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Biomedical subjects

K Hirokawa

Publications and source records attributed to K Hirokawa.

At least 109 records · Page 6Linked to original sources
PubMed1995

Changes in glutathione in gastric mucosa of gastric ulcer patients.

To clarify the role of glutathione (GSH), an antioxidative substance, and its association with the gastric mucosal defense mechanism, we examined the gastric mucosal GSH and GSH-dependent enzymes in gastric ulcer patients. The subjects of this study were 10 patients with active ulcer on the lesser curvature side in the lower part of the gastric body and 11 normal controls. At the time of gastric endoscopy, gastric mucosal specimens were obtained by routine forceps biopsy from a site several millimeters apart from the ulcer margin, and these specimens were used for measurement of GSH, glutathione peroxidase (GSH-Px), glutathione-S transferase (GST) and gamma-glutamyl transpeptidase (gamma-GTP). The GSH level and the GSH-Px and GST activities in the patients with gastric ulcer were lower than those in the control group. The GSH-Px activity at the healed stage after treatment was increased compared with the pre-treatment value, while the GSH level was not markedly increased and the GST and gamma-GTP activities were similar to the pre-treatment value. The GSH level and GSH-Px activity remained decreased in the non-responder group. These results suggest that gastric mucosal GSH and GSH-dependent enzymes are closely related to the etiology and course of gastric ulcer.

Adult↗
PubMed1995

Characterization of intermediate T-cell receptor cells expanding in the liver, thymus and other organs in autoimmune lpr mice: parallel analysis with their normal counterparts.

Autoimmune MRL-lpr/lpr (lpr) mice were previously demonstrated to have an abnormal proliferation of intermediate T-cell receptor (TCR) cells of extrathymic origin in the liver. Despite this situation, thymectomy in lpr mice resulted in amelioration of autoimmune disease. To understand the underlying mechanism, we investigated associated T-cell differentiation in the thymus and other organs of these mice. When the disease was evoked, T cells with extrathymic properties, i.e. intermediate TCR-alpha beta cells expressing double-negative (DN) CD4-8- phenotype and interleukin-2 (IL-2) receptor beta-chain, became prominent not only in the liver, but also in the thymus. Such thymic T cells mainly resided in the medulla. A small-scale localization of such T cells was seen in the thymic medulla even in normal control mice. There was a heterogeneity among intermediate TCR cells in terms of the composition of DN cells and the expression of CD2 and B220 antigens, depending on the organs and the sites in the same organ. Intermediate TCR cells in the liver, thymus and autoimmune target organs (e.g. kidney) contained a high proportion of the active form (CD2+B220-), while intermediate TCR cells accumulating in peripheral organs, the spleen and lymph nodes, were mainly of the inactive form (CD2-B220+). The active form had an ability to proliferate in response to IL-2 and SEB, whereas the inactive form did not. The present results suggest that the proliferation of intermediate TCR cells occur at multiple sites; this may explain the effect of thymectomy, namely, the retarded onset of disease, in lpr mice.

Animals↗
PubMed1995

Proliferative activity and p53 over-expression of ovarian epithelial tumors.

Proliferative activity (PA) and p53 over-expression were assessed in 68 cases of primary ovarian epithelial tumors of variable grades of malignancy by immunohistochemical methods using antibodies to PCNA (proliferative cell nuclear antigen) and p53 molecule. First, we compared the values in benign tumors, tumors of borderline malignancy and malignant tumors. Malignant tumors possessed higher PA value (26.8 +/- 14.7%) than benign tumors (1.6 +/- 1.4%), and tumors of borderline malignancy exhibited an intermediate value (11.4 +/- 5.1%). Intranuclear accumulations of p53 product were more frequently observed in malignant tumors (16/32, 50%) than in tumors of borderline malignancy (3/9, 33%). None of the benign tumors exhibited p53 over-expression. In malignant tumors, PA correlated well with the histologic grade of tumors, although the histologic type and stage of the diseases did not correlate significantly with PA. Then, we focussed on the cases of malignant ovarian cancer composed of heterogeneous lesions showing a different grade of malignancy; invasive lesion (IL), non-invasive lesion (NIL), and benign appearing lesion (BAL). PA of NIL was almost identical with that of IL (19.6 +/- 13.5% vs. 23.3 +/- 12.6%), while BAL showed significantly lower PA (2.1 +/- 3.0%, p < 0.001) than the above two lesions and was similar to that of benign tumors. Furthermore, p53 over-expression was never observed in BAL, even in cases in which IL and/or NIL showed p53 over-expression. Thus, the results indicated that histologically benign-appearing lesions of malignant ovarian epithelial tumors possessed a biologic character similar to benign tumors. Collectively, all these findings would support the concept that a part of malignant ovarian epithelial tumors would be derived from benign tumors through progressive transformation.

