Identification of 6-methylmercaptopurine ribonucleoside 5'-diphosphate and 5'-triphosphate as metabolites of 6-mercaptopurine in man.
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Biomedical subjects
Publications and source records attributed to D J Nelson.
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Synthetic methodology was developed for the preparation of chondrotin-4-sulfate reagents that could be specifically attached to the surface of diaspirin cross-linked hemoglobin (DCLHb), a chemically stabilized human hemoglobin. The surface-modified hemoglobin solutions had a significantly higher colloidal osmotic pressures (COP) than DCLHb. The P(50) of the modified DCLHb was dependent upon the reactive end group of the chondrotin-4-sulfate reagents that was used for the protein modification. Modification of DCLHb with the chondroitin-4-sulfate derivatives containing the maleimide end group 23 provided a hemoglobin with a P(50) value of 23 mmHg, while the P(50) of hemoglobins prepared from chondroitin-4-sulfate derivatives containing the aldehyde end group 13 and 18 remained unchanged from that of DCLHb.
Novel polyamides were developed that can be used as cross-linking agents for proteins such as hemoglobin. Water-soluble, nonimmunogenic polyamides containing oxygen and sulfur atoms in the backbone were prepared by the polycondensation of the diacids bis(carboxymethyloxyacetyl)-1,4-diaminobutane (1a) or 3, 3'-thiodipropionic acid (1b) with diethylene glycol bis(3-aminopropyl) ether (2). The resulting alpha,omega-diacids were converted to the corresponding activated esters using any of a variety of carboxylic acid activating reagents including the novel reagent diphenyl(1-methylimidazol-2-thiyl)phosphonate (9). The resulting polyamides could be activated with a broad spectrum of groups that allow for the cross-linking and surface modification of proteins.
Diaspirin cross-linked hemoglobin (DCLHb), a human hemoglobin that is intramolecularly cross-linked between the alpha chains (lysine 99(alpha)(1)-lysine 99(alpha)(2)), was polymerized with a number of water-soluble, nonimmunogenic polyamide cross-linking agents. The degree of polymerization and the oxygen-carrying capacity depended upon the polyamide reagent, the starting concentration of DCLHb, the molar ratio of the polyamide reagent to DCLHb used, the reaction pH, and whether oxy- or deoxy-DCLHb was used in the polymerization reaction.
The extracellular patch clamp technique developed by Neher et al. to record the responses of single channels in skeletal muscle has provided firm evidence for the two-state nature of the conductance event in nicotinic endplate channels. We report here the use of the extracellular patch technique to record single-channel responses from tissue-cultured chick skeletal muscle cells. The temperature dependence of channel conductance and gating kinetics shows no evidence of discontinuous behaviour between 17 and 37 degrees C.
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BACKGROUND: We performed a meta-analysis to: (1) assess the disputed issue of in-hospital cardiopulmonary resuscitation (CPR) success rates among elderly patients, (2) investigate the possibility of a declining CPR success rate between 1960 and 1990, (3) provide an overview estimate of CPR effectiveness in specific patient groups, and (4) assess CPR risks. METHODS: Ninety-eight reports providing in-hospital CPR survival-to-discharge rates were included in this overview. These reports were identified from MEDLINE searches, previous reviews, and reference citations. RESULTS: A pooled analysis revealed that 2994 (15 percent) of 19,955 patients were successfully resuscitated (survival to discharge). The rate of successful CPR has not changed in 30 years (r = -0.14, P > 0.05), but there has been a steady decline in the optimism regarding its value (r = -0.29, P < 0.01). Patients younger than 70 years of age had a success rate of 16.2 percent (odds ratio = 1.36; 95 percent confidence interval, 1.20 to 1.53) versus 12.4 percent for patients older than 70 years (P < 0.001). Community hospitals had a higher CPR success rate than teaching hospitals (18.5 percent versus 13.6 percent, P < 0.001). Although 72.9 percent of the post-CPR deaths were within 72 hours, prolonged in hospital survival in a vegetative state did occur; 1.6 percent of successfully resuscitated patients had a permanent neurological impairment. CONCLUSION: The increasing pessimism about the value of CPR, specifically, its futility in the elderly patient, is not supported by this review. The results of this meta-analysis should assist both the physician and the patient in determining the probable outcome of CPR.