Readings: health and medicine, 20 October 2007

The text following each item is quoted material, except for editorial comments, which are in color.

BubR1 Protein: A Key Regulator of Aging

Hoping to find a way to help people maintain their independence and quality of life as they grow older, Jan van Deursen, Ph.D., and a team of collaborators are investigating the relationship between common aging-associated diseases and the protein BubR1. He became interested in aging-related research after observing that mice deficient in the protein BubR1 age faster than normal mice. They say BubR1 deficient mice may hold the key to preventing or delaying disorders such as cataracts, muscle weakness and cardiovascular disease.

Aging and the Growth Hormone Crash: What Comes First?

"If pituitary hormones were released like water from a faucet into a bathtub, there'd be a constant slow filling of the tub in proportion to its size and whether or not the drain was open — you could solve that with high school physics," explains Dr. Veldhuis. "One of the complexities is that the pituitary squirts out a pulse of hormones at random times."

The pituitary gland, a pea-sized structure located at the base of the brain, regulates many key functions in the body. It secretes seven hormones in response to commands from the hypothalamus of the brain. Dr Veldhuis is interested in observing the pituitary response for its influence on aging. He is most interested in its secretion of the growth hormone (GH), which stimulates protein synthesis and cell division in cartilage and bone tissue. GH has a tendency to remove intra-abdominal fat, which is associated with diabetes and heart disease (metabolic syndrome).

Hormone dilemma, 5 years on

Five years ago this month, a landmark study dashed the belief that hormone treatment is the key to keeping women of a certain age sexy, healthy and young.

On the contrary, maintaining estrogen and progestin at abnormally high levels after menopause was shown to be risky for their hearts, brains, breasts and blood vessels.

The government study abruptly transformed the use of hormone therapy - and, in the ensuing years, has undermined the idea that women who don't get long-term treatment are doomed to decrepitude. ...

The landmark research remains bitterly controversial, its findings incredibly complex. In recent months, reanalyses of the data have found that while hormones raise heart risks for women long past menopause, they pose no such danger - and may have cardiac benefits - for recently menopausal women.

Critics of the study - known as the Women's Health Initiative - have argued for five years that it overstated the heart risks for younger women.

While the science is still evolving, hormones have been firmly reestablished in a limited role: to relieve the passing discomforts of dwindling estrogen.

And yet the risk of breast cancer from estrogen therapy has been reaffirmed in recent studies – under certain circumstances. But uncertainties still remain. See here, here, and here.

Can Fat Be Fit?

Two years ago Katherine M. Flegal, a re­search­er at the Centers for Disease Control and Prevention, did a new statistical analysis of national survey data on obesity and came to a startling conclusion: mildly overweight adults had a lower risk of dying than those at so-called healthy weights. ...

Stampfer cites the Flegal study as a prime example of the errors the critics make. The reason being overweight seemed to reduce mortality is because Flegal used the wrong comparison group, he says. The lean group in her study included smokers and people with chronic illnesses—both of whom have increased mortality risks, but not because they are slim. “When you get sick, you lose weight, and you die,” Stampfer says. Compared with those who are smokers or chronically ill, people who are overweight come out looking better than they should.

Eating Made Simple

Studies focusing on one nutrient in isolation have worked splendidly to explain symptoms caused by deficiencies of vitamins or minerals. But this approach is less useful for chronic conditions such as coronary heart disease and diabetes that are caused by the interaction of dietary, genetic, behavioral and social factors. If nutrition science seems puzzling, it is because researchers typically examine single nutrients detached from food itself, foods separate from diets, and risk factors apart from other behaviors. This kind of research is “reductive” in that it attributes health effects to the consumption of one nutrient or food when it is the overall dietary pattern that really counts most.

Cutting Cholesterol, an Uphill Battle

About 85 percent of the cholesterol in your blood is made in your body. The remaining 15 percent comes from food. But by reducing dietary sources of saturated fats and cholesterol and increasing consumption of cholesterol-fighting foods and drink, you can usually lower the amount of harmful cholesterol in your blood. My college roommate, for example, recently adopted a mostly vegetarian-and-fish diet, minus cheese but with occasional meat and chicken, and lowered her total cholesterol from 240 to 160 milligrams.

Deadly Inheritance, Desperate Trade-Off

Mrs. Platt is part of a study aimed at preventing pancreatic cancer in people who are at high risk for it, by finding precancerous growths and removing all or part of the pancreas to get rid of them. So far, about 20 people have had the preventive surgery at Johns Hopkins, and a small number of others have undergone it at other centers.

In essence, these patients are trading the risk of cancer for the reality of diabetes, and their willingness to do it is a measure of the fear and desperation that pancreatic cancer provokes.

“With pancreatic cancer you don’t have much opportunity to save lives, and we are, with this approach,” said Dr. Canto, the director of endoscopy at Johns Hopkins.

Electric fields have potential as a cancer treatment

Yoram Palti, of the Technion–Israel Institute of Technology in Haifa, and his colleagues have demonstrated another way to disrupt cell division: alternating electric fields with intensities of just 1–2 V/cm. The fields they use, with frequencies in the hundreds of kilohertz, were previously thought to do nothing significant to living cells other than heating them. But Palti and colleagues have conducted a small clinical trial showing that the fields have an effect in slowing the growth of tumors.

Science begins at home

Chemotherapy drugs, like most medicines, reach cells by slipping through narrow spaces in the walls of blood vessels that crisscross the body.

But all blood vessels are not alike.

The abnormal, leaky vessels that supply cancer cells have openings up to 100 times larger than those found in healthy vessels -- it's like comparing a soccer ball with a Goodyear blimp.

In a way, this biological quirk was the reverse of the problem he faced in seeking a molecular petroleum sieve.

Instead of creating a mesh, he wanted to bulk medicines up so their molecules wouldn't pass through the wall of normal blood vessels. At the same time, they needed to remain small enough to fit through pores of vessels feeding cancerous cells.

One anecdotal example of the difficulties of developing new and better drug therapies.

Mysteries of autoimmune diseases unravel

Scientists say immune disorders, which range from common diseases such as juvenile diabetes or lupus to some so unusual that many doctors have never heard of them, are among the most mysterious of ailments, genetically complex and so diverse that estimating their true prevalence is a guessing game. But with major advances in genetics and exponential growth of knowledge about the immune system, scientists say important discoveries are tantalizingly within reach. ...

Immune system disorders often cluster in families and within an individual, says Virginia Ladd, president of the American Autoimmune Related Diseases Association. "Once you have one, you have others. Some patients say if you live long enough, you can collect them."

Visualizing the Molecules that Cause Infectious Disease: Seeing with Supercomputers

CAMDL specializes in developing computer simulated models aimed at the discovery of new treatments for infectious diseases and cancer. It is one of few labs conducting advanced research in computational, medicinal, synthetic and combinatorial chemistry under one roof.

