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In other recent research, a dissimilarity in tissue type between mother and fetus has been found in many women with rheumatoid arthritis who improve during pregnancy. This finding suggests that the mismatch induces an immunologic reaction that suppresses the arthritis.
Lyme disease, which has both arthritis and skin disease among its major manifestations, has become a national problem. It is now the most common insect-borne disease in the Nation, and its distribution is worldwide. NIAMS is giving high priority to both research and outreach programs for Lyme disease. The Institute has recently funded several new basic research grants to increase understanding of how the infectious agent causes the disease, with the hopes of improving diagnosis and treatment, and providing the foundation for development of an effective vaccine. NIAMS is also supporting a clinical trial to determine if antibiotics can prevent Lyme disease from emerging in people who have been bitten by the deer tick. Programs to better inform both the public and health professionals about the dangers and prevention of Lyme disease are under way. A data base on educational materials was recently completed; and in early March 1991, a workshop on Lyme disease will be held with panels of experts to develop up-to-date vital information for physicians on both the diagnosis and treatment of Lyme disease.
One of the most exciting breakthroughs this year was the identification of a gene that causes a form of osteoarthritis, the most common form of arthritis,
a disease in which the cartilage that covers and cushions the joints breaks NIAMS-supported investigators at two different grantee institutions, working together, isolated and characterized a faulty gene for collagen II, the main structural protein that strengthens cartilage.
Another exciting breakthrough in arthritis this year was the successful induction, by transgenic transfer, into inbred rats of both the human gene (HLA-B27) for spinal arthritis and the entire clinical spectrum of the group of diseases (spondyloarthropathies) associated with spinal arthritis. found in over 90 percent of patients with spinal arthritis, and in only 8 percent of the general population. These diseases associated with spinal arthritis comprise the most common forms of arthritis in young men. The striking mimicry between the disease manifestations found in this animal model and those found in humans opens avenues for research, including the testing of
innovative therapies, that were unimaginable just a few years ago.
Ongoing NIAMS epidemiological investigation of Native Americans in Alaska and Siberian Eskimos--populations that have a high prevalence of spondylitis--promises to shed light on the roles of genetic factors and environmental triggers, such as bacterial infections.
Systemic lupus erythematosus (lupus) is an immune-mediated inflammatory disease that afflicts numerous Americans, largely young women, especially black women of child bearing age. The disease affects the skin, joints, kidneys, brain, and other organs. Recently, a new antibody was identified that is clearly associated with psychiatric disorders due to lupus; this antibody will make better diagnosis possible.
The Institute has set up a task force to study lupus in high-risk
With advice from the task force, NIAMS is developing instructive kits that will help health care providers and community organizations conduct health promotion programs targeted to young black women. The Institute also plans to sponsor an international workshop on systemic lupus erythematosus to assess current knowledge and develop directions for future research.
Scleroderma is a serious disorder of connective tissue and the fine blood
Besides damaging the skin, muscles, and joints, the disease may also affect internal organs, such as the kidneys, heart, and lungs, making it lifethreatening in some people. Women are affected three times more often than men. The first symptom of scleroderma is usually Raynaud's phenomenon, wherein blood vessels in the fingers narrow as the result of vasospasm, causing the hands to become pale and cold. There is also pathologic evidence of vascular disease seen under the microscope. Accordingly, there is keen interest in exploring vascular abnormalities that may contribute to the etiology of the disease. NIAMS will issue a program announcement to stimulate more research on causal mechanisms in scleroderma.
Over 100 different conditions are included among the heritable connective tissue disorders, all of which stem from abnormalities of connective tissue, the scaffolding that girds bone, skin, blood vessels, and the protective coverings of internal organs. Although the disorders are uncommon, they are
In April 1990, NIAMS cosponsored a multidisciplinary
scientific workshop on heritable connective tissue disorders.
participants made it clear that sophisticated research methods are enabling scientists to unravel the complex biology of connective tissue and to uncover the several defects that cause the disorders. The Institute is encouraging additional research in this area, and is exploring the possibility of a patient registry to facilitate progress against these diseases.
Reducing the risk of sports injury is important to millions of Americans who participate in exercise programs and athletics. The Institute's mission includes responsibility for research on exercise physiology and sports medicine. Basic facts about how muscles function at the molecular level are
now being discovered.
Recent research has revealed a mechanism by which a
serious knee injury can destroy a joint. In April 1991, the Institute, in concert with the National Advisory Board, will hold a workshop on scholastic sports injuries to monitor the causes of athletic injuries and identify ways to prevent them.
