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Biomedical subjects

T Yanagawa

Publications and source records attributed to T Yanagawa.

At least 19 recordsLinked to original sources

Suppression of development of diabetes in NOD mice by lactate dehydrogenase virus infection.

It has been reported that lactate dehydrogenase virus (LDV) selectively infects a subpopulation of macrophages, thereby affecting the immune system. We studied the effects of LDV infection on the development of diabetes in non-obese diabetic (NOD) mice. Five-week-old female NOD mice were infected with LDV (10(8) ID50/mouse) and observed until 23 weeks of age. None of the 21-LDV-infected mice developed diabetes, whereas 10/14 (71.4%) uninfected mice did. Although the subpopulations of T cells and the percentage of Mac1-positive cells in the NOD murine spleen and the number of harvested peritoneal macrophages were unaffected by LDV infection, the proportions of Ia-positive peritoneal macrophages were significantly decreased in LDV-infected compared with uninfected mice (1.1 +/- 0.2%, 6.5 +/- 2.9%; P < 0.01). In LDV-infected NOD mice, insulitis of the same grade as that seen in uninfected NOD mice was observed. In another experiment, 3, 5, 10 or 16-week-old female NOD mice were infected with LDV. None of the mice infected with LDV at 3, 5 or 10 weeks of age developed diabetes and only one of six infected at 16 weeks of age did. These findings indicate that LDV infection suppresses the development of diabetes in female NOD mice by reducing the capacity of Ia-positive macrophages, and suggest that the development of human type 1 diabetes may be suppressed by certain viral infections.

Animals

Heparan sulfate as a mediator of herpes simplex virus binding to basement membrane.

Explants of human lip and oral mucosa were infected with herpes simplex virus (HSV) in vitro and the expression of viral antigen was investigated by immunofluorescent antibody staining. Viral antigen was demonstrated in the cells of basal cell layer and lower prickle cell layers. Moreover, an accumulation of viral antigen in the epithelial-mesenchymal junction was observed. To examine the possibility that the basement membrane has an affinity for HSV, the interaction between HSV and major basement membrane components including type IV collagen, laminin, fibronectin, and heparan sulfate was investigated. When tested by a plaque-reduction assay, only heparan sulfate inhibited HSV plaque formation by competing for the virus adsorption to HEp-2 cells. The inhibitory effects of heparan sulfate and heparin were not affected by pre-incubation of these glycosaminoglycans with antithrombin III, whereas de-N-sulfation resulted in a significant reduction of their inhibitory activity. These findings suggest that heparan sulfate is involved in the binding of HSV to the basement membrane and that N-sulfated glucosamine residues of heparan sulfate are essential for HSV binding. The basement membrane may act as a reservoir of HSV in muco-cutaneous tissues.

Antigens, Viral

Effect of dibutyryl cyclic adenosine 3',5'-monophosphate on morphological features and biological markers of human salivary myoepithelial cell line in culture.

We have found the emergence of myoepithelial cells (HSG-AZA1) in neoplastic human salivary intercalated duct cell line HSG in culture after treatment with 5-azacytidine. When HSG-ZAZ1 cells were cultured in the presence of N6,O2-dibutyryl cyclic adenosine 3',5'-monophosphate (dB-cAMP), they formed long cytoplasmic processes which were densely packed with ample microfibrils in addition to microtubule bundles. The expression of neuron-specific enolase, synaptophysin, and catecholamine as well as neurofilaments in the treated HSG-AZA1 cells was found by the immunofluorescence staining technique, immunoblotting, immunoelectron microscopy, or catecholamine fluorescence. Both the anchorage-independent and anchorage-dependent growths of HSG-AZA1 cells were suppressed in the presence of dB-cAMP. After the removal of dB-cAMP from the culture, the treated cells returned rapidly to the phenotype and growth rate of the untreated cells. These findings indicate that reversible differentiation into the neuron-like cells of HSG-AZA1 cells occurs in growth medium containing dB-cAMP.

Analysis of Variance

Enhanced replication of herpes simplex virus by hexamethylene bisacetamide.

Hexamethylene bisacetamide (HMBA) is a potent inducer of differentiation of tumor cells. The effect of HMBA on cell growth and replication of herpes simplex virus (HSV) was investigated in HEp-2 epidermal cells, IMR-32 neuronal cells, K562 myeloid cells, Daudi Burkitt lymphoma cells, and CCRF-CEM T-lymphoid cells. The growth of HEp-2 and IMR-32 cells was not affected by HMBA at concentrations from 0.5 through 2 mM. The growth of K562, Daudi, and CCRF-CEM cells was inhibited by HMBA at concentrations from 1 through 5 mM. When HSV-infected cells were incubated with 0.5 through 5 mM HMBA, a dose-dependent increase in virus yield was observed in HEp-2 and IMR-32 cells, but not in the other cell lines. These findings indicate that HMBA enhances the replication of HSV in epidermal and neuronal cells and that HMBA therapy may be responsible for the development of herpetic lesions.

