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Biomedical subjects

N Tokuda

Publications and source records attributed to N Tokuda.

At least 55 records · Page 3Linked to original sources

[Prostatic carcinoma presenting as an abdominal mass: a case report].

Prostatic carcinoma presenting as an abdominal mass is a very rare disorder. A 64-year-old man was referred to our hospital with the chief complaint of a right lower abdominal mass on March 6, 1984. Physical examination revealed a firm, smooth, fixed, non-tender, pulseless fist size mass in the right lower abdomen. Rectal examination revealed an apple size, smooth and elastic firm prostate which had an induration. Needle biopsy of the prostate showed well-differentiated adenocarcinoma. At first we regarded the abdominal mass as retroperitoneal tumor unassociated with prostatic carcinoma. After preoperative irradiation (20 Gy) to the pelvis, the abdominal mass was resected and bilateral orchiectomy was performed on April 11, 1984. The mass was histologically diagnosed as a metastatic lesion from prostatic carcinoma. On the basis of these findings, we considered the mass to be due to pelvic lymph node metastasis from prostatic carcinoma. His postoperative course was uneventful. In April 1991, he is still alive without evidence of recurrence or bone metastasis.

Adenocarcinoma↗

Effects of FK506 on rat thymic epithelial cells; immunohistochemical study.

The effects of FK506, a new immunosuppressive agent, on the rat thymus were investigated using the immunoperoxidase technique and flow cytofluorometry using monoclonal antibodies. Flow cytometric analysis of the thymus revealed that the proportion of cells labelled positively with OX7 (Thy-1 antigen), OX8 (CD8, T cytotoxic/suppressor cells) and W3/25 (CD4, T helper cells and macrophages) increased following treatment, with FK506, 1 mg/kg body weight for 14 days. A marked reduction of the thymic medulla following treatment was clearly demonstrated by staining with OX18 (MHC class I) and OX6 (MHC class II). Changes produced by FK506 were also observed in the cortical area of the thymus, being especially marked in the subcapsular area and around the blood vessels by staining with OX6, PKK-1 (alpha-cytokeratin), AB-1040 (type IV collagen), and AB-1220 (laminin). Eventually FK506 treatment resulted in patchy reduction of OX-6, PKK-1, AB-1040 and AB-1220 positive area in the cortex. This evidence suggests that FK506 may impair the thymic microenvironment and subsequently disturb the thymocyte maturation.

Animals↗

1,25-Dihydroxyvitamin D3 down-regulation of HLA-DR on human peripheral blood monocytes.

The regulatory activity of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on human leucocyte antigen (HLA)-DR (MHC class II) antigen expression in monocytes from normal human peripheral blood was examined. Using forward light and side scatter by flow cytometry most cells within the discrete monocyte area expressed high levels of HLA-DR antigens following 4-day culture in medium alone (culture-enhanced HLA-DR) and expression was further up-regulated in the presence of interferon-gamma (IFN-gamma) (IFN-gamma-enhanced HLA-DR). Treatment with 1,25-(OH)2D3 markedly inhibited both culture and IFN-gamma-enhanced HLA-DR but not HLA-ABC (MHC class I). This 1,25-(OH)2D3 inhibition was as effective as PGE2 and hydrocortisone. To ascertain if HLA-DR was specifically down-regulated on monocytes, the effect of vitamin D3 analogues in CD33+ cells was examined. Incubation of the CD33+ cells with 1,25-(OH)2D3, 24-25-(OH)2D3 and 25-OHD3 resulted in dose-dependent inhibition of culture-enhanced HLA-DR paralleling the vitamin D3-receptor affinities of these compounds. Northern analysis also demonstrated that 1,25-(OH)2D3 treatment markedly decreased both expression of culture-enhanced and IFN-gamma-enhanced HLA-DR beta chain messenger RNA (mRNA) in monocyte-enriched populations. In total, our findings are consistent with the proposal that vitamin D3 analogues can contribute to down-regulating immune responses as a consequence of inhibiting class II expression.

Antigens, CD↗

[Cavernous hemangioma of the spermatic cord: a case report].

