Biomedical subjects
Publications and source records attributed to R Rajagopalan.
The products of CO2 fixation by heterotrophically grown Haloferax mediterranei were analysed. The main 14C-labelled alpha-ketoacid detected following incubation with NaH14CO3 and pyruvate or propionate was pyruvate. In presence of these organic acids and NH4+, 14CO2 was incorporated into glutamic and aspartic acids and alanine.
Explore the source record for details and available documents.
A series of 6- and 7-aminoacyl derivatives of 7-deacetylforskolin was prepared to provide water-soluble derivatives of the potent cardioactive diterpenoid forskolin. The compounds were evaluated for positive inotropic and blood pressure lowering properties in pharmacological models. Several derivatives displayed potent positive inotropic activity in guinea pig atria (EC50 = 0.16-3.0 micrograms/mL). In the most active compounds, the amino moiety of the aminoacyl chain corresponded to a cyclic amine, and the acyl moiety to a C2-C4 alkanoyl group. In vivo biological evaluation led to the selection of 6-(piperidinoacetyl)-7-deacetylforskolin hydrochloride (49) as a candidate for clinical development.
Direct effects of antimicrobial agents on macrophages functions are not well precised. However, antimicrobials can enhance phagocytosis of bacteria by macrophages in vitro, at subinhibitory concentrations. This enhancement is related to the antibiotic effect. It is dependent of the nature of the antimicrobial agent, of the experimental procedure and some discrepancies appeared in the results. The precise mechanism, effect on the bacterial wall, or on the bacterial protein synthesis is uncertain. The third type of interaction concerns the intracellular penetration and activity of antimicrobial agents within macrophages. In a human monocyte-derived macrophage model, the intracellular growth of Legionella pneumophila was inhibited by erythromycin, rifampicin and fluoroquinolones at concentrations clearly lower than their MICs; doxycycline and cotrimoxazole were inhibitory at concentrations closed to their MICs. Cefoxitin was not inhibitory even at high concentrations despite a low MIC value. This confirms the good intracellular activity of macrolides and fluoroquinolones and the low intracellular activity of beta-lactams.
A monoclonal antibody (8G11-C6) that is directed to a region near the ligand-binding site of the glucocorticoid receptor was obtained by an auto-anti-idiotypic route, using a derivative of triamcinolone coupled to thyroglobulin to immunize a mouse. The resulting hybridomas were screened for anti-idiotypic antibody (anti-antisteroid) with Fab fragments of affinity-purified polyclonal rabbit anti-triamcinolone antibody. The anti-idiotypes were then screened for binding to rat cytosol glucocorticoid receptor by a depletion procedure, yielding a clone, 8G11-C6, whose specificity for receptor was verified by sucrose density and Western blot analyses. Depletion was not significantly reduced by prelabeling the cytosol with [3H]triamcinolone acetonide. The anti-idiotype (8G11-C6) bound to Fab fragments of antisteroid and to partially purified receptor in a concentration-dependent manner. Both binding reactions were inhibited only by rabbit serum albumin conjugates of steroids known to bind to the glucocorticoid receptors. Triamcinolone derivatives of lysine and of oligopeptides containing up to six amino acids inhibited the binding of the anti-idiotype to the Fab fragments but not to the receptor, implying that the target epitope of the antisteroid antibody may be closer to its glucocorticoid-binding site than the cross-reacting epitope of the receptor. Our findings demonstrate further the versatility of the auto-anti-idiotypic route for the preparation of anti-receptor antibodies.
Effect of actinomycin D, an antibiotic, was investigated on the biological function of tubulin from bovine brain. The microtubule assembly was inhibited nearly completely when an equal molar ratio of actinomycin D and tubulin was used. The depolymerisation of the same, however, was not altered under the same conditions. The competence of tubulin to bind colchicine and GTP was also not affected. Chromatographic and the spectrophotometric studies showed that 0.94 mol of actinomycin D binds per mole of tubulin.
A decision analytic model (a decision tree) was constructed for use in the labor room. Probabilities and (dis)utilities were estimated by obstetricians and computerized. A sensitivity analysis on six branches of the decision tree uses estimates of four obstetricians and proves that the decisions resulting from the model are stable and insensitive to differences in probability estimates within reasonable limits. Therefore it is concluded that we can construct a decision tree that is a practical, valuable, and stable tool for consistent decision making.
Explore the source record for details and available documents.
A new amiloride analogue, "amiloride-caproic acid," was synthesized, coupled to albumin, and used as a hapten to raise anti-amiloride antibodies in rabbits. The antibodies were affinity purified with an amiloride affinity column and characterized. Binding studies using [3H]benzamil showed a dissociation constant of 0.8 nM. Amiloride and amiloride-caproate inhibited [3H]benzamil binding; epsilon-guanidinocaproic acid showed no inhibition. Anti-amiloride antibodies reversed the inhibition by amiloride of sodium transport across toad urinary bladder. Anti-amiloride antibodies and an amiloride affinity column should provide useful tools for the characterization of the epithelial sodium channel.
The effect of rifampicin on the biological properties of bovine brain tubulin was investigated. Assembly of microtubules was almost completely blocked by rifampicin, whereas the depolymerization was not affected. The drug was found to inhibit both colchicine and GTP binding to tubulin. Association of rifampicin with tubulin was confirmed by spectrophotometric method. Binding of rifampicin was found to be dependent both on temperature and time. At 0 degrees for 1 hr 0.84 moles of rifampicin were bound per mole of tubulin.
Alfathesin and thiopentone were compared in a double blind study where each drug was given by intravenous infusion supplemented with fentanyl and nitrous oxide, in 54 healthy female patients under-going therapeutic abortion. The two drugs were similar in terms of changes in cardiorespiratory variables, side effects, clinical efficacy, and patient acceptability. Alfathesin produced a significantly more rapid recovery from anaesthesia, without the high incidence of dreams found with thiopentone in this study. Alfathesin would seem to be the preferable drug for use in outpatients undergoing minor surgical operations.
The effects of fentanyl (1 microgram/kg) supplementing an alfathesin infusion technique were assessed in a double blind study in 53 healthy unpremedicated female patients undergoing therapeutic abortion as outpatients. The addition of fentanyl reduced the tachycardia, tachypnoea and hyperventilation seen in those patients receiving alfathesin alone, without unduly prolonging recovery time. Two patients receiving alfathesin alone developed marked coughing or laryngospasm. Fentanyl would seem to be a desirable addition to an alfathesin infusion technique in unpremedicated patients presenting for outpatient anaesthesia.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.