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T Otsubo

Publications and source records attributed to T Otsubo.

50 records · Page 3Linked to original sources
PubMed1988

Natural killer and natural killer-like cell activity of peripheral blood and intrathyroidal mononuclear cells from patients with Graves' disease.

This study was undertaken to investigate the natural killer (NK) and natural killer-like (NK-like) cell cytotoxic activity toward autologous thyrocytes of peripheral blood mononuclear cells (PB-MNC) and thyroid gland mononuclear cells (TG-MNC) from previously hyperthyroid patients with Graves' disease, and the effects of recombinant interleukin-2 on such cytotoxic activity. The average cytotoxicities of PB-MNC from Graves' patients toward K562 cells (NK-sensitive cells), Raji cells (NK-resistant cells), and autologous thyrocytes were 23.9 +/- 10.8 (+/- SD) lytic units (LU), 7.4 +/- 3.8 LU, and 11.7 +/- 4.4 LU, respectively. There were no differences in the NK and NK-like cell activity of PB-MNC between Graves' disease patients and normal subjects. In contrast to PB-MNC from patients with Graves' disease, NK and NK-like cell activity was markedly decreased in TG-MNC (NK cell activity, 2.1 +/- 2.3 LU; NK-like cell activity, 1.5 +/- 1.5 LU). TG-MNC from Graves' patients had no cytotoxic activity against autologous thyrocytes. Using the monoclonal anti-Leu 7 and anti-CD16 antibodies and a two-color immunofluorescence method, the NK cell subsets were examined in PB-MNC and TG-MNC from Graves' patients. The percentage of CD16+ cells was significantly decreased in TG-MNC compared to PB-MNC, whereas there was no significant difference in the percentage of Leu 7+ cells between PB-MNC and TG-MNC. Incubation of TG-MNC with medium only did not increase the NK and NK-like cell activity of these cells. Furthermore, incubation of autologous PB-MNC with supernatants of minced thyroid tissues did not alter their NK and NK-like cell activity. The decreased NK and NK-like cell activity of TG-MNC was augmented when these cells were incubated with recombinant interleukin-2. These results suggest that the reduction of NK cell activity in TG-MNC may allow perpetuation of B-cell activation and lead to excessive production of autoantibody in thyroid tissue.

Adolescent↗
PubMed1988

Phenotypic analyses and concanavalin-A-induced suppressor cell dysfunction of intrathyroidal lymphocytes from patients with Graves' disease.

The expression of phenotypic markers and Concanavalin-A-induced suppressor activity was compared among mononuclear cells isolated from thyroid glands and peripheral blood of thionamide-treated patients with hyperthyroid Graves' disease and peripheral blood from normal subjects. Intrathyroidal lymphocytes were obtained by two different methods (TG-1 and TG-2 cells), gradient centrifugation of supernatants of minced thyroid tissue and overnight culture of thyroid debris after mechanical disaggregation and enzymatic digestion, respectively. The percentages of CD3+ cells (all mature T cells) among peripheral blood and TG-1 and TG-2 cells from Graves' patients were similar, but the percentages of B1+ cells (pan B cells) among the TG-1 and TG-2 cells were markedly increased compared to that in peripheral blood. The percentages of CD4+ cells among the TG-1 and TG-2 cells were significantly less than that in peripheral blood. The percentages of CD4+2H4+ cells among CD4+ cells in TG-1 and TG-2 cells also were significantly less than that in peripheral blood. The percentage of CD4+4B4+ cells among CD4+ cells in thyroid glands was markedly higher than that in peripheral blood. The percentages of CD8+ cells and CD8+CD11b- cells (cytotoxic T cells) in thyroid glands were significantly higher than those in peripheral blood from Graves' patients and peripheral blood from normal subjects. The CD8+CD11b+ cells were subdivided into two subpopulations on the basis of CD8 antigen density. The percentage of dull CD8+CD11b+ cells (natural killer cells) among TG-2 cells was lower than that in peripheral blood, but there was no significant difference in bright CD8+CD11b+ cells (suppressor-effector T cells) between thyroid glands and peripheral blood. The percent suppression induced by Concanavalin-A in both TG-1 and TG-2 cells was significantly decreased compared with that in peripheral blood. These results suggest that impairment of suppressor cell activity and an increased number of B cells exist in thyroid glands of patients with Graves' disease compared to those in peripheral blood. It, thus, appears likely that both B cell hyperactivity and suppressor T cell dysfunction may induce excess production of autoantibodies in the thyroid glands of such patients.

