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Biomedical subjects

M Matsunaga

Publications and source records attributed to M Matsunaga.

At least 109 records · Page 6Linked to original sources

CD4+CD45RA+ cells (suppressor-inducer T cells) in thyroid tissue from patients with Graves' disease.

Previously, we used dual immunofluorescent analysis and showed that the thyroid gland from patients with Graves' disease had a reduced number of CD4+CD45RA+ cells, but an increased number of complementary CD4+CDw29+ cells. An immunohistochemical study, however, produced opposite results; interstitial lymphocytes predominantly expressed the CD45RA+ rather than the CDw29+ phenotype. Because the difference in findings may be due to differences in the techniques used, we did the following experiments: Mononuclear cells were treated with various amounts of collagenase (50-1000 mg/l) which had no effect on the cell surface antigens CD3, CD4 and CD45RA. A dual immunofluorescent study showed that the numbers of CD4+CD45RA+ and CD8+CD45RA+ cell population among CD45RA+ cell population were markedly decreased in the thyroid tissue, and that the CD45RA antigen on the intrathyroidal mononuclear cells was mainly expressed on the CD20+ cells. As the thyroid section had been fixed with acetone before immunohistochemical staining, CD45RA- cells were treated with acetone and stained with anti-CD45RA monoclonal antibody using an avidin-biotin peroxidase complex method. The results of this experiment suggest that there are cell surface molecules which react with anti-CD45RA monoclonal antibody after treatment with acetone in CD45RA- cells. The above findings confirm our previous results which showed that the thyroid glands of patients with Graves' disease have decreased numbers of suppressor-inducer T cells. Also, several problems exist in the detection of CD45RA+ cells when using an immunohistochemical method.

Acetone↗

Biochemical and functional analysis of mixed isotype A beta E alpha class II molecules in Ed alpha transgenic mice.

We demonstrated the existence of mixed isotype A beta E alpha class II molecules in Ed alpha gene-introduced C57BL/6 (B6Ed alpha) transgenic mice. Immunoprecipitation and two dimensional (NEPHGE/SDS-PAGE) gel electrophoresis analysis of labeled B6Ed alpha spleen cell lysates using monoclonal anti-Ab beta antibody showed Ed alpha spots in addition to Ab beta and Ab alpha spots. We obtained alloreactive T cell clones from B6 anti-B6Ed alpha long-term cultures that recognized the Ab beta Ed alpha molecule. We also obtained antigen reactive T cell clones that recognized antigen in the context of Ad beta Ed alpha mixed isotype class II molecules. The importance of the mixed isotype class II molecules in relation to the expansion of the T cell specificity repertoire as well as autoimmune induction is discussed.

Animals↗

[Mechanism of F-wave conduction delay in acute Guillain-Barré syndrome].

We measured M-wave and F-wave conduction time between the wrist and the elbow in 16 median nerves of acute phase of Guillain-Barré syndrome. Studies were carried out within 14 days after the onset of the weakness. In 20 healthy subjects, conduction times of M- and F-waves were almost similar, while F-wave conduction time was longer than the corresponding M-wave conduction time in the acute phase of the illness. This dissociation between the F-wave and the M-wave conduction time was exaggerated when the minimal F-latency was longer. The results suggest that an F-wave with the minimal latency does not always conduct through the fastest motor fiber which determines the onset of M-wave, but may represent a conduction through motor fibers with slower velocity. This disproportionately-prolonged conduction time of the F-wave was never seen during the recovery phase, 12 weeks after the onset of the illness. A conduction block of the fastest motor fiber in the proximal segment is supposed to be a cause of the conduction delay of the F-wave with minimal latency in the acute stage of the Guillain-Barré syndrome.

Acute Disease↗

[Subfrontal schwannoma: a case report].

A case of a 63-year-old woman with subfrontal schwannoma of the left side is presented. The patient had a two-month history of recent memory disturbance and unstable gait. Computed tomography represented an isodense mass lesion with large and small cystic components in the anterior cranial fossa, enhancing homogeneously after intravenous injection of contrast medium. Cerebral angiograms revealed a noticeable hypovascularity. She underwent total resection of the tumor on May 21, 1986. It was verified that the tumor was attached to the left olfactory groove and had invaded the ethmoid bone. It was suggested that this tumor arose from one of the meningeal branches of the trigeminal nerve or of the anterior ethmoid nerve. Histological examination proved that this neoplasm was of schwannoma.

