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Biomedical subjects

M Setoyama

Publications and source records attributed to M Setoyama.

At least 55 records · Page 3Linked to original sources

In vitro induction of cytotoxic T lymphocytes against HTLV-I-infected T-cells from adult T-cell leukemia patients, asymptomatic HTLV-I carriers and seronegative healthy donors.

We investigated an in vitro method to produce cytotoxic T lymphocytes (CTLs) against HTLV-I-infected T-cells using peripheral blood mononuclear cells (PBMC) of adult T-cell leukemia (ATL) patients, asymptomatic HTLV-I carriers (AC) and seronegative healthy donors. The PBMC were restimulated repeatedly for 4 weeks with HLA-matched HTLV-I-infected T-cells which had been pretreated at 56 degrees C for 30 min to inactivate infectious HTLV-I. The culture medium included 10-100 units/ml of recombinant lymphokines (rIL-1, rIL-2, rIL-4, rIL-6 and rIL-7) and 10% fetal calf serum in RPMI-1640 medium. The cytotoxic activity was measured against HLA-matched HTLV-I-infected T-cell lines after CD4+ or CD8+ cells were positively panned from the cultured PBMC. The PBMC of ATL, AC and healthy donors were able to produce either CD4+ or CD8+ CTLs against HTLV-I-related antigens (env, gag, p21x, p27rex and p40tax) as well as the antigen(s) of as-yet unknown specificity expressed on HTLV-I-infected T-cells. All the CTLs recognized the specific antigens in the context of either class I or class II HLA types. These results indicated that ATL patients, AC and healthy donors were immunocompetent to generate CTLs against HTLV-I-infected T-cells and probably against HTLV-I-transformed T-cells.

Adult↗

Desmosomal dissolution in Grover's disease, Hailey-Hailey's disease and Darier's disease.

Proteins involved in the formation of desmosomes and simpler adherens junctions were studied in three types of non-immune acantholytic diseases; specifically, four cases of Grover's disease (GD), one case of Hailey-Hailey's disease (HHD) and one case of Darier's disease (DD), and these were compared to two cases of immune-mediated acantholytic disease pemphigus vulgaris (PV). The proteins studied included: 1. The intracellular desmosomal proteins, desmoplakin I and II and plakoglobin; 2. The intercellular desmosomal proteins, desmoglein and CD44; and 3. vinculin, which is a major intracellular protein of the simpler aherens junctions. In GD, HHD and DD, immunostaining showed a loss of desmoplakin I and II and plakoglobin from the desmosomes, and a diffuse staining in the cytoplasm. In contrast, in pemphigus vulgaris, these proteins seemed intact and were localized to dot-like spots on the cell surface. Also, desmoglein, and CD44 were slightly affected in GD, and moderately affected in HHD and DD. Absence of desmosomal attachment plaques, the lack of labeling with desmoglein in the affected desmosomes and a diffusion of the labels into cytoplasm were demonstrated with electron microscopy using an immunogold technique. In PV, desmoglein III is one of the target antigens for the autoantibodies in this disease and was only partially preserved in a small number of lesional cells, while CD44 was mostly preserved. Vinculin was intact in GD, HHD and DD, but was lost in PV. This study, our previous work, and that of others, suggest that: 1. In GD, HHD and DD, the proteins of the desmosomal attachment plaque are primarily affected; 2. In PV, the intercellular glycoproteins are primarily involved; and 3. Simple adherens junctions are intact in GD, HHD and DD, but are damaged in PV.

Acantholysis↗

Multiple bursitis--a case with an unusual skin manifestation.

Bursitis is a periarticular rheumatism which occurs as a result of trauma, infection, metabolic disease or rheumatoid arthritis. The disease is usually manifested as a solitary lesion except in a few reported cases of multiple lesions. We describe here a case of bursitis in a 58-year-old woman with multifocal cystic lesions containing sterile bloody or yellowish fluid in the four extremities. Serological abnormalities were also noted, suggesting the presence of rheumatoid arthritis or another autoimmune connective tissue disease.

Arthritis, Rheumatoid↗

Junctional proteins of keratinocytes in Grover's disease, Hailey-Hailey's disease and Darier's disease.

