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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 595 records · Page 33Linked to original sources

Role of endothelin 1 in hemorrhagic shock-induced gastric mucosal injury in rats.

BACKGROUND/AIMS: Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators regulating this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1) in hemorrhagic shock-induced gastric mucosal damage in rats. METHODS: ET-1 contents in plasma and gastric mucosa were measured and gastric mucosal damage was evaluated during a control period, 60 minutes of ischemia, 15 minutes of reperfusion, and 30 minutes of postreperfusion. Next, effects of BQ-123, an endothelinA receptor antagonist, on the gastric mucosal damage and hemodynamics were studied. RESULTS: Both plasma and mucosal ET-1 significantly increased after ischemia and reperfusion compared with the control values, but only mucosal ET-1 continued to increase after reperfusion, leading to the development of gastric mucosal damage. BQ-123, administered just before reperfusion, reduced mucosal damage in the postreperfusion period dose-dependently and improved mean gastric mucosal blood flow and mucosal hemoglobin oxygen saturation during the 30-minute postreperfusion period. CONCLUSIONS: These results suggest that endogenous ET-1 plays an important role in the pathogenesis of hemorrhage shock-induced gastric mucosal damage through impairment of mucosal microcirculation. Further, endothelinA antagonists may have therapeutic benefits for shock-induced gastric mucosal damage.

Animals↗

Involvement of apoptosis antigen Fas in clonal deletion of human thymocytes.

Apoptosis appears to play a major role in the differentiation and selection of T and B lymphocytes, but the mechanisms of clonal deletion of T cells in thymus are not well understood. We have prepared an anti-human Fas IgM mAb with associated apoptosis-inducing activity in Fas antigen-positive target cells including human T cells. We analyzed the expression of apoptosis antigen Fas on human thymocytes by cytofluorometry showing low, but significant amounts of Fas antigen on double-negative and double-positive undifferentiated thymocytes. On the contrary, most of the differentiated thymocytes (single-positive or CD3-brightest) expressed undetectable levels of Fas antigen. About 1-2% of thymocytes expressed high amounts of Fas antigen, and these cells, which were CD3-bright, were CD4-bright and CD8-low at the stage of late double-positive lineage. Immunohistological analysis shows these Fas-bright cells on the edge of the medulla. Stimulation through the TCR complex was shown to induce the expression of Fas antigen on thymocytes at the late double-positive stage and prolonged stimulation through the TCR complex rendered the Fas-bright thymocytes sensitive to apoptosis-inducing activity of anti-Fas. To show the involvement of the Fas system in the negative selection/clonal deletion of thymocytes, we organ-cultured human thymus in the presence of the superantigen, staphylococcus enterotoxin B (SEB), and new antagonistic anti-Fas mAb, which can inhibit the apoptosis-inducing activity of the original anti-Fas mAb. The SEB-reactive TCR complex on thymocytes was at first down-regulated by SEB, then the SEB-reactive clone was deleted by apoptosis, which was inhibited by an antagonistic anti-Fas mAb. Thus, Fas antigen is shown to be involved in the negative selection/clonal deletion of superantigen-reactive thymocytes.

Antibodies, Monoclonal↗

Cellular kinetics and lectin distribution in hamster buccal carcinomas.

As part of an evaluation of the progression to malignancy, the cellular kinetics of DMBA-induced tumors in the buccal mucosa of hamsters were examined using 5-bromodeoxyuridine (BrdU), peanut agglutinin (PNA), Ulex europaeus agglutinin I (UEA-I) and wheat germ agglutinin (WGA). BrdU-positive cells were localized in the basal layer in both normal and hyperplastic epithelium, whereas they were distributed from the basal to the prickle cell layer in squamous cell carcinoma (SCC). The extent of BrdU labeling increased as the tissues progressed towards malignancy. PNA and UEA-I showed binding only in the prickle cell layer of normal and hyperplastic epithelium, and WGA showed binding mainly in the prickle cell layer. However, in SCC, PNA and UEA-I showed no binding in the prickle cell layer and WGA binding was observed throughout the epithelium. A study of cellular kinetics using BrdU labeling and the lectin binding pattern may be useful in the evaluation of tissue changes on the way to malignancy.

9,10-Dimethyl-1,2-benzanthracene↗

Role of human major histocompatibility complex DQ molecules in superantigenicity of streptococcus-derived protein.