Cavernous hemangioma of the spermatic cord is a very rare disorder. A 26-year-old man was admitted to our hospital with chief complaints of right intrascrotal mass and hematospermia on October 19, 1990. Physical examination revealed a hard, non-transilluminated mass in the right spermatic cord. The mass was resected via the groin. Pathological examination showed cavernous hemangioma. The patient's postoperative course was uneventful. This is only the fourth case of cavernous hemangioma of the spermatic cord to be reported in the literature in Japan.

Adult↗

Interferon-gamma induces the expression of major histocompatibility antigens by human retinal glial cells.

Retinal glial cells normally do not express major histocompatibility (MHC) molecules. However, the expression of MHC antigens by retinal glial cells under certain pathological conditions suggests that these cells may play a role in immune responses of the retina. At present, the identity of molecules that may regulate the expression of class I and class II MHC antigens by retinal glial cells has not been established. Since interferon-gamma (IFN-gamma) induces MHC antigens in a variety of cell types, we examined the effect of this lymphocyte product on class I and class II antigen expression by human retinal glial cells in culture. Glial cells derived from post-mortem donor eyes were exposed to recombinant human IFN-gamma. Cells with MHC class I or class II antigens were detected with the use of specific monoclonal antibodies that were labeled directly or indirectly with fluorescent probes. Fluorescence of labeled cells was assayed by flow cytometry. Exposure to IFN-gamma increased the expression of class I and class II antigens by the retinal glial cells. Double labeling studies showed that 90% of the glial cells induced to express class II antigens also had class I antigens. Overall, the results show that IFN-gamma can regulate the expression of MHC molecules by human retina glial cells in culture. These findings are consistent with the concept that glia may play a role in immunological disorders affecting the retina.

Adult↗

[Clinical evaluation of intramuscular imipenem/cilastatin sodium in surgical infections].

A multi-center clinical study was carried out at the first Department of Surgery, Okayama University Medical School and its affiliated institutions to evaluate the efficacy and safety profiles of intramuscular imipenem/cilastatin sodium (IPM/CS) in surgical infections, which were mainly biliary tract infections and peritonitis. The following results were obtained: 1. The efficacy rate was 72.0% in a total of 25 evaluable patients and 81.8% in patients with cholecystitis. 2. The efficacy rates in patients with and without underlying diseases were 70.0% and 73.3%, respectively, and they were 71.4% in patients with mild or moderate infections and 75.0% in patients with severe infections. 3. Bacteriologically, the eradication rate was 100% for Gram-positive bacteria and 62.5% for Gram-negative bacteria, with an overall eradication rate of 78.6%. The eradication rate for monomicrobial infections was 71.4% and that for polymicrobial infections was 100%. 4. Out of 25 patients, one developed diarrhea as a drug-related adverse reaction, and laboratory abnormalities attributable to the treatment were observed in 5 patients. None of them was serious, however. 5. The overall usefulness rate was 60.0%, and the usefulness for cholecystitis (72.7%) was superior to that for cholangitis (33.3%).

Adult↗

Differential regulation and expression of major histocompatibility complex (MHC) and Ly-6 gene products on mouse testicular Leydig and Sertoli cell lines.

The expression and regulation of Class I and Class II major histocompatibility complex (MHC) and Ly-6 antigens were examined in BALB/c testicular cells. Studies were performed utilizing differentiated murine Leydig (TM3) and Sertoli (TM4) cell lines. Neither Class I (Dd) nor Class II (IA/Ed) MHC antigens were detectable on untreated TM3 cells. However, concanavalin-A activated spleen cell supernatant (Con-A sup) or interferon-gamma (IFN-gamma) treatment resulted in the marked induction of both Class I and Class II MHC antigens on virtually all of the Leydig cells. MHC Class II mRNA, which was not detected in resting cells, was clearly induced following IFN-gamma incubation. Sertoli cells were found to constitutively express low levels of Class I (Dd) but not Class II (IA/Ed) antigens. However, in contrast to the enhanced MHC expression in TM3 cells, Con-A sup or IFN-gamma treatment of TM4 cells resulted in marked augmentation of Class I, but not Class II, MHC antigens. Northern blot analysis failed to detect Class II mRNA in either the resting or IFN-gamma treated TM4 populations. Neither ethanol nor tumor necrosis factor (TNF) alone, or together with IFN-gamma head significant effects on MHC expression by TM3 and TM4 cells. Ly-6 antigens, predominantly expressed on hematopoietic cells, were found to be present on both TM3 and TM4 cells. Expression of this non-MHC encoded product was also shown to be markedly enhanced by IFN-gamma treatment on both testicular cell lines. In total, these findings demonstrated that cytokines can differentially affect discrete cell populations arising from a particular tissue with respect to the un-regulation of MHC and non-MHC gene products. These findings are discussed in the context of autoimmune responses directed against this tissue.