Adolescent↗
PubMed1988

In vitro cellular interactions among thyrocytes, T cells and monocytes from patients with Graves' disease.

In order to investigate the cellular interactions among thyrocytes, T cells and monocytes in thyroid glands from patients with Graves' disease, we determined alterations of HLA-DR antigen expression on thyrocytes and T cells, and the production of interferon-gamma during coculture of thyrocytes, T cells and monocytes obtained from patients with Graves' disease. Thyroid glands were obtained at operation from 17 patients with Graves' disease. When thyrocytes and autologous peripheral blood T cells were cocultured for 7 days, the percentage of HLA-DR antigen expression on thyrocytes was significantly increased by T cells and that on T cells was also significantly increased by thyrocytes. Addition of autologous monocytes to the mixtures of thyrocytes and T cells significantly increased the expression of HLA-DR antigens on both thyrocytes and T cells compared with mixtures without monocytes. In culture supernatants, interferon-gamma was detected in 4 of 14 cocultures of thyrocytes and T cells, in 5 of 10 cocultures of thyrocytes, T cells and monocytes, but not in any cultures of thyrocytes alone, T cells alone and T cells and monocytes. Induction of HLA-DR antigen expression on thyrocytes and T cells was blocked by addition of anti-interferon-gamma monoclonal antibody to the mixture. These results suggest that HLA-DR antigen positive thyrocytes are able to induce the HLA-DR antigen expression of T cells in the presence of monocytes, and the activated T cells are capable of producing interferon-gamma which acts on thyrocytes to induce and maintain the expression of HLA-DR antigens.

Adolescent↗
PubMed1988

The effects of cytokines, antithyroidal drugs and glucocorticoids on phagocytosis by thyroid cells.

The present study was undertaken to examine whether thyrocytes possess phagocytic activity and whether the phagocytic activity is influenced by cytokines, such as interleukin 1, 2 (IL 1, IL 2) and interferon-alpha, -beta, and -gamma (IFN-alpha, beta, and gamma), and drugs, such as methimazole and dexamethasone. Thyroid glands were obtained from patients with Graves' disease. Thyrocytes were prepared by collagenase digestion. Thyrocytes were pre-incubated in the presence or absence of cytokines and drugs at 37 degrees C for 20 h and were further incubated with fluoresceinated latex beads at 37 degrees C for 60 min. The number of phagocytic thyrocytes was determined by FACS IV. Phagocytosis of latex beads was indeed seen within thyrocytes and gradually increased in a time-dependent manner. The rate of phagocytosis in thyrocytes was extremely slow as compared with that in macrophages. Phagocytic activity was detected in thyrocytes from patients with Graves' disease and from normal thyroid tissue adjacent to thyroid cancer. Phagocytosis was inhibited by IL 1, but was enhanced by IL 2. Although the enhanced phagocytosis with IFN-beta was consistently seen, little effect was detected with IFN-alpha and -gamma. Both methimazole and dexamethasone markedly inhibited phagocytosis. These results indicated that thyrocytes had phagocytic properties and that their phagocytic activity was modulated by cytokines, antithyroidal drugs and dexamethasone.

Antithyroid Agents↗
PubMed1988

Synergy in antigen presentation by thyroid epithelial cells and monocytes from patients with Graves' disease.

