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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,333 records · Page 74Linked to original sources

Comparative effects of chlorozotocin and BCNU on hematopoietic precursor cells.

Comparative studies to determine the suppressive effects of chlorozotocin (2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose) and BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) on mouse and human hematopoietic precursor cells: granulocyte-macrophage precursor cells (CFU-gm), late erythroid precursor cells (CFU-e), and early erythroid precursor cells (BFU-e) were performed after in vitro incubation of 1 h with drug concentrations based on clinical administration levels. The suppressive effect of chlorozotocin on CFU-gm, BFU-e, and CFU-e hematopoietic precursor cells in the mouse was less than that of BCNU with the most significant difference seen in CFU-e colony formation. For human hematopoietic progenitor cells, however, the suppressive effect of chlorozotocin was far less than that of BCNU. When the effects of 40 micrograms/ml of chlorozotocin and 20 micrograms/ml of BCNU on human marrow were compared, there were statistically significant differences found for CFU-gm colony formation, and BFU-e and CFU-e colony numbers were significantly different for the two drugs at all comparable concentrations tested. Our results confirm the clinical data, and establish that the effects of chlorozotocin on human hematopoietic precursor cells are minimal.

Animals↗

Psychiatric disorders as they relate to aviation: the problem in perspective.

The major causes of licence loss among pilots during 1965-81 are discussed in relation to the effect of recent changes in licensing practices, such as permission to use beta-blockers. Mental disorders comprised the second highest cause of licence loss during 1965-77 (13.0%) and remained at a high level during 1977-81 (14.7%). The age-related incidences of alcoholism, psychoses and neuroses, and idiopathic and reactive flight phobia are detailed.

Adult↗

Primary cell-mediated lympholysis response to a maternally transmitted antigen.

Mta-specific cytotoxic T lymphocyte (CTL) can be generated in primary cultures of (NZB X B10.D2)F1 spleen cells with H-2-compatible BALB/c stimulator cells. The CTL lyse reciprocal Mta+ (B10.D2 X NZB)F1 as well as H-2-disparate targets, such as B10, B6, and B6-Tlaa; they do not lyse targets from NZB or any F1 hybrid of an NZB mother. The lysis of 51Cr-labeled B10 targets is completely inhibited by unlabeled targets from Mta+ (B10.D2 X NZB)F1, but not from the reciprocal Mta- F1, thus demonstrating H-2-unrestricted lysis of Mta.

Animals↗

Self-association of myelin basic protein: enhancement by detergents and lipids.

Self-association of basic protein has been proposed to be of functional significance in central nervous system myelin. In aqueous solution this protein self-associates, previous data being consistent with the formation of dimers, which then undergo an indefinite isodesmic self-association [Smith, R. (1980) Biochemistry 19, 1826-1831]. As this protein is membrane bound in vivo, we have now examined the effects of amphiphiles on the self-association equilibria. Contrary to the expected effects, at low molar ratios dodecyl sulfate, deoxycholate, Triton X-100, and lysophosphatidylcholine increased protein intermolecular attraction. The anionic detergents led to partial precipitation even at 1:1 protein:detergent molar ratios whereas the zwitterionic lipid and the nonionic detergent exerted less pronounced effects. Sedimentation velocity and equilibrium measurements have been used to define quantitatively the effects of lysophosphatidylcholine. The sedimentation coefficient increases up to a lipid:protein ratio of 4:1 and then remains constant up to a ratio of 12:1. The sedimentation equilibrium data suggest that the mode of protein-protein interaction is the same as in the absence of lipid but with substantially increased association constants. The dimerization constant is increased from 1.20 X 10(2) M-1 to 1.0 X 10(3) M-1 and the isodesmic association constant from 3.4 X 10(4) M-1 to 1.2 X 10(5) M-1. The effects of detergents on myelin basic protein are compared with the effects on other proteins, and the implications for the state of the protein with myelin are discussed.

Animals↗

Effect of short-term infusion of sodium nitroprusside on mortality rate in acute myocardial infarction complicated by left ventricular failure: results of a Veterans Administration cooperative study.

Eight hundred twelve men with presumed acute myocardial infarction and left ventricular filling pressure of at least 12 mm Hg participated in a randomized double-blind placebo-controlled trial to assess the efficacy of a 48-hour infusion of sodium nitroprusside. The mortality rates at 21 days (10.4 per cent in the placebo group and 11.5 per cent in the nitroprusside group) and at 13 weeks (19.0 per cent and 17.0 per cent, respectively) were not significantly affected by treatment. The efficacy of nitroprusside was related to the time of treatment: the drug had a deleterious effect in patients whose infusions were started within nine hours of the onset of pain (mortality at 13 weeks, 24.2 per cent vs. 12.7 per cent; P = 0.025) and a beneficial effect in those whose infusions were begun later (mortality at 13 weeks, 14.4 per cent vs. 22.3 per cent; P = 0.04). Nitroprusside should probably not be used routinely in patients with high left ventricular filling pressures after acute myocardial infarction. However, the results in the patients given late treatment suggest that those with persistent pump failure might receive sustained benefit from short-term nitroprusside therapy.

Aged↗

The natural history of the Q wave in inferoposterior myocardial infarction.

One hundred and twenty-five patients who had suffered transmural inferior myocardial infarctions were followed up for a mean period of 55 months. On electrocardiography the area under the pathological Q waves in the inferior leads was measured serially. Eighty-one patients (65%) showed a highly significant time-related diminution in Q-wave area. The ECGs of 17 subjects (14%) became normal and there was no electrocardiographic evidence of the previous myocardial infarction. The Q waves of the remaining 44 subjects (35%) remained constant or increased. A discussion of the possible mechanisms of changes in Q-wave size follows.

Adult↗

Correlation of ventricular ectopic activity and exercise-related ST-segment changes.

Same-day exercise electrocardiography and ambulatory electrocardiographic (Holter) monitoring were performed on 167 patients, all of whom had suffered myocardial infarctions over the past 12 years. A significant correlation (P less than 0,0001) was found when comparing exercise testing for ischaemic ST-segment changes and the number of complexity of ventricular arrhythmias found on Holter monitoring. Two different methods of arrhythmia classification were used and the results were similar. The value of simultaneous Holter monitoring and exercise electrocardiography to detect 'late' exercise-related ventricular arrhythmias was not found to be sufficient to warrant their widespread simultaneous use.

Adult↗