We are continuing to make progress in research on the numerous skin diseases that affect so many Americans. In epidermolysis bullosa, a devastating inherited blistering disease that affects the skin and mucous membranes, researchers have found that the anchoring fibrils--which link the outer layer of the skin to the inner layer--are conspicuously absent or altered. Recent investigations have also shown that type VII collagen, the major structural protein of anchoring fibrils, can be broken down by both collagenase and gelatinase. Other research, utilizing patients assembled by the National Epidermolysis Bullosa Registry, suggests that abnormal synthesis of type VII collagen be responsible for the reduced number of anchoring
Alopecia areata is a disease of the hair follicle that results in patchy or total loss of hair. The psychological impact of the disease can be debilitating, especially in young people. In October 1990, NIAMS and the National Alopecia Areata Foundation sponsored a 2-day research workshop on the Experts in a wide variety of areas were convened for an open exchange of information on clinical and histopathologic features of alopecia areata,
factors controlling hair growth, autoimmune aspects of the disease, pharmacologic interventions, and animal models. A new anatomic site that controls hair growth has been discovered, and the ability to grow hair in a test tube has been achieved. These findings open new avenues of research that
will be pursued.
Psoriasis is a common chronic skin disease characterized by scaling and redness produced by skin cells that divide rapidly. For many years, psoriasis was treated with preparations of tars and chemotherapeutic agents, such as methotrexate. Recently, clinical studies established the efficacy of cyclosporine A, an immuno-suppressive drug in the treatment of psoriasis. turn, this has led investigators to explore the role of immune-mediated factors in causing the disease and to search for alternative drugs that cause fewer side effects than does cyclosporine A. The NIAMS is encouraging further exploration of molecular, immunologic, and pharmacologic aspects of psoriasis. Significant strides have been made in the Institute's Intramural Program. This past year two new laboratories were established to expand the scope of research: the Laboratory of Skin Biology and the Laboratory of Structural Biology Research. Fundamental studies of proteins responsible for maturation of the epidermis, the skin's outer layer, are the focus of research in the Laboratory of Skin Biology. In the Laboratory of Structural Biology Research, new sophisticated instrumentation is facilitating analysis of extremely small structures, including membrane-associated components of the AIDS virus.
In the area of orthopaedic research, Intramural scientists have identified the various phases through which an injured bone must pass to heal properly. They have detected the presence of a specific natural protein, transforming growth factor-beta (TGF-beta), between and around the ends of fractured bone; and determined that TGF-beta not only initiates a repair response, but also controls the rate of fracture healing.
Another ground-breaking accomplishment achieved by intramural scientists was the development of an animal model for eosinophilia-myalgia syndrome (EMS), a new epidemic inflammatory disease associated with ingestion of contaminated L-tryptophan. Symptoms range from those of the flu, to severe rashes and permanent nerve and muscle damage. The new animal model provides the first direct, experimental evidence linking EMS to contaminated batches of the dietary supplement L-tryptophan.
Collaborations between NIAMS and the Department of Defense continue in
studies of skin manifestations in human immunodeficiency virus (HIV)-infected
Establishment of a new interagency agreement will significantly increase the rate of accrual of HIV-positive subjects into the studies to give us an earlier estimate of the prevalence of skin disorders and accelerate the pace of this research.
Mr. Chairman, the budget request for NIAMS for fiscal year 1992 is
I will be pleased to answer any questions you may have.
BIOGRAPHICAL SKETCH OF DR. LAWRENCE D. SHULMAN
July 25, 1919, Boston, Massachusetts
Education: Harvard University, A.B., 1941; Yale University Graduate
Professional Organizations: American Association for the Advancement of Science, American College of Physicians, American Federation for Clinical Research, American Rheumatism Association (President, 1974-75), American Society for Bone and Mineral Research, The Arthritis Foundation, Brazilian Society of Rheumatology, Carla Curzio Neapolitan Society, Lupus Foundation of America, New York Academy of Science, Pan American League Against Rheumatism (President, 1982-86), Society for Clinical Trials, Sydenham Society, Society for Investigative Dermatology.
Honors Awards: Senior Investigator Award, The Arthritis Foundation, 195762. Pemberton Memorial Lecture, 1963. Fellow, American College of Physicians, 1967. Wallace R. Graham Memorial Lecture: Toronto, 1973. The Heberden Medal for Research in the Rheumatic Diseases, Heberden Society, London, 1975. Distinguished Service Award, The Arthritis Foundation, 1979. Honorary Member, Brazilian Society of Rheumatology, 1980. Honorary Member, Chilean Society of Rheumatology, 1981. Knowles Lecture: San Francisco, 1982. Honorary Member, Costa Rican Association of Rheumatology, 1984. Honorary Member, Australian Rheumatism Association, 1985. The Public Health Service Superior Service Award, 1985. National Lupus Hall of Fame, 1986. Honorary Member, Swiss Society of Rheumatology, 1987. Elected Master, American Rheumatism Association, 1987.