The present study was undertaken to examine the ability of thyrocytes from Graves' patients to present purified protein derivative (PPD) to autologous peripheral blood T cells. Normal human thyrocytes which were pre-cultured with interferon-gamma were able to induce the proliferation of T cells in response to PPD antigen, but unstimulated thyrocytes failed to do. Thyrocytes from Graves' patients on which HLA-DR antigens were expressed have an ability to induce the proliferation of T cells. Thyrocytes from Graves' patients which were pulsed with PPD antigen for 4 h were capable of stimulating proliferation of the T cells. However, the stimulation index of T cells co-cultured with thyrocytes and PPD were significantly lower than that of T cells co-cultured with monocytes and PPD. Sub-optimal numbers of monocytes which by themselves were unable to support T-cell proliferation synergistically augmented antigen presentation by thyrocytes. These results suggest that cellular interactions among thyrocytes, monocytes and T cells may perpetuate immune or autoimmune responses in thyroid tissues from Graves' patients.

Adolescent↗
PubMed1987

Reduction in the suppressor-inducer T cell subset and increase in the helper T cell subset in thyroid tissue from patients with Graves' disease.

The expression of surface markers associated with activation and characterization was compared among T cells in thyroid glands and peripheral blood of 10 patients with Graves' hyperthyroidism receiving chronic antithyroid drug therapy, in peripheral blood of 15 patients with untreated hyperthyroid Graves' disease, and in peripheral blood of 21 normal subjects using two-color flow cytometry. In the chronically treated Graves' disease patients, the percentage of activated T cells (HLA-DR+ T cells) among total T cells was significantly higher in thyroid tissue than in peripheral blood, and the increase in percent activated T cells was also significant among both helper/inducer T cell (CD4+ cell) and suppressor/cytotoxic T cell (CD8+ cell) subsets. The percentage of activated T cells in peripheral blood was not significantly different between chronically treated hyperthyroid Graves' patients and normal subjects, whereas the percentage of activated T cells in the peripheral blood from untreated hyperthyroid Graves' disease patients was significantly higher than that in normal subjects or chronically treated hyperthyroid Graves' patients. The percentages of CD4+ cells and CD8+ cells among total T cells were not different between thyroid tissues and peripheral blood in patients with chronically treated hyperthyroid Graves' disease. When CD4+ were further divided into helper T cells (CD4+2H4- cells) and suppressor-inducer T cells (CD4+2H4+ cells) using two-color flow cytometry, the percentage of helper T cells among CD4+ cells was significantly higher in thyroid tissue than in peripheral blood, resulting in an increased ratio of CD4+2H4- cells to CD4+2H4+ cells. The percentage of CD4+2H4+ cells in peripheral blood, however, was not significantly different among untreated and chronically treated Graves' disease patients and normal subjects. From the findings of abnormalities in intrathyroidal T cell subsets, we suggest that the decrease in the function of suppressor T cells within the thyroids of Graves' disease patients may be due to a decrease in CD4+2H4+ cells within thyroid tissue.

Adolescent↗
PubMed1987

Dysfunction of suppressor T cells in thyroid glands from patients with Graves' disease.