The laboratory houses supercomputing hardware and software used to process highly complex biological data, and develop comprehensive databases of three-dimensional molecules. Dr. Pang has adapted his imaging concepts from the small computer screen to a large wall screen where visitors are drawn into a three-dimensional, sub-microscopic world. Researchers can examine and study, in simulation, microsecond-scale proportions of proteins and enzymes associated with malaria, avian flu and severe acute respiratory syndrome (SARS). This ability has led to significant discoveries in the lab that Dr. Pang says will impact the prevalence and spread of infectious diseases.

Small-Scale Solutions

Chemists first invented lab-on-a-chip devices to analyze gases in the 1970s, but the effort to make practical microfluidics tools for biological studies has gained traction only in the past decade. One major advance, led by George Whitesides at Harvard University in the late 1990s, was to fabricate the chips from cheap, flexible rubber rather than the expensive, stiff silicon used to manufacture computer chips. In a method dubbed "soft" lithography, Whitesides and his colleagues started with the same photographic processes that computer-chip companies use to cast an integrated-circuit blueprint in a single wafer of silicon, but they poured rubber into the chip-making molds instead.

Vaccines and Their Promise Are Roaring Back

By the mid-1990s, however, innovation in vaccines had virtually come to a halt. Only a handful of companies even tried to develop new ones, compared with 25 in 1955.

But in a stunning reversal, innovators today are chasing dozens of vaccines, stimulated by some recent high-profile successes. ...

The allure of the silver bullet — of wiping out an entire class of related diseases with a single injection — remains a powerful symbol of technological advance.

Tags: aging, cancer, hormones, endocrine system, cholesterol, autoimmune disease, health, medicine

The role of hostility, anger, and depression in inflammation

Hasn't it "always" been known that anger and hostility raises one's blood pressure? However that may be, a recent study shows that the connection of hypertension with chronic anger and hostility may involve a disturbed immune system and inflammation – in addition to the well-known blood vessel constriction that is a part of the "fight or flight" stress response.

Hostile Men Could Have Greater Risk For Heart Disease

Men who are hostile and prone to frequent intense feelings of anger and depression could be harming their immune systems and putting themselves at risk for coronary heart disease as well as related disorders like type 2 diabetes and high blood pressure, a new study finds.

The results were found in a 10-year study of U. S. veterans of the Vietnam war.

The men had a series of blood levels taken on three occasions between 1992 and 2002. Researchers measured two immune system proteins known as C3 and C4. Both are markers of inflammation, which is the body’s response to injury or infection. Changes in C3 and C4 are associated with a number of diseases, including some that negatively can affect the arteries around the heart, such as diabetes.

Men whose psychological screening showed the highest level of hostility, depressive symptoms and anger had a 7.1 percent increase in their C3 levels, while men with low levels of these attributes showed no change over the 10-year study period.

Here's another report on this research: Hostility, anger linked to chronic inflammation

But a 2004 study had already demonstrated a stronger correlation between psychological variables and a marker of inflammation (C-reactive protein):

Anger, Hostility And Depressive Symptoms Linked To High C-reactive Protein Levels

Researchers at Duke University Medical Center have discovered that otherwise healthy people who are prone to anger, hostility and mild to moderate depressive symptoms produce higher levels of a substance that promotes cardiovascular disease and stroke.

The substance, C-reactive protein (CRP), has garnered considerable attention for its role in both promoting and predicting cardiovascular disease and stroke in initially healthy people. It is produced by the liver in response to inflammation, and inflammation has recently been shown to underlie the plaque that forms inside arteries as they clog.

The Duke study is the first to link this combination of negative psychological attributes with higher levels of CRP in people without traditional risk factors for heart disease...

More specifically,

121 healthy men and women were asked to complete standard personality questionnaires in which they described their psychological attributes, including anger, hostility and depression. The volunteers did not have any pre-existing conditions -- such as smoking, high blood pressure, diabetes or heart disease -- that would predispose them to having high CRP levels. High-sensitivity blood tests were then conducted to measure CRP levels.

Respondents who were prone to anger, had high hostility levels, and showed mild to moderate symptoms of depression had two to three times higher CRP levels than their calmer counterparts. The more pronounced their negative moods, the higher CRP levels they had, the study showed.

In addition, the researcher had previously shown a relation between the psychological variables and another inflammatory substance (interleukin-6):

[H]ostile people who exhibit symptoms of depression have higher levels of stress hormones and circulating levels of an inflammatory substance called interleukin 6, another marker of inflammation that has been shown to predict heart disease in initially healthy people.

A number of other studies have demonstrated relationships between psychological stress conditions and disease states that involve the immune system, such as this one from 2006:

Anger And Hostility Speed Up Decline In Lung Power

The authors point out that hostility and anger have been associated with cardiovascular disease, death, and asthma, and that previous research has suggested that changes in mood can have short term effects on the lungs.

Anger and hostility will alter neurological and hormonal processes, which in turn may disturb immune system activity, producing chronic inflammation, suggest the authors.

An accompanying editorial comments that the physiological components of anger and stress overlap, and stress is well known to affect the immune system.

Bottom line: Get control over anger and depression if you want to stay healthy.

Of course, this is all closely related to what I discussed just a couple of weeks ago on stress and weight gain and in particular the extensive research of Robert Sapolsky summarized here.

Additional references:

• Coping With Stress Improves Cholesterol
  
• High Hostility May Predict Heart Disease More Than Other Risk Factors Such as Cholesterol and Smoking
  
• Hostility is among best predictors of heart disease in men
  

Tags: inflammation, stress, anger, hostility, depression, cardiovascular disease, hypertension

Stress and weight gain

There is, apparently, truth to the idea that people under stress may gain weight – and it's not just that people simply choose to escape their problems by eating. And this is only one of the reasons stress isn't good for your general health.

Scientists Discover Key To Manipulating Fat; Pathway Also Explains Stress-induced Weight Gain

In the paper, the Georgetown researchers describe a mechanism they found by which stress activates weight gain in mice, and they say this pathway -- which they were able to manipulate -- may explain why people who are chronically stressed gain more weight than they should based on the calories they consume.

The key to the process that was found is a peptide (small protein) neurotransmitter called neuropeptide Y (NPY). NPY is produced under conditions of stress, as a by-product of the "fight-or-flight" response mediated by the sympathetic nervous system. An animal under conditions of chronic stress will have higher levels of NPY. The hormone was discovered 25 years ago, and earlier research indicates that it acts in the brain to increase appetite. (Although other aspects of the response may suppress appetite, which is why some overly stressed people may be emaciated.) The appetite-suppressing hormone leptin acts by inhibiting the activity of neurons that contain NPY.

What the new research found, however, is that, more importantly, NPY, acting outside the brain in adipose tissue, also alters an animal's metabolism to increase storage of fat:

As part of the study, Zukowska and her team examined the effect of several forms of chronic stress that mice in the wilderness can encounter, such as exposure for an hour a day over a two-week period to standing in a puddle of cold water or to an aggressive alpha mouse, and they conducted the experiments in combination with a regular diet or with a high-fat, high-sugar diet. Stressed animals fed a normal diet did not gain weight, but stressed mice given a high-fat diet did. In fact, the researchers found these mice put on more weight than expected given the calories they were consuming.

