[Clinical application of angiotensin II derivatives].
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Biomedical subjects
Publications and source records attributed to F Oseko.
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Effects of des-asp1-angiotensin II (angiotensin III) on blood pressure and aldosterone secretion were examined in man. Angiotensin III was equipotent with val5-angiotensin II amide in the stimulation of aldosterone production, but had only 20% of the pressor activity of the later. These results are consistent with those previously reported by other investigators in animals.
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To elucidate the effects of sulpiride-induced (300 mg daily) long-term (64 days) hyperprolactinemia on basal and hCG-stimulated plasma testosterone (T), hCG was given to five normal men five times at 2-week intervals (before sulpiride administration and at 2, 4, 6 and 8 weeks). Mean integrated hCG responses of plasma T did not change significantly as compared with baseline. However, mean (+/- SEM) basal plasma levels of T decreased significantly (P less than 0.05) from 1011 +/- 148 ng/dl to 852 +/- 13 at 2 weeks, 520 +/- 53 at 4 weeks, 572 +/- 137 at 6 weeks and 554 +/- 140 at 8 weeks. These results suggest that sulpiride-induced hyperprolactinemia (73.8 ng/ml, the average of mean values obtained at 2, 4, 6 and 8 weeks) for 64 days does not suppress secretion of T in response to hCG in spite of a decrease in basal plasma T concentrations. It is unlikely that the low concentrations of plasma T are due to direct effects of hyperprolactinemia on the testis.
In order to elucidate the relationship between plasma dehydroepiandrosterone (DHA) and sulpiride-induced hyperprolactinemia (of 60 day duration) in normal men, five normal men (aged 27-46) were administered daily 300 mg of sulpiride orally for 60 days to induce hyperprolactinemia. Plasma levels of prolactin, DHA and cortisol were measured by radioimmunoassay before sulpiride treatment, at day 14 and day 60 after initiation of the treatment. Plasma levels of prolactin after the administration rose significantly (P less than 0.001) to 71.6-95.3 ng/ml in four out of the five subjects compared with those of the controls. In the same four subjects the mean DHA values in plasma were elevated significantly (P less than 0.05) to 877 +/- 160 ng/dl from the mean baseline values (669 +/- 91 ng/dl). The elevated values remained during sulpiride treatment. Plasma levels of cortisol did not change significantly during sulpiride administration in all subjects. Our results suggest that sulpiride-induced hyperprolactinemia sustained at least 14-60 days in normal men stimulates the adrenal cortex to secrete DHA.
The natural killer (NK) cell activity of patients with pulmonary tuberculosis (TB) was studied using blood samples. The patients with pulmonary TB showed higher NK activity to 10 out of 12 NK-sensitive target cell lines than healthy subjects did. When NK activity was compared between active and inactive stages of the disease, the patients with active TB demonstrated higher NK activity than did patients with inactive TB. Furthermore, active patient displayed cytolysis to one out of 4 NK-resistant target cell lines. In study of NK cell cyotoxicity at single cell level, higher killing activity than binding activity to target cells was observed in patients at an active stage. Morphological and surface marker analysis of peripheral mononuclear cells showed an increase in CD16+ cells in patients with pulmonary TB. These results suggested that NK cell activity is augmented qualitatively and quantitatively in patients with pulmonary TB.
Sixty-eight patients with various malignancy was examined for their natural killer (NK) cell activity against 14 target cell lines. The group consisted of 10 patients with gastric cancer, 10 patients with lung cancer, 8 patients with hepatoma, 11 patients with cancer of female genital organs, 14 patients with malignant lymphoma and 15 patients with acute myelogenous leukemia (AML). The target cells from a variety of lineage were selected to examine the disease-related specificity in NK cell activity. The peripheral mononuclear cells from patients with gastric cancer did not show a decrease in NK activity against 14 targets including gastric cancer cell lines. Other patients except for AML demonstrated low NK activity against one or two target cells out of 14 targets. Whereas, NK activity in patients with AML was remarkably depressed against 10 target cells out of 14. At single cell assay, killing ability rather than binding activity to target was markedly impaired in AML. Comprehensively, the data demonstrated the marked difference in the NK level between the patients with solid tumor and the patients with hematopoietic malignancy. There existed neither disease-related specificity in NK cytolysis, nor correlation in NK levels and clinical severity in the patients with malignancy. These results suggested that it was very difficult to evaluate the anti-cancer capacity in patients with malignancy by NK activity alone.
The natural killer (NK) cell activity of the blood and marrow was studied in patients with acute myelogenous leukemia (AML). NK activity of the cells from blood and marrow was significantly decreased in AML to three target cell lines. Both binding and killing capacities of the effector cells were deeply depressed in the blood as well as in the marrow at single cell assay. Surface phenotypic analysis showed a significant decrease in CD 11+ cell subsets, but not in CD 16+ or Leu-7+ cells, in both blood and marrow cells from AML. A significant decrease of large granular lymphocytes (LGL) was also displayed in these samples at morphological examination. The effector cells from AML patients poorly responded to interferon stimulation in NK cytolysis. Taken together, a decrease in CD 11+ cell population with LGL morphology appeared to be responsible for the impaired NK activity in patients with AML.
The mechanism which produces marrow failure in idiopathic aplastic anemia is still unknown. Recent investigations have suggested the crucial role of NK cells in the regulation of normal hematopoiesis. In this study, the cytotoxic activity of mononuclear cells from human bone marrow and peripheral blood was examined against three NK-sensitive target cell lines in 15 patients with aplastic anemia as well as 21 normal subjects. Marrow mononuclear cells from aplastic anemia demonstrated a high cytotoxicity comparable to peripheral blood NK cells to these target cells. Neither large granular lymphocytes nor the cells expressing known NK cell surface phenotypes increased in aplastic marrow cell elements. The aplastic marrow cells showed strong killing activity rather than binding at single cell assay. They consisted of non-adherent and adherent cell population in plastic adherence and were unresponsive to IFN treatment. The existence of cytotoxic cells with high NK-like activity may be responsible for the mechanism of marrow failure in aplastic anemia.