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Biomedical subjects

M Azuma

Publications and source records attributed to M Azuma.

At least 217 records · Page 12Linked to original sources

Alpha-fetoprotein production by a hepatoid adenocarcinoma of the uterus.

A case of a 62 year old Japanese woman with an endometrial adenocarcinoma producing alpha-fetoprotein (AFP) is described. Microscopically, the tumour was composed of a major medullary portion and a minor tubular adenocarcinoma which had invaded the myometrium, the myometrial lymphatics and blood vessels. Neoplastic cells in the medullary portion were polygonal with glycogen-rich cytoplasm. Vascular permeation by neoplastic cells was prominent. Extensive hepatoma-like features were observed. The tumour cells lacked features suggestive of a diagnosis of embryonal carcinoma or endodermal sinus tumour. The production of AFP by the tumour cells was demonstrated immunohistochemically using the PAP technique. Only two cases of AFP producing endometrial adenocarcinomas have been reported previously.

Adenocarcinoma↗

Relationship of the strain and the intraocular amount of herpes simplex virus types 1 and 2 in the induction of anterior-chamber-associated immune deviation.

We investigated the induction of anterior-chamber-associated immune deviation (ACAID) by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). Two strains of HSV-1 (VR-3 and F) and four strains of HSV-2 (UW-268, 186, SL, and MS) were inactivated with ultraviolet light, and the anterior chamber of BALB/c mice was inoculated with a viral strain. Immunization against delayed-type hypersensitivity (DTH) was done subcutaneously on day 7 after anterior chamber inoculation. On day 10 after DTH immunization, each virus was inoculated into the foot pad. DTH was evaluated by measuring the foot pad thickness at 24 h after the inoculation into the foot pad. DTH was suppressed by anterior chamber inoculation with more than 10(3) plaque-forming units (PFU) of the VR-3, UW-268, 186, and SL strains, and with 10(5) PFU of the F strain, but not by the MS strain. Until now, HSV-2 was believed not to induce ACAID, however, our results indicate that some HSV-2 strains induce ACAID.ACAID induction by HSV-1 and HSV-2 may depend on both the viral strain and the amount of ocular viral antigen.

Animals↗

Upregulatory effects of interleukin-4 and interleukin-13 but not interleukin-10 on granulocyte/macrophage colony-stimulating factor production by human bronchial epithelial cells.

Airway epithelial cells are known to produce a granulocyte/macrophage colony-stimulating factor (GM-CSF), which induces eosinophilic inflammation in bronchial asthma. Interleukin-4 (IL-4), IL-10, and IL-13 produced by Th2 cells are involved in the pathogenesis of bronchial asthma. To assess their contributions to airway inflammation, we examined their effects on GM-CSF production by bronchial epithelial cells. Human bronchial epithelial cells were obtained under bronchoscopy from 21 patients with various respiratory diseases and incubated with or without IL-4, IL-10, or IL-13. Then the GM-CSF concentrations in the cell-free supernatants were measured by enzyme-linked immunosorbent assay. Results showed that IL-4 and IL-13 stimulated GM-CSF production by the epithelial cells dose-dependently, whereas IL-10 did not. The eosinophil survival-stimulating activity in the culture supernatants was closely correlated with GM-CSF concentration and was neutralized by anti-GM-CSF antibody. Thus, IL-4 and IL-13 may contribute to airway inflammation by upregulating GM-CSF production by bronchial epithelial cells.

Adult↗

Adhesion molecule expression on eosinophils in idiopathic eosinophilic pneumonia.