"They gained twice as much fat as would be expected, and it was all in their belly area," Kuo said. Stressed versus non-stressed animals ate the same amount of food, but the stressed animals processed it differently, she said, explaining, "the novel finding here is that NPY works on fat tissue, not in the brain."

In part, the research showed that NPY experimentally delivered in a mouse activated a G-protein coupled receptor called (naturally) a neuropeptide Y2 receptor (Y2R). (This is just one of 5 known NPY receptors.) Activation of Y2R was observed to promote storage of fat in adipose tissue:

[The] pathway involves two players -- a neurotransmitter (neuropeptide Y, or NPY) and the receptor (neuropeptide Y2 receptor, or Y2R) it activates in two types of cells in the fat tissue: endothelial cells lining blood vessels and fat cells themselves. In order to add fat selectively to the mice they tested, researchers injected NPY into a specific area. The researchers found that both NPY and Y2R are activated during stress, leading to apple-shape obesity and metabolic syndrome.

So NPY can lead to increased fat storage. But the converse is, happily, also true: blocking the NPY receptor shrinks fat:

Both the weight gain and metabolic syndrome, however, were prevented by administration of Y2R blocker into the abdominal fat.

Metabolic syndrome, you recall, comprises several undesirable elements, such as hyperglycemia, high blood pressure, central obesity, decreased HDL cholesterol, and elevated triglycerides. All of these can lead to more serious health problems, such as diabetes and cardiovascular disease. So there is the possibility that blocking Y2R could be beneficial to humans:

"We are hopeful that these findings might eventually lead to control of metabolic syndrome, which is a huge health issue for many Americans," [the study's senior author, Zofia Zukowska] said. "Decreasing fat in the abdomen of the mice we studied reduced the fat in their liver and skeletal muscles, and also helped to control insulin resistance, glucose intolerance, blood pressure and inflammation. Blocking Y2R might work the same way in humans, but much study will be needed to prove that."

Another account of this research reports expressions of optimism for development of human drugs to control stress-induced health problems:

Stress can be fattening, study finds

Mary F. Dallman of UC San Francisco said in an editorial in the same journal: "A large gap in our understanding of how chronic stressors lead to abdominal obesity has been filled…. Their results were remarkable and have profound implications for new drug development."

But it's not a sure thing. There is another hormone, called PYY, Pancreatic Peptide YY, or Pancreatic Peptide YY_3-36. PYY is structurally similar to NPY and in fact can activate some NPY receptors. It has been found to decrease appetite when it activates NPY receptors in the brain. At least two biotech companies (Amylin and Nastech) have investigated using PYY directly as a drug to induce weight loss. So far this effort has had only mixed results.

Here's another report on the research discussed above: How we can stop stress from making us obese. And here's a blog post that raises some good questions about this research: Scientists Stressed About Weight Loss.

Apart from the effects of NPY, chronic stress can cause a variety of health problems besides weight gain, obesity, and their knock-on effects. Robert Sapolsky of Stanford has done copious research into the ill effects of chronic stress. He points out that the fight-or-flight response of animals in the wild, which is activated during periods of acute danger (predators), and is adaptive in those circumstances, can turn harmful when stress is chronic, as happens frequently with primates such as humans:

Why Do Humans And Primates Get More Stress-related Diseases Than Other Animals?

Why do humans and their primate cousins get more stress-related diseases than any other member of the animal kingdom? The answer, says Stanford University neuroscientist Robert Sapolsky, is that people, apes and monkeys are highly intelligent, social creatures with far too much spare time on their hands.

"Primates are super smart and organized just enough to devote their free time to being miserable to each other and stressing each other out," he said. "But if you get chronically, psychosocially stressed, you're going to compromise your health. So, essentially, we've evolved to be smart enough to make ourselves sick."

Tags: stress, obesity, weight gain, neuropeptide Y

Health benefits of omega-3 fatty acids

Omega-3 fatty acids are now getting credit for health benefits in a surprising range of disease conditions.

Just to review a little, fats and fatty acids are said to be saturated if they have the maximum possible number of hydrogen atoms attached. In particular, a fatty acid is unsaturated if it has at least one double C-C bond on its main hydrocarbon chain. (An atom of hydrogen could potentially be attached there.) It is polyunsaturated if it has at least two. By definition, an omega-3 fatty acid is polyunsaturated, and in addition one of its double bonds occurs as close as possible to the end of the main chain that is opposite the carboxyl (COOH) group required in a fatty acid.

Curiously enough, this simple chemical property – rather than any more complicated chemical configuration – appears to be sufficient to confer a variety of health benefits on omega-3 fatty acids.

Perhaps the best-known benefit, for which there is evidence in studies of particular (not all) omega-3 fatty acids, is related to coronary heart disease (e. g. atherosclerosis or "hardening of the arteries"). The omega-3 fatty acids most frequently involved are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

But recent research has encompassed many other disease conditions, for example, abnormal blood vessel growth that can cause blindness, such as that which may occur in retinopathy of premature infants, diabetic retinopathy, and "wet" age-related macular degeneration.

Omega-3 fatty acids protect eyes against retinopathy, study finds

The researchers studied the effect of the omega-3 fatty acids EPA and DHA, derived from fish, and the omega-6 fatty acid arachidonic acid on the loss of blood vessels, the re-growth of healthy vessels, and the growth of destructive abnormal vessels in a mouse model of oxygen-induced retinopathy. The retinopathy in the mouse shares many characteristics with retinopathy of prematurity (ROP) in humans. ROP is a disease of the eyes of prematurely born infants in which the retinal blood vessels increase in number and branch excessively, sometimes leading to bleeding or scarring. Infants who progress to a severe form of ROP are in danger of becoming permanently blind. There are also aspects of the disease process that may apply to diabetic retinopathy, a disease in which blood vessels swell and leak fluid or grow abnormally on the surface of the retina, and age-related macular degeneration (AMD), a disease of the macula, the part of the retina responsible for central vision, and a leading cause of vision loss in Americans 60 years of age and older.

Typical Western diets are lacking in omega-3 fatty acids, which are found mainly in shellfish and oily fish (e. g. salmon, sardines), and instead have a much higher percentage of omega-6 fatty acids. (In an omega-6 fatty acid, the only difference is that the first C-C double bond occurs farther from the end of the hydrocarbon chain that is opposite the carboxyl group. See these Wikipedia articles for more details: essential fatty acids, essential fatty acid interactions.) It turns out, oddly enough, that omega-6 fatty acids can have deleterious effects, just the opposite of omega-3 effects.

The researchers found that increasing omega-3 fatty acids and decreasing omega-6 fatty acids in the diet reduced the area of vessel loss that ultimately causes the growth of the abnormal vessels and blindness. Omega-6 fatty acid contributes to the growth of abnormal blood vessels in the retina.