To investigate the suppressor function of intrathyroidal (TG) T cells in Graves' disease, the percentage of suppressor T cell subsets and the suppressor function of TG and peripheral blood (PB) lymphocytes in Graves' disease were compared by determining the in vitro production of immunoglobulin G (IgG) in reconstituted mixtures of separated B, CD4+ (helper/suppressor-inducer T), and CD8+ (suppressor/cytotoxic T) cells. TG lymphocytes were obtained by gradient centrifugation of the supernatants of minced thyroid tissues. T Cells were separated by E-rosette formation, and CD4+ and CD8+ cell-rich populations were separated by a panning method using monoclonal anti-CD8 antibody. Mixtures of 5 X 10(4) B (PB1 or TG) cells, 2 X 10(4) CD4+ (PB or TG) cells, and 5 X 10(3) macrophages (PB or TG) were cultured with various numbers of CD8+ (PB) or CD8+ (TG) cells for 7 days with pokeweed mitogen, and IgG synthesis was determined by solid phase RIA. T cell subpopulations were quantitated by a direct immunofluorescence method using monoclonal anti-CD3, anti-CD4, and anti-CD8 antibodies. There was no difference in the percentages of CD8+ cells among total T cells between thyroid glands and peripheral blood from Graves' disease patients [mean PB, 39.8 +/- 9.8% (+/- SD); TG, 42.5 +/- 13.8%; n = 10]. IgG production by mixtures of B and CD4+ cells isolated from peripheral blood was not different from that by cells isolated from thyroid glands [mean PB, 1635 +/- 248 (+/- SE) ng/mL; TG, 1081 +/- 128 ng/mL; n = 19; P = NS]. The nonspecific suppressor activity of thyroid gland CD8+ cells was less than that of CD8+ (PB) cells [percent suppression of IgG production by mixtures of B (PB) and CD4+ (PB) cells, 12.5% vs. 57.0% (P less than 0.01); by mixtures of B (TG) and CD4+ (TG) cells, 5.8% vs. 38.9% (P less than 0.01)]. The suppressor-inducer function of CD4+ (TG) cells was also decreased compared with that of CD4+ (PB) cells. These results suggest that the impairment of suppressor cell activity may lead to excessive production of autoantibody in thyroid glands from patients with Graves' disease.

Adult↗
PubMed1987

The remarkable proliferation of helper T cell subset in response to autologous thyrocytes and intrathyroidal T cells from patients with Graves' disease.

We have studied cellular interactions among thyrocytes, intrathyroidal T cells and peripheral blood T cells from Graves' patients. In the autologous mixed lymphocyte reaction of Graves' patients, CD4+ cells were able to proliferate vigorously against autologous non-T cells, whereas CD8+ cells responded weakly to non-T cell stimulators. Furthermore, the proliferative response of the CD4+ 2H4+ suppressor-inducer T cell subset was increased like that of the CD4+ 2H4- helper T cell subset. In contrast to peripheral blood non-T cell stimulators, thyrocytes and intrathyroidal T cells had the ability to activate the CD4+ 2H4- helper T cell subset but were not able to cause proliferation both of CD4+ 2H4+ suppressor-inducer T cell and CD8+ suppressor/cytotoxic T cell subsets. The marked reduction in proliferative responses of CD4+ 2H4+ cells and CD8+ cells could not be attributed to a difference in kinetics or altered response to variable number of stimulator cells. On the basis of these findings, it is suggested that the concentration of the helper T cell subset may be progressively increased and suppressor circuits may be unable to be activated in thyroid tissues. These abnormalities in cellular interactions may induce the excessive production of autoantibodies.

Adolescent↗
PubMed1986

Class II major histocompatibility complex antigen expression and cellular interactions in thyroid glands of Graves' disease.

Class II major histocompatibility complex (MHC) antigens have been demonstrated on the surface of thyroid epithelial cells (thyrocytes) from patients with autoimmune thyroid disease. The present study was designed to investigate how the expression of class II MHC antigens is involved in autoimmune processes in Graves' disease by studying cellular interactions among thyrocytes, lymphocytes within thyroid glands (TG), and peripheral blood (PB) lymphocytes. Thyrocytes were prepared by collagenase digestion, and T or non-T cells were separated by E-rosette formation. Thyrocytes were cocultured in the presence or absence of interferon-gamma, and the expression of HLA-DR antigens on cultured thyrocytes was examined by an indirect immunofluorescence method using monoclonal anti-HLA-DR antibody and monoclonal anti-HLA-DQ antibody. The cellular interactions were assessed as the proliferative response of T cells to autologous stimulators, such as thyrocytes or lymphocytes. Expression of HLA-DR antigens on thyrocytes after culture for 18 h in the absence of interferon-gamma was found in two thirds of the patients with Graves' disease studied (n = 18). Interferon-gamma induced and maintained the expression of HLA-DR antigens on thyrocytes. The percentages of HLA-DR+T cells were significantly higher among TG-T cells than among PB-T cells [32.6 +/- 12.4% (+/- SD) vs. 12.2 +/-5.0%; n = 18; P less than 0.01]. Thyrocytes from Graves' patients induced proliferation of both autologous PB-T cells and TG-T cells, and TG-T cells stimulated proliferation of autologous PB-T cells. In conclusion, interferon-gamma induces HLA-DR antigen expression on thyrocytes from patients with Graves' disease, and these cells induce proliferation of autologous T cells, which may, in turn, act on thyrocytes to perpetuate the process.