Idiopathic eosinophilic pneumonia (IEP) is characterized by the accumulation of eosinophils in the alveolar spaces and the interstitium of the lung, frequently accompanied by peripheral eosinophilia. To clarify the roles of adhesion molecules of eosinophils in the pathogenesis of eosinophilic pneumonia, we analysed their expression by eosinophil and T-lymphocyte populations in peripheral blood and bronchoalveolar lavage fluid (BALF) obtained from 11 patients with eosinophilic pneumonia, using flow cytometric methods. Cell differentials in BALF showed increased numbers of eosinophils, the increase correlating with the number of activated T-lymphocytes in BALF. The expressions of CD11a (lymphocyte function-associated antigen-1 (LFA-1)), CD11b (Mac-1), CD18, CD49d (very late activation antigen-4 (VLA-4)), and CD62L (L-selectin) by eosinophils in BALF were all lower than those of eosinophils in peripheral blood. In contrast, CD54 (intercellular adhesion molecule-1 (ICAM-1)) was expressed by eosinophils in BALF, but not by those in peripheral blood. These results indicate that intercellular adhesion molecule-1 expression by eosinophils in bronchoalveolar lavage fluid but not in peripheral blood may be induced by locally activated T-cells or macrophages and may be important in the pathogenesis of idiopathic eosinophilic pneumonia.

Bronchoalveolar Lavage Fluid↗

Meisenheimer rearrangement of azetopyridoindoles. VIII. Synthesis and antiviral activities of 12-carbaeudistomin analogs.

Eudistomins, isolated from the colonial tunicate Eudistoma olivaceum, have been a synthetic target due to their strong antiviral activity against Herpes simplex virus (HSV-1) and activities against certain types of tumors in vivo. In order to examine the structure-activity relationship of eudistomins, 12-carbaeudistomin analogs were synthesized and their activities against influenza A and B virus, HSV-1, HSV-2 and human cytomegalovirus were investigated. Among them, racemic 6-methoxy-12-carbaeudistomin showed similar activity to (-)-debromoeudistomin K, synthesized as a control compound.

Animals↗

Afferent projections of the infralimbic cortex (area 25) in rats: a WGA-HRP study.

The afferent connections of the infralimbic area (area 25) of the medial prefrontal cortex in rats were studied using WGA-HRP as the tracer. The present results confirm previously reported afferent connections of the infralimbic area and further reveal additional inputs from the anterior amygdaloid area, anterior cortical amygdaloid nucleus, posterolateral cortical amygdaloid nucleus, ventral reunions, lateral preoptic area, dorsal hypothalamic area, posterior hypothalamic nucleus, supramammillary nucleus and medial mammillary nucleus. Only afferent projections were found from CA1 of the hippocampus and amygdalo-piriform transition area. The results also confirm extensive afferent connections of the infralimbic cortex from the central autonomic nuclei and, together with previous results on efferent connections of the infralimbic cortex, provide further support for an essential role of this nucleus as a cortical center of the autonomic nervous system.

Afferent Pathways↗

[Home oxygen therapy (HOT) in patients with pulmonary tuberculosis sequelae--comparison between patients medically treated and those surgically treated].

In Japan there are about 40,000 patients under home oxygen therapy (HOT), of whom about 30 to 40% are pulmonary tuberculosis sequelae (TBS). These patients can be divided into three groups depending on the treatments they had, Group 1: those who had medical treatments only, Group 2: those who had artificial pneumothorax, and Group 3: those who had thoracoplasties or other surgical treatments. The purpose of this study was to observe the distributions and possible differences in the survival rates among these groups. The study included 1537 patients with TBS under HOT followed at National Hospitals and Sanatoriums nationwide in Japan. In 819 patients the treatments were specified and of those 354 were in Group 1, 29 in Group 2, and 436 in Group 3, so that the proportion of surgically treated patients in PTS was estimated between 28.4% (436/ 1537) to 53.2% (436/819). The ages at the onset of tuberculosis, at the start of HOT and the intervals in between were 36.6, 66.2 and 29.8 in Group 1, and 26.8, 65.5, and 38.1 in Group 3 respectively. Though the ages at the start of HOT were the same, those at the onset of tuberculosis were about ten years younger in Group 3 than in Group 1. Comparing Group 1 and 3, the survival rates after the initiation of HOT (Kaplan-Meier method) was better in Group 2 (surgically treated) than in Group 1 (medically treated). It is speculated that the reason could be a better preservation of the function of the remaining lung in the surgically treated and a higher incidence of obstructive impairments in the medically treated patients.

Adolescent↗

Perforin-positive leukemic cell infiltration in the aortic tissue of a patient with T-cell prolymphocytic leukemia.