To further test the apparent beneficial effect of omega-3 fatty acids, the researchers studied mice fed a diet modeled after a traditional Japanese diet (more omega-3 than omega-6 fatty acids) and mice fed a diet modeled after a traditional Western diet (lower amounts of omega-3 fatty acids). In addition, they studied mice genetically altered with a gene which mammals normally lack that converts omega-6 into omega-3 fatty acids. They found that the mice with higher amounts of omega-3 had a nearly 50 percent decrease in retinopathy.

Most importantly, this research identified a likely mechanism of action by which omega-3 fatty acids confer their benefits. The mechanism involves suppression of inflammation, especially involving the inflammatory cytokine TNF-α. In particular, this would apply to atherosclerosis, in which inflammation is generally regarded as a significant problem. Such anti-inflammatory properties, if indeed present, could account for the benefits of omega-3 fatty acids in other circumstances also. Another report on the same research describes this:

Can Blindness Be Prevented Through Diet?

Omega-3 fatty acids like DHA and EPA are thought to dampen inflammation in the body. ...

The researchers demonstrated that the omega-3-based diet suppressed production of TNF-alpha, reducing the inflammatory response in the retina, whereas the omega-6-based diet increased TNF-alpha production. The retinas of omega-3-fed mice also had increased production of the anti-inflammatory compounds neuroprotectinD1, resolvinD1 and resolvinE1. These compounds, derived from omega-3 fatty acids, also potently protected against pathological vessel growth, and they were not detected in the retinas of mice fed the omega-6 diet.

Cancer is a rather more controversial case in connection with possible health benefits of omega-3 fatty acids. Many epidemiological studies have been done to try to identify cancer-protective effects of omega-3 in the diet, with varying results. Meta-analysis of such studies does not identify a conclusive connection. However, such studies are hampered by uncertainties about the actual diets consumed by participants. Additionally, a lot may depend on individual genetic factors. In animal studies it is possible to be much more quantitatively precise. For instance, we have this:

Omega-3 Fatty Acids May Help Slow Prostate Cancer Growth

The mice were fed either a diet high in omega-3 (ratio of omega-6 to omega-3 was 1:1) a diet low in omega 3 (ratio omega-6 to omega-3 was 20:1), or a diet high in omega-6 (ratio of omega-6 to omega-3 was 40:1). The scientists compared survival rates and weighed the animals' prostates to measure tumor progression.

Mice with the tumor suppressor gene remained free of tumors and had 100 percent survival, regardless of diet. In mice with the gene defect, survival was 60 percent in animals on the high omega-3 diet, 10 percent in those on the low omega-3 diet and 0 percent in those on the high omega-6 diet.

"This suggests that if you have good genes, it may not matter too much what you eat," said [senior researcher Yong Q.] Chen, a professor of cancer biology. "But if you have a gene that makes you susceptible to prostate cancer, your diet can tip the balance. Our data demonstrate the importance of gene-diet interactions, and that genetic cancer risk can be modified favorable by omega-3 PUFA."

In a rather different direction, there has been a lot of suspicion, and some epidemiologial and experimental evidence, that omega-3 fatty acids and higher omega-3:omega-6 ratios have beneficial effects in connection with psychological and mood disorders. So it makes sense that omega-3 could be useful with the symptoms of agitation and depression associated with Alzheimer's disease. It turns out that benefits may be significantly dependent on genetic factors related to the disease:

Omega-3 Supplements Can Help With Alzheimer's Symptoms, Study Suggests

Omega-3 supplements can, in certain cases, help combat the depression and agitation symptoms associated with Alzheimer's disease, according to a clinical study conducted at the Swedish medical university Karolinska Institutet.

A number of epidemiological studies have shown that eating fatty fish provides a certain degree of protection against Alzheimer's and other dementia diseases--an effect often thought attributable to the omega-3 fatty acids it contains. Some studies also suggest that omega-3 can have a therapeutic effect on some psychiatric conditions.

The results were not straightforward, to put it mildly. There is a well-known susceptibility gene for Alzheimer's, APOE4. Carriers of the gene experienced benefits for agitation symptoms, while non-carriers had benefits for depression symptoms!

There was no observable difference in therapeutic effect between the patients receiving the omega-3 and the placebo group. However, when the researchers took into account which of the patients carried the susceptibility gene APOE4 and which did not, an appreciable difference appeared. Carriers of the gene who had received active treatment responded positively to the omega-3 as regards agitation symptoms, while non-bearers of the gene showed an improvement in depressive symptoms.

Tags: omega-3 fatty acid, retinopathy, macular degeneration, prostate cancer, Alzheimer's disease

Disease genes

This is old news (over a month), and it was widely reported in the general media, so I'm sure most readers are aware of it. But it seems important enough to note here, just for the record. It might be considered one of the most important science stories of the year.

Largest Ever Study Of Genetics Of Common Diseases Published

The Wellcome Trust Case Control Consortium, the largest ever study of the genetics behind common diseases such as diabetes, rheumatoid arthritis and coronary heart disease, published its results in the journals Nature and Nature Genetics.

The £9 million study is one of the UK's largest and most successful academic collaborations to date. It has examined DNA samples from 17,000 people across the UK, bringing together 50 leading research groups and 200 scientists in the field of human genetics from dozens of UK institutions. Over two years, they have analysed almost 10 billion pieces of genetic information.

Information about a couple of autoimmune diseases figured prominently in the results.

Amongst the most significant new findings are four chromosome regions containing genes that can predispose to type 1 diabetes and three new genes for Crohn's disease (a type of inflammatory bowel disease). For the first time, the researchers have found a gene linking these two autoimmune diseases, known as PTPN2.

The study has also confirmed the importance of a process known as autophagy in the development of Crohn's disease. Autophagy, or "self eating", is responsible for clearing unwanted material, such as bacteria, from within cells. The may be key to the interaction of gut bacteria in health and in inflammatory bowel disease and could have clinical significance in the future.

"The link between type 1 diabetes and Crohn's disease is one of the most exciting findings to come out of the Consortium," says Professor John Todd from the University of Cambridge, who led the study into type 1 diabetes. "It is a promising avenue for us to understand how the two diseases occur. The pathways that lead to Crohn's disease are increasingly well understood and we hope that progress in treating Crohn's disease may give us clues on how to treat type 1 diabetes in the future."

There were also findings about genetic factors in obesity, type 2 diabetes, and heart disease. In fact, seven major disease in all:

These are bipolar disorder, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes.

Interestingly, rheumatoid arthritis is also an autoimmune disease. And the immune system (especially in regard to inflammation) probably plays some role in other ailments on this list.

Most readers here probably understand that very seldom is a single gene ever the sole "cause" of a particular disease. Instead, what has been found, in this study and in others, is a number of variants (called alleles) of a variety of genes, where one of more of the variants, if present in an individual, increases the person's risk of eventually developing the disease – conditioned on the presence of other genetic variations, environmental conditions, and so forth. As another account explains:

Sick Genes

[G]enes, although potent predictors, are not always the sole cause of particular diseases. For instance, environmental factors, lifestyle (diet, exercise, etcetera) and exposure to infections can all play roles in determining whether an individual will develop heart disease, for example. "It's about hundreds of genes in your genome contributing a threshold of genetic susceptibility," Todd says. "It's not about one gene."