Brain Neoplasms↗

Antigen-reactive T cell clones restricted by mixed isotype A beta d/E alpha d class II molecules.

Mixed isotype A beta dE alpha d class II molecule-restricted antigen-reactive T cell clones were obtained from (BALB/c x B6E alpha d)F1 mice. These T cell clones responded to keyhole limpet hemocyanin in the presence of (BALB/c x B6E alpha d)F1 but not CBF1 APCs. Both anti-A beta d and anti-E alpha mAbs blocked the proliferative responses of these clones. The frequency of such mixed isotype A beta E alpha-restricted T cell clones in (BALB/c x B6E alpha d)F1 mice was estimated to be approximately 10% from our limiting dilution cloning. The existence of such mixed isotype class II molecule-restricted T cells would have important implications for the expansion of the T cell repertoire as well as the induction of autoimmunity.

Animals↗

Cadherin-mediated cell-cell adhesion and neurogenesis.

Cadherins constitute a molecular family which confers adhesive specificities on cells. Their expression is spatio-temporally regulated in embryos and the multiple types of cadherins are expressed in the nervous system. The inhibition of cadherin action with antibodies resulted in the perturbation of the histogenesis of neural tissues. The sites for determining the binding specificities of cadherins reside in their amino terminal 113 amino acid region. Possible roles of cadherins associated with these properties in neurogenesis are discussed.

Animals↗

Synthesis and structure-activity relationships of dynorphin A-(1-8) amide analogues.

In order to study the structure-activity relationships of dynorphin A-(1-8) amide [Dyn(1-8)-NH2], 20 analogues were synthesized by the solution method. Their biological activities were determined in the three bioassays [guinea pig ileum (GPI), mouse vas deferens (MVD), and rabbit vas deferens (RVD)] and in the mouse tail-pinch test after intravenous administration. Some analogues that showed interesting activity in the bioassays and/or in the analgesic tests were further characterized in mu-, delta-, and kappa-representative binding assays. The obtained data indicate that modification of the enkephalin segment to give metabolically stable analogues with high affinity and selectivity for the kappa receptor is strictly limited and that introduction of MeArg in position 7 protects the Arg6-Arg-7 bond from enzymatic degradation without potency drop and change of opioid receptor selectivity. [MeTyr1,MeArg7,D-Leu8]Dyn(1-8)-NHEt (18) [IC50 (nM) = 0.3 (GPI), 7.4 (MVD), and 2.6 (RVD); tail pinch ED50 (mg/kg) = 0.75] showed opioid activity similar to that of dynorphin A in the three bioassays and relatively high kappa-receptor selectivity in the binding assays and produced a 2.5-fold more potent analgesic effect than morphine. [D-Cys2-Cys5,MeArg7,D-Leu8]Dyn(1-8)-NHEt (20) showed a 40-60-fold more potent opioid activity than 18 in the three bioassays and produced a 3.4-fold more potent analgesic effect than 18. In the binding assays, however, 20 showed higher affinity for mu and delta receptors than for the kappa receptor.

Amino Acid Sequence↗

Neurinoma in the cavernous sinus: report of two cases.

Two cases of trigeminal neurinoma located solely in the cavernous sinus are reported. Preoperatively, magnetic resonance imaging provided the accurate localization of the lesions, allowing precise planning of the surgical approach, that is, a subtemporal lateral approach and a pterional superior approach, respectively. The neurinomas inside the cavernous sinus were removed successfully, and the patients developed no new neurological deficits except for anesthesia in the 1st division of the trigeminal nerve. The characteristic magnetic resonance imaging findings of trigeminal neurinoma in the cavernous sinus are presented, and the different surgical approaches are discussed.

Adult↗

Cytokine regulation of HLA on thyroid epithelial cells.

The regulation of class I and class II HLA expression in human thyroid follicular cells was studied in vitro. Tumour necrosis factor-alpha (TNF-alpha) enhanced the expression of class I antigen on thyrocytes, but these cytokines had little effect on the expression of class II antigen. Interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) did not affect class I and class II antigen expression. The combination of interferon-gamma (IFN-gamma) with TNF-alpha or IL-1 beta enhanced the induction of class I and class II antigens, compared with the effect of IFN-gamma alone. Neither class I nor class II expression was induced by IL-6 alone or in combination with IFN-gamma. These findings suggest that TNF-alpha and IL-1 beta may have an important role in inappropriate expression of HLA antigens on thyrocytes in thyroid gland.

