIH AIDS Research, echoed the plea Desrosiers that more money go to, innovative studies at risk.

The trigger for unusually harsh public criticism of the field came last fall when a vaccine against AIDS that many considered the best prospect in developing bombed in large clinical trials ( science , 16 November 07, p. 1048). Recapping this failure, Desrosiers, who is testing vaccines against AIDS in monkeys, went to claim that an effective vaccine is not even on the horizon. "None of the products in the pipeline any chance of being effective," said Desrosiers, because the field is hampered by many unknowns, such as understanding of the immune responses that a vaccine must elicit. "We must make a better job of making the clinical trial only products that show very promising. "

clinical studies receive about a third of the nearly $ 0 million that the NIH dedicated to the research of vaccine against AIDS year, the majority from the National Institute of allergy and infectious diseases (NIAID). in January, Desrosiers and 13 other private researchers wrote NIAID Director Anthony Fauci about their concerns that the field was the drift. "the letter was a good outside tweak something I was already thinking," said Fauci Science at the meeting here. Fauci said NIAID plans to organize a vaccine against AIDS day "summit" on March 25 to explore how to move forward. It will be open to the public and webcast. "The real question is the balance we want between research and development of discovery," Fauci said. "We need to take a time out."

Related Sites

• conference home page
• More information on vaccines against AIDS

can fat - even lots of it - to be healthy? A provocative study of fat grafts in mice suggests for the first time that the answer may be yes. Although some types of fat are known to be worse than others, no one had directly investigated whether certain types of fat can be a good thing. Researchers say the work is preliminary, but intriguing

For most overweight people, excess fat is in one of two areas :. Deep inside the abdomen (visceral fat) or around the hips and legs (subcutaneous fat). Researchers have recognized for some time that visceral fat is the greatest evil. People with lots of it are much more prone to diabetes, heart disease and other problems that people with excess subcutaneous fat. But he does not know exactly why. The fat itself different, or because of its location in the question of the body?

To probe this question, C. Ronald Kahn, director of obesity research at the Joslin Diabetes Center in Boston, and colleagues designed a relatively simple experiment. They transplanted fat in 42 mice naturally plump, healthy. The mice were divided into four groups that have undergone different types of operations. In some cases, the researchers added visceral fat and subcutaneous abdominal. In others, they nestled visceral fat or subcutaneous fat in the flanks of the animal, the approximate equivalent hips. Thirteen other animals formed a control group; they were made, but received no additional fat.

Kahn team found some surprising benefits to the subcutaneous fat. The mice with fat transplanted subcutaneously into the abdomen won only about 60% of the weight packed with the control group, who, like most mice, continued to grow. These transplant recipients also had higher levels of glucose and insulin. Mice that got subcutaneous fat in additional subcutaneous areas also performed better than controls, but not as good as the first group. Those who had visceral fat added to their visceral cavity were the worst off, the group said today in Cell Metabolism . Autopsies on the mice confirmed that the transplanted fat was still in place.

The conclusion suggests that subcutaneous fat may be beneficial to health, says Kahn. "That's the surprise twist in the story."

The implications are that "the subcutaneous fat produces something that is good for you, and that visceral fat produces something that is bad for you," says Richard Bergman, diabetes and obesity researcher at the University of Southern California in Los Angeles. Although some studies have correlated excess subcutaneous fat in people with improved insulin levels, the new work is "the most comprehensive study to date" consideration of this, says Philipp Scherer, diabetes and obesity researcher at the University of Texas Southwestern Medical Center in Dallas.

But for Bergman, the conclusion was so unexpected that it is keen to see more evidence, including an index on "magic factor" that could explain the interest of health. "Putting the subcutaneous fat in the visceral compartment is something that happens naturally, so it is difficult to interpret," he said.

Peer pressure can lead adolescents to start smoking, but their DNA keeps hooked on the buzz of nicotine in their adult lives. So says a new study that found that people with variations in specific genes are more likely to become addicted if they start smoking in adolescence. The work may explain why some people find it harder to quit smoking and also stresses the importance of preventing children from smoking in the first place.

