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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 613 records · Page 34Linked to original sources

Inhibition of tumor cell growth by low-boiling-point-saturated fatty acids isolated by molecular distillation and reversed phase liquid chromatography of hydrolysates of uncytotoxic wool grease secreted from sheep sebaceous gland.

We showed that massive growth of mouse Ehrlich ascites carcinoma (EAC) cells was not inhibited by wool grease secreted from the sheep sebaceous gland, whereas wool fatty acids separated by saponification of wool grease was growth-inhibitory. We then fractionated wool fatty acids into 9 fractions using molecular distillation (80-200 degrees C; 1 x 10(-2) mmHg) and found a marked antitumor activity in a low-boiling-point (< 80 degrees C) fraction (MW 200-300; C10-C20), which was further separated by reversed phase liquid chromatography on an octadecylisilica gel column, resulting in 5 fractions. The second most hydrophobic fraction (C8Si-4) obtained was the most growth-inhibitory to EAC cells cultured or implanted into mice, more marked than the antitumor glycopeptide bleomycin. C8Si-4 was suggested to be a mixture of a normal-chain C16-saturated fatty acid and two branched-chain kinds of saturated C16-iso- and C19-anteiso-fatty acids without hydroxyl groups according to gas chromatography-mass spectrographic analysis. Thus low-boiling-point saturated fatty acid moieties in some wool grease molecules were shown to become growth-inhibitory in vitro and in vivo only after released in the free acid form by esterolysis.

Animals↗

[Bronchial hyperresponsiveness before and after percutaneous transluminal mitral commissurotomy in patients with mitral stenosis].

To study the effects of percutaneous transluminal mitral commissurotomy (PTMC) on bronchial responsiveness to inhaled methacholine in patients with mitral valve stenosis (MS), methacholine inhalation tests and pulmonary function tests were done in 10 patients with MS before and one week after PTMC. The mean log cumulative dose producing a 35% decrease in respiratory conductance (PD35Grs) was significantly higher after PTMC in nine patients in whom PTMC was successful (p < 0.05). There were no significant changes in the results of pulmonary function tests after PTMC. One patient had severe mitral regurgitation after PTMC, and a decrease in PD35Grs. Six of the other nine patients in whom PTMC was successful continued to be hyperresponsive to inhaled methacholine. These data show that bronchial hyperresponsiveness in patients with MS is less severe after PTMC, concomitant with the relief of pulmonary congestion, and they suggest that the remaining bronchial hyperresponsiveness is responsible for peripheral airway narrowing with organic remodeling.

Bronchial Hyperreactivity↗

[Bronchial hyperresponsiveness and relaxability in patients with mitral stenosis].

To study the differences in bronchial responsiveness to inhaled methacholine and salbutamol between patients with mitral valve disease those with bronchial asthma a bronchial provocation test (Astograph) and pulmonary function tests were done in 25 patients with mitral stenosis (MS) and 18 patients with bronchial asthma (BA). We derived an index of airway reloxability from the effect of salbutamol after precontraction with inhaled methacholine. This index was the change in respiratory conductance (Grs) over time during inhalation of salbutamol (SGrs-d). It was computed as SGrd = delta Grs/delta t. Eighteen patients with MS (72%) showed bronchial hyperresponsiveness (BHR) to methacholine. The MS patients with BHR (MS(+)) had lower values of the ratio of the forced expiratory volume in one second to the forced vital capacity (FEV/FVC) and maximal expiratory flow at 25% of vital capacity (V25) than MS patients without BHR (MS(-)). There was a significant correlation between V25 and the log cumulative dose producing a 35% decrease in respiratory conductance (PD35Grs) in MS(+). The mean log Dmin of MS(+) was significantly higher than that of the patients with BA (0.14 +/- 0.64 log units and -0.30 +/- 0.65 log units, p < 0.05, respectively). The mean log PD35Grs of MS(+) was also significantly higher than that of the patients with BA (1.09 +/- 0.53 log units and 0.45 +/- 0.66 log units, p < 0.01, respectively). Indices of relaxability (SGrs-d and SCrs-d/Grs-d) in MS(+) were significantly lower than in BA patients. Indices of hyperresponsiveness and relaxability were both significantly lower in patients with MS than in patients with BA.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗

Inhibition of skin xenograft rejection by depleting T-cell receptor alpha beta-bearing cells without T-cell receptor gamma delta-bearing cells or natural killer cells by monoclonal antibody.

