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(Anatomy) (Health) Hands and Feet: Cholesterol and Digits

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PostPosted: Sat Apr 22, 2006 6:41 am    Post subject: (Anatomy) (Health) Hands and Feet: Cholesterol and Digits Reply with quote

Cholesterol gets ‘thumbs up’ for role in digit development

April 21, 2006
by Melissa Marino
The Reporter, Vanderbilt Medical Center

When a new mother counts her newborn's fingers and toes, she probably doesn't realize that cholesterol may be to thank for baby's complete set of 20 digits.

Although cholesterol has a bad rap as the sticky, fatty substance responsible for clogging arteries, Vanderbilt University Medical Center researchers recently found that the attachment of cholesterol to an important developmental protein controls the development of fingers and toes in mice. Without cholesterol, mice developed extra digits, as well as digits in the wrong places.

The new study published online in the Proceedings of the National Academy of Sciences (PNAS) last week helps to clear up some of the conflicting data about cholesterol's controversial role in limb development, said senior author on the study, Chin Chiang, Ph.D., associate professor of Cell and Developmental Biology.

The developmental protein at work here, named Sonic hedgehog after the video game character, was discovered in the early 1990s and shown to have important roles in patterning the developing embryo, including proper digit patterning.

Chiang led the early studies showing that mice without Sonic hedgehog developed only a single digit — a thumb on the front paw (or a “big toe” on the back paw).

The Sonic hedgehog protein is produced by a specialized group of cells located at the posterior part of the developing limb bud, which eventually develops into the pinkie finger or toe. At the site of its synthesis, Sonic hedgehog concentrations are high. It then diffuses out across the developing limb bud, and the declining concentrations (or gradient) of the protein dictate the identity of the other digits.

“Questions have remained about what regulates the Sonic hedgehog gradient,” said Chiang. “And we've been working on that for a number of years.”

One clue about this regulation came when other researchers discovered Sonic hedgehog's rather unusual requirement — the protein had to have a cholesterol molecule attached to work properly.

“In fact, Sonic hedgehog is the only protein known to be modified by cholesterol,” Chiang said.

Because cholesterol is typically found in cell membranes and thought to 'tether' proteins to cells, scientists speculated that cholesterol might inhibit the movement of Sonic hedgehog through the developing tissue. This unique modification might explain why concentrations of the protein were high at the site of its production and then tapered off with increasing distance from the synthesis site.

But previous studies in mice suggested that cholesterol promoted the movement of Sonic hedgehog, a counterintuitive proposal given cholesterol's supposed tethering ability.

To try and clear up cholesterol's role in digit patterning and the Sonic hedgehog gradient, Chiang and colleagues created mice with an altered form of the Sonic hedgehog protein to which cholesterol cannot attach.

They found that mice lacking cholesterol-modified Sonic hedgehog developed with malformed and ectopic, or out of place, digits. The second, or “index,” digits were stunted and misshapen, appearing more similar to a thumb than a normal second digit.

The researchers also examined mice in which only half of their Sonic hedgehog proteins could attach to cholesterol. Those mice developed normal digits 2 through 5 (index through pinkie), but had duplication of these digits anteriorly.

The findings suggested that Sonic hedgehog without cholesterol traveled further than normal, triggering the anomalous digit duplications.

Chiang and colleagues confirmed this microscopically, showing that the protein spread out more evenly across the limb bud (a weaker gradient) in mice lacking cholesterol-modified Sonic hedgehog compared to normal animals.

“We found that, without cholesterol, Sonic hedgehog moves more readily, far from its site of synthesis, all the way to the anterior part of the limb bud where it is normally never detected,” Chiang explained.

When Sonic hedgehog travels to tissue where it normally would be absent (as it does when cholesterol is missing), extra digits may form — a condition known as polydactyly.

Although the causes of polydactyly in humans are not fully understood, mutations in some part of the Sonic hedgehog signaling pathway are high on the list of suspects.

In addition to limb deformities, errors in Sonic hedgehog signaling are involved in a number of other human conditions including cancer and a condition known as holoprosencephaly, a congenital malformation of the forebrain.

Chiang is currently examining the role of cholesterol-modified Sonic hedgehog in the developing brain and spinal cord.

“We are finding some surprises,” Chiang said, “suggesting that the function of cholesterol is different in these different tissues.”