Cell Survival↗

Synthesis and biological activity of [MeTyr1,MeArg7,D-Leu8]-dynorphin A(1-9)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-dynorphin A(1-9)-NH2.

The opioid activities of [MeTyr1]-Dyn(1-7)-NH2, [MeTyr1,D-Leu8]-Dyn(1-8)-NH2, [MeTyr1,D-Leu8]-Dyn(1-9)-NH2, [MeTyr1,D-Leu8]-Dyn(1-10)-NH2, [MeTyr1,D-Leu8]-Dyn(1-11)-NH2, and [MeTyr1,D-Leu8,12]-Dyn(1-13)-NH2 were examined in the bioassays (guinea pig ileum, mouse vas deferens and rabbit vas deferens). Because [MeTyr1,D-Leu8]-Dyn(1-9)-NH2 showed the most potent opioid activity of the peptides tested, the biological activities of two kinds of Dyn(1-9) analogues, [MeTyr1,MeArg7,D-Leu8]-Dyn(1-9)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1-9)-NH2 were determined and compared with those of [MeTyr1,MeArg7,D-Leu8]-Dyn(1-8)-NHEt and [D-Cys2-Cys5,MeArg7,D-Leu8]-Dyn(1-8)-NHEt in the three bioassays, in the receptor binding assays, and in the mouse tail pinch test after subcutaneous administration. The results suggest that the extension of the C-terminal in the peptide chain of [MeArg7,D-Leu8]-Dyn(1-8)-NH2 analogues by Arg is ineffective for increasing the kappa-opioid activities, kappa-receptor selectivity and/or analgesic effects of the peptides.

Amino Acid Sequence↗

Phenotypic characterization of lymphocytes infiltrating synovial tissue from patients with rheumatoid arthritis: analysis of lymphocytes isolated from minced synovial tissue by dual immunofluorescent staining.

The phenotypic markers of mononuclear cells in synovial tissue from 19 patients with active rheumatoid arthritis (RA) were identified by a dual immunofluorescent method. The mononuclear cells were isolated from synovial tissue by mechanical disaggregation and an enzymatic digestion technique. The results revealed a marked reduction in CD4+2H4+ cells (suppressor inducer T cells) and an increment in CD4+4B4+ cells (helper T cells) among CD4+ cells in synovial tissue. The percentage of CD8+CD11b+ cells (suppressor effector T cells) was significantly lower in synovial tissue than in peripheral blood from patients with RA, resulting in an increased percentage of CD8+CD11b-- cells (cytotoxic T cells). The synovial tissue had higher percentages of pan B cells (B1+ cells), differentiated B cells (B1+B2-- cells) and plasma cells (PCA-1+ cells). These findings suggest that a combination of the increment in helper T cells, the reduction in suppressor T cells, and the increment in differentiated B cells may lead to excessive production of autoantibodies.

Adult↗

Inhibitory effects of gold sodium thiomalate on the proliferation and interferon-gamma induced HLA-DR expression in human endothelial cells.

Our study was undertaken to investigate the effects of gold sodium thiomalate (GSTM) on the proliferation and HLA-DR antigen expression of human umbilical vein endothelial cells (EC). The proliferation of the EC was determined by 3H-thymidine incorporation into the EC. The expression of HLA-DR antigen on the surface of the EC was detected by an indirect immunofluorescent method using a fluorescent flow cytometer. When GSTM was added at the start of the EC culture, GSTM at a low concentration could inhibit the proliferative response of the EC to endothelial cell growth supplement. Furthermore, when the EC were cultured with recombinant interferon-gamma (rIFN-gamma) and GSTM, GSTM was also able to suppress the HLA-DR antigen expression on the surface of EC induced by rIFN-gamma. On the time-kinetic study of the effects of GSTM on the HLA-DR antigen expression induced by rIFN-gamma, the pretreatment of GSTM was able to suppress the HLA-DR antigen expression, whereas GSTM did not affect the HLA-DR antigen expression already induced by rIFN-gamma. Our findings suggest that the therapeutic effects of gold compounds in patients with rheumatoid arthritis may be attributed to the interference of the proliferation and HLA-DR antigen expression of the EC.

Antigens, Surface↗

Existence of mixed isotype A beta E alpha class II molecules in Ed alpha gene-introduced C57BL/6 transgenic mice.