Nevertheless, on average, having one copy of some of the newly identified genes raises a person's chances of developing one of the seven studied diseases by 20 to 40 percent, and those with two copies face nearly double that risk, researchers say. "What hasn't been clear is exactly which bits of the genome have an effect and which variants make people more [or less] likely to get a disease," Donnelly notes.

Additional news reports: here, here, here, here.

Tags: genetics, disease genes

News dump: inflammation

I've already done one news dump on the subject of inflammation (here), and there's been a lot of interesting stuff since then. This is just the first installment of new stuff, in reverse chronological order.

Schizophrenia may be linked to inflammation: study (3/21/07)

Many patients with schizophrenia also have autoimmune diseases. Using a technique called whole genome association researchers have located a gene variant common to many schizophrenics. The variant is located close to genes that produce receptors for two cytokines, which are immune system signals whose production is a first step in causing inflammation. Although the result is intriguing, the evidence for a relation to inflammation is still circumstantial.

Why Aerobic Exercise Is Good For The Heart (3/21/07)

The biological mechanisms connecting exercise and cardiovascular health are not fully understood. This study shows how exercise decreases inflammation, which reduces the risk of atherosclerosis, which in turn causes most cases of heart disease. Blood samples were taken from experimental volunteers before and after aerobic exercise. The samples were stimulated with an infectious agent and then analyzed for levels of tumor necrosis factor (TNF), an initial step in the inflammatory cascade. Substantially lower levels of TNF were found after aerobic training

Inflammation May Play Role In Metastasis Of Prostate Cancer (3/19/07)

This research strongly suggests that inflammation associated with the progression of tumors plays a key role in the metastasis of prostate cancer. It appears that inflammation in the tumor may lead to production of a cytokine called RANK. This eventually results in turning down the expression of a gene called Maspin, which has well-established anti-metastatic activity in breast and prostate cancers.

Researchers Identify Molecular Basis Of Inflammatory Bowel Disease (3/15/07)

The category of inflammatory bowel diseases includes Crohn's disease and ulcerative colitis. A likely molecular basis for such diseases has been identified in a mouse model. It appears that there is an underproduction of the signaling molecule NF-kB, which helps cells cope with stress, in the intestinal epithelium. With insufficient NF-kB, epithelial cells are more likely to die, and as a result bacteria can penetrate the epithelium. This results in activation of the intestinal immune system, producing a strong immune response and inflammation. The inflammation leads to death of more epithelial cells due to lack of NF-kB, perpetuating the cycle.

Obstructive Sleep Apnea Patients Show Silent Brain Infarction Lesions (3/15/07)

Patients with sleep apnea often have high levels in their blood of inflammatory markers. Cardiovascular disease is commonly characterized by ongoing inflammatory responses that can enhance blood platelet activation and increase the risk of silent brain infarction (stroke). Treatment of patients with obstructive sleep apnea using devices to create positive airway pressure led to lower blood levels of C-reactive protein and levels of two markers of platelet activation, suggesting that the apnea played a causal role in inflammation.

Belly Fat May Drive Inflammatory Processes Associated With Disease (3/14/07)

This research strongly suggests that visceral fat present in significant amounts surrounding organs in the midsection of the body may be a major source of inflammatory molecules. The resulting inflammation is suspected to play an important role in diseases such as insulin resistance, hypertension, type 2 diabetes, and atherosclerosis, and possibly Alzheimer's, cancer, and general aging. The study was done by analyzing blood taken from the portal vein (which drains organs surrounded by visceral fat) during gastric bypass surgery. Elevated levels of the inflammatory cytokine IL-6 were found, along with higher levels of C-reactive protein.

C-Reactive Protein Liver Protein Induces Hypertension, Researchers Find (2/22/07)

Researchers claim to have found that C-reactive protein is not merely a marker of the risk of hypertension, it actually induces hypertension. Using a mouse model having an engineered gene for CRP that was regulated by another gene responsive to carbohydrate in the diet, the researchers determined that raising CRP levels increased blood pressure, while lowering CRP levels lowered blood pressure. (It has been known for some time that high CRP levels are correlated with risk of hypertension and atherosclerosis.) Further investigation showed that the experimental mice were highly sensitive to the blood pressure regulating protein angiotensin II, and this was due to alterations in key proteins in the vascular wall that are involved with angiotensin II. The mechanism involves a lack of nitric oxide in the artery wall, and a connection was found between nitric oxide and proteins responsible for angiotensin II activity. Remaining to be shown is whether the same mechanism operates in humans.

Inflammatory Genes Linked To Salt-sensitive Hypertension (12/30/06)

A team of researchers is investigating interrelations among genetic variations, stress, inflammation, and hypertension. One hypothesis is that sodium handling goes awry because of mutations in genes for the inflammation-related proteins IL-6, IL-6 receptor, cytokine signal transducer, and C-reactive protein. Stress is involved because of a suspicion that the connection between stress, inflammation and hypertension is the kidneys’ ability to release sodium. When stress activates the sympathetic nervous system, the body increases production of IL-6, which ultimately leads to production of other inflammatory factors such as CRP. Stress also prompts the body to hold onto sodium to help temporarily raise blood pressure in order to deal with the situation.

Tags: inflammation, immune system, cancer, hypertension, obesity, C-reactive protein, cardiovascular disease, diabetes, insulin resistance

Finding protection from tumor growth in unexpected places

As just about anyone who takes even the simplest medications knows, almost everything has side-effects. Generally, there's no free lunch. The aspirin that reduces your fever and (maybe) makes your hangover a little less painful can also cause ulcers and stomach bleeding.

Among the many thousands of proteins, hormones, enzymes, and the like that are active naturally in your body at any one time, most presumably are there for a beneficial purpose. But not always. Some have a distinct Jekyll/Hyde quality about them.

Consider, in particular, the hormone known as angiotensin II. It is part of what is called the renin-angiotensin system, which helps regulate blood pressure. Overlooking a number of details, one of the key functions of angiotensin II is to quickly constrict blood vessels, to minimize blood loss in the event of serious injury. However, because it raises blood pressure, the body needs for it not to be around most of the time, to avoid dangerous hypertension.

The way the body handles this is by producing a slightly different hormone instead, angiotensin I, which can be quickly converted, when required, into angiotensin II by means of an enzyme called simply angiotensin-converting enzyme (ACE). It's ACE we're really here to talk about in this note, because it appears to have several other functions besides the one it's named for. Ironically, one of the strategies for treating hypertension is to inhibit ACE, because of the need to keep blood pressure under control. Yet some of its side effects, unrelated to blood pressure, seem beneficial.

