Muscle cells self-destruct rather than grow with use

Muscle cells that should grow stronger with use instead self-destruct when a protein called BAG3 isn't around, researchers have shown.

Mice missing BAG3 seem fine at birth, but when they start using their muscles to breathe and stand, muscle cells rapidly degenerate and cannot regenerate, says Dr. Shinichi Takayama, cell and molecular biologist at the Medical College of Georgia.

The finding illustrates BAG3's importance in maintaining mature skeletal muscle, researchers say in the September issue of the American Journal of Pathology.

They hope it will lead to prevention of muscle atrophy that

characterizes diseases such as muscular dystrophy, heart failure and a

lesser-known condition called myofibril myopathy, which affects the tiniest muscle fibers. Dr. Takayama believes his BAG3 knockout is a model for the worst case of this rare disease.

"Basically we think that the degeneration starts because of usage of muscles, which should make them stronger," Dr. Takayama says.

Instead, cells previously dormant in utero start dying. "They cannot breathe, they cannot use their muscles and they die quickly," he says of BAG3 knockout mice.

"When a muscle contraction happens, cytoskeletal degeneration occurs naturally," he says. Interestingly, degeneration normally stimulates regeneration, but not in these mice. Instead cells take another option: when they can't be fixed, they kill themselves.

This mass suicide in the absence of BAG3 is not a huge surprise.

Dr. Takayama, the first to clone five members of the BAG family, says the proteins help regulate heat shock protein 70, which helps other proteins fold and function properly. The BAG family also has an anti-death function called antiapoptosis. Dr. Takayama is still dissecting the relationship between the anti-death function and BAG's regulatory role with the heat shock protein. "If protein folding is not happening to a cell, that cell should die, so I think the two functions are related," he says.

Without BAG3, researchers believe something goes wrong in the supporting structure of Z-discs, which help muscles contract. "The structure is tightly regulated by cytoskeletal proteins and something is wrong in the cytoskeleton of these mice," he says. They found evidence of changes in the Z-discs that predate cell death, leading them to postulate that BAG3 is required for maintaining the integrity of Z-discs and other supporting components of the muscle cytoskeleton that helps strengthen and organize cells. "The muscle, in structure, seems normal at birth," Dr. Takayama says. "But after four days, their Z-disc structure is disrupted." Myofibrils, thin, cylindrical filaments that run the length of muscle cells, then begin to degenerate.

He first cloned BAG1 as an antiapoptotic protein more than 10 years ago while looking for a way to kill cancer cells. "BAG is one of the things that helps cancer cells survive," says Dr. Takayama. In fact, BAG3 is highly expressed in cancer cells.

Last year, his group's work published in Nature Neuroscience showed a BAG1 knockout experiences massive brain cell death as an embryo. He's working on a mouse that over expresses BAG in muscle only, saying that should prevent cell death and atrophy.

The research was funded by the National Institutes of Health and the Muscular Dystrophy Association.

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Uninsured Numbers Keep Climbing

BETHESDA, MD, 22 September 2006 — The number of Americans without health insurance climbed to a record high in 2005, with 46.6 million people, or 15.9% of the population, saying they lacked coverage for medical care, according to the Census Bureau's annual update of income, poverty, and health insurance coverage.

This means that 1.3 million Americans were added to the rolls of the uninsured last year, according to the most recent Census Bureau data, which were released August 29. Nearly 1 million of those affected were working adults 18–64 years of age, and the remainders were children.

The figures on insurance coverage continue a trend that began in 2000—a trend that many health policy experts would like to halt.

"Our health system does not work well for far too many families," Commonwealth Fund President Karen Davis said in a statement. "These findings point to the need for a national solution to ensure that all Americans have affordable and comprehensive health insurance coverage and access to needed health care."

Our country desperately needs bold thinking and brave leadership to fix this crisis," echoed a statement from Risa Lavizzo-Mourey, president of the Robert Wood Johnson Foundation. "The alternative is to continue to watch the inevitable, as the health care system of the United States...slips further into a fractured state of haves and have-nots."

Kathleen Stoll, health policy director for the advocacy group Families USA, likewise decried the recent health coverage news. She stated that the numbers would have been worse without the availability of publicly financed insurance programs like Medicaid and called for steps to preserve those programs.

The proportion of insured Americans who received their benefits through Medicaid, Medicare, or other government-funded sources was unchanged from 2004 to 2005 at 27.3%, according to Census Bureau data.

Of those with insurance coverage in 2005, 59.5% received the benefit from an employer-sponsored health plan—a drop from the previous year, when 59.8% of insured Americans had health benefits through an employer. A declining proportion of Americans received medical coverage from other private sources; in all, private insurance coverage rates fell from 68.2% in 2004 to 67.7% last year.

David Johnson, chief of housing and household economic statistics for the Census Bureau, acknowledged during an August 29 media briefing that the entire increase in the uninsured rate was caused by the decline in private insurance coverage.

Putting a face on the numbers. An issue paper published in August by the Kaiser Family Foundation's Commission on Medicaid and the Uninsured found that three major national estimates of the uninsured population paint a reasonably consistent picture of the number and characteristics of uninsured Americans.