We compared the effects of in vivo administration of the anti-T-cell receptor (TCR) alpha beta monoclonal antibody (mAb) (H57-597) to those of the anti-CD3 mAb (145-2C11), with or without anti-NK1.1 mAb (PK136), on xenogeneic skin graft survival in mice. In anti-TCR alpha beta mAb-treated B6 mice, F344 rat skin grafts survived for about 54 days, whereas in anti-CD3 mAb-treated B6 mice with or without anti-NK1.1 mAb treatment grafts survived about 25 days. In anti-TCR alpha beta mAb-treated B6 mice, TCR alpha beta-bearing T-lymphocyte function was completely abrogated, although TCR gamma delta-bearing T-lymphocyte function was still intact on day 9. In the anti-CD3 mAb-treated mice, the functions of both types of T lymphocytes were completely abrogated. On day 32, when most of the skin xenografts had been rejected in the anti-CD3 mAb-treated mice, the functions of both T lymphocytes had recovered considerably, and could actually respond to F344 antigens. In contrast, the function of TCR alpha beta-bearing cells had only partially recovered in the anti-TCR alpha beta mAb-treated mice. Finally, natural killer (NK) activity in the anti-TCR alpha beta mAb-treated mice was intact on day 32, when rat skin grafts still survived. In contrast, NK activity in the anti-CD3 mAb plus anti-NK1.1 mAb-treated mice did not recover on day 32, when skin xenografts had already been rejected. These results suggest that TCR gamma delta-bearing T cells and NK cells by themselves, at least in the absence of TCR alpha beta-bearing T cells, do not mediate xenogeneic skin graft rejection in mouse/rat combinations.

Animals↗

[HLA-linked susceptibility to intractable vasculitis syndrome].

Sixty-four patients with Takayasu arteritis, 204 patients with rheumatoid arthritis (RA), 53 patients with systemic lupus erythematosus (SLE) and 64 patients with mixed connective tissue disease (MCTD) in the Japanese population were typed for HLA class II genes at DNA level. The results suggest that susceptibility to Takayasu arteritis is controlled by HLA-B52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1 *0601-DPA1*02-DPB1*0401 haplotype, because the frequency of that HLA haplotype was increased with statistical significance in the patients as compared with that in the healthy controls. On the other hand, the HLA-DRB1*0405-DQA1*0301-DQB1*0401 haplotype was associated with the susceptibility to RA. Susceptibility to SLE and MCTD are controlled by the HLA-DRB1 *1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype and the HLA-DRB1*0401-DRB4*0101- DQA1*0301-DQB1*0301, haplotype respectively. These observations clearly indicate the presence of HLA-linked disease susceptibility genes to Takayasu arteritis, RA, SLE and MCTD, and the difference in HLA-linked genetic background between these four diseases.

Amino Acid Sequence↗

A case of acute pancreatitis with hyperlipemia and hyperglycemia induced by alcohol abuse.

A case of acute pancreatitis with hyperlipemia and hyperglycemia induced by alcohol abuse is reported. The case is a 34-year-old man who was admitted to our hospital with a complaint of severe abdominal pain. He had been drinking 700ml approximately 1400ml of whisky daily prior to admission. At the time of admission, his serum amylase was elevated to 1833 U. Abdominal computerized tomography revealed edematous swelling of the pancreas. His serum glucose level was 926 mg/dl, cholesterol 754 mg/dl and triglyceride 3,530 mg/dl. Following successful treatment of acute pancreatitis and hyperglycemia with gabexate mesilate and insulin, his serum glucose, lipid and pancreatic enzyme levels decreased to the normal range. This case is considered to be one of acute pancreatitis with diabetic lipemia induced by alcohol abuse.

Acute Disease↗

Morphological studies on the placenta.

Morphological studies were done on 109 placentae of 6 to 43 gestational weeks. Soft x-ray figures are useful for detecting the development of the placenta, which is closely correlated to enlargement of cotyledon and vascular growth in the chorionic villi. At histological figures, chorionic villi, corresponding to intermediate mature villi at the early gestational weeks, reveal large size with edematous stroma and prominent interstitial cells. Their size becomes smaller with aging, with decreased interstitial cells and stroma. At the early gestational period until 23 weeks, chorionic villi are lined by two cell layers of S-(syncytial) and C-(cytotrophoblastic) cells. After 24 gestational weeks C-inner lining decreases in number. Syncytial knots become marked after 32 weeks. As aging, the intervillous space becomes narrow and is occupied by the small sized terminal and mature chorionic villi with congestive capillaries. Syncytial knots and fibrin deposit around chorionic villi are increased with placental aging. By the immunohistoenzymatical examination, S-lining is positive by hCG (human Chorionic Gonadotropin) at the early gestation, but is markedly positive by hPL(human Placental Lactogen) and SP-1 (Specific Protein 1) lately.