Animals↗

Precocious puberty in a seven-year-old boy due to human chorionic gonadotropin producing pineal tumor detected by nuclear magnetic resonance computed tomographic scanning.

We report a 7-year-old boy who developed incomplete sexual precocity due to a human chorionic gonadotropin (HCG)-producing tumor in the pineal region. The patient presented enlarged testes (3 x 2 x 2 cm) bilaterally, enlarged penis, pubic hair development of Tanner Stage III, advanced bone age and growth spurt. Initial hormonal studies showed an adult male level of testosterone (13 ng/ml) and a high level of HCG as well as HCG-beta subunit. A high basal level of LH, probably due to immuno-cross-reactivity with HCG, and low basal level of FSH, probably suppressed by testosterone, did not respond to LH-RH infusion. Search for the site of HCG production failed at the initial workup, but calcification without definite signs of tumor in the pineal region was found by conventional brain CT scan. Because of subsequent progression of clinical and laboratory findings of sexual precocity, nuclear magnetic resonance computed tomographic (NMR-CT) scan was performed, which confirmed the presence of a pineal tumor three months later. The patient was treated with 4,500 rad. of radiation therapy, and responded dramatically to this regimen. He has been followed for more than two years without any signs of recurrence. We have reported here a very rare case of incomplete sexual precocity due to an HCG-producing intracranial tumor in the pineal region. An NMR-CT scan is a very useful tool for the diagnosis of some types of pineal tumor, such as germinoma, which are highly radiosensitive.

Brain Neoplasms↗

1,25-Dihydroxyvitamin D3 antagonizes interferon-gamma-induced expression of class II major histocompatibility antigens on thyroid follicular and testicular Leydig cells.

Interferon-gamma (IFN gamma) induces production and expression of major histocompatibility complex class II molecules on both marrow-derived and nonbone marrow-derived cell types. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], a seco-steroid derived from vitamin D3, has previously been reported to enhance such expression alone or together with IFN gamma on a number of monocyte/macrophage tumorigenic lines. In contrast, the present studies have found that 1,25-(OH)2D3 inhibited the ability of IFN gamma to induce class II antigen expression on nontransformed rat thyroid follicular epithelial cells (FRTL-5) and mouse testicular Leydig cells (TM3). Although 1,25-(OH)2D3 inhibited the induction of both IA and IE class II locus products, IFN gamma augmentation of class I major histocompatibility complex antigens was not affected. 1,24-(OH)2D3 and 24,25-(OH)2D3 also inhibited class II induction by IFN gamma. Notably, the relative inhibitory ability of these compounds paralleled the strength of their binding affinities for the 1,25-(OH)2D3 receptor, indicating that this antagonistic effect probably requires receptor-ligand interaction. Other steroid hormones, such as hydrocortisone or testosterone, had no inhibitory effect on IFN gamma-induced class II expression on Leydig cells. Additionally, the failure of indomethacin to reverse the effect of 1,25-(OH)2D3 and the finding that exogenous prostaglandin E2 did not inhibit class II induction in these cells indicated that prostaglandins are probably not responsible for this anti-IFN gamma activity. In total, these results suggest that an endocrinological mediator is capable of inhibiting class II induction on resident endocrine tissue populations and, therefore, could help to diminish local CD4+ T-cell recognition of these cells.

