[Instruction on the basis of nursing in combination with lectures and clinical training].
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Biomedical subjects
Publications and source records attributed to A Matsuda.
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Ontogenic development and the lymphokine responsiveness of human NK cell activity against K562 target cells in peripheral blood lymphocytes were evaluated in fetuses, premature infants, and term neonates by using a 4-hr 51Cr-release assay. Basal NK activity and NK boosting by lymphokines were comparatively assayed after an 18-hr incubation with medium alone, recombinant human IFN-gamma (1000 U/ml), and recombinant human IL 2 (25 U/ml), respectively. Lymphocytes from 20-wk-old fetuses lacked NK cell activity even after the pretreatment with IFN-gamma. Low, but significant levels of NK activity and NK boosting by IFN-gamma were observed in premature infants after 27 wk of gestation, with a progressive intrauterine maturation of these activities. Both basal NK activity and NK boosting by IFN-gamma in term neonates were still lower than those of adult controls. The grade of NK boosting by IFN-gamma appeared to depend on the development of basal NK activity. Contrary to IFN-gamma, IL 2 could induce marked NK activity even in 20-wk-old fetuses who lacked both basal and IFN-gamma inducible NK activities. NK boosting by IL 2 was much more efficient than that by IFN-gamma at any period of human life. The facts that IL 2-induced NK boosting could occur without any appreciable production of IFN-gamma in neonatal lymphocytes, and that ample neutralizing doses of anti-IFN-gamma antibody hardly suppressed IL 2-mediated NK boosting even in adult lymphocytes, indicated that the effect of IL 2 on NK boosting might be independent of IFN-gamma production. On the basis of the ontogenic differences in the development of the lymphokine responsiveness of NK cell activity and on the different NK boosting mechanisms of these lymphokines it was suggested that so-called human "pre-NK cells" might be divided into IFN-gamma sensitive and IL 2-sensitive cells. Whether these cell populations belong to different cell lineages or different maturation stages of the same cell line, however, remains unsettled.
Human newborn natural killer (NK) cell activity against K562 target cells was observed to be low compared with adult controls. Although Leu-7 (HNK-1)+ cells were negligible in cord blood, the proportions of Leu-11+ cells were equal to those of adult peripheral blood. Leu-11+ cells sorted from cord blood lymphocytes, as well as from adult lymphocytes exhibited the morphology of granular lymphocytes. In this study, we have investigated the phenotypic characterization of recombinant interleukin 2 (rIL 2)-induced cytotoxic lymphocytes against K562 cells by using anti-Leu-11 monoclonal antibody. Spontaneous cytotoxicity of lymphocytes was restricted to Leu-11+ cells in cord blood, as well as in adult blood, but this activity was low in cord blood Leu-11+ cells as compared with that of adult ones. NK cell activity of adult Leu-11+ cells could not be additionally enhanced after an 18-hr incubation with rIL 2(25 U/ml), whereas rIL 2 could potentiate the cytotoxicity of cord blood Leu-11+ cells approximately to the adult levels. It should be noted that cytotoxic activity of both Leu-11- cells from cord blood and adult blood that had no basal NK cells activity could be significantly potentiated by rIL 2. On the other hand, lymphokine-activated killer cells cytotoxic for HL-60 cell line could not be generated, and no proliferation of the lymphocytes was detected after an 18-hr incubation with rIL 2. It was shown that rIL 2 could not enhance the ability to bind to target cells in Leu-11+ and Leu-11- cells by means of a single cell conjugate assay, but the rate of target lysis of Leu-11+ cells from cord blood was significantly enhanced by rIL 2. These results suggested that rIL 2-induced cytotoxic effector cells were heterogeneous, and rIL 2 might potentiate the cytotoxicity of functionally immature NK cells or NK precursor cells.
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A procedure for the simultaneous analysis of brain pipecolic acid, proline, gamma-aminobutyric acid and glycine--amino acids with potent inhibitory actions on the central nervous system--was developed. The identification and quantification of the amino acids were performed with a gas chromatographic--mass spectrometric--computer system using deuterium-labelled amino acids as the internal standards. After separation of the amino acids by high-performance liquid chromatography, the methyl ester heptafluorobutyryl derivatives were prepared. The lower limit of quantification for this method is at the picomole level. The usefulness of this chromatographic procedure has been demonstrated by measurement of trace amounts of pipecolic acid in rat brain.
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At various times after clinical embolism, bronchial arteriography was performed in 23 patients with documented pulmonary embolism. In 17 patients with no radiologic infiltrates, chronic stage bronchial arteriograms demonstrated bronchial-to-pulmonary arterial collaterals with antegrade filling of distal pulmonary arteries. No collateral circulation was detected at the acute stage. In one case of massive pulmonary embolism with well-developed bronchial-to-pulmonary arterial collaterals and antegrade filling of distal pulmonary arteries, brisk back-bleeding occurred at surgery, and an excellent therapeutic result following thromboembolectomy was gained. By contrast, in six patients with radiologic infiltrates, only one patient (subacute stage) showed bronchial-to-pulmonary arterial collaterals; these were peripheral and associated with retrograde, not antegrade, filling of distal pulmonary arteries. Bronchial arteriography has provided information about the development of collateral circulation in pulmonary embolism, and might be useful when thromboembolectomy is planned.