Acetamides

Herpes simplex virus type 1 and type 2 infection in human oral mucosa in culture.

To examine the sensitivity of human oral mucosa to herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection, human gingival mucosa explants were infected with either HSV-1 or HSV-2 in vitro and the expression of virus specific antigen was examined by the immunofluorescent antibody technique. HSV-2 antigen was found in the basement membrane, basal cell layer and lower prickle cell layer. This finding was consistent with the HSV-1 infection. Electron microscopic study revealed the presence of nucleocapsids and enveloped virus particles in the basal cells of HSV-2-infected organ cultures. These findings indicate that human gingival mucosa is sensitive to infection with HSV-2, as well as HSV-1, and that the virus may replicate in the undifferentiated epithelial cells of mucosal epithelium.

Adolescent

The suppressive effect of anti-asialo GM1 antibody on low-dose streptozotocin-induced diabetes in CD-1 mice.

To elucidate the role of natural killer (NK) cells in the pathogenesis of diabetes in streptozotocin-induced diabetes, we examined whether treatment with anti-asialo GM1 antibody prevents the occurrence of diabetes in CD-1 mouse model. Anti-asialo GM1 antibody was injected intraperitoneally 2-3 times a week starting three days before the first streptozotocin injection. In controls, rabbit immunoglobulin or saline was injected instead of anti-asialo GM1 antibody. Three of twelve anti-asialo GM1 antibody-treated mice developed diabetes, however eight of eight (100%) rabbit immunoglobulin injected mice and 20 of 23 saline-injected mice developed diabetes. The incidence of diabetes in the anti-asialo GM1 antibody-injected group was significantly higher than in the two control groups (p less than 0.01, p less than 0.01, respectively). The NK-cell activities of spleen cells from anti-asialo GM1 antibody-treated mice were significantly lower than in control mice. Flow-cytometry analysis demonstrated that anti-asialo GM1 antibody-positive cells had disappeared from spleens of anti-asialo GM1 antibody-injected mice but no suppression of T-lymphocytes could be demonstrated. These results suggest that NK cells play a role in the pathogenesis of streptozotocin-induced diabetes in CD-1 mice.

Animals

Anti-asialo GM1 antibody suppression of cyclophosphamide-induced diabetes in NOD mice.

To elucidate the role of natural killer (NK) cells in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse, we examined whether or not cyclophosphamide-induced diabetes occurs in NOD mice intraperitoneally (i.p.) injected with anti-asialo GM1 antibody. Two weeks after a single intraperitoneal injection of cyclophosphamide, none of the 24 NOD mice which had previously been treated with antiasialo GM1 antibody, 2-3 times per week for either 2 or 3 weeks, had developed indications of diabetes such as glycosuria or a high plasma glucose level. On the other hand, signs of diabetes were found in 10 of 24 control NOD mice injected with normal rabbit Ig instead of anti-asialo GM1 antibody (p less than 0.01). The NK cell activities of spleen cells from anti-asialo GM1 antibody-treated mice were significantly lower than those of control mice (p less than 0.01). Flowcytometry analysis demonstrated that anti-asialo GM1 antibody-positive cells had disappeared from the spleens of anti-asialo GM1 antibody-injected mice but no suppression of CD8+ and CD4+ cells could be demonstrated. These observations suggest that NK cells are involved in the development of diabetes in NOD mice.

Animals

Induction of cells with phenotypic features of neuronal cells by treatment with dibutyryl cyclic adenosine 3',5'-monophosphate in a human parotid gland adenocarcinoma cell line in culture.

A human parotid gland adenocarcinoma cell line, with an intercalated duct cell phenotype of the salivary gland and expression of vasoactive intestinal polypeptide and amylase, was cultivated in the presence of dibutyryl cyclic adenosine 3',5'-monophosphate (dB-cAMP). Morphological changes occurred; cells formed long cytoplasmic processes densely packed with ample microfibrils, as well as microtubules, and grew in a netlike appearance. In addition, it has been found by the immunofluorescence staining technique, immunoblotting, or immunoelectron microscopy that the cells treated with dB-cAMP express neurofilaments, neuron-specific enolase, synaptophysin, and HNK-1 antigen, as well as the alpha- and beta-chains of tubulin, whereas these antigens are not detected in untreated cells. The expression of vasoactive intestinal polypeptide detected diffusely in the cytoplasm of untreated cells was restricted to the cell membranes during the cultivation of cells in the presence of dB-cAMP, while expression of amylase persisted in the treated cells in a fashion similar to that in untreated cells. Moreover, both anchorage-independent and anchorage-dependent growth of the cells was markedly suppressed in the presence of dB-cAMP. After removal of dB-cAMP from the culture, the treated cells returned rapidly to the phenotype and growth rate of the untreated cells. These findings indicate that reversible conversion into cells with phenotypic features of neuronal cells of a human parotid adenocarcinoma cell line occurs in growth medium containing dB-cAMP.

