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Biomedical subjects

S A Rich

Publications and source records attributed to S A Rich.

21 records · Page 2Linked to original sources

Troleandomycin effects on methylprednisolone and methylprednisone interconversion and disposition in the rabbit.

A study of the effects of troleandomycin (TAO) on the disposition of intravenous methylprednisolone in rabbits was performed in order to develop an animal model to further evaluate the mechanism of TAO/steroid beneficial effects in severe asthma. The plasma concentration-time profiles of methylprednisolone and methylprednisone were determined in the presence and absence of single and multiple dose TAO regimens. Pharmacokinetic analysis revealed a significant decrease in total plasma clearance of methylprednisolone in the presence of multiple dose TAO. Alterations in the disposition of the reversible metabolite, methylprednisone, were also observed. The TAO-methylprednisolone interaction may involve decreasing the degree of interconversion between the steroid and its reversible metabolite. TAO also decreases metabolite turnover more than three-fold. The antibiotic does not cause marked deviation from linear biexponential elimination of methylprednisolone as observed in man. The rabbit may serve as a useful animal model for further studies of the TAO/methylprednisolone interaction.

Animals↗

Localization of interferon-induced lupus inclusions demonstrated by computer image reconstruction of monensin-treated Daudi cells.

A structural analysis of cells that contained the interferon-alpha-induced lupus inclusions (LI) was performed using a high-voltage electron microscope to determine the exact cellular location of LI and their association with normal cell organelles. LI were induced in the human B lymphoblastoid cell line, Daudi, by culturing with the pure recombinant human leukocyte interferon, IFLrA. Just prior to harvesting, a portion of the cells was treated with monensin to selectively swell the Golgi apparatus, and thereby simplify their identification using the electron microscope. Organellar associations between LI and the outer nuclear envelope and Golgi apparatus were identified in stereopairs of 1-micron sections prepared from both cells that were not treated with monensin and those that were treated with monensin. Serial 0.25-micron sections of the monensin-treated cells were prepared, and seven arbitrarily chosen cells were examined. Each of these cells contained a single LI, and it formed throughout an endoplasmic-reticulum region that made contact with both the outer nuclear envelope and the Golgi vesicles. Reconstruction of a cell by computer from the digitized negatives of serial sections clearly illustrated these relationships. This study reports the first determination of the association between LI and the Golgi apparatus. It also identifies the presence of only one LI in every cell, and the routine association of the LI with both the outer nuclear envelope and the Golgi apparatus. The unique cell location of LI formation suggests their functioning in membrane biogenesis, the trafficking of proteins to the plasma membrane or to cytoplasmic vesicles, or the processing of proteins for secretion.

Acquired Immunodeficiency Syndrome↗

Reappraisal of thromboplastin.

Proficiency testing surveys in the state of New York indicate that despite increased sophistication in instrumentation, there has been no real improvement in interlaboratory reproducibility in prothrombin-time determinations over the last 10 years. This lack of improvement most pronounced in the therapeutic range of 20 to 30 sec. One reason may be that between types produced by the same manufacturer. While it has been possible in several laboratories to synthesize experimentally a thromboplastin with known content of lipid and active protein, no efforts have been made to make such a product by the same manufactures. While it has been made to make such a product commercially available. Blood levels of of warfarin were measured but cannot be reliably used to monitor anticoagulation. In a preliminary study, factor Xa activity was measured using chromogenic substrate S2222. Factor Xa activity gave a positive correlation with prothrombin times of patients receiving warfarin therapy. Chromogenic substrate factor assays may represent a future method of choice for controlling anticoagulant therapy.

Animals↗