Finding Protection From Tumor Growth In Unexpected Places

Researchers have discovered that an enzyme commonly involved in regulating blood pressure also provides protection from tumor growth when strongly expressed in immune cells.

ACE, in fact, is involved in a surprising number of other processes in addition to restraining tumor gowth via its immune system activity.

Angiotensin-converting enzyme (ACE) plays a direct role in controlling blood pressure and is a common therapeutic target in hypertension. However, it also plays roles in such diverse processes as fertility, immune cell development, and atherosclerosis, and a few studies have even suggested a role for ACE in generating an effective immune response.

The researchers used experimental mice (ACE 10/10 mice) that express ACE only in their macrophages. The findings were quite intriguing.

When injected with aggressive melanoma cells, normal mice developed large melanoma tumors whereas ACE 10/10 mice developed only very small tumors. The resistance of ACE 10/10 mice to melanoma growth was confirmed using several different melanoma cell lines and by using different strains of mice expressing high levels of ACE in macrophages. Interestingly, the small tumors of ACE 10/10 mice contained significantly higher numbers of white blood cells, suggesting a large anti-tumor immune response.

To confirm the existence of an ACE-specific anti-tumor immune response, normal mice were depleted of their bone marrow and transplanted with ACE 10/10 bone marrow. When the transplanted normal mice were then injected with melanoma cells, they too were able to control tumor growth. The immune response involved not just the ACE-expressing macrophages but also increased numbers of cytotoxic T cells and levels of immune-activating chemicals and decreased levels of immune-suppressing chemicals. Finally, the ACE 10/10 macrophages alone could direct the immune response and convey protection as direct injection of these cells into melanoma tumors of normal mice yielded decreased tumor size.

It will be very interesting to learn what further research reveals about how ACE enhances the immune system.

Tags: angiotensin-converting enzyme, cancer, immune system

How cells can cheat death

To begin with, we have to point out that for a cell to cheat death is usually not a good thing. The reason is that cell death is usually the result of a process called apoptosis, and this process has been carefully developed (by evolution) to dispose of cells that have become "sick" because of infection (by a virus) or damage that can occur to the cell's DNA in a variety of ways. Your body needs healthy cells to function, not sick ones. Especially it does not need cells with damaged DNA, which may well become cancerous.

Apoptosis is needed in other contexts as well. In a developing embryo apoptosis is needed to remove unnecessary tissue. In addition, failure of apoptosis can lead to autoimmune diseases as well as cancer. (This is why some anti-cancer drugs are also able to treat some autoimmune diseases.)

The following research announcement, which we'll look at in more detail, has a nice capsule summary of apoptosis.

Cells Re-energize To Come Back From The Brink Of Death

Apoptosis is triggered by a variety of factors, including gene mutations that can make the cell become cancerous. During apoptosis, the membrane covering the cell's mitochondria develop holes and leak a molecule called cytochrome c, which triggers the activity of enzymes called caspases. In turn, caspases trigger a series of events that kills the cell.

To amplify a little, here are some of the conditions that can initiate a cell's apoptosis program:

• P53 protein may detect damaged DNA during the G1 phase of the cell division cycle. If it does not prove possible to repair the damaged DNA, P53 can invoke apoptosis.
  
• The cytokine TNF (tumor necrosis factor) produced by the immune system (specifically, activated macrophages) is an external signal to initiate apoptosis. As the name implies, this is another anti-cancer mechanism.
  
• Signals produced by cytotoxic T cells of the immune system can also induce apoptosis. This may occur in response to a virus-infected cell. (Much more on T cells: here.)
  

However, there is a weak spot in the apoposis process: it requires the presence of caspase enzymes. If something has blocked production of essential caspases (which some tumors are able to do), then apoptosis won't work.

Because of this, nature (i. e. evolution) has provided a backup mechanism for programmed cell death, one that does not rely on caspases. The mechanism is called, appropriately, caspase-independent cell death (CICD), and the research announcement mentioned above has this to say about it:

The process by which the membranes develop holes--mitochondrial outer membrane permeability (MOMP)--is often the "point of no return" for self-destruction, said Douglas Green, Ph.D., chair of the St. Jude Immunology department and the study's senior author. MOMP triggers apoptosis, but if apoptosis fails because there is no caspase available, the backup program called caspase-independent cell death (CICD) takes over the process.

Previous research has shown that cells that become cancerous lack caspase and other proteins needed to support apoptosis after MOMP releases cytochrome c. But this victory over death is short-lived if CICD is activated.

Unfortunately, tumors (successful ones anyway) eventually develop the ability to cheat this death program as well:

However, some cancerous cells not only dodge death from apoptosis by eliminating caspase activation, but they also foil CIDC. "Our study sought to understand how a cancer cell without caspase activation bypasses CICD as well," Green said.

The St. Jude team discovered that a cell that lacks caspase activation and cannot undergo apoptosis increases the levels of an enzyme called GAPDH in order to counteract CICD. GAPDH appears to prevent CICD by supporting the functioning of the mitochondria and triggering the activity of certain genes that prevent or repair cell damage. The findings also suggest that the increase in GAPDH provides energy to increase autophagy--the process by which a cell "chews up" debris and broken components, such as damaged mitochondria. After disposing of damaged mitochondria the cell can replace these vital components.

"We found that in the absence of caspase activation, cells that avoided CICD took about a week or so to begin multiplying again," Green said. "This might represent the time it takes for the cell to restore enough mitochondria to allow the cell to function normally."

Cancer cells are (unfortunately) amazing in their resourcefulness. Of course, this results from a kind of evolutionary process, in which cancer cells that are successful at cheating death and reproducing are those which have developed, by chance, the necessary mutations.

The role played by mitochondria and caspases in apoptosis is quite important for an understanding of both cancer and autoimmune diseases. It's worth remembering the connection, since further research will certainly tell us a lot more about these interrelated processes. Here's an example of earlier research on the subject: Proteins are Key to Cell Death in Heart Disease, Stroke and Degenerative Conditions

Tags: apoptosis, caspase, mitochondria, cancer

Some causes of atherosclerosis

There is a certain sort of person who likes to find a single, simple cause behind diverse phenomena. For instance, regarding disease, such a person likes to view it as preponderantly the result of poor nutrition, pollution, pesticides, infections (bacterial, viral, or both), lack of antioxidants in the diet to quench "free radical cascades", negative thoughts, or whatever.

Sometimes, evidence even comes along that, surprisingly, fingers a favored disease mechanism that most observers had not suspected. For instance, stomach ulcers, long believed to be due to "stress" and "anxiety", have turned out actually to be caused by a bacterium, Helicobacter pylori.

Although such simplistic views of disease etiology tend to be wrong in general, new cases continue to turn up, as we learn more, where the simple theory does work. (Or, at least, it is a factor, since many if not most diseases can have multiple "causes".) Infection, by bacteria, viruses, or other parasites, is a frequent example.

Here are two recent instances, both involving atherosclerosis:

Cytomegalovirus exacerbates atherosclerosis through an autoimmune mechanism

A new study conducted by researchers from the University of Verona and the Institute G. Gaslini in Genova, Italy, confirms the pivotal role played by Cytomegalovirus infection in the pathogenesis of atherosclerosis.