Adenocarcinoma

Coexpression of intermediate-sized filaments in sialadenoma papilliferum and other salivary gland neoplasms.

The neoplastic cells present in a sialadenoma pappiliferum were found by immunoperoxidase method and immunofluorescent staining technique to co-express 3 different types of intermediate-sized filaments (IFs) defined by monoclonal antibodies to cytokeratin, vimentin and desmin. When other salivary gland tumors such as 18 pleomorphic adenomas, 15 adenolymphomas, 2 oxyphilic adenomas, 7 mucoepidermoid tumors, 5 acinic cell tumors, 8 adenoid cystic carcinomas and 6 adenocarcinomas were examined immunohistochemically for the expression of IFs, no tumors with all 3 types of IFs observed in sialadenoma papilliferum were found.

Adenocarcinoma

Herpes zoster of the maxillary branch of the trigeminus nerve. Virological and serological studies.

A 70-year-old male had erythematous and vesiculous lesions in the area of the right maxillary branch of the trigeminus nerve and was clinically diagnosed as having herpes zoster; virological and serological investigations of this case were carried out. Consequently, an electron microscopic observation revealed a great number of virus particles of herpes type in the vesiculous lesion and in baby hamster kidney BHK21/WI-21 cells, cultured after inoculating the fluid from the vesicle formed on the patient's upper lip or from serum harvested during the viremia. When BHK21/WI-21 cells infected with this virus were tested for antigenicity by an indirect immunofluorescent staining technique, they showed a positive staining to antivaricella-zoster virus. When serum of this patient was assayed fof the antibody level against varicella-zoster virus by the complement fixation test at various time intervals during the therapeutic period, this antibody titer on recovery period showed a threefold increase in comparison to that at onset. From these findings, this infectious disease was precisely diagnosed as herpes zoster.

Aged

Fine structure of a glomus tumor of the tongue and expression of C type virus in its tumor cells.

A glomus tumor in the tongue of a 29-year-old Japanese male is presented. Ultrastructural examination demonstrated this tumor to be composed of the tumor cells having structural features in common with smooth muscle cells, and mast cells as the less frequent type cell. Moreover, a small number of C type virus particles were found to be in the cytoplasm or in the intercellular spaces. In this communication, besides the detailed description of the morphology of the glomus tumor, the possible involvement of C type virus in processes of tumor formation is discussed.

Adult

Attenuated mumps virus therapy of carcinoma of the maxillary sinus.

This paper presents treatment of carcinoma of the maxillary sinus with an attenuated mumps virus. The mumps virus was inoculated into two cases of very advanced carcinoma of the maxillary sinus by local and general injection. Shortly after injection, relief from severe cancer pain and growth inhibition or necrosis of tumor were observed in both cases. In this communication, we discuss a possible mechanism of antitumor effect of mumps virus by utilizing immunologic tests and interferon assay.

Carcinoma, Squamous Cell

Immunological features and corticosteroid therapy of midline granuloma.

This paper presents treatment of midline granuloma with corticosteroids and immunological features of this disease. The cellular immunity state of this patient was examined by counting T cell subpopulation and lymphocyte blastformation index (BI) by phytohemagglutinin at various time intervals during the corticosteroid therapy. Consequently, the percentage of T cells and BI became greatly increased according to the subsiding of the primary lesion, whereas non-T cell production and its function were depressed. In this communication we discuss a possible autoantibody mechanism and impared lymphocyte transformation in midline granuloma.

Cheek

Designing case-control studies.

Identification of confounding factors, evaluation of their influence on cause-effect associations, and the introduction of appropriate ways to account for these factors are important considerations in designing case-control studies. This paper presents designs useful for these purposes, after first providing a statistical definition of a confounding factor. Differences in the ability to identify and evaluate confounding factors and estimate disease risk between designs employing stratification (matching) and designs randomly sampling cases and controls are noted. Linear logistic models for the analysis of data from such designs are described and are shown to liberalize design requirements and to increase relative risk estimation efficiency. The methods are applied to data from a multiple factor investigation of lung cancer patients and controls.

Disease