Adenocarcinoma, Clear Cell↗
PubMed1994

JAK3 Janus kinase is involved in interleukin 7 signal pathway.

Interleukin (IL) 7 is an important cytokine regulating both T and B cell development and inducing the formation of lymphokine-activated killer cells and cytolytic T lymphocytes. This study reports the role of JAK family kinases in the IL-7 signalling pathway in a T cell clone. The results have shown that out of 4 members of JAK family tyrosine kinases (JAK1, JAK2, JAK3 and Tyk2), only JAK3 was tyrosine-phosphorylated and activated in cells of a T cell clone by stimulation with IL-7. Furthermore, STAT1 alpha (STAT, the signal transducers and activators of transcription) and p44 of MAPK (mitogen-activated protein kinases) were tyrosine phosphorylated by IL-7 stimulation, indicating that the two signal pathways might be involved in IL-7 signal transduction.

Animals↗
PubMed1994

Cholinergic stimulation modulates apoptosis and differentiation of murine thymocytes via a nicotinic effect on thymic epithelium.

Effects of cholinergic agonists/antagonists on apoptosis and differentiation of murine thymus cells were investigated in two in vitro models. Treatment with 10(-7) M carbachol was found to counteract the effects of a cortical thymus epithelial cell line (TEC 1.4), on apoptosis and the ratio of CD4 CD8 DP/DN cells in cocultured fetal thymus lobes. A medullary line (TEC 2.3) did not influence apoptosis in fetal thymus lobes. Both TEC lines had the same strong apoptotic effect on thymus cells in suspension, but only the effect of TEC 1.4 was counteracted by carbachol. This cholinergic influence on TEC 1.4 cells is mediated via nicotinic cholinergic receptors, since d-tubocurarine, but not atropine, effectively blocked the effect of carbachol. The results suggest that cholinergic signals to thymic epithelial cells may have regulatory influence on thymic differentiation and selection processes.

Animals↗
PubMed1994

Presence of functional cyclic AMP responsive element in the 3'-untranslated region of the human thrombomodulin gene.

We characterized the transcriptional regulatory function of the 3'-untranslated region of the thrombomodulin gene by transient transfection assays in human umbilical endothelial cells. Deletion analyses of the 3'-untranslated region indicated that the region containing the consensus sequence of the cyclic AMP (cAMP) responsive element (position 2092) showed an increased transcriptional activity in response to cAMP. Gel-shift analysis showed that a band representing the fragment containing position 2092 was retarded when incubated with nuclear extracts from the cells treated with cAMP. In addition, the region downstream of the cAMP responsive element was found to function negatively in the gene expression. These results indicate that the 3'-untranslated region has a functional cAMP responsive element and plays an important role in the regulation of the thrombomodulin gene expression.

Base Sequence↗
PubMed1994

Gene expression of CD24 core polypeptide molecule in normal rat tissues and human tumor cell lines.

