Research on women's health.

KIE: The Acting Associate Director for Research on Women's Health describes the background and purpose of the Office of Research on Women's Health, established in September 1990 as part of the National Institutes of Health (NIH). The Office is responsible for assuring that research conducted and/or supported by NIH appropriately addresses issues regarding women's health, and that there is appropriate participation by women in clinical research.^ieng

The National Institute of General Medical Sciences probes cellular and molecular bases of life.

The National Institute of General Medical Sciences has as its mission the support of research and research training in the basic biomedical sciences. Grantees of the Institute have made major discoveries about cell structure and function, the synthesis and transport of body proteins, drug actions in the body, and the body's responses to severe trauma and burns. Advances in the field of genetics--including the development of recombinant DNA technology, in which Institute grantees have been leaders--are beginning to pay off in scientists' ability to understand the growth, differentiation, and development of cells, tissues, and organs; the regulation of gene activity; and the bases of certain genetic diseases. But while much has been learned, the cellular and molecular mechanisms of many illnesses are only beginning to be understood. For this reason, the Institute's support of studies of life processes at their most fundamental levels is expected to continue to produce findings of great importance to the understanding, prevention, and treatment of human disease.

Parathyroid necrosis and hypocalcemic tetany induced in rabbits by L-asparaginase.

Fifty percent of New Zealand white rabbits became profoundly weak, had generalized seizures and died between 22 and 47 hours after an intravenous injection of 1000 IU/kg of L-asparaginase. The biochemical correlate of this syndrome is severe hypocalcemia associated with marked, single cell, oxyphilic necrosis in the parathyroid glands. Although survivors remained clinically well, they also developed hypocalcemia and parathyroid necrosis but to a lesser degree. Rabbits given an equivolumetric amount of saline did not develop alterations in any of these parameters. L-Asparaginase, therefore, exerts a direct toxic effect on the parathyroid glands of rabbits. The implications of this finding for man are briefly discussed.

Respiratory diseases in cyclophosphamide-treated mice. I. Increased virulence of Mycoplasma pulmonis.

Mice infected intranasally with Mycoplasma pulmonis were treated with cyclophosphamide, a potent immunologic suppressor. In place of a chronic smouldering infection with little mortality (2%), a rapidly lethal infection with high mortality (66%) was produced. M. pulmonis was able to be isolated from several organs during the course of the unmodified infection. In the infected animals treated with cyclophosphamide, dissemination occurred earlier, and higher titers of mycoplasma were found. Reconstitution experiments with spleen cells from previously infected animals reversed the effect of cyclophosphamide, indicating that immunity plays an important role in containment of the infection and eventual recovery.

Respiratory diseases in cyclophosphamide-treated mice. II. Decreased virulence of PR8 influenza virus.

Mice infected intranasally with the PR8 strain of influenza virus were treated with cyclophosphamide, a potent immunologic suppressor. During the first week of infection, mortality in the unmodified influenza infection averaged 65%, whereas in those animals also treated with cyclophosphamide it averaged 22.5%. After the first week, the mortality rate in the infected cyclophosphamide-treated animals rose to that seen during the first week in the animals only infected. This decreased mortality in the first week was found despite the fact that the cyclophosphamide-treated and infected animals had higher virus titers which persisted longer, decreased circulating antibody, and a decreased interferon response. This delayed mortality appeared to be related to the finding of decreased cellular infiltration in the lungs of infected cyclophosphamide-treated animals.

Immunoperoxidase localization of herpes zoster virus and simian virus 40 in cell culture.

The immunoperoxidase technique was used in an electron microscopy study to localize the virions of herpes zoster virus and simian virus 40 in cell cultures. Intranuclear and intracytoplasmic virions of herpes zoster virus were easily and specifically identified due to intense staining by the finely granular, black reaction product. With simian virus 40, intranuclear virions were not stained, whereas intracytoplasmic particles appeared densely black. There was essentially no background staining. Advantages of this technique over the ferritin-labeled antibody method include simpler preparative procedures for reagents, greater penetrability of the antibody conjugate, and internal amplification which substantially improves the ability to localize sites of antigen-antibody reaction. We believe that the immunoperoxidase method can be successfully applied to a wide variety of problems involving viral antigens.

Lack of significant oncogenicity of biological products in hamsters.

A variety of biological products which included live and inactivated viral vaccines, inactivated rickettsial and bacterial vaccines, toxoids, and a multiple bacterial antigen product did not appear to be oncogenic for newborn hamsters following a single subcutaneous inoculation. The incidence of spontaneous tumors was approximately 4.7%, and this figure was not significantly altered by the inoculation of any of the test materials.