In this study the existence of mixed isotype Ab beta Ed alpha molecules in Ed alpha gene-introduced C57BL/6 (B6Ed alpha) transgenic mice is demonstrated. Biosynthetically labelled B6Ed alpha transgenic spleen cells were immunoprecipitated with anti-Ab beta or anti-Ed alpha monoclonal antibody (mAb) and analysed by two-dimensional gel electrophoresis (NEPHGE/SDS-PAGE). Anti-Ab beta mAb precipitated Ed alpha molecules in addition to Ab beta and Ab alpha molecules. Anti-Ed alpha mAb precipitated Ab beta molecules in addition ot Eb beta and Ed alpha molecules. No Ed alpha molecule was precipitated by anti-Ab beta mAb from B10.A(3R) spleen cells, which have a very similar organization of class II molecules to B6Ed alpha transgenic mice. Since this B6Ed alpha transgenic mouse was shown to have 20-40 copies per cell of the Ed alpha transgene (Kashiwamura et al., 1988), it is speculated that large amounts of Ed alpha transgene are made but, according to the data presented here, only a small amount actually associates with Ab beta as opposed to Eb beta.

Animals↗

Neural cadherin: role in selective cell-cell adhesion.

Cadherins are a family of Ca2+-dependent intercellular adhesion molecules. Complementary DNAs encoding mouse neural cadherin (N-cadherin) were cloned, and the cell binding specificity of this molecule was examined. Mouse N-cadherin shows 92 percent similarity in amino acid sequence to the chicken homolog, while it shows 49 percent and 43 percent similarity to epithelial cadherin and to placental cadherin of the same species, respectively. In cell binding assays, mouse N-cadherin did not cross-react with other mouse cadherins, but it did cross-react with chicken N-cadherin. The results indicate that each cadherin type confers distinct adhesive specificities on different cells, and also that the specificity of N-cadherin is conserved between mammalian and avian cells.

Amino Acid Sequence↗

Increment in the Ta1+ cells in the peripheral blood and thyroid tissue of patients with Graves' disease.

The present study utilized the anti-Ta1 mAb to characterize the cell surface phenotypes of peripheral blood and intrathyroidal lymphocytes in patients with Graves' disease. We found an increase in PBL bearing the Ta1 Ag in untreated patients. The euthyroid patients in remission, induced by antithyroidal drugs, radioisotope therapy, and subtotal thyroidectomy, had lower percentages of Ta1+ cells than did untreated patients. An increased percentage of Ta1+ cells in untreated patients was found in both CD4+ cells and CD8+ cells. The ratio of CD4+Ta1+ cells to CD8+Ta1+ cells in untreated patients was significantly higher than that of normal subjects. There was a positive correlation between the percentage of Ta1+ cells and the level of anti-TSH receptor antibody. In this prospective study, the proportion of Ta1+ cells was decreased in parallel with the reduction in anti-TSH receptor antibody and free T3 levels. In the chronically treated patients, the proportion of Ta1+ cells in the thyroid tissue was, yet similar to that in the peripheral blood, markedly increased in comparison to that of normal subjects. In contrast to Ta1+ cells, the thyroid tissue had a significantly higher percentage of HLA-DR+ T cells than did the paired peripheral blood. The proliferative responses of the Ta1+ cell-enriched population isolated from untreated patients toward thyroglobulin and microsomal Ag were markedly higher than those in a Ta1+ cell-depleted population, but both populations were able to respond equally to PHA. These results suggest that the Ta1+ cells may include Ag-triggered memory cells that are reactive with thyroid-specific Ag. Furthermore, monitoring such cells may provide an objective measure of abnormal immunologic activity.

Adolescent↗

Cadherin-mediated specific cell adhesion and animal morphogenesis.

Cadherins are a family of transmembrane glycoproteins which are responsible for Ca2+-dependent cell-cell adhesion. Each member of the family displays a unique pattern of tissue distribution. The expression of cadherin molecules in an embryo is spatiotemporally regulated so as to be associated with a variety of morphogenetic events. Antibodies against cadherins perturb the morphogenesis of tissues, indicating their importance in tissue formation. When cells were transfected with cDNAs encoding cadherins, they expressed the exogenous cadherin molecules and these were functional. Using these transfected cells, we tested whether each member of the cadherin family has a binding specificity, and found that cells preferentially adhere to those expressing the identical cadherin type. The cadherin-mediated specific adhesion also occurred in the attachment of neurites to the surface of other cells. These observations suggest that cadherins are crucial for the selective adhesiveness of cells, and thus for the embryonic morphogenetic processes in which specific adhesive interactions of cells are involved.

Animals↗