CD24 antigen is a glycoprotein expressed on haematopoietic cells, including B cells, T cells and granulocytes and on non-haematopoietic cells, including neural cells, ganglion cells and the cells of the adrenal medulla. The antigen is also expressed on renal cell carcinoma, small cell lung carcinoma and neuroblastoma. We have cloned rat cDNA encoding core polypeptide of CD24 antigen from embryonic brain and shown that the core molecule is highly expressed in embryonic brain and non-neural tissues. Rat tissue and various human neoplastic cell lines were investigated for the gene expression of CD24 core polypeptide by in situ hybridization. The transcript was localized in gastrointestinal epithelia, ductal and acinar epithelia of the salivary gland, the bronchiolar epithelium, renal tubular epithelium, the epithelium of the oviduct, follicular cells of the thyroid, medullary cells of the adrenal gland, Auerbach's plexus, B blastoid cells in lymph nodes, hair follicles, and the sweat glands of the skin. Among the various human neoplastic cell lines investigated, the transcript was detected in squamous cell carcinoma of the lung, gastric carcinoma, colon carcinoma, choriocarcinoma and renal cell carcinoma. The result suggest that the core molecule of CD24 antigen may be expressed in a wider range of epithelial cells and carcinoma cell lines than has been reported. Furthermore, we show that gene expression of CD24 core polypeptide is confined to the proliferative zone of the gastrointestinal mucosa, suggesting that core molecule is transiently expressed on the surface of epithelial cells in the process of cellular maturation. We discuss a possible role for CD24 antigen in the maturation of epithelial cells in the gastrointestinal tract.

Animals↗
PubMed1994

Understanding the mechanism of the age-change of thymic function to promote T cell differentiation.

Immunological functions peak at around puberty and gradually decline thereafter with advancing age. The immunological decline mainly occurs in the T cell-dependent immune system and is generally associated with an increase in not only susceptibility to infections but also incidence of autoimmune phenomena. The age-related changes in T-cell dependent immune functions can be mainly ascribed to the physiological thymic involution which starts in the early phase of life. The age-related thymic involution can be ascribed to either extrinsic or intrinsic factors. Bone marrow stem cells can be one of the extrinsic factors for the thymic involution, but their role is estimated to be marginal as compared with alteration of the thymic microenvironment. With advancing age, the thymic capacity to promote T-cell differentiation declines together with a change in the composition of T-cell subsets produced. Such an alteration of the thymic environment is responsible for the age-related change in peripheral T cells in number and in composition. Age change is observed in several intrinsic factors in the thymic environment which influence proliferation of thymocytes. These thymic intrinsic factors can either promote or inhibit proliferation of thymocytes, and promoting factors generally decrease with age with a concomitant increase in inhibitory factors. Various endocrine hormones are important extrinsic factors influencing the thymic function. In fact, physiological thymic involution can be intervened by manipulation of the endocrine system, sometimes resulting in rejuvenation of immune functions to a certain extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Changes in the subsets of CD4+ T cells in Trypanosoma musculi infection: delay of immunological cure in young mice and the weak ability of aged mice to control the infection.

After a 3 week course (approximately), during which there is marked lymphoid hyperplasia, Trypanosoma musculi infections in young-adult mice are cured by an immune mechanism involving antibodies of the IgG2a isotype. Both the lymphoid hyperplasia and IgG2a antibody response are T-cell-dependent events and both processes appear to be defective in aged mice. The purpose of the studies reported here was to elucidate the effects of T. musculi infection on subsets of T cells for two reasons: (i) to gain insight into the probable roles of selected cytokines (IL-2, IL-4 and IFN-gamma) in facilitating the production of curative, IgG2a antibodies, and (ii) to examine the hypothesis that aging affects the competence of CD4+ T cells to participate in immunological control of infections. The major conclusions from these studies are that: (i) T. musculi infection of mice induces rapid change in the CD4+ T cell population toward predominance of the activated or memory (CD45RBloCD44hi) phenotype, cells which produce IFN-gamma, II-3, IL-4 and IL-5, accompanied by profound inhibition of IL-2 production, and (ii) in the old mice these changes are superimposed on the natural age-associated changes in the same direction (i.e. toward predominance of CD45RBloCD44hi T cells). Thus, in the old animals, the combined changes of aging and infection, moving in the same direction, are devastating, resulting in the aged animals being unable, or barely able, to control infection.