Previous research has shown that people who start smoking in adolescence are more likely to be heavy smokers as adults; They also find it more difficult to quit than those who start first turn later in life. Some genes may influence whether people are hooked on cigarettes during their teenage years, but no one had shown that. Three recent studies have shown that people with only one change of base nucleotides in genes encoding cell receptors that bind to nicotine - the chemical addictive in cigarettes - were more likely to develop lung cancer ( Science NOW, April 2). Because genes help produce the buzz of nicotine, a team led by Robert Weiss, a geneticist at the University of Utah in Salt Lake City, wanted to determine whether the variations in their sequences determine if people develop stronger addiction to cigarettes.

The research team compared the genes of receptors 2827 adults currently smoke more than a pack a day and have been enlightening on average for more than 30 years. 1051 smokers who started smoking at 16 or younger were 1.5 times more likely to have an addiction to nicotine worse if they had a particular pattern of six changes from a single base in the genes than those with other genetic models. However, subjects who had the same gene pattern, but started smoking after 16 years had no increased risk of a more severe habit, suggesting that addiction risk window of this particular genetic variation opens only during the teen years, the researchers report today in PLoS Genetics .

It is unclear how the genetic variant increases the chances of being caught young smokers. One possible explanation is that the adolescent brain responds differently to nicotine. "It could be that your brain matures, you become less susceptible to the addictive effects of nicotine because the genetic component that affects how nicotine interacts with these receptors may have less effect," said Chris Amos, genetic epidemiologist at University of Texas MD Anderson Cancer Center in Houston, who was not involved in the study.

Norman Edelman, a pulmonologist at the medical Center of Stony Brook University in New York, said the results show highlight the need to focus more on preventing adolescents from smoking. "most smokers, perhaps 0%, are hooked on cigarettes as adolescents or young people," he notes. "We spend a lot of 'efforts on smoking cessation in adults, but we do not spend enough on the prevention of smoking among children, which is really important because this place where the damage is done, according to this study. "

Fifteen years of genetic sleuthing finally paid .: researchers have nailed the gene that seems to cause an inherited form of neuroblastoma, a cancer of the nervous system that primarily affects children. Scientists are optimistic that the results will help them develop disease screening for some families, and lead to potential new therapies.

about 15 years, a family riddled with neuroblastoma arrived at the Philadelphia Children's Hospital (CHOP); even a grandmother had developed the disease. Pediatric oncologist John Maris realized that he had a rare clue to his hands. Only 700 children in North America are diagnosed with neuroblastoma, and only 1% of those with familial, transmitted through other family members. Maris asked permission to draw blood for DNA tests and was invited to a barbecue with the family; he came armed with needles and collected blood samples at the kitchen table. Over time, Maris and his colleague Yael Mosse reached to hospitals in Belgium, Italy and elsewhere to look for other families like this. Finally, they found 20 to 1 total of 49 people with neuroblastoma and 127 without

In search of the shared DNA, the researchers quickly hosted on a region of chromosome 2. This led them to mutations in a gene called. ALK , which, when activated, can promote cancer. The defective form of ALK , a dominant allele, appeared in all concerned, as well as in healthy parents, who had passed down, reports Team online this week in Nature . They also found ALK some brothers and sisters who were healthy, making them wonder if these young people were high-risk neuroblastoma. ALK has also been implicated in lung cancer and lymphoma, although there are different molecular defects.

The families studied here who wear ALK mutation, make up a small minority of those affected by neuroblastoma, however. Most children are the only ones in their family with the disease, develop spontaneously for no apparent reason. Could the discovery of ALK family in neuroblastoma help children who inherit the gene?

To find out, researchers studied tumor samples from children with neuroblastoma who did not inherit the disease. They found that 12% had ALK mutations in their tumors. In addition, a handful of children with no family history of the mutation carried ALK mutations in all cells of the body, which means they have developed a spontaneous mutation in utero before continuing to develop neuroblastoma. Together, these pieces suggested ALK had a role in neuroblastoma spontaneous and familial, although oncologists are still trying to unravel exactly what it might be.

Meanwhile, CHOP is preparing to offer ALK tests for all patients newly diagnosed neuroblastoma. This will help doctors determine how common ALK mutations in neuroblastoma tumors and help to identify children who may have developed mutations before birth. For those who are ALK carriers - harboring the gene in their normal cells as well as cancerous - CHOP offer tests for the brothers and healthy sisters, in the sense that if these children are also testing positive, they can be given regular, non-invasive screening to catch the disease in its early stages. Mosse considers it essential, because by his estimation, the risk of developing neuroblastoma when wearing a ALK mutation is at least 50%. Most children with neuroblastoma are diagnosed when the disease has already spread and has a rate of approximately 30% survival.

