Spontaneous platelet aggregation in whole blood: dependence on age and haematocrit.
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Biomedical subjects
Publications and source records attributed to S Green.
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Using male hooded Lister rats the effects of GABAergic and serotonergic treatments alone and with chlordiazepoxide (CDP) were compared with the behavioral effects of CDP in a conditioned conflict procedure with three components; Reward, Time Out, and Conflict. CDP (2.5, 5.0, and 10.0 mg/kg ip) dose- relatedly increased punished and time out responding, but increased rewarded responding in an inversely dose-related manner. Punished responding was enhanced by chronic treatment to a rate which remained stable between 9 and 19 injections. The GABA transaminase inhibitor ethanolamine-O-sulfate (EOS), given chronically in drinking water (5.0 mg/ml), increased punished responding linearly to a high stable level after 2-3 weeks. Rewarded and time out responding were less substantially increased. CDP given with EOS dose- relatedly increased time out and punished responding substantially above the rates found with either treatment alone. The GABA antagonist picrotoxin blocked the increase in punished and time out responding found with EOS and CDP alone. The tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA; 100 mg/kg x 3) linearly increased punished responding for the first week of treatment. CDP with PCPA selectively and significantly increased punished responding above the rates for either treatment alone, but the increases were not as substantial as those with EOS + CDP. The serotonin reuptake inhibitor Wy 25093 reduced increases in time out and punished responding under CDP, and the precursor 5-hydroxytryptophan (5-HTP) counteracted increases in punished responding under PCPA but also substantially reduced rewarded responding. These results provide evidence that both increased GABA and decreased serotonin transmission are involved in the anticonflict effects of CDP, as EOS and PCPA both mimicked and potentiated effects of CDP, while picrotoxin, Wy 25093, and 5-HTP counteracted them.(ABSTRACT TRUNCATED AT 250 WORDS)
The study was designed to determine whether the neural lateralization of vocal perception in Japanese macaques depends on the acoustic properties of the calls used or their communicative significance. Four monkeys--two Japanese macaques and two comparison macaques--were trained to discriminate among monaurally presented exemplars of two classes of vocalizations from the Japanese macaque's repertoire. Once the subjects mastered the discrimination, they performed at equivalent accuracy levels for 150 sessions. However, during this time the Japanese monkeys showed a right ear performance advantage, whereas the comparison monkeys showed no ear advantage. In order to assess whether the comparison and Japanese monkeys were attending to the same acoustic cue when performing the discrimination, a generalization test was conducted with 27 novel vocalizations. The individual monkeys' generalization gradients were highly similar and revealed that all subjects were in fact listening to the same feature of the calls. These findings, coupled with the fact that the calls were of biological significance to the Japanese monkeys alone, suggest that the laterality effect is related, in some fashion, to the communicative valence of the signals rather than their purely physical characteristics.
Previous studies have shown reduced levels and total urinary excretion of prostaglandin E2 in a heterogeneous population of patients with hypertension. The following study was undertaken to extend these observations to focus on the influence of age and blood pressure on renal prostaglandin E2 excretion in males. Four groups of human subjects were studied on an ad libitum diet of at least 2 g salt per day: group 1 consisted of normal young men; group 2 consisted of young men with essential hypertension; group 3 consisted of older nonhypertensive men; group 4 consisted of older hypertensive men. Reduced urinary prostaglandin E2 excretion was seen in the elderly hypertensive group but not the young hypertensives. Thus, when all hypertensives were compared to control the reduced prostaglandin E2 excretion was accounted for primarily by the elderly hypertensives. The reduction of prostaglandin E2 excretion could not be accounted for by normal ageing alone. Whether cause or effect, alterations of renal prostaglandin physiology accompanied hypertension in elderly men. No clear alteration of prostaglandin E2 physiology was noted in young male hypertensives.
Normal human globulin fraction 1 (NHG-1) produced cytotoxicity and/or cytostasis as well as inhibition of protein synthesis in 8 well-characterized human tumor cell lines (4 breast cancer, 1 colon cancer, 1 melanoma, and 2 leukemia) and in 2 variants of murine B-16 melanoma. NHG-1 was not cytotoxic for the Chang liver cell line, a normal kidney embryo line, or for normal lymphocytes or macrophages when used in lower concentrations but was growth inhibitory for normal cells in higher concentrations. Although lymphocyte blastogenesis with phytohemagglutinin (PHA) was inhibited by high concentrations of NHG-1, augmentation of the lymphocyte PHA response was seen at lower concentrations, suggesting a lymphokine-like effect. Preincubation with the mitogen partially nullified these NHG-1 effects (suggesting the need for cell surface binding). Although NHG-1 antitumor activity was confirmed in selected human and murine tumor cell lines, the mechanism of its activity is unknown. Occurrence of NHG-1 in the alpha 2-globulin region (an area rich in immune-regulating factors) suggests that NHG-1 may have general "cytokine"-like effects and may be capable of regulating replication of both normal and transformed cells.