Antigenicity of peptic extract from type 12 group A streptococci (PEAST12) for T cells was examined in major histocompatibility complex (MHC) class II transgenic mice. PEAST12 was mitogenic for murine T cells when antigen-presenting cells were obtained from human MHC (HLA)-DQ4 alpha beta transgenic mice or from DQ6 alpha beta transgenic mice but was not mitogenic in DR alpha transgenic, DR51 alpha beta transgenic, E alpha transgenic, or nontransgenic mice. In addition, PEAST12 showed mitogenicity for murine T cells in DQ4 alpha singly transgenic mice but not in DQ4 beta singly transgenic mice. T-cell stimulation by PEAST12 was unrestricted by but dependent on the expression of HLA-DQ molecules on antigen-presenting cells, and PEAST12 selectively activated T-cell receptor V beta 11-, V beta 15-, and V beta 18-positive T cells in mice. We propose that PEAST12 contains a superantigen which binds preferentially to the alpha-chain of HLA-DQ molecules. The well-known phenomenon that peptic extracts from group A streptococci are mitogenic in humans but not in mice is likely due to structural differences in MHC class II molecules between these two species of mammals.

Animals↗

Long-term follow up in type A insulin resistant syndrome treated by insulin-like growth factor I.

Insulin-like growth factor I (IGF-I) is a useful therapeutic agent in insulin resistant diabetes mellitus due to insulin receptor disease because of its hypoglycaemic effects through the IGF-I receptor. A girl with typical type A insulin resistant syndrome was treated with IGF-I for two years and the treatment was effective in ameliorating hyperglycaemia. Overproduction of testosterone in polycystic ovaries was aggravated with this treatment, however. Therefore, IGF-I treatment may be used for glycaemic control but with caution because of its possible side effect of aggravating hyperandrogenism in these patients.

Acanthosis Nigricans↗

Two species of antiganglioside antibodies in a patient with a pharyngeal-cervical-brachial variant of Guillain-Barré syndrome.

A patient with a pharyngeal-cervical-brachial variant of Guillain-Barré syndrome had anti-GT1a and anti-GD1a antibodies (IgG) in the serum. The activities of anti-GT1a antibodies were stronger than anti-GD1a antibodies and their activities declined later in the clinical course. These two different antibodies bound independently to each ganglioside in an absorption study with polystyrene beads coated with GT1a or GD1a.

Adult↗

Identification of the disease-related T cell epitope of ovalbumin and epitope-targeted T cell inactivation in egg allergy.

An ovalbumin (OVA)-specific T cell line (TCL) was established from a patient with hen egg allergy. The TCL was CD4+, expressed alpha beta T cell receptor, and recognized OVA presented by HLA-DR10. Based on the response of the TCL to synthetic OVA peptides, it was found that the TCL recognized OVA 323-339, which is a major T cell epitope presented by murine I-Ad. The TCL secreted high levels of IL-5, but undetectable amounts of IL-2, interferon-gamma, and IL-4 when stimulated with OVA or the OVA 323-339 peptide. Since IL-5 is an important growth and chemotactic factor for eosinophils, it is possible that these OVA 323-339-specific T cells can contribute to human egg allergy. To our knowledge, this is the first demonstration of food allergen-specific TCL establishment and identification of a T cell epitope possibly related to the allergic reaction to food antigens. An analog peptide of the OVA 323-339 which is known to strongly bind to I-Ad partially inhibited the response of the TCL to OVA 323-339 presented by HLA-DR10, raising the possibility of peptide-based immunotherapy of food allergy.

Amino Acid Sequence↗

Respiratory muscle strength and hemodynamics in chronic heart failure.

To examine whether respiratory muscle weakness is associated with cardiac function and/or exercise capacity in chronic heart failure (CHF), 23 patients with CHF were evaluated with respiratory muscle strength, pulmonary function tests, cardiac catheterization, and exercise test. The subjects were divided into three groups on their New York Heart Association (NYHA) functional class. Group A consisted of 13 patients with NYHA functional classification class 3 or 4, group B consisted of 10 patients with NYHA classification class 2, and group C consisted of 15 age-matched normal controls. Respiratory muscle strength was assessed with maximal static inspiratory mouth pressure at residual volume level and expiratory mouth pressure at total lung capacity level (PImax, PEmax, respectively). Pulmonary functions in patients with CHF showed almost normal. PImax in group A was significantly less than that in group B or C, although PImax in group B was not significantly different from that in group C. In the patients with CHF, PImax correlated positively with cardiac index and maximal oxygen consumption (r = 0.460 and r = 0.503, p < 0.05, respectively). These findings suggest that inspiratory muscle strength, which was impaired in patients with severe CHF, may be dependent on cardiac function and may be one of the limiting factors on impaired exercise capacity in the patients with CHF.

Aged↗

Effect of posture on bronchial reactivity to inhaled methacholine in patients with mitral valve stenosis.

To compare the effects of posture on bronchial reactivity in 12 patients with mitral valve stenosis (MS) and 10 with bronchial asthma (BA), a methacholine inhalation test was performed 2 h after being in either a supine or sitting position. All patients showed bronchial hyperreactivity to inhaled methacholine before the study. In MS patients, logarithmic values of the cumulative dose producing a 35 percent decrease in respiratory conductance (log PD35Grs) were significantly lower 2 h after being in a supine position than in those after being in a sitting position (0.71 +/- 0.78, 1.02 +/- 0.53 log units, respectively, p < 0.05). In BA patients, however, log PD35Grs did not show significant changes (0.42 +/- 0.51, 0.58 +/- 0.48 log units, respectively). Variables of pulmonary function tests showed no significant differences between the two positions in both patients with MS and BA. We conclude that the bronchial hyperreactivity in MS is enhanced after the supine position for 2 h and that the supine posture may play an important role in the pathogenesis of cardiac asthma.

