Faculty Bibliography

Lipoarabinomannan (LAM) is a component of the mycobacterial surface which has been associated with a variety of deleterious effects on immune system function. Despite the importance of LAM to the pathogenesis of mycobacterial infection, there is no information available on its fate in vivo. In this study, we determined the pharmacokinetics and tissue distribution of exogenously administered LAM in mice. For measurements of serum and tissue LAM concentrations, we developed an enzyme-linked immunosorbent assay which used monoclonal antibodies of different isotypes to capture and detect LAM at concentrations of >/=0.4 microg/ml. Intravenous administration of LAM to mice resulted in transient serum levels with organ deposition in the spleen and in the liver. Immunohistochemical studies localized LAM to the spleen marginal zone macrophages and, to a lesser degree, to liver macrophages. When LAM was administered to mice previously given a LAM-binding immunoglobulin M (IgM), LAM was very rapidly cleared from circulation. In those mice, deposition of LAM in the spleen was significantly reduced while LAM deposition in the liver increased. Administration of LAM-binding IgM resulted in significant levels of IgM to LAM in bile consistent with an increased hepatobiliary excretion of LAM in the presence of specific antibody. Bile, liver extracts, and bile salts were found to rapidly inactivate the immunoreactivity of LAM. The results indicate that serum clearance and organ deposition of LAM in mice are affected by the presence of LAM-binding antibody and suggest a mechanism by which antibody could modify the course of mycobacterial infection.

This study decomposes the detrimental effects of increased sibship on educational attainment by the sex of the respondent and his/her siblings. Previous theories regarding the interaction of gender and sibship sex composition are reviewed and a new hypothesis is offered: a revision of the sex minority hypothesis, positing that an increased number of siblings of the opposite sex (regardless of the of the respondent's gender) are harmful to educational achievement since sex minority children may find their gender-specific needs unmet, may suffer from socialization by the family that conflicts with sex role expectations within the educational system, or because there may exist returns to scale for "gender-specific" goods within the household. Findings reveal that it is the number of opposite sex siblings that most hurts educational attainment efforts, marshalling support for the revised sex minority hypothesis, (C) 2000 Academic Press.

OBJECTIVE: To assess genetic diversity and drug resistance of Mycobacterium tuberculosis isolates collected at Christian Medical College Hospital (CMCH), Vellore, India, between July 1995 and May 1996. MATERIALS AND METHODS: Isolates were subjected to IS6110-based restriction fragment length polymorphism (RFLP) analysis and tested for resistance to isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide, and DNA from selected strains was sequenced in regions associated with drug resistance. RESULTS: One hundred and one M. tuberculosis isolates were collected from 87 patients with pulmonary tuberculosis. Charts of 69 patients were reviewed for history of tuberculosis illness and treatment. DNA from 29 strains was sequenced in katG, rpoB, and gyrA, and sometimes pncA regions. Analysis by RFLP revealed a high degree of genetic diversity, with no identifiable clusters of infection. Of the strains tested, 51% were resistant to at least one antibiotic, and 43% were resistant to more than one drug. There was a high rate of resistance observed in patients whose charts indicated a history of improperly administered tuberculosis treatment, whereas little drug resistance was observed in patients never previously treated for tuberculosis. Sequencing of genes associated with drug resistance revealed several previously unreported mutations in resistant strains. CONCLUSIONS: This analysis suggests that the cases of tuberculosis in the sample are largely reactivation of long-standing infections and that the drug resistance among patients in CMCH is largely acquired or secondary rather than attributable to the spread of drug-resistant strains

MOST Americans view the immigrant experience through the bold strokes of struggle and assimilation. They barely notice the underside of immigration--the rules for inspecting, admitting and excluding newcomers to American shores.