The continued study of the wide-ranging actions of Sonic hedgehog promises to expose the incredible secrets of the developing embryo and could provide clues for preventing devastating birth defects.

Yina Li, Huimin Zhang and Ying Litingtung, Ph.D., were co-authors on the paper. The research was supported by grants from the National Institutes of Health and the March of Dimes Foundation.


Questions to explore further this topic:

Why do we have two hands, two feet. two eyes?

What are fingers?

What is polydactylism?

Exercises for your fingers

Fingers and the sense of touch

Fingers, toes and mathematics

Anatomy of the hand


"I dreamt I had a lot of toes"

Anatomy of the foot

What is cholesterol?

Cholesterol: animated lessons

Cholesterol and kids

What is a cholesterol test?

Cholesterol and arteries

Cholesterol levels

What is high blood cholesterol?

What is a low cholesterol diet?

What is the sonic hedhehog protein?

Cholesterol and hedgehog proteins


Last edited by adedios on Sat Jan 27, 2007 4:32 pm; edited 2 times in total
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PostPosted: Wed Sep 27, 2006 10:05 pm    Post subject: Finger length ratio may predict women's sporting prowess Reply with quote

BMJ Specialty Journals
27 September 2006

Finger length ratio may predict women's sporting prowess

The Big Finger: The second to fourth digit ratio is a predictor of sporting ability in women
The difference between the lengths of a woman's index and ring fingers may indicate her sporting prowess, suggests research published ahead of print in the British Journal of Sports Medicine.

The finding supports other research indicating a possible link between this ratio and fertility, vulnerability to serious disease, intellectual ability, certain personality traits, and musical talent.

Most of the sporting research in this area has so far focused exclusively on men.

The researchers base their findings on x ray pictures of the right and left hands of 607 female twins, whose average age was 53. Most were right handed.

The second to fourth finger ratio was calculated by dividing the length of the index (second) finger by that of the (fourth) ring finger.

Study participants were also asked to rank their highest achievement in a wide range of individual and team sports, since the age of 11.

Participation levels were highest for swimming, cycling, tennis and running in descending order.

The association with finger ratio was highest for running, soccer, and tennis. The highest achievement in any sport was strongly linked to a low second to fourth finger ratio. Running ability was particularly associated with a low (male pattern) ratio.

It has been suggested that this finger ratio is established while in the womb, and that it is subject to the amount of exposure to sex hormones, say the authors. But the same group found that genetic factors, rather than womb environment, influenced finger ratio in a recent twin analysis.

The ratio tends to remain the same throughout life, the authors add, with men tending to have a lower ratio.
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PostPosted: Thu Oct 26, 2006 7:05 am    Post subject: Discovery of a molecular mechanism underlying limb architect Reply with quote

Institut de recherches cliniques de Montreal

Discovery of a molecular mechanism underlying limb architecture

Montreal, October 24, 2006 – A genetic study performed by Dr. Marie Kmita, a researcher at the Institut de Recherches Cliniques de Montréal (IRCM), in collaboration with Drs Basile Tarchini and Denis Duboule of the University of Geneva in Switzerland, sheds light on the origins of the architecture of arms and legs. The results of their research, to be published in the October 26 issue of the prestigious journal Nature, describe how the operational mode of several "architect" genes has been recycled in the course of evolution to enable limb formation.

The establishment of the body architecture is genetically controlled and involves a family of "architect" genes called the Hox genes which has been conserved throughout evolution. The ancestral function of the Hox genes is to set up "foundations" of the body by defining positional information that instruct cells about their fate. This is how the body is shaped and how organs and skeletal elements are positioned. In the course of evolution, some of these genes have been reused to control limb development. Indeed, previous research by Dr. Kmita showed that without these genes, limbs would not form.

The particular feature of Hox genes is that they are aligned along the DNA molecule in the same order as the structures they will form. The sequential activation of these genes is therefore responsible for the defined distribution of organs and various parts of the skeleton along the anterior-posterior axis (from the head to the feet). The study, carried out by Dr. Kmita and her colleagues, shows that the ancestral strategy underlying Hox genes' activation was recycled during the emergence of vertebrate limbs to set up the architecture of arms and legs. In embryonic limb buds, the Hox genes are sequentially activated so that their domains of activity overlap along the anterior-posterior axis (from the thumb to the little finger), with a maximum activity in the posterior domain. It is precisely this peak of activity that triggers the activation of a "polarizing" gene called Sonic Hedgehog, specifically in the posterior region of the developing limb, thereby generating the asymmetry of our limbs (for example, the fact that our fingers are different from each other).