Aging↗
PubMed1994

Signal-sensing mechanisms of the putative osmosensor KdpD in Escherichia coli.

The KdpD protein is a membrane-located sensory kinase (or signal transducer) critically involved in the regulation of the kdpABC operon that is responsible for a high-affinity transport system in Escherichia coli. In this study, a set of KdpD mutants, each resulting in a single amino acid substitution around the membrane-spanning regions of KdpD, was isolated. Amino acid substitutions in these KdpD mutants were located non-randomly, particularly within the C-terminal half of the membrane-spanning regions. This set of KdpD mutants exhibited altered transmembrane-signalling properties in response to external K+ and other stimuli. In particular, these mutants were found to be insensitive, if not completely, to the K+ signal. However, they were able to respond to other stimuli such as high-salt stress, as in the wild type. Therefore, in contrast to the wild type, the cells carrying these mutations exhibited high levels of the steady-state expression of kdp, regardless of external K+, provided that high concentrations of ionic solutes were supplemented to the cultures. More interestingly, the set of KdpD mutants could also respond to high concentrations of external non-ionic solutes such as sucrose and D-arabinose, thereby increasing substantially the steady-state expression of kdp in response to the medium osmolarity. Furthermore, it was found that certain chemicals, ethanol, chlorpromazine and procaine, could function as effectors for the KdpD mutants at relatively low concentrations in the media. Based on these findings, we have examined the primary signal(s) that regulates the function of KdpD. We propose here that KdpD can be considered to be an environmental sensor that exhibits sensing mechanisms in response to both the level of K+ and the physico-chemical state of the cytoplasmic membrane.

Amino Acid Sequence↗
PubMed1994

Induction of nitric oxide synthase in cultured vascular smooth muscle cells: the role of cyclic AMP.

1. Interleukin-1 beta (IL-1 beta) is a potent stimulant of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide (NO) production in vascular smooth muscle (VSM) cells in culture. These studies investigate the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in this process. 2. Dibutyryl cyclic AMP (db cyclic AMP, 0.1-1 mM), forskolin (1-10 microM) and the phosphodiesterase inhibitor, Ro 20-1724 (1-10 microM), all of which increase intracellular cyclic AMP, had no effect on NO production when added alone but markedly enhanced NO production by IL-1 beta-stimulated VSM cells in a dose-dependent manner. Consistent with a cyclic AMP-mediated action, isoprenaline (1-10 microM) increased NO production from IL-1 beta-stimulated cells. Dibutyryl cyclic GMP (db cyclic GMP) had no effect at concentrations up to 1 mM. 3. Pursuing these observations, iNOS protein levels were examined by Western blot analysis and iNOS mRNA levels were measured by reverse transcription and amplification of the resultant cDNA using the polymerase chain reaction. In addition to enhancing NO production, db cyclic AMP increased iNOS protein and mRNA above that produced by IL-1 beta alone. 4. These data demonstrate a major effect of cyclic AMP on cytokine-induced NOS activity in VSM cells, mediated at least in part by regulating synthesis of iNOS, and has implications for the pathogenesis and management of septic shock.

Amino Acid Oxidoreductases↗
PubMed1994

Inhibition of nitric oxide synthesis in vascular smooth muscle by retinoids.