Adolescent↗
PubMedDate not supplied

Enhancement of cytolytic activity of human peripheral blood lymphocytes by sodium periodate (IO4) possible involvement of protein kinase C.

Sodium periodate (IO4) exerts a number of biological effects including the enhancement of lymphocyte activation. In this study, we investigated its effects on cytotoxicity of human peripheral blood lymphocytes (PBL) and explored the mechanism whereby it exerted these effects. In vitro treatment of human PBL with IO4 augmented their cytotoxicity against K562 myelogenous leukemia cells. IO4 oxidative treatment increased the frequency of effector-to-target cell binding. It also increased cellular ATP levels in effector cells, suggesting that the post-binding cytolytic functions of these cells were also enhanced after treatment with IO4. Moreover, IO4 treatment significantly increased the protein kinase C (PKC) activity of effector cells and induced the translocation of activity in the membrane fraction from the cytosol. H-7, a potent PKC inhibitor, significantly reduced this enhancement of membrane-associated PKC activity at 10 microM and significantly reduced the enhanced cytotoxicity of PBL at the same concentration. These results indicated that IO4 enhanced the binding capacity and post-binding cytolytic functions of PBL and that PKC activation was one mechanism to explain the IO4-induced cellular activation.

Adenosine Triphosphate↗
PubMedDate not supplied

Relapse of panic disorder induced by a single intravenous methamphetamine injection.

The authors reports a case of a 33-year-old woman who had a relapse and worsening of panic disorder following a single injection of methamphetamine after a long period of remission. Her first panic attack had occurred when she was a 14-year-old high school student, but the course had persisted only for 1 month. Soon after an intravenous injection of methamphetamine, she had a relapse of panic disorder, and depression and agoraphobia developed. Psychotropic medication was not fully effective.

Adult↗
PubMedDate not supplied

Liver regeneration and restoration of liver function after partial hepatectomy: the relation of fibrosis of the liver parenchyma.

BACKGROUND/AIMS: Patients who survive partial hepatectomy sometimes have unsatisfactory liver regeneration and restoration of liver function. Although the extent of resection should be adjusted to attain favorable liver regeneration and restoration of liver function, a guiding principle for this has not been established. METHODOLOGY: Seventy patients with hepatic tumors associated with liver disorders of various severity who underwent hepatectomy were studied. We calculated the removal rate of the liver and the regeneration rate of the remnant liver using computed tomography. The liver function was investigated using ICG R-15 (retention rate of indocyanine green). Liver disorder was classified into 4 groups, according to the severity of fibrosis. RESULTS: The regeneration rates of the remnant liver indicated a significant decline in patients with severe fibrosis. In the no fibrosis and mild fibrosis groups, an increased removal rate was associated with increased regeneration rate, and post-operative ICG R-15 improved with time. However, in the moderate fibrosis and severe fibrosis groups, an increased removal rate was not associated with increased regeneration rate, and post-operative ICG R-15 showed no change or became worse with time. CONCLUSIONS: Severe fibrosis of the liver parenchyma is associated with poorer regeneration of the remnant liver leading to poor restoration of post-operative liver function. The severity of fibrosis is useful as a predictive factor for liver regeneration and restoration of liver function after partial hepatectomy.

Adult↗