Chorionic Villi↗

Pathological studies on the placenta from pre-term and term maternal toxicosis.

Fifty one placentae with maternal pre-term and term toxicosis were studied pathologically. In the severe pre-term maternal toxicosis, the placenta reveals hyperplasia of syncytial cytotrophoblasts(S-cells) with knots, fibrin deposit at their surface, fibrinoid degeneration of the stroma, in addition to marked interstitial fibrosis of chorionic villi. The basement membrane is thick and cytotrophoblasts(C-cells) are scattered beneath it. Decidual arteries are hyalinized, but a few decidual arteries are thick and almost obstructed in their lumina. On the other hand, the placenta of maternal term toxicosis show chorionic villi with few C-cells under the thin S-cell lining. Their basement membrane is thin with well developed vasculosyncytial membrane. Decidual arteries are more hyalinized and widened. These pathological changes seen in term maternal toxicosis are the severer than those of placental aging.

Eclampsia↗

Bone turnover and calcium metabolism during 20 days bed rest in young healthy males and females.

Bone is a dynamic tissue that functions not only as a mechanical support, but also as a major component of the metabolic and endocrine systems maintaining mineral homeostasis. It has been shown that immobilization induces decalcification of bone. To evaluate the effect of immobilization on bone mineral density and calcium metabolism, we investigated 9 young healthy males and females during 20 days bed rest. Three methods for measuring bone mineral density were performed to quantify whole body and regional bone changes: 1) dual energy X-ray absorptiometry, 2) quantitative computed tomography, and 3) multiple scanning X-ray photodensitometry, respectively. Bone mineral density showed a rapid decreasing tendency, especially in both lumbar and metacarpal bones (mean +/- SE: 4.6 +/- 0.6% and 3.6 +/- 0.4%, respectively). Urinary daily excretion of deoxypyridinoline, a sensitive marker of bone matrix resorption, tended to increase by day 10, and to decline by day 20 (mean +/- SE: 42.2 +/- 1.4, 27.6 +/- 2.2 nmol day-1, respectively). However, neither alkaline phosphatase nor tartrate-resistant acid phosphatase, both markers of osteoclast and mature osteoblast function, changed. These results showed that in the early stage of immobilization, bone matrix might be resorbed without any activation of osteoclasts, resulting in rapid decalcification of vertebral and cortical bones without any discernible changes in anatomical structure.

Absorptiometry, Photon↗

Metabolic turnover of bone and peripheral monocyte release of cytokines during short-term bed rest.

Immobilization induces abnormal bone metabolism and rapid decalcification. Measurements of bone mineral content disclosed rapid decalcification, especially in lumbar vertebral and metacarpal bones in our short-term 20-day bed rest study. Many factors could contribute to the marked demineralization. The activities of osteoclasts and osteoblasts were studied by following serum levels of tartrate-resistant acid phosphatase and alkaline phosphatase, biomarkers for osteocyte activity. There were no alterations in these enzymes during bed rest. However, urinary excretion of pyridinium cross-links, resorption markers of bone matrix itself, increased by day 10 with subsequent decrease at day 20. So decalcification was induced without any relation to osteoclast activity. As cytokines strongly modulate the function of osteoclasts, peripheral monocyte release of interleukin 1 alpha and tumor necrosis factor alpha were assayed to determine the contribution to this rapid demineralization. Cytokines were released transiently by day 7 and later rapidly decreased. However, there was no correlation between cytokine release and bone matrix resorption.

Acid Phosphatase↗

Psychological effects of bed rest in young healthy subjects.

In order to evaluate the effect of immobilization during bed rest on mental health, we performed psychosomatic investigations of 6 young males and 3 young females before, during and after 20 days bed rest. The psychological state was repeatedly assessed by measuring the following indices: 1) Zung's self-rating depression scale, 2) Cornell medical index, and 3) the General Health Questionnaire. Zung's self-rating depression scale is a measure of the state of depression, while Cornell medical index and the General Health Questionnaire are utilized for detection of neurosis. Although no influence of bedrest on Cornell medical index was seen, Zung's self-rating depression scale and the General Health Questionnaire displayed a tendency to development of depression and neuroses, respectively. This tendency had disappeared 2 months after the bed rest study. Both Zung's self-rating depression scale and the General Health Questionnaire may be appropriate indices to evaluate the effects of relatively short-term psychological stress due to bed rest. The urinary excretion of 17-hydroxycorticosteroid was used as an indicator of endocrine stress factors, but no significant variation due to bed rest was seen. We concluded that there is a need for further studies combining physiological research with psychosomatic investigations.

17-Hydroxycorticosteroids↗

[Giant serpentine aneurysm followed up for more than 10 years: report of a case and review of the literature].