This discovery explains how limb asymmetry is genetically set up. This is an important finding as limb asymmetry is required for the broad range of motion of our hands, which make them man's primary tool.

References for the article will be available on the Nature Web site.

Dr. Marie Kmita is currently Director of the 'Genetics and Development' research unit at the Institut de recherches cliniques de Montréal (IRCM). She also holds the Canada Research Chair in Genetics and Molecular Embryology.

This work was supported by funding from the Louis-Jeantet Foundation, the canton of Geneva, the Swiss National Research Fund, the National Center for Competence in Research (NCCR) 'Frontiers in Genetics,' and the EU program 'Cells into Organs'.

The IRCM ( is recognized as one of Canada's top-performing research centres. Its mission is to bring the benefits of research to the patient, promote disease prevention, and train the next generation of front-rank scientists. The IRCM, which is affiliated with the Université de Montréal, currently houses 37 research units and employs nearly 450 people.
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PostPosted: Sun Jan 21, 2007 9:18 am    Post subject: Carbohydrate intake and HDL in a multiethnic population Reply with quote


Carbohydrate intake and HDL in a multiethnic population
Anwar T Merchant, Sonia S Anand, Linda E Kelemen, Vlad Vuksan, Ruby Jacobs, Bonnie Davis, Koon Teo, Salim Yusuf for the SHARE and SHARE-AP Investigators

From the Population Health Research Institute, Hamilton, Canada (ATM, SSA, RJ, BD, KT, and SY); McMaster University, Hamilton, Canada (ATM, SSA, RJ, BD, KT, and SY); Hamilton Health Sciences, Hamilton, Canada (SSA, KT, and SY); Mayo Clinic College of Medicine, Rochester, MN (LEK); and University of Toronto, Toronto, Canada (VV); for the SHARE and SHARE-AP Investigators

Background:Ethnic differences in serum lipids are not explained by genetics, central adiposity, lifestyle, or diet, possibly because dietary carbohydrate has not been considered.

Objective:The aim was to evaluate the relation between carbohydrate intake and HDL and triacylglycerol concentrations in a multiethnic population.

Design:We conducted a population-based cross-sectional study of 619 Canadians of Aboriginal, South Asian, Chinese, and European origin with no previously diagnosed medical conditions. Energy-adjusted carbohydrate intake was measured by a validated food-frequency questionnaire.

Results:South Asians consumed the most carbohydrate, followed by European, Aboriginal, and Chinese persons. Mean (95% CI) HDL concentrations in the lowest and highest categories of carbohydrate intake after adjustment for age, sex, ethnicity, physical activity, smoking, the waist-to-hip ratio, body mass index, alcohol intake, and intakes of total energy, protein, and fiber were 1.21 mmol/L (1.16, 1.27 mmol/L) and 1.08 mmol/L (1.02, 1.13 mmol/L), respectively, and HDL cholesterol was significantly (P < 0.01) higher in the lowest tertile of carbohydrate intake than in the highest tertile. High carbohydrate intake was associated with higher fasting triacylglycerols (P = 0.04); the adjusted mean fasting triacylglycerol concentrations in the lowest and highest categories of carbohydrate intake were 1.43 mmol/L (1.28, 1.60 mmol/L) and 1.71 mmol/L (1.57, 1.87 mmol/L), respectively. Fewer servings of sugar-containing soft drinks, juices, and snacks were associated with higher HDL (P for trend = 0.02); the multivariate-adjusted mean HDL in the lowest and highest categories of carbohydrate intake was 1.22 mmol/L (1.17, 1.27 mmol/L) and 1.11 mmol/L (1.06, 1.26 mmol/L), respectively.

Conclusions:Differences in HDL and triacylglycerols observed in different ethnic groups may be due in part to carbohydrate intake. Reducing the frequency of intake of sugar-containing soft drinks, juices, and snacks may be beneficial.