Atherosclerosis is the main cause of morbidity and mortality worldwide. Classic risk factors including smoking, diabetes, hypertension and high cholesterol levels are known to play a pivotal role in the pathogenesis of the disease that also recognises a genetic influence. However, it is well known that acute cardiovascular events may happen without the presence of the mentioned common risk factors. Recently inflammation and infectious agents have been shown to play an important role in the onset of acute cardiovascular events.

Bacterial Infection May Contribute To Cardiovascular Disease

A new dissertation shows that Chlamydia pneumoniae can contribute to cardiovascular disease. Half of the population of Swedish twenty-year-olds are carriers of the bacterium Chlamydia pneumoniae, an ubiquitous pathogen previously known to cause acute respiratory disease. It now appears that this bacterium also contributes to cardiovascular disease, the single greatest killer disease in the western world.

In a new thesis in the field of pharmacology, Hanna Kälvegren demonstrates that the respiratory bacterium Chlamydia pneumoniae stimulates the process that leads to hardening of the arteries. This in turn causes heart attacks and stroke, by increasing the risk of thrombus, or blood clots.

Tags: heart disease, atherosclerosis

Addiction to tanning?

Summer is coming in the northern hemisphere, which means, perhaps, more time in the sun. We had a look here at the surprising role that the anti-cancer protein p53 plays in tanning. Beyond that, we know that getting a tan feels good, if not overdone (so to speak).

(And by the way, studies like this one have shown that vitamin D, which is a byproduct of tanning, has beneficial anti-cancer effects for breast and colorectal cancer, in spite of the risk of melanoma from too much UV exposure. Other studies show protective effects of vitamin D for ovarian cancer, pancreatic cancer, and prostate cancer too.)

Anyhow, it seems that some people can't get enough sun tanning, in spite of the risks. Perhaps it's addictive:

New Study Indicates Tanning May Be Addictive

Despite repeated health warnings about the dangers of tanning from sunlight and artificial light sources, there are still those whose mantra “bronzed is beautiful” remains unshaken. Dermatologists have long suspected that some people may be addicted to tanning – similar to addictions to drugs or alcohol – and refuse to alter their behaviors, even knowing they have an increased risk of developing skin cancer. Now, a new study of college co-eds indicates that some people may be addicted to ultraviolet (UV) light.

Why would this be? Most likely for the same reason that the process of getting a tan feels good. Dermatologist Robert Hornung, who led a questionnaire study to investigate the motivations of dedicated tanners, explains:

“We also know from previous experiments that UV light causes endorphin release, similar to the euphoric sensation associated with intense exercise commonly referred to as ‘runner’s high’ or other pleasure-seeking behavior. Our study set out to find whether certain individuals, particularly those who classify themselves as frequent tanners, exhibit addictive behaviors toward tanning.”

However, it's not clear from what's reported here whether frequent tanners have an actual chemical dependency to their own endorphins. For instance, do they have withdrawal symptoms if they stop tanning abruptly? Are there other signs of a biochemical effect?

Perhaps its time to head to Maui to do a little more research... Or perhaps the nearest nudist resort would be a good choice for some field work. I'd volunteer. Wonder where to apply for a grant...

Tags: sun tanning, endorphins, cancer, vitamin D

Top 10 Health Stories of 2006

Having recently posted a note on physics stories of 2006, I guess I should do health/medicine news next. So there's this: The Top 10 Health Stories of 2006.

I won't quibble with inclusion of any of the choices, but I do have comments on some of them (numbers keyed to items in the article):

• 1. HPV vaccine – This isn't exactly a vaccine "against cancer". Cancer vaccines are under active development, but they're a different animal. This is a vaccine against human papillomavirus (HPV), which is responsible for about 70% of cervical cancers. I've written about it here.
  
  
• 4. Treatment for macular degeneration – Since macular degeneration is caused by misplaced and uncontrolled growth of blood vessels in the eye, any drug that can inhibit angiogeneisis may be a potential treatment for the problem. It just so happens that anti-angiogenesis drugs are also possible treatments for solid cancers, since the drugs can inhibit blood supply to a tumor. Such a drug, with the trade name Avastin, was approved by the FDA in 2004. Avastin is a monoclonal antibody developed by Genentech, and may become a blockbuster drug for many types of cancer.
  
  Not coincidentally, the new macular degeneration drug, Lucentis, that the FDA approved this year is also from Genentech. It consists, essentially, of a portion of the Avastin antibody. Avastin has actually been used off-label to treat macular degeneration, and there is some controversy about the fact that Genentech hasn't run clinical trials of such use, even though Avastin is sold for a considerably cheaper price than Lucentis.
  
  Both Avastin and Lucentis target a protein called vascular entothelial growth factor (VEGF). A number of other drug companies are working on anti-angiogenic drugs that target VEGF. Some of them may be much more powerful than Avastin and Lucentis, such as one called a VEGF trap, from Regeneron Pharmaceuticals. (More information about that.)
  
  
• 6. Vaccines – Vaccines are of two kinds: preventive and therapeutic. Both types work by conditioning the immune system. The former, more familiar, type wards off infectious diseases by stimulating the immune system to attack the agent of infection (usually a virus). Therapeutic vaccines are designed to mobilize the immune system in order to treat an existing disease condition. Of course, vaccines of both types are aggressively being sought to combat AIDS and cancer. But there's also a lot of research and development going into vaccines for conditions you might not expect, such as nicotine addiction and alcoholism. See this news article for an example dealing with nicotine.
  
  
• 10. Vitamin D – The article mentions reports of beneficial effects of vitamin D for cancers of the breast and pancreas. This has been suspected for some time, as this story from 2004 indicates. Other studies have shown beneficial effects in prostate cancer (see here, here, here), ovarian cancer (see here, here), and colon cancer (see here, here).
  

There's one thing I think that the article misses. Even though it discusses cancer in relation to HPV and vitamin D, there has actually been an absolute flood of new research results on cancers of all types. Much of the research has dealt with the basic biology of cancer, such as the roles played by many different genes, the process of metastasis, and the involvment of stem cells in the onset of cancer. Although such research hasn't yet led to clinical trials of new drugs and therapies, I see this as a very important sign for the future. I'll try to write about "top stories of 2006 in cancer biology" some time after the new year.

Also related to cancer, there have been some new drugs approved for bone/blood cancer-like diseases such as multiple myeloma and myelodysplasia (e. g. Revlimid).

There has also been a lot of progress in understanding the biology of Alzheimer's disease. Not enough, yet, to fully understand the disease mechanism, but quite a lot is being learned. There may be some breakthroughs here before too long.

Tags: health, medicine

HPV vaccine revisited

We wrote about it here: Human papilloma virus vaccine.

