Johns Hopkins Magazine - June 1996 Issue

In Short - Health & Medicine

By Elise Hancock and Melissa Hendricks
A protein that shows surprising promise how fingerprints can spare unnecessary surgery why marriage can be risky in Thailand

Periodontal repair--and more

A protein purified and cloned by Hopkins biochemist Hari Reddi has repaired periodontal damage in baboons, surprising researchers in the process.

The protein is one of a family discovered about five years ago called bone morphogenetic proteins (BMPs). Reddi, a professor of orthopedic surgery at the School of Medicine, had earlier shown that BMPs regulate differentiation of cartilage and bone. So the research team, Reddi and a South African group, had expected the protein to help baboons regrow surgically excised jawbone around several teeth. As it did.

No one expected to see new periodontal ligament, however. Or new cementum, the connective tissue that covers the roots of teeth and attaches them to bone. Yet both grew in response to the protein treatment.

"We got very faithful repair," Reddi reported at the 1996 meeting of the American Association for the Advancement of Science. "These proteins actually appear to serve several different functions, depending on what's around them."

Placed in cavities in bone, BMPs induce bone formation; placed in muscle, they result in both bone and cartilage. Evidently the proteins recruit progenitor cells for the bone (or whatever) from surrounding tissues, says Reddi. "The cells actually crawl toward the proteins."

BMPs turn out to be extremely ancient, at least 600 million years old, and are similar in vertebrates and invertebrates. A BMP-related protein from Drosophila--which do not have bones--will induce new bone to form in rats.

Such a high degree of evolutionary conservation implies that whatever BMPs do, it is central to animal life. For example, the gene for the protein used in the baboon jaws, BMP-7, is also strongly expressed in kidneys. Mice with the gene for BMP-7 "knocked out," so they do not express the protein, develop normal bones--but die for lack of a kidney. The protein is also found in the central nervous system.

So far, at least a dozen human BMPs have been identified, and each works slightly differently. One helps broken skullcaps and facial bones mend. Another seems to mediate formation of the structures that hold bone marrow in place. Looking at them as a group, Reddi believes that BMPs orchestrate the formation of structural patterns during development, embryonically and for many functions in later life.

If so, their obvious promise for periodontal surgery is only the beginning. Clinical trials with BMPs are under way in France and South Africa. In the U.S., trials in dental surgery and for long bones that fail to heal may soon begin.

Husbands major AIDS risk for Thai women

For women in Thailand, marriage is the number one risk factor for becoming infected with AIDS, according to a study by researchers at Johns Hopkins and other institutions. The women become infected by their husbands, who become infected by prostitutes.

The great majority of Thai men, of every age and marital and socioeconomic status, customarily visit prostitutes--85 percent in 1995, according to David Celentano, professor of health policy and management at the School of Public Health. The percentage has dropped from 96 percent of men in 1993, "but business is still thriving," says Celentano, lead author of the study (it was recently published in the Journal of the American Medical Association).

The Thai government supplies condoms to brothels and tests prostitutes for HIV and sexually transmitted diseases. Brothels are notified of test results. Nevertheless, Celentano says that women who are known to be HIV-positive "generally remain working until they develop symptoms."

The Hopkins team studied 1,932 healthy men, ages 19 to 23, who were drafted into the Royal Thai Army and Air Force from northern Thailand. Because the draft is universal, the men represent a cross-section of young Thai men. During the 22-month study, 85 men became infected with HIV.

Its AIDS epidemic growing rapidly, Thailand is expected to harbor 2 million AIDS cases by the year 2000, in a population of about 58 million people.

The only country where AIDS is spreading faster than in Thailand is India, the site of a two-year study recently reported in the Journal of Infectious Diseases.

In this study, with Indian researchers, a Hopkins team led by Robert Bollinger, a specialist in infectious diseases, followed patients attending sexually transmitted disease (STD) clinics in Pune, India. People with STDs have double to triple the risk of AIDS infection, seven times the risk if they have open genital sores.

By 1993, one-fifth of patients at STD clinics in Pune were already positive for HIV. Studying 851 uninfected patients, the researchers found that 9.4 percent of the men became infected each year, as did 14.1 percent of women. The risk for prostitutes stood at 26.1 percent per year. By the end of this decade, India is expected to have the largest burden of HIV in the world.

More happily, the study found that among people who used condoms for a three-month period, risk of infection dropped 56 percent.

Fingering a culprit illness

A tool of the detective trade is now providing an important clue for doctors. According to Hopkins gastroenterologist Marvin Schuster, fingerprints can help spot a difficult-to-diagnose and sometimes life-threatening illness called chronic intestinal pseudoobstruction (CIP).

Schuster finds that 54 percent of CIP patients have an unusual fingerprint pattern called the digital arch configuration. In comparison, arch fingerprints appear in only 7 percent of the general population.

A new diagnostic tool for CIP is desperately needed, says Schuster. The illness, which afflicts 50,000 Americans, masquerades as an intestinal obstruction (thus the "pseudo" in CIP). Patients experience intense stomach pain, vomiting, nausea, and diarrhea alternating with constipation. But when surgeons go hunting for a blockage, they don't find one. That's because CIP stems from degeneration of the nerves or muscles that control the gastrointestinal system, and in some cases is of unknown cause.

CIP patients typically undergo numerous exploratory surgeries, which can leave scars that can lead to more surgery. Though there is no cure for CIP, the best treatment is to avoid unnecessary surgery, says Schuster. (Certain medications that enhance movement of the gut or counter spasms of gut muscles also help some patients.)

Schuster made the connection between the digital arch and CIP, "the way many things are found, through serendipity," he says. A patient was referred to Johns Hopkins with what appeared to be a heart murmur, abdominal pain, and severe constipation. Schuster examined the woman and determined that she had CIP. At the same time, cardiologist Sheldon Gottlieb diagnosed a mitral valve prolapse, a heart condition that may cause heart palpitations but is very rarely serious. Gottlieb also knew that there was an association between mitral valve prolapse and the digital arch pattern, so he examined the woman's fingerprints. Indeed, she had the unusual digital arches on nine of her fingers. The random chance of a person having nine digital arch prints is 1 in 20,000, says Schuster.

Schuster then started to take note of the fingerprint patterns of his other CIP patients. During the next seven years, he collected prints from 43 of them. Fifty-four percent had digital arches on one or more fingers. Furthermore, 40 percent had mitral valve prolapse. Digital arch prints and mitral valve prolapse appear to be markers for CIP, Schuster concludes.

Why should an unusual fingerprint pattern be associated with a gastrointestinal illness? "We think there's a congenital linkage," says Schuster, which means the group of conditions is present at birth. The constellation of symptoms may be genetically linked, or stem from environmental factors that occur in utero. Primitive fingerprints appear during the sixth or seventh week of development and are completed by the 24th week, and arise from a tissue similar to the one that forms the mitral valve and gut, says Gottlieb. But no one can be certain why the conditions often appear together. For now, Schuster is taking their association on faith. He examines the fingerprints of every patient whose symptoms suggest CIP. Digital arch fingerprints, along with mitral valve prolapse, says Schuster, can help pinpoint CIP earlier, and spare the patient unnecessary surgery.

Written by Elise Hancock and Melissa Hendricks.

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