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PostPosted: Mon Feb 19, 2007 9:40 am    Post subject: Scientists Regrow Human Fingers Reply with quote

Scientists Regrow Human Fingers

By Malcom Ritter
Associated Press
posted: 18 February 2007
08:12 pm ET

NEW YORK (AP)—Researchers are trying to find ways to regrow fingers—and someday, even limbs—with tricks that sound like magic spells from a Harry Potter novel.
There's the guy who sliced off a fingertip but grew it back, after he treated the wound with an extract of pig bladder. And the scientists who grow extra arms on salamanders. And the laboratory mice with the eerie ability to heal themselves.

This summer, scientists are planning to see whether the powdered pig extract can help injured soldiers regrow parts of their fingers. And a large federally funded project is trying to unlock the secrets of how some animals regrow body parts so well, with hopes of applying the the lessons to humans.

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PostPosted: Mon Apr 23, 2007 9:59 am    Post subject: Are higher doses of cholesterol drugs worth the extra money? Reply with quote

University of Michigan Health System
23 April 2007

Are higher doses of cholesterol drugs worth the extra money? Only sometimes, study says

Method used in study could help evaluate cost-effectiveness of other drugs, too
ANN ARBOR, Mich. -- When it comes to cholesterol-lowering drugs, more is better. At least, that’s what heart doctors and heart patients have been hearing in recent years. And as a result, more patients are taking higher doses of drugs called statins – leading to lower heart and stroke risk, but higher prescription drug costs and more frequent side effects.

Now, a new study looks at whether those higher doses, and higher costs, are really going to pay off for some patients. For those with a recent heart attack or what doctors call ‘acute coronary syndrome’, the answer is yes, the researchers say.

But the picture is less clear for those patients with known heart blockages who have stable symptoms. For them, the usual dose of their statin may provide adequate heart-protecting benefit, and the higher cost of high-dose statins may provide only marginal benefit at much greater cost, especially if they use generic statins.

The study, from a team at the University of Michigan Cardiovascular Center and the VA Ann Arbor Healthcare System, is published online in the journal Circulation, and will be in the May 8 print issue of the journal. It’s based on a sophisticated computer analysis of data from thousands of patients.

The team finds that patients with a recent history of acute coronary syndrome (ACS) – either a heart attack or hospital stay for chest pain – get so much benefit from higher doses of statins (over four additional quality-adjusted months of life) that the extra cost of the increased dose is worthwhile, even if the difference is a few dollars a day.

But for patients with stable coronary artery disease (CAD), whose arteries have been narrowed by plaque but who haven’t had a recent heart attack or hospitalization for chest pain, the much smaller gain (about 5 weeks of quality-adjusted life) from a higher dose of a statin may not be sufficient to outweigh the extra cost.

The researchers also point out that the type of analysis they performed for this study could be used to assess the cost-effectiveness of other medications and treatments. It could be especially useful when doctors, patients and insurers need to choose between two options that have different costs and benefits to particular patients.

"Clinical trials have effectively demonstrated that high-dose statins reduce cardiovascular endpoints in patients with established coronary artery disease. However, we found that whereas high-dose statin therapy reduced mortality in patients with acute coronary syndromes, patients with stable coronary artery disease had no mortality benefit from high-dose statins, but only reductions in stroke and repeat heart attack risk," says Paul Chan, M.D., M.Sc., the study’s lead author and a fellow in cardiovascular medicine at the U-M Medical School.

"Our study illustrates that simply having a ‘positive’ clinical trial may not be as informative as reporting what the actual gains in life expectancy and quality of life are with positive trials, and we propose using decision analysis as a way to appreciate the impact of trials that use multiple end points that are dissimilar (e.g., death and rehospitalization)," says Chan, who is also a member of the VA Health Services Research and Development Center of Excellence at VA Ann Arbor.

The authors point out that one reason for the rapid rise in health care spending is the overuse of new drugs and technologies. "Many times, clinical trials report a small but statistically significant benefit in an outcome, and this leads to widespread adoption of a treatment, even though the long-term benefits of using that treatment are small. Our methods of analyzing these results begin to address the question of where we really get value from medical care," says Sandeep Vijan, the senior author and an associate professor of general internal medicine at U-M.

He adds, "In this study, we found that intensive treatment with statins, a treatment with ‘proven’ effectiveness, has very different effects depending on who you are. If you are a very high-risk patient who was just in the hospital for a heart attack, you get lots of benefit from high doses of statins, and treatment is therefore cost-effective."