For example, the commission reported that estimates of the uninsured population for 2003 varied from 41.1 million, using data from the National Center for Health Statistics (NCHS), to 46 million, according to the Agency for Healthcare Research and Quality's Medical Expenditure Panel Survey, or MEPS. The Census Bureau estimate for that year fell in the middle, with an estimated 44.7 million people lacking insurance.

Differences in the figures are partly attributed to whether the survey defines people as uninsured if they lack insurance when interviewed, as NCHS does, or if they were uninsured for the entire year, as the Census Bureau does. The MEPS survey polls the same respondents at different intervals to determine insurance status and monthly coverage estimates over an extended period.

According to the Kaiser analysis, all three surveys agreed that adults account for about 80% of uninsured Americans. About 50–60% of uninsured working-age adults have incomes under 200% of the federal poverty level, the surveys find.

Also common to the surveys is the finding that the vast majority of uninsured adults—67–78%—work at least part-time but are not offered insurance by their employers or cannot afford employer-based coverage.

About a quarter to a third of uninsured adults did not finish high school, and about a third received their diploma but did not go to college. Jobs available to those with less than a college education are less likely than jobs open to more educated people to offer health insurance, the report noted.

Income and the great divide. The Census Bureau report on health insurance coverage also included current statistics on income and poverty in the United States. Overall, the report stated, median household income was $46,300 in 2005, a 1.1% increase from 2004.

Despite gains in household income, median inflation-adjusted wages fell 1.8% for working men and 1.3% for women between 2004 and 2005. This marks the second consecutive year of wage declines for men and the third for women, Johnson said.

He attributed the overall gains in household income in the face of declining wages to the inclusion of investment income in household earnings and the fact that a household can contain multiple wage earners.

As in 2004, half of the nation's overall household wealth gain went to those in the top 20% of the income spectrum, but just 3.4% went to the bottom 20%. Johnson called the top 20% of the income bracket the "great divide" in the nation's income distribution.

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Warn Patients: Long fingernails carry harmful bacteria

BETSY BATES (Los Angeles Bureau)

PORTLAND, ORE. — Cosmetic nails are here to stay, so physicians would do well to learn about the glittery accessories driving a $6.8 billion a year industry, Dr. Phoebe Rich said at the Pacific Northwest Dermatological annual scientific conference.

“Nail cosmetics are not inherently dangerous,” the Portland, Ore.-based dermatologist stressed. “They're used by millions of women who really don't have any trouble at all with them.” However, when trouble does brew beneath the bright, rock-hard surfaces of acrylic nails, it can be nasty.

Dr. Rich offered these tips on nail cosmetics complications:

• Allergic reactions. Many allergens are involved in the process of creating artificial nails, but the site of the reaction will often reveal the source of the problem, she said.

Patients whose itching and burning is centered in the periungual and subungual regions probably have an acrylic allergy. “This material polymerizes very quickly, in less than a minute,” she said.

The allergen is basically trapped at the site where it is applied.

Enamel nail polish, on the other hand, may continue to induce dermatitis until the substance fully dries, which may take up to 48 hours. You may see reactions anywhere the patient's fingers touched: on the face, neck, or eyelids, for example.

Dr. Rich noted that a host of sensitizing agents are available in nail products that can be purchased at the local drugstore, not just in professional salons. An example is formaldehyde, an ingredient in Nail Magic, a nail hardening product that is not supposed to come in contact with the skin, but does, of course.

Many upscale nail salons are replacing highly allergenic materials with more expensive, less durable alternatives in response to customer allergies, she said.

• Irritant reactions. Nail polish remover containing acetone or acetate is the No. 1 culprit in drying out the nails, causing brittleness, fragility, onycholysis, paronychia, and friable keratin granulations.

There is a new alternative available over the Internet for sensitive patients: a water-based nail enamel that avoids the need for nail polish remover, since it peels off the nails or can be taken off using ethyl alcohol.

The nail colors sold at www.naturellacosmetics.com do not have the telltale solvent odor that makes most nail polishes so pungent.

• Trauma. “Women who are the most successful at using acrylic nails keep them short,” Dr. Rich explained.

“A long nail acts as a lever,” prying the rigid artificial nail off the nail bed, just as it did when one of Dr. Rich's patients caught her nail in the hinge of a lawn chair.

A natural nail, by contrast, is flexible, and would bend or break in such a scenario.

• Infection. The vivid, nearly impenetrable nail colors painted on cosmetic nails can hide all manner of infections, from “red-hot staph infections,” to onychomycosis “teeming with yeast.”

One problem is disruption of the cuticle with “clippers, drills, and all these little implements that they use to poke and prod and scrape.”

A word to patients to “nurture your cuticles” could help to avoid problems that arise because when aggressive cuticle trimming provides access to organisms that thrive in the moist, dark, warm place underneath the nail.

Infection sources in nail salons are reused files (which cannot be easily sterilized) and improperly cleaned pedicure tubs, which can incubate bacteria that find hospitable hosts in each pair of newly shaved legs that dip into the warm water baths they contain.