Adult↗

Relaxant effects of calcitonin gene-related peptide on isolated small renal arteries in stroke-prone spontaneously hypertensive rats.

The relaxant effects of calcitonin gene-related peptide (CGRP) on the 3rd branches of renal arteries obtained from stroke-prone spontaneously hypertensive rats (SHRSP), and Wistar-Kyoto rats (WKY) were investigated in vitro. CGRP elicited concentration-dependent relaxation, and the relaxant response was not affected by the mechanical removal of endothelium in either SHRSP or WKY. The CGRP-induced relaxant response was markedly greater in SHRSP than in WKY, whereas there was no significant difference in acetylcholine-induced relaxation, which was endothelium-dependent, between the two groups. Additionally, significantly enhanced reactivity to CGRP was also shown in spontaneously hypertensive rats compared to WKY; however, this reactivity was less than that observed in SHRSP. There were also no significant differences between WKY and SHRSP in the relaxation induced by forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine (IBMX). CGRP-induced relaxation was significantly potentiated in similar manner by the pretreatment with IBMX in both WKY and SHRSP. Incubation with glibenclamide (10(-6) M) had no effect on CGRP-induced relaxation in either group, the WKY or the SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the small renal arteries in the rat, and that the increased CGRP-induced relaxant response found in SHRSP may not be associated with the altered vasodilation mediated by cyclic AMP, or with functional changes in ATP-sensitive potassium channels.

Acetylcholine↗

Remission of recurrent primary intracranial malignant lymphoma after high-dose intra-arterial corticosteroid administration and intra-arterial chemotherapy--case report.

A 39-year-old male presented with rapidly growing recurrent primary intracranial malignant lymphoma, manifesting as intractable headache, recent memory disturbance, and left hemiparesis during the previous month. He had received irradiation and chemotherapy for primary intracranial malignant lymphoma 15 months before admission. Signs of uncal herniation developed soon after admission. High-dose intra-arterial corticosteroid infusion followed by intra-arterial chemotherapy (etoposide and cisplatin) successfully relieved the symptoms of uncal herniation. Magnetic resonance imaging demonstrated a dramatic remission in the size of the tumor and associated mass effect. Sequential administration of corticosteroid and chemotherapy agents is a possible treatment for recurrent malignant lymphoma.

Adrenal Cortex Hormones↗

HLA antigens in Japanese patients with systemic lupus erythematosus.

To determine the association of HLA antigens with SLE and the clinical findings of the disease, HLA antigens were tested in 58 Japanese patients with SLE, who fulfilled the ARA diagnostic criteria, along with 97 normal controls. HLA class I and II antigens were typed serologically using the antisera provided by the 11th HLA Workshop. Among the HLA class II antigens, further DRB, DQ and DP alleles were defined by DNA typing using the PCR/SSOP method. There were significantly more SLE patients with HLA-B39, DRB1*1501, DRB5*0101 and DQB1*0602 than normal controls. This result suggested that the haplotype of HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 consists of the SLE-associated MHC markers in Japan. There were some positive and negative associations between the HLA antigens and clinical or serological findings in SLE. There is a possibility that some HLA alleles might be related to the clinical and/or serological subsets of SLE.

Alleles↗

Totally synthetic analogues of siastatin B. III. Trifluoroacetamide analogues having inhibitory activity for tumor metastasis.

A trifluoroacetamide analogue of siastatin B, (3S,4S,5R,6R)-6-(trifluoroacetamido)-4,5-dihydroxy-3-piperidine carboxylic acid has been chemically synthesized. This compound, as well as the previously synthesized analogue, (3R,4R,5R,6R)-6-(trifluoroacetamido)-3,4,5-trihydroxy-3-piperid inecarboxylic acid, showed marked inhibitory activity against beta-glucuronidase and significant inhibition of experimental pulmonary metastasis of the highly metastatic melanoma B16.

Acetamides↗

Antibody to hepatitis C virus in volunteer blood donors of the Hospital de Especialidades, National Medical Center, Mexico City.

The present survey was performed to assess the hepatitis C virus seroprevalence in volunteer blood donors of the National Medical Center, Hospital de Especialidades, Mexico City. Serum samples from 1100 individuals were collected. We selected second generation enzyme-linked immunosorbent assay (ELISA) (Abbott HCV EIA) test for the screening. The antibodies against hepatitis C virus (anti-HCV) in the volunteer blood donors were positive in 0.7%. The second generation ELISA test is useful as a screening test and may lead to decreasing the incidence of posttransfusional hepatitis C virus infection.

Blood Donors↗