"We have the chance not only to have found this gene, but to be able to do something about it," said Mosse. She is particularly grateful that the culprit is a gene that is activated to cause cancer - as opposed to one that is silenced, then triggers the disease - because the drugs can suppress. One ALK inhibitor is in a Phase I trial for lung cancer, and the company, Pfizer, is ready to test it in neuroblastoma. Mosse awaiting trial to open in 6 months.

"It is clear that these changes are real," said pediatric oncologist Susan Cohn of the University of Chicago Comer Children's Hospital. "It is incredibly exciting." One thing that is unknown, she said, is whether ALK inhibiting drugs work on all types of neuroblastoma tumors, because all tumors carry them. This is something that only clinical trials will tell, she said.

As if black rats have a bad reputation already. A study published today in PLoS One suggests that a century ago, these rodents, already blamed for the spread of bubonic plague in medieval Europe and considered one of the worst invasive species on planet, wore a disease that killed off two species of native rats of Christmas island in the Indian ocean.

Ocean islands are notorious extinction hotspots, because endemic species evolved with few predators or competition. When invasive species (or people) arrive, the native animals are often as helpless as the flightless dodo, which was hunted to extinction in the 17th century.

The same fate awaited Maclear of rats and Bulldog, who lived on Christmas Island. Both species were abundant at the time of the first scientific expedition to the island in 1887, but their populations began to decline in 1899, when black rats arrived with the SS Hindustan . In 108, the two species have been declared extinct. Shortly before their final disappearance of Maclear rats were reported sick and seen crawling along the trails. Visit naturalists of the time attributed the symptoms to a type of sickness (trypanosomiasis) transmitted by invasive black rats to sleep, but many modern researchers instead suggested the crossing with black rats as the main cause of extinctions.

Alex Greenwood of Old Dominion University in Norfolk, Virginia, and colleagues set out to solve the mystery of extinctions. They collected samples of 21 historic rat skins of Christmas Island, stored in natural history museums in the United Kingdom. 100 years specimens were then examined for genetic signs of interbreeding and the presence of pathogens sleeping sickness.

The researchers analyzed the skins of black rats, both extinct and alleged cross. The results showed "no consistent genetic difference" between the black rats and supposed hybrids, say the authors, that the specimens labeled as hybrids are actually black rats. Greenwood, results eliminate hybridization as the main cause of extinction.

Some also tested positive for skin Trypanosoma lewisi , a parasite from the group of organizations responsible for the fatal bedroom sickness and Chagas disease in humans. The trypanosome is transmitted by fleas carried by black rats, which are immune to its effects. But for endemic rats that had no resistance, the parasite would probably have been fatal. Greenwood says this study implies that invasive species and environmental destruction are not the only causes of extinction. "The disease can play a role as well," he added.

Amy Pedersen, parasitology at the University of Sheffield in the UK said that despite the small number of samples, " excellent arguments for authors extinction mediated disease ". It is likely that infectious diseases could contribute to future extinctions, especially species that are also facing other challenges, she added.

Rod cells in our eyes help us see in dim light. They also ensure that the cones, other light-sensitive cells on which we depend for vision, enough food, a new study reveals. The findings may shed light on a common cause of blindness.

Approximately 100,000 people in the United States have retinitis pigmentosa, a hereditary retinal incurable disease that leads to blindness. Over 40 genes may contribute to disease, often damaging important proteins in the cells of the retina. initial symptom loss, night vision disease, occurs when stems begin to die off. This attrition usually begins in childhood, and even if it is inconvenient, most people get by with their cones - the photoreceptor cells that operate in bright light. But when those affected reach adulthood, the cones begin to die, too, ultimately resulting in total blindness. This has confused the scientists, because defective genes are not active in the cones, as in the stems.

To crack this mystery, Constance Cepko biologist from Harvard University and his colleague Claudio Punzo, a postdoctoral researcher, first evaluated earlier theories. Some researchers believe that when the stems are dead, they produced a toxin that killed cones. Others have speculated that, because the stems use a lot of oxygen in the retina, their death could leave a large amount of oxygen that overloads and damages the remaining cones. But none of them seemed to match the trend, Cepko said, so he and Punzo decided to look for a new explanation.

The researchers measured the activity of genes in four different strains of mice with defective stem cells. They found more than 0 genes that are activated at about the same time, the cones began to die, many of them related to cell metabolism.