You know, the good news on October 6 about how one of several HPV vaccines now under development proved 100% effective at preventing cervical cancer and precancerous lesions. We also referenced a report from last April that some fundie Christians like the Family Research Council were gearing up to oppose use of this vaccine, because, just like the original birth control pill over 40 years ago, anything that can reduce the risks of having sex is bound to play havoc with the fundies' abstinence agenda.

Well very soon after our last report, this controversy was back in the news, with a vengeance.

First we have a straight, factual story about what this vaccine means to both women and men:

Cervical cancer vaccine (October 20, 2005)

Genital warts are caused by a virus called Human Papilloma Virus, or HPV. HPV is passed from person to person through sex and comes in many different forms, some of which cause genital warts, some of which have no noticeable symptoms at all. Almost 80 per cent of the adult population – whether they notice it or not – will at some point in their lives be infected with this virus.

Well, so what? Here's what:

But then in the 80’s a German scientist discovered that this common and seemingly insignificant virus causes cervical cancer.

Worldwide, cervical cancer is the second most common cancer in women, behind breast cancer. It’s most common in 30 to 50 year old women and nearly half a million women worldwide developed cervical cancer in 2002. Each year in Australia, about 740 new cases of cervical cancer are diagnosed and around 270 women die from it.

Now we know that not only does HPV cause cervical cancer, it’s the sole cause. In a study published in 1999, researchers found traces of HPV DNA in 99.7 per cent of the cervical cancer cases they looked at.

That was the bad news. But here's the good news:

Some time in 2006 we should see a new vaccine enter the market. Recent trials have shown that this vaccine, designed to protect against the two main cancer-causing forms of HPV (HPV-16 and HPV-18), prevents persistent infection by the virus in 100 per cent of the vaccinated women, and reduces cervical abnormalities by 90 per cent.

The promise of this vaccine will be to demote cervical cancer from a major to a very minor cancer. Researchers hope that it will reduce rates of cervical cancer in women across the world by 70 per cent and save around 200,000 lives every year.

Wonderful, no? Something that could, every year, save the lives of 200,000 young people who would, except for cervical cancer caused by HPV, mostly be healthy adults. Of course, there are a few legitimate questions:

Cervical cancer vaccine raises questions (October 26, 2005)

Some people are also concerned about whether existing cervical cancer screening programs will suffer, if vaccinating against some HPV strains will lead to other strains "taking over" and how to convince parents that vaccinating their children against sexually transmitted infections (STIs) is a good idea.

Fair enough. That's a legitimate scientific concern. But remember the Christian fundies, who were already on this case, as mentioned earlier? Well guess what, they're still on the case:

Cervical Cancer Vaccine Gets Injected With a Social Issue (October 31, 2005)

A new vaccine that protects against cervical cancer has set up a clash between health advocates who want to use the shots aggressively to prevent thousands of malignancies and social conservatives who say immunizing teenagers could encourage sexual activity.

And not only that, but the Bush administration has slotted the fundies into positions of governmental power:

The jockeying reflects the growing influence that social conservatives, who had long felt overlooked by Washington, have gained on a broad spectrum of policy issues under the Bush administration. In this case, a former member of the conservative group Focus on the Family serves on the federal panel that is playing a pivotal role in deciding how the vaccine is used.

"What the Bush administration has done has taken this coterie of people and put them into very influential positions in Washington," said James A. Morone Jr., a professor of political science at Brown University. "And it's having an effect in debates like this."

Some reader reaction to this article makes additional good points:

Moral Choices in a Cancer Vaccine (November 3, 2005)

The concerns about vaccination voiced by the Christian Medical and Dental Associations and the Family Research Council reveal a "better dead than red" mentality by which these organizations place their "values" above the lives of millions of women.

To put it even more bluntly, these conservative organizations prefer that women should die, rather than have the opportunity of safer sex. So much for their propaganda about a "culture of life". Another commentator, Cenk Uygur, says it well:

Why the Christian Right Doesn't Want to Fight Cervical Cancer (November 5, 2005)

But this isn’t just about controlling our sex lives anymore. This is a matter of life and death. Now they’ve gone way past acceptable. Letting over 3,000 women die of cervical cancer each year because you think it might lead to promiscuity and pre-marital sex? This is the point where your religious fanaticism ceases to be anachronistically amusing and becomes downright dangerous.

Stay tuned. There's more to this story. Much more.

--------------------------------------

Tags: human papilloma virus

Human papilloma virus vaccine

First large test shows vaccine prevents cervical cancer

THE ASSOCIATED PRESS

October 6, 2005, 11:26 AM EDT

TRENTON, N.J. -- The first large study of an experimental cervical cancer vaccine found it was 100 percent effective, in the short term, at blocking the most common cause of the disease, the vaccine's maker said Thursday.

Merck's genetically engineered vaccine prevents cervical cancer by blocking infection from the human papilloma virus strains that cause 70 percent of cervical cancers.

Other types of HPV, which is sexually transmitted, also can cause cervical cancer and painful genital warts. About 20 million Americans have some form of HPV.

The final-stage study of the vaccine included 10,559 sexually active women ages 16 to 26 in the United States and 12 other countries who were not infected with the HPV strains 16 or 18. Half got three vaccine doses over six months; half got dummy shots.

Among those still virus-free after the six months, none who received the vaccine developed either cervical cancer or precancerous lesions likely to turn cancerous over an average two years of follow-up, compared with 21 who got dummy shots.

"To have 100 percent efficacy is something that you have very rarely," Dr. Eliav Barr, Merck's head of clinical development for the vaccine called Gardasil, told The Associated Press. "We're breaking out the champagne."

Other articles about this: here, here , here, here.

Sounds like good news, right? Well, consider this earlier story from April:


Will cancer vaccine get to all women?

The trouble is that the human papilloma virus (HPV) is sexually transmitted. So to prevent infection, girls will have to be vaccinated before they become sexually active, which could be a problem in many countries.

In the US, for instance, religious groups are gearing up to oppose vaccination, despite a survey showing 80 per cent of parents favour vaccinating their daughters. "Abstinence is the best way to prevent HPV," says Bridget Maher of the Family Research Council, a leading Christian lobby group that has made much of the fact that, because it can spread by skin contact, condoms are not as effective against HPV as they are against other viruses such as HIV.

And attitudes may be even worse in other cultures:

"We found that some Asian women in Britain are afraid even to get tested for HPV infection, because they say if it is positive they will be killed, never mind that their husbands probably gave it to them," says Szarewski. She feels that such attitudes may mean that HPV vaccination may be a non-starter in such communities.

What a shame that religious and cultural prejudices contribute to millions of avoidable deaths. This is consistent with a "culture of life"?

Tags: human papilloma virus

Avian flu

Flu Wiki

I don't have anything to add to this topic at the moment -- there's an awful lot of information out there already, and the Flu Wiki is a good place to start. Just feeling sort of guilty about not mentioning it. It's a very important topic.

As my absolutely minimal contribution, here's a link to a good summary of the topic, with many other links, that covers both policy and science aspects: Bird Flu - What's A Reasoned Approach? Part II.