We report a case of a giant serpentine aneurysm (GSA) located at the left internal carotid artery (ICA) and middle cerebral artery (MCA) treated by ligation of the left ICA with superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. The aneurysm form changed variously during the follow-up period. A 35-year-old man was admitted with severe headache and convulsion. CT scan demonstrated subarachnoid hemorrhage. Left carotid angiogram demonstrated a giant serpentine aneurysm. Ligation of the ICA with STA-MCA anastomosis was performed because of the difficulty involved in clipping. Right carotid angiogram obtained 5 years later revealed disappearance of the tortuous vascular channel and a new aneurysmal shadow at the left carotid bifurcation. The size of the aneurysmal shadow increased gradually over 10 years. MRI and MR angiography which clearly demonstrated the presence of the aneurysm and the vascular channel simultaneously were considered useful methods for diagnosis of GSA. The authors reviewed previous reports of 19 cases and investigated the mechanism of GSA.

Adult↗

Inhibition of allograft rejection by anti-T-cell receptor-alpha beta monoclonal antibodies preserving resistance to bacterial infection.

Anti-CD3 monoclonal antibody (mAb) has been administered in clinical organ transplantation to reverse acute allograft rejection; however, severe immunodeficiency can result from such mAb treatment and cause an increased incidence of opportunistic infections. Therefore, new model systems are required in order to establish better methods for suppressing allograft rejection while preserving resistance to opportunistic infections. In this study, we compared the effects of the in vivo administration of anti-T-cell receptor-alpha beta (TcR alpha beta) mAb, H57-597, with those of anti-CD3 mAb, 145-2C11. Much to our surprise, the in vivo administration of anti-TcR alpha beta mAb prior to skin grafting led to a longer allograft survival than that of anti-CD3 mAb at any of the comparable dosages examined. In the lymphoid organs of mice treated with anti-TcR alpha beta mAb, TcR alpha beta-bearing cells were almost completely depleted, while TcR gamma delta-bearing cells remained at a relatively increased level on day 14 after anti-TcR alpha beta mAb treatment. The in vitro stimulation by anti-TcR gamma delta mAb clearly showed that such TcR gamma delta-bearing cells were functionally intact. Furthermore, the mice treated with anti-TcR alpha beta mAb, but not anti-CD3 mAb, were observed to be resistant to infection with Listeria monocytogenes. Finally, treatment with H57-597, but not with 145-2C11, led to a marked prolongation of skin allograft survival in the thymectomized mice. These results strongly suggest that anti-TcR alpha beta mAb, which partially preserved anti-bacterial resistance, may be more effective in preventing graft rejection than anti-CD3 mAb in the periphery, and indicate that anti-TcR alpha beta mAb may thus be potentially applicable for human transplantation. In addition, these results also indicate that the TcR gamma delta-bearing cells alone, at least in the absence of TcR alpha beta-bearing cells, do not contribute to allograft rejection in vivo.

Animals↗

Role of nitric oxide in ethanol-induced perturbation of hepatic microcirculation in rat liver.

Microcirculatory disturbance is one of the main pathogenetic features of alcoholic liver damage. We have demonstrated that ethanol increased portal pressure, leading to hepatic hypoxia and hepatocellular necrosis. In this ethanol-induced hepatic vasoconstriction, nitric oxide, an endothelial derived relaxing factor, dilated constrictive hepatic vasculature and reduced liver injury by improving the microcirculatory disturbance.

Animals↗

Cytochrome d axial ligand of the bd-type terminal quinol oxidase from Escherichia coli.

Using various spectroscopic techniques, we studied the structure of the dioxygen reduction site of the bd-type terminal quinol oxidase in the aerobic respiratory chain of Escherichia coli. Resonance Raman and FT-IR spectroscopies identified the v(Fe(2+)-CO) and v(C-O) stretching frequencies at 471 and 1980.7 cm-1, respectively, at the cytochrome d center of the dithionite-reduced CO-bound enzyme. The CO ligation in the cytochrome bd complex is considerably different from those of the heme-copper terminal oxidases. Anaerobic addition of NO to the air-oxidized enzyme caused an exchange of cytochrome d-bound dioxygen with NO leading to an appearance of cytochrome d-NO EPR signal. But there is no superhyperfine structure originating from the cytochrome d proximal 14N ligand in the central resonance of the NO EPR signal. These results suggest that cytochrome d axial ligand of the cytochrome bd complex is likely a histidine residue in an anomalous condition or other than a histidine residue and, therefore, the molecular structure around the dioxygen-binding site is different from that of the heme-copper terminal oxidases.

Binding Sites↗