24,25-Dihydroxyvitamin D 3↗

Establishment of a novel method to induce tolerance in adult mice across fully allogeneic (entire H-2 plus multiminor histocompatibility) antigen barriers, using supralethal irradiation followed by injection of syngeneic bone marrow cells plus (donor X recipient) F1 spleen cells.

A novel method was established which can regularly induce profound tolerance in mice across entire H-2 plus multiminor histocompatibility (H) antigen (fully allogeneic) barriers. When recipient AKR/J Sea (AKR; H-2k) or C3H/He Slc (C3H; H-2k) mice were irradiated with 900 rad followed 1 day later by injection of 1 X 10(7) T cell-depleted syngeneic bone marrow cells plus 5 X 10(7) viable, but not mitomycin C-treated, [C57BL/6 Slc(B6) X AKR (or C3H)] F1 spleen cells via intravenous (i.v.) route, a specific tolerant state was induced against B6 (H-2b) antigens. In the tolerant C3H mice, the EL-4 tumor, which originates from B6, was accepted in a tolerogen-specific manner. Moreover, B6 skin grafts were permanently accepted in most of the tolerized AKR and C3H mice. Immunological parameters, including cytotoxic T lymphocyte (CTL) activity and the mixed lymphocyte reaction (MLR), were almost completely suppressed in the tolerant mice. An assay for chimerism using a direct immunofluorescence method revealed that the tolerant AKR mice were chimeric for the first 5 weeks after tolerance induction but not definitely chimeric thereafter. In the tolerant AKR mice, strong suppressor cells were not detected. This method could be used in order to investigate mechanisms of tolerance to allogeneic antigens in future experiments.

Animals↗

The effect of T cell depletion from spleen cell allografts on graft-versus-host disease and long-term immune reconstitution in H-2 haplotype-identical murine combinations.

Graft-versus-host disease (GVHD) and states of immune reconstitution in allogeneic chimera mice across minor histocompatibility antigens were analyzed in excess of 9 months after injecting AKR/JSea (AKR) spleen cells into irradiated C3H/HeSlc (C3H) mice. When T cell-depleted AKR spleen cells were used as inoculum cells, neither graft failure nor GVHD was seen for 9 months postgrafting in the C3H mice irradiated with 660 rad or more. In an AKR - C3H (850 rad) model, Thy1.1+ or L3T4+ T cell depletion from donor AKR spleen cells abolished both acute and chronic GVHD in lethally irradiated C3H mice. Lyt2+ T cell depletion, however, resulted in acute and chronic GVHD in more than half of the recipient C3H mice. Moreover, actual existence of donor (AKR)-type T cells with L3T4 phenotype, but not Lyt2 phenotype, was always observed in the spleen of the C3H mice suffering from acute GVHD. In addition, the C3H mice that were irradiated with 850 rad, grafted with AKR spleen cells depleted of Lyt2.1+ T cells, escaped from acute GVHD and survived for more than 10 mo postgrafting, showed impaired activities of immune responses such as delayed footpad reaction to sheep red blood cells, antibody production tested by IgM plaque forming cells and reactivity to an intracellular bacterium. Listeria monocytogenes as compared with the C3H mice reconstituted with syngeneic C3H spleen cells or Thy1.1+ or L3T4+ T cell-depleted AKR spleen cells. These results suggest that L3T4+ T cells, rather than Lyt2+ T cells, contained in the grafted cells not only cause acute GVHD but also a long-term immunodeficient state (chronic GVHD) in recipient mice in the H-2-identical murine combinations examined here.

Animals↗

The nature of tolerance in adult recipient mice made tolerant of alloantigens with supralethal irradiation followed by syngeneic bone marrow cell transplantation plus injection of F1 spleen cells.