1. These studies examine the effect of retinoids on interleukin 1 beta (IL-1 beta)-induced nitric oxide synthase (NOS) activity in cultured rat aortic vascular smooth muscle (VSM) cells and isolated rat aortic rings. 2. All-trans-retinoic acid (all-trans-RA, 0.1-10 microM) and its active analogues produced concentration-dependent inhibition of IL-1 beta (0.1-10 ng ml-1)-induced nitrite production in cultured VSM cells. In contrast, the inactive retinoid, Ro 14-6113 (0.1-10 microM), had no effect on IL-1 beta-induced nitrite production. 3. Since some of the actions of retinoids are mediated by induction of transforming growth factor beta (TGF-beta), its effect on inducible NOS activity in VSM cells was examined. TGF-beta produced concentration-dependent (0.1-10 ng ml-1) inhibition of IL-1 beta-induced nitrite production and the maximum effect (approximately 90% inhibition) was significantly greater than that seen with all-trans-RA (approximately 70% with 10 microM). However, an anti-TGF-beta antibody (50 micrograms ml-1) which blocked the effect of exogenous TGF-beta (5 ng ml-1) did not significantly reverse the inhibitory action of all-trans-RA (10 microM). 4. In addition to inhibiting IL-1 beta-induced nitrite production, all-trans-RA (10 microM) reduced substantially inducible NOS mRNA and protein levels in IL-1 beta-induced VSM cells (P < 0.01). 5. Incubation of isolated rat aortic rings with IL-1 beta (10 ng ml-1) caused a progressive resistance of the rings to the vasoconstrictor action of phenylephrine (10 nM to 10 microM). This effect was abolished by the addition of the nitric oxide synthase inhibitor L-NG-monomethyl-L-arginine (L-NMMA, 1 mM). All trans-RA (10 micro M) also markedly and significantly reversed this IL-1p-induced vascular hyporeactivity(P<0.01).6. These data show that all-trans-RA and other active retinoids are able to block cytokine-stimulated expression of inducible NOS in cultured VSM cells and isolated aortic rings.

Amino Acid Oxidoreductases↗
PubMed1994

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↗
PubMed1994

Expression of vimentin in gastric cancer: a possible indicator for prognosis.

Expression of vimentin in gastric cancer was immunohistologically examined in 85 surgically resected specimens and evaluated in terms of various clinicopathological features. Vimentin expression was more pronounced in gastric cancers of more advanced type and in those exhibiting a higher degree of infiltrative growth, lymph node involvement and vascular invasion. These results indicate that vimentin expression by gastric cancer might be related to the invasion and metastatic process of cancer cells and could be useful as a prognostic indicator for patients with gastric cancer.

Aged↗
PubMed1994

Epithelial class II MHC antigen normally expressed by submandibular glands of elderly people.

Immunohistochemical studies were made on 81 submandibular glands obtained from over 60-year-old autopsy cases. Those patients who had had either sialolithiasis or autoimmune diseases were not included in this study. HLA-DR expression was observed in the great majority (95.1%) of the aged submandibular glands, especially on the serous acinar cells and the intercalated duct cells, regardless of the appearance of focal lymphocytic infiltration. The incidence of HLA-DP expression was slightly lower (85.2%) and HLA-DQ was much lower (42.0%) than that of HLA-DR. These data support the proposal that epithelial expression of class II antigens in aged glands is a focal sign of age-related immunological disorders.

Aged↗
PubMed1993

Effects of a protein-free diet or food restriction on the immune system of Wistar and Buffalo rats at different ages.

The effects of a protein-free diet or food restriction on the immune system were examined in two rat strains, Wistar and Buffalo, in different age-groups. Unlike Wistar rats, Buffalo rats have an unusually hyperplastic thymus and a large number of peripheral T cells. The protein-free diet (PFD) in rats resulted in marked thymic involution together with a reduction of splenic T cells, both in number and in antibody response to sheep red blood cells. The depressive effect of the PFD on the immune system was more serious in young immature rats than in older rats, but less serious in Buffalo rats having enhanced T cell functions regardless of age. Thymic involution was also accelerated in both strains of rats by feeding them a restricted amount of the control diet containing well-balanced nutrients (food restriction, FR). In the FR experiment, no significant change was observed in immune functions of Wistar rats. A slight reduction was observed in the immune functions of Buffalo rats with FR, but absolute levels were distinctly higher in Buffalo rats than in Wistar rats even after FR. These results suggested (1) that the thymic function is sensitive to protein deficiency; (2) that a well-balanced dietary condition is necessary for immunological maturation in the early stage of life and preservation of immune functions at older age; (3) that animals having higher immune functions are more resistant to malnutrition than ordinary ones.

Aging↗