"That was our first clue that maybe the cells do not receive enough nutrients," says Cepko. Several of these genes were linked to a protein known as the mammalian target of rapamycin, or mTOR, which leaves the cell whether it has enough nutrients. - especially glucose But if the harsh famine long enough, mTOR directs the cell to digest is exactly what the cones were

in determining whether a drop-off glucose was killing cones, the researchers injected abdominally some of the mice with insulin to increase their glucose levels. the shots do not cause the cones to hang on a little longer long, but they still died a few weeks later.

Cepko and Punzo think the cones could starve because of crumbling architecture of the retina. a thin layer of cells, known as name of the retinal pigment epithelium (RPE), covers the rods and cones like a circus tent and provides their nutrients. Rods outnumber cones in the retina significantly, so that when they die, most of the "tent poles" of RpEs die with them. Collapses tents, cones lose their nutrient connection, and they starve slowly. The study is published online this week in Nature Neuroscience .

"I think it's very exciting," said Rafael Caruso, an ophthalmologist with the US National Eye Institute in Bethesda, Md. "It's a new approach to the problem." Caruso said researchers "do a pretty convincing case for their conclusions," especially because the same mutations in mice tested are also found in humans.

Unfortunately, both Cepko Caruso and agree that the finding does little to researchers seeking treatments. But it suggests a new framework for thinking about the problem. Exploring different ways to get nutrients into the cones, Cepko said, researchers may one day be able to help people with retinitis pigmentosa retain their daytime vision for a longer period of time.

Stem cells fans are in a frenzy about the upcoming change in presidential politics and held press conferences Abrim enthusiastically, if not the content. But at a meeting today at the Center for American Progress (CAP) in Washington, DC, to publish a report A Life Sciences Crucible , some differences emerged on how the new administration should proceed to normalize stem cell research and from political winds that buffeted during the Bush administration.

CAP wants President-elect Barack Obama to quickly issue a decree clearing the restrictions Bush and Congress to pass a bill that explicitly allows researchers funded by the federal access to cell lines derived human embryonic stem after August 01.

But Amy Comstock Rick, chief patient-centered Coalition for the advancement of medical research, warned that it was important to see how the decree reads . Orders may come and go, she noted, so it should not be used to specify search criteria. Instead, she said the order is to simply put the whole subject "where it belongs" - in the capable hands of the NIH. Similarly, she said, his group opposes a new law which she said would not be "conducive to making flexible decision."

CAP also calls for a special working group for clinical research using embryonic stem cells to create within recombinant DNA Advisory committee of the NIH. the Coalition for the advancement of medical research disagrees with that, too. It's just another layer of national oversight on matters that should be left to committees existing institutional oversight, said Rick. "separate Special Structures" to oversee the research on stem cells still smack of political motivations.

looks like the cries may have disappeared from the world of politics on stem cells, but it is far from over.

National Institutes of Health will devote most of its $ 8.2 billion to research the economic stimulus bill for requests of grant funding it has already received and to complement existing grants. A smaller amount of approximately $ 100 million to $ 0 will go to new grant applications it receives in the coming months.

Speaking Wednesday afternoon in Washington, DC, to a packed auditorium of representatives of universities and associations, Acting Director Raynard Kington said NIH would soon issue a request for applications for new grants "challenge" of up 'to $ 500,000 per year for 2 years. These grants will challenge for research on certain areas of science or public health think that NIH can make significant progress within 2 years. NIH will create an abbreviated application process for these grants, peer-reviewed, but did not say which areas will be targeted.

Because the NIH must spend stimulus money in these 2 years, he is under pressure to start sending money to the beneficiaries as soon as possible. Therefore, Kington said, it will not issue a massive call for new applications. Instead, it will mainly seek to add money to existing grants and fund grant requests it has received and reviewed by peers.

All grants 2 years resulting from the stimulus package will come with the unusually rigorous reporting requirements, Kington said, including reporting the number of jobs created or maintained. He has repeatedly said that the NIH would be "embarrassed" if the institutions do not spend money or increase their local economies. He expects the beneficiaries to "hire people and make purchases and advance science," he said.

Because the goal of the stimulus bill is to improve the economy of the nation, Kington said NIH would also be sensitive to the geographic distribution of subsidies it gives.

Kington gave few details about NIH plans, but said more details would be available soon.