The length of time after syngeneic bone marrow reconstitution when tolerance to alloantigens can be induced in adult mice during T cell differentiation from bone marrow cells was studied by exposing those T cells to (recipient x donor)F1 spleen cells. Supralethally irradiated C3H/He Slc(C3H; H-2k) mice were reconstituted with 1 x 10(7) syngeneic T cell-depleted bone marrow cells and then injected intravenously with 5 x 10(7) (C3H x C57BL/6[B6])F1 (B6C3F1; H-2bxk) or (C3H x AKR/J[AKR])F1 (AKC3F1; H-2kxk) spleen cells at various intervals. In the fully allogeneic combination of B6C3F1----C3H, EL-4 tumor originating from B6 was accepted, and survival of grafted B6 skin was significantly prolonged in the tolerant C3H mice treated with irradiation on day -1 followed by injection of syngeneic bone marrow cells on day 0 plus B6C3F1 spleen cells on days 0, 5, or 10, in a tolerogen-specific manner. In the multiminor histocompatibility antigen-disparate combination of AKC3F1----C3H, AKR skin grafts were permanently accepted in the tolerant C3H mice treated with AKC3F1 spleen cells on days 0, 5, 10, or 15. Immunological parameters, including cytotoxic T lymphocyte activity and delayed foot-pad reaction (DFR), were almost completely suppressed in C3H mice made tolerant of B6 or AKR antigens. A chimeric assay using a direct immunofluorescence method revealed that the tolerant C3H mice given B6C3F1 spleen cells on day 0 were mixed-chimeric for at least 8 weeks after syngeneic bone marrow reconstitution, but not definitely chimeric thereafter. The C3H mice given AKC3F1 spleen cells on day 0 were chimeric even 43 weeks after syngeneic bone marrow reconstitution, but the C3H mice given AKC3F1 spleen cells on day 15 showed temporal chimerism that disappeared within 43 weeks. The untolerant mice were never detectably chimeric. These data suggest that the earlier the timing of the injection of F1 spleen cells after syngeneic bone marrow reconstitution was, the more profound tolerance was induced. Moreover, the stronger the antigenic disparity between donor and recipient, the earlier the injection of F1 spleen cells was required to induce tolerance.

Aging↗

[Clinical experience of tapered distal ileum for construction of a continent colonic urinary reservoir].

Construction of continent colonic urinary reservoir was performed in 44 patients after exenteration for invasive bladder carcinoma or various gynecologic tumors. The distal ileum was tapered over a 14 French red rubber catheter. The ileocecal valve was reinforced with three circumferential silk sutures in a purse-string fashion. Full continence was obtained in all patients (100%). A non-tunneled, non-refluxing ureterocolonic anastomosis was performed in all 88 ureters. No obstruction or reflux was observed in 84 ureters (95%). There were 7 early postoperative complications and 3 of them required reoperation (pelvic abscess 1, urinary leak from ureterocolonic anastomosis 1, pouch-vaginal fistula 1). Moreover, there were 7 late complications and 3 of them required reoperation (stomal stenosis 1, parastomal hernia 2). These results suggest that this method is a safe, simple and useful one for permanent urinary diversion.

Abscess↗

Drug-induced in vitro tolerance to allogeneic antigens. II. Further analysis of in vitro-tolerized spleen cells in a fully allogeneic murine combination.

C3H/HeSlc (C3H, H-2k) spleen cells were made tolerant in vitro to C57BL/6CrSlc (B6, H-2b) at the cell-mediated cytotoxicity (CMC) level by in vitro stimulation for 48 hr with mitomycin C (MMC)-treated B6 spleen cells, and treatment with 5 micrograms/ml of 5-fluorouracil for a further 9 hr. These cells were given intraperitoneally to neonate (C3HxB6) F1 mice to examine whether these tolerized spleen cells would cause lethal graft-versus-host disease (GVHD). Despite the lack of CMC, the tolerized C3H spleen cells caused lethal GVHD in most of the neonate F1 mice. Evaluating from various immune parameters, it was evident that T cell populations responsible for IL-2 production, cytostasis, and delayed footpad reaction (DFR) were retained intact after in vitro tolerance induction, probably because of their less-proliferative characteristics in response to fully allogeneic antigen stimulation, and were considered to be responsible for lethal GVHD. Contribution of natural killer (NK) cells to lethal GVHD was not ruled out.

Animals↗