But if you are a patient who has more stable heart disease, the benefit is much lower – only about one-quarter of that seen in the high-risk group – and the treatment is probably not cost-effective most of the time. "This is further compounded by the fact that the higher-dose treatments are less well-tolerated, and my clinical experience is that once patients decide the drugs are hard to tolerate, they often won’t even take the lower dose drugs, which are enormously beneficial," Vijan adds.

The team based its analysis on data from four very large clinical trials – those whose results led to recommendations of higher doses of statins for ACS and CAD patients. They combined those data with data on cost and a range of estimates about how long the drug’ beneficial effect would last.

In general, statin drugs lower the levels of cholesterol in the blood, which is thought to slow the formation of plaque along artery walls. But they also appear to play a role in reducing inflammation, which is also a major factor in heart disease. Studies that have compared high and standard doses of statins have shown significant differences in the risk of negative events among the patients taking the higher doses. And that has helped lead to the current recommendations by the federal National Cholesterol Education Program and others, which call for aggressive statin treatment.

But, the team says, the results from these studies are often expressed in terms of "composite end points" – for instance, the risk of death, heart attack and stroke put together, rather than the risk of each. That practice yields the most dramatic differences between high-dose and standard-dose statin treatment, but it masks the fact that there may not have been significant differences between the two groups in some of those individual events (death, heart attack or stroke). It also assumes that each of these events is viewed equally by doctors and patients, which is clearly not the case.

So, for the new study, the team pooled the clinical trial data from all patients with a history of ACS, and in a separate pool, all patients with CAD. They looked at all the differences between the high-dose and standard-dose patients in those pools, including their risk of cardiovascular events during the study period. They then used this information to create a computer model of hypothetical 60-year-olds taking different doses of statins, and calculated what reduction in risk might be related to those doses, any how many "quality adjusted life years" they might gain from that reduction in risk.

The researchers then calculated how much each of those life years would cost, given different costs of statins and differences in cost between the two possible doses of statins. Cost-effectiveness is based on how many dollars each quality-adjusted life year costs. In the end, high-dose statins were cost effective for ACS patients, but they would be cost-effective for stable CAD patients only if the difference in cost between standard and high doses was small to moderate.

That’s an important point for insurers and patients, especially given that some popular statins have already become available in generic form or will soon do so, says Chan.

"As the generic statins continue to drop in price with the entry of even more generic manufacturers in the upcoming months, high-dose statin therapy may not remain cost-effective in patients with stable coronary artery disease," he explains. For example, if the daily cost difference between a high and conventional statin dose exceeds $1.40 (or $500 per year), high-dose statin therapy may no longer be considered cost-effective in stable patients. "In contrast, because of the greater life gains in patients with acute coronary syndromes, high-dose statin therapy would remain cost-effective compared with conventional-dose statin therapy even when the cost difference was $3.50 a day or $1,280 per year," he says.

This kind of analysis may be important as more new treatments come on the market and others become available in less-expensive generic form, the authors say.

In addition to Chan and Vijan, the study’s authors are Brahmajee Nallamothu, M.D., MPH, and Hitinder Gurm, M.D., both assistant professors of cardiovascular medicine; and Rodney Hayward, M.D., professor of general internal medicine and director of the VA HSR&D center. The study was supported by the National Institutes of Health.
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PostPosted: Wed May 23, 2007 7:45 am    Post subject: Finger Length Predicts SAT Performance Reply with quote

Finger Length Predicts SAT Performance
By LiveScience Staff

posted: 22 May 2007 07:00 pm ET

A quick look at the lengths of children's index and ring fingers can be used to predict how well students will perform on SATs, new research claims.

Kids with longer ring fingers compared to index fingers are likely to have higher math scores than literacy or verbal scores on the college entrance exam, while children with the reverse finger-length ratio are likely to have higher reading and writing, or verbal, scores versus math scores.

Scientists have known that different levels of the hormones testosterone and estrogen in the womb account for the different finger lengths, which are a reflection of areas of the brain that are more highly developed than others, said psychologist Mark Brosnan of the University of Bath, who led the study.

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PostPosted: Sun Jul 29, 2007 3:20 pm    Post subject: Cursing The First Bipedal Apes Reply with quote

Cursing The First Bipedal Apes
By Meredith F. Small, LiveScience's Human Nature Columnist

posted: 27 July 2007 11:35 am ET

There are 26 bones in the human foot. These bones are connected to each other by ligaments, attached to muscles by tendons and interact at 33 joints.

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