The family history of diabetes in parents and siblings was analyzed in relation to the age of onset and previous obesity in patients with non-insulin-dependent diabetes mellitus (NIDDM). The frequency of a positive family history of diabetes in parents was higher in patients with the onset of diabetes earlier than 40 years of age than in those who developed diabetes after 50 years of age (32% vs 12%, p less than 0.001). The frequency of a positive family history in siblings was about 20% and fairly constant in patients who became diabetic after 30 years. The prevalence of diabetes in siblings was higher in patients with diabetic parents than in those without diabetic parents (p less than 0.001). The higher frequency of diabetes in parents of young-onset patients remained significant even in a comparison of patient groups of similar ages (50-59 years) at the interview. Patients with definite obesity in the past had a significantly lower frequency of family history of diabetes in parents (p less than 0.001), and a lower prevalence of diabetes in their parents (p less than 0.001) and siblings (p less than 0.05) than did patients without obesity. The frequency of patients who had diabetic siblings did not differ between obese and lean groups. These data suggest that implications of the presence of diabetes in parents and in siblings are different in family history studies.(ABSTRACT TRUNCATED AT 250 WORDS)
The pulmonary fibrosis caused by peplomycin (PEP) was studied in terms of oxygen toxicity using ICR mice. When 16 micrograms of PEP was administered intratracheally in mice after exposure to the air containing 75% O2 for 10 days, the pulmonary fibrosis was completely suppressed, while when mice were exposed to 75% O2 after the administration of PEP, the fibrosis was much severe than that of mice raised in atmospheric air. In 50% O2, similar oxygen effect was also observed, but it was weaker than that in 75% O2. In 90% O2, the oxygen toxicity was observed in mice without administration of PEP. When mice were exposed to 75% O2, the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which are relevant to the detoxication of active oxygen species, were not increased in the lung, but the levels of reducing agents such as glutathione and ascorbic acid, and high molecular substances having 1O2-scavenging activity were enhanced. The results suggest that these materials have some roles to decrease the pulmonary fibrosis caused by PEP.
Anticancer activity and pulmonary toxicity of bleomycin and peplomycin in mice were found to be dependent on administration schedules and routes. That is, at the same total dose of 50 mg/kg, the anticancer activity against Lewis lung carcinoma was most strongly exhibited by continuous infusion of peplomycin for 7 days among all schedules tested and decreased in the order of the continuous infusion greater than 4 times injections per day for 10 days greater than daily injection for 10 days greater than daily injection for 2 days. In contrast, the pulmonary toxicity occurred lowest in the continuous infusion and strongest in daily injection for 10 days among the schedules. With respect to administration routes, the anticancer activity and the pulmonary toxicity of them were strongly exhibited in the order of i.v. much greater than i.m. greater than s.c. greater than i.p., except that no route dependency was observed in the continuous infusion. The pulmonary toxicity of peplomycin was lower than that of bleomycin in every administration schedules and routes. From these results, the continuous infusion was concluded to be the best schedule to increase the anticancer activity and to reduce the pulmonary toxicity.
Biological effect of bestatin in combination with bleomycin against rat ascites hepatoma AH 66 was investigated. The combined use of bestatin and bleomycin both at a dose of 0.5 mg/kg was found to have a strong inhibition of the tumor growth. The combined effect was also confirmed histologically as follows. In combination group, increase of necrobiosis area in the tumor lesion, augmentation of infiltration of lymphocytes and macrophages around the solid tumors, and marked replacement of necrotic area by fibrous granular lesion were stronger and more rapidly than that in the other group.
A method was developed to synthesize 2'-deoxy-8,2'-methylene-cycloadenosine (1) and -cycloguanosine (2) which were new carbon-bridged cyclopurine nucleosides fixed in a high-anti torsional angle region. 3',5'-Di-O-acetyl-8-methanesulfonyl-2'-O-p-toluene-sulfonyladenosine+ ++ (3) or 2-acetamido-9- (3,5-di-O-acetyl-2-O-p-toluenesulfonyl-beta-D-ribofuranosyl)-6- ethoxy-8-methanesulfonyl-purine (9) was treated with sodium salt of ethyl malonate to give the cyclized nucleosides (4 and 10) in good yields, respectively. Subsequent decarboxylation and deblocking of 4 and 10 afforded 1 and 2 in crystalline form, respectively.
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The authors report spongy degeneration in experimental scrapie (second passage) in mice. The scrapie agent was originally isolated from Suffolk sheep imported from Canada and diagnosed histopathologically to be infected with scrapie by intracerebral inoculation into JCL/ICR mice. Ten female SIc/ICR mice, 4 weeks of age, were injected intracerebrally in the right frontal lobus with 20 microliter of 10(-1) or 10(-4) dilution of JCR/ICR mice brain homogenate involving scrapie agent. All animals showed signs of the advanced stages of the disease, clinically manifested by lassitude, arched backs, lethargy and paresis of hind quarters. They were sacrificed five to six months post inoculation, and sections of the brain and spinal cord were examined by light and electron microscopy. Focal symmetrical spongiform lesions were seen light microscopically in the cerebral mantle, thalamus, hypothalamus, midbrain, medulla oblongata, cerebellum and cervical mark. There was evidence that these lesions tended to be more intense in the mice inoculated a higher concentration of scrapie agent. Astrocytic proliferation was present in the deep layer of cerebral gray matter, white matter, corpus callosum, dorsal part of hippocampus and thalamus. No leukocytic infiltration was observed. Electron microscopically, the spongiform lesions were shown to be caused by vacuolation or swelling within the neuropil, and vacuolation and focal swelling in the neuronal perikaryon. The changes in the neuronal perikaryon were caused by enlargement of endoplasmic reticulum and cisterns of the Golgi apparatus, accompanied by spherical swelling of a part of the cytoplasm. The vacuolation near or within the neuron produced deformation of the cell contours and displacement of the nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)