Here we report a rare case of T-cell prolymphocytic leukemia in which leukemic killer cells, expressing a cytolytic factor perforin, infiltrated the aorta as well as the heart and may have directly injured aortic vascular cells which strongly expressed human leukocyte antigens (HLAs) and intercellular adhesion molecule-1 (ICAM-1) as well as costimulatory molecules B7 and B70, which are ligands for CD28 expressed on T-cells. In spite of chemotherapy against leukemic cells, this autoimmune process finally caused fatal multi-organ failure.

Adult↗

beta-Carotene accumulation in mouse tissues and a protective role against lipid peroxidation.

Mice were supplemented with beta-carotene in beverage for 10 days. After the supplement, beta-carotene accumulated mainly in the liver and to some extent in the blood plasma, kidney and lung. The beta-carotene administration was associated with an increase in the amount of retinyl ester and retinol in the liver, but not in the amount of retinol in blood plasma. Lipid peroxidation in vivo was induced by the injection of carbon tetrachloride under the dorsal skin of mice. As an index of lipid peroxidation, thiobarbituric acid-reacting substances (TBARS) were assayed in urine and tissue homogenates. Urine and kidney TBARS were reduced by the supplementation of beta-carotene. The amounts of TBARS in kidney, liver and lung, decreased with increasing amounts of beta-carotene accumulated in these tissues, i.e. inverse correlations were obtained. These results indicate that beta-carotene can suppress lipid peroxidation in mouse tissue.

Animals↗

Potentiation by ouabain of catecholamine secretion from bovine adrenal chromaffin cells in culture induced by pituitary adenylate cyclase-activating polypeptide: evidence for involvements of Na+ and Ca2+ movements.

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on catecholamine secretion with ouabain, an inhibitor of Na(+)-K+ ATPase, in cultured bovine adrenal chromaffin cells was examined, to determine whether movement of Na+, as well as Ca2+, is involved in the secretory process. PACAP (10(-10)-10(-6)M)-induced catecholamine secretion was markedly potentiated by addition of ouabain (10(-5)M). When cultured cells were preincubated with PACAP for 30 min in Ca(2+)-free medium in the presence of ouabain and then stimulated for 15 min with Ca(2+)-containing medium without PACAP or ouabain, their catecholamine secretion was dependent on the external Ca2+ concentration, and 45Ca2+ influx into the cells was increased. When the cells had been preincubated with PACAP and ouabain in Na(+)-free sucrose medium, their Ca(2+)-induced catecholamine secretion was greatly reduced. PACAP increased 22Na+ influx into cells treated with ouabain. These results suggest that stimulation by PACAP and inhibition of the Na(+)-pump both increase the intracellular Na+ level, resulting in increase in Ca2+ influx and catecholamine secretion.

Adenylyl Cyclases↗

Rapid development of murine AIDS is dependent of signals provided by CD54 and CD11a.

Murine AIDS (MAIDS) is induced by infection with the replication-defective virus (BM5def) component in the LP-BM5 murine leukemia virus (MuLV) mixture. The disease is characterized by polyclonally activated CD4+ T cells and B cells. It is known that BM5def is expressed at highest levels in B lymphocytes and that B cells serve as viral antigen-presenting cells. Full and sustained activation of CD4+ T cells against a conventional Ag usually requires both TCR and costimulating signals. Among various molecules known to provide costimulatory function, the expression of CD54 (ICAM-1) and CD11a/CD18 (LFA-1) on MAIDS B cells was increased, whereas that of CD2, heat-stable Ag (CD24), CD80 (B7-1), and CD86 (B7-2) was unchanged from normal. C57BL/6 mice depleted of both CD54 and CD11a expression as a result of chronic administration of mAb had developed no MAIDS at 4 wk and 8 wk after LP-BM5 MuLV infection. In addition, the proliferative response of B cells to mitogen was well conserved, whereas MAIDS-associated increases in serum Ig levels were inhibited. Replication of BM5def was suppressed markedly in infected mice treated with the CD54 and CD11a mAbs. These results suggest that the CD54/CD11a signal transduction pathway is a critical determinant of MAIDS development, and the lack of an immune response against viral Ag is enough to suppress BM5def replication and to prevent MAIDS.