Antihypertensive medications have a variable effect on renal hemodynamics and may contribute to renal insufficiency in some patients. Since clonidine has actually been found to improve renal hemodynamics in patients with essential hypertension, we studied the effects of clonidine therapy in patients with renal transplant hypertension. Baseline measurements of BP and renal hemodynamics were made in six patients after two weeks of therapy with furosemide. Clonidine was then added and titrated until BP was controlled. Repeated measurements of renal hemodynamics were made four and 16 weeks after clonidine therapy was begun. Glomerular filtration and effective renal plasma flow as assessed by inulin and aminohippurate sodium clearances were preserved during prolonged clonidine therapy.
Rate nephelometry is a fast and convenient method for Lp(a) quantification. The linearity in the range of the physiological serum concentrations is good and there is good correlation with other immunochemical methods. The antibody consumption is some 50% higher when compared to the Laurell procedure if light scatter is measured in the RU mode. Measurements in the SU mode on the other hand consume less antibody than the Laurell procedure. The endpoint method, however, is more time-consuming and considered to be less accurate. In addition, only clear samples should be used. Lipemic sera should be cleared by lipase treatment or by high speed centrifugation. The treatment of samples with detergents causes a pronounced reduction of the immunochemical response and thus should be avoided.
5-Fluorouracil (5-FU) and 2 alpha-methyldihydrotestosterone propionate (MDTP) have effectively induced complete regressions of induced rat mammary carcinomas; in combination, regressions were additive and synergistic. Present aims were to determine whether similar antitumor effects were obtainable with a human mammary carcinoma, MCF-7, and to affirm the synergism of 5-FU and MDTP. After incubation in vitro for 3 days and exposure to drug for another 2 days, cell counts and/or determinations of total cell protein revealed growth inhibitions of 16-87% by 5-FU at 130-1300 micrograms/ml and 16-94% by MDTP at 0.36-360.5 micrograms/ml. Combinations of 5-FU and MDTP at the same inhibitory doses (ID) yielded approximately additive growth inhibitions. Algebraic and geometric (isobole) methods of analyses showed that these inhibitions were additive or synergistic, depending on the iso-effective dose used. Precursor incorporation into macromolecules also showed approximately additive effects for MCF-7 cells treated with 5-FU and MDTP, each at ID15. These data demonstrate significant additive growth-inhibitory activity of 5-FU and MDTP in combination against MCF-7 in vitro, thus affirming their antitumor effects in vivo.
Platelet dynamics in chronic liver disease have been studied using 111Indium-8-hydroxyquinolone (111In-oxine) as a platelet label. In 20 patients, mainly with alcoholic cirrhosis, the platelet mean life span was reduced in 12 and the splenic platelet pool increased, often markedly so, in 15. However, the platelet count was not significantly related to mean bile span, the splenic platelet pool, or spleen size. Whereas splenic platelet pool size is related to spleen size in most of the haematological 'big-spleen' syndromes, this did not apply to those patients with chronic liver disease. Technically, 111In-oxine is a more appropriate platelet label than 51Cr in ill and thrombocytopenic patients with liver disease.
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The study of nucleic acid hybridization is facilitated by computer mediated fitting of theoretical models to experimental data. This paper describes a non-linear curve fitting program, using the 'Patternsearch' algorithm, written in BASIC for the Apple II microcomputer. The advantages and disadvantages of using a microcomputer for local data processing are discussed.
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The tumor necrosis-inducing factor (TNF) found in sera of Corynebacterium parvum-treated, endotoxin-stressed BALB/C and outbred albino CD-1 mice has been purified to a single band of protein by polyacrylamide gel electrophoresis after identification and removal of contaminating albumin and transferrin. This purified TNF has a molecular weight of 140,000, is glycoprotein in nature, and migrates on free electrophoresis as an alpha 2-globulin. TNF activity was continuously monitored during purification by bioassay in vitro (tumor cell lysis) and was confirmed by demonstration of induction of tumor necrosis in vivo. A single target tumor cell line, murine myelomonocytic leukemia (WEHI/3), was used in both assays. In the in vivo assay, controls were heat-inactivated samples of TNF. As additional controls, a line of TNF-resistant WEHI/3 cells was used in the in vitro assay. Results from in vivo radiolabeling of TNF-sensitive and TNF-resistant cells indicated a difference between their cytoplasmic peptide profiles. Optimal TNF production was not altered in C. parvum-endotoxin-treated mice by treatment with silica, a substance that is specifically toxic for macrophages. Exposure of mice to 650 rad whole-body radiation, which is not markedly damaging to macrophage elements in the reticuloendothelial system, completely abrogated the ability of the mice to produce TNF after C. parvum-endotoxin treatment. These findings suggest that in the sera of C. parvum-endotoxin-treated mice the protein that induces necrosis in tumors may not be of macrophage origin.
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