Alterations of junctional structures in non-immune mediated acantholytic diseases (Grover's, Hailey-Hailey's and Darier's diseases) were examined using monoclonal antibodies against desmosomal attachment constituents (desmoplakin I & II and plakoglobin), desmosomal intercellular cement glycoprotein (desmoglein), protein of adherens junction (vinculin), and protein of gap junction (43Kd connexin). Universal cell surface (transmembrane) glycoprotein CD44 was also studied. In acantholytic foci of these diseases, attachment plaque proteins had dissolved and diffused into the acantholytic cells. The normal dotted linear pattern of immunostaining on the cell membrane was totally lost. In contrast, CD44 was well preserved on the cell membranes of acantholytic cells. Adherens junction and gap junction proteins were mostly preserved. Acantholytic cells of pemphigus vulgaris were similarly studied. In these cells, desmosomal attachment plaque proteins were very well preserved, while intercellular cement substance (desmoglein), adherens junctional proteins (vinculin), and gap junction protein (connexin) were totally absent, either on the cell membrane or in the cytoplasm. Electron microscopy confirmed an early dissolution of attachment plaque. Internalized desmosomal structures were seldom found in acantholytic cells of non-immune diseases. It was concluded that the primary event in acantholysis in these three diseases is the dissolution of desmosomal attachment plaque.

Acantholysis↗

Erythema multiforme associated with superficial fungal disease.

An extremely rare case of erythema multiforme associated with dermatophytosis by Trichophyton rubrum infection was reported in a 19-year-old woman. She had a reddish plaque resembling annular ringworm on her left arm. Treatment with an antifungal cream (clotrimazole) on the infected site cleared the condition in three weeks. Spontaneous regression of erythema multiforme in different parts of the body was recognized when the ringworm infection resolved. In recent years, only two cases have been reported in the English literature.

Adult↗

HTLV-I messenger RNA is expressed in vivo in adult T-cell leukemia/lymphoma patients: an in situ hybridization study.

Adult T-cell leukemia/lymphoma (ATLL) is a malignancy involving peripheral blood, lymph nodes, skin and other organs. Human T-cell leukemia virus type I (HTLV-I) is etiologically associated with ATLL but cannot be detected by conventional methods in fresh samples of peripheral blood and skin taken from ATLL. The aim of this study was to investigate the feasibility of an in situ hybridization technique for detection of HTLV-I mRNA in atypical lymphoid cells of peripheral blood and skin lesions of patients with ATLL. We detected variable amounts of HTLV-I tax mRNA in the nuclei and cytoplasm of these cells in fresh peripheral blood samples and skin lesions from ATLL patients, and also in asymptomatic HTLV-I infected donors to a lesser extent. Out of 10 patients with ATLL, 7 showed strong positive in situ hybridization whereas the other 3 were only weakly positive. However, in the last 3 cases, the reaction became strongly positive after cells had been cultured for 24 hr. Furthermore, all 3 asymptomatic HTLV-I-infected donors exhibited a weakly positive response in their apparently mature lymphoid cells.

Adult↗

Pigmented ameloblastic fibro-odontoma with melanophages.

A case of pigmented ameloblastic fibro-odontoma in the mandible of a 9-year-old Japanese girl is reported. In this tumor, melanin was widely distributed in the nests of the odontogenic epithelial component, and an aggregation of large round melanophages with a large amount of melanin similar to nevus cells was observed in the areas of the connective tissue component. A considerable number of dendritic cells that were considered to be melanocytes were scattered in the epithelial nests. This is the first case of pigmented odontogenic tumor that showed such extensive pigmentation with an aggregation of melanophages.

Child↗

Cutaneous arterial fibromuscular dysplasia: a case report and electron-microscopic study.

A case of a 39-year-old female with fibromuscular dysplasia (FMD) manifesting subcutaneous pulsatile nodules on the right side of her forehead and on her right wrist is reported here. These nodules proved to be FMD aneurysms of the frontal ramus of the right superficial temporal artery and the right radial artery. The patient had also suffered a stroke with subarachnoidal bleeding as a result of this disease. Angiographic examination showed aneurysms in the union and the bilateral vertebral arteries, a branch of the right renal artery, and one the right lumbar artery. A biopsy specimen taken from the frontal branch of the right superficial artery revealed segmental intimal thickening consistent with intimal fibroplasia type FMD upon histological examination. Electron-microscopic findings were also discussed in connection with the histogenesis of the disease. This appears to be the second case of FMD involving arteries in the skin to be reported in the dermatological literature.

Adult↗

Immunohistochemical study of c-erbB-2 oncoprotein expression in extramammary Paget's disease.

Sections of formalin-fixed, paraffin-embedded tumor tissue from 20 patients with noninvasive extramammary Paget's disease and 2 patients with invasive extramammary Paget's disease were stained immunohistochemically by means of anti-c-erbB-2 product monoclonal antibody. Membrane staining of intraepidermal tumor cells was found in only 3 of 20 cases of noninvasive extramammary Paget's disease. In the 2 