Animals↗

Stoichiometry of K+/H+ antiport helps to explain extracellular pH 11 in a model epithelium.

The stoichiometry of K+/H+ antiport was measured fluorometrically by the static head method in highly purified vesicles from goblet cell apical membranes of larval lepidopteran midgut. The measured stoichiometry of 1 K+/2 H+ explains how the antiport results in electrophoretic exchange of extracellular H+ for intracellular K+, driven by the voltage component of the proton-motive force of an H+ translocating V-ATPase that is located in the same membrane. In turn, the exchange of K+ for H+ helps to explain how the midgut contents are alkalinized to a pH of 11.

Animals↗

CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL.

Signals initiated through both the TCR complex and CD28 are required for optimal activation of T lymphocytes. Recently, it has been demonstrated that CD28 interacts with two different ligands, designated CD80 (B7/B7-1) and CD86 (B70/B7-2). We have produced stable transfectants that express CD80, CD86, or both ligands and have examined their ability to costimulate T cell proliferation, cytokine production, and the generation of CTL. When we used small, resting human peripheral blood T cells as responders, both CD80 and CD86 transfectants efficiently costimulated anti-CD3 mAb-induced proliferation and the secretion of IL-2 and IFN-gamma. Additionally, both CD80 and CD86 transfectants were able to generate functional CTL. The magnitude and kinetics of these responses were similar, which indicates that both ligands provide efficient costimulatory signals. Because many APCs coexpress both CD80 and CD86, we compared the ability of anti-CD80 and anti-CD86 mAbs to inhibit allogeneic MLR stimulated with B lymphoblastoid cell lines and showed that it is necessary to inhibit interactions with both ligands to optimally block CD28-dependent proliferation. Given the limited homology of CD80 and CD86, it was surprising that the binding of CD28-Ig fusion protein to CD80 and that to CD86 transfectants were essentially indistinguishable. Binding of CTLA-4-Ig fusion protein to both transfectants also was quite similar, but was of higher affinity than CD28-Ig binding. Results from these studies indicate that both CD80 and CD86 are potent and similar costimulators of T lymphocytes. Therefore, the role of CD80 and CD86 in an immune response may be determined primarily by their differential expression on APC.

Adult↗

Preferential dependence of autoantibody production in murine lupus on CD86 costimulatory molecule.

Blockade of the interactions between CD28/CTLA-4 and their ligands, CD80 (B7, B7.1)/CD86 (B70, B7.2), seems an attractive means to induce antigen-specific peripheral tolerance in organ transplantation and autoimmune disease. Recently, diversities between CD80 and CD86 in expression, regulation, and function have been reported in certain cell populations and murine experimental disease models. To investigate the possible differential role of CD80 and CD86 in the development of lupus, we treated lupus-prone NZB/W F1 mice with specific monoclonal antibodies (mAb) against CD80, CD86, or both. The treatment with a combination of anti-CD80 and CD86 mAb before the onset of lupus completely prevented autoantibody production and nephritis, and prolonged survival. Interestingly, we found that anti-CD86 mAb alone, but not anti-CD80 mAb, efficiently inhibited autoantibody production. Subclass study on IgG anti-double-stranded (ds) DNA antibody revealed that the treatment with anti-CD86 mAb almost completely inhibited both IgG1 and IgG2b, but not IgG2a production. The incomplete reduction of IgG2a anti-dsDNA antibody by anti-CD86 mAb was compensated by the addition of anti-CD80 mAb. A significant reduction of mRNA for interleukin (IL)-2, interferon-gamma, IL-4 and IL-6 was observed in mice treated with a combination of anti-CD80 and CD86 mAb or anti-CD86 mAb alone. Treatment with both mAb after the onset of lupus resulted in a significantly prolonged survival with reduction of autoantibody production. These results suggest that CD86 plays a more critical role in autoantibody production, and CD86, but not CD80, contributes to Th2-mediated Ig production. However, the blockade of both CD80 and CD86 are required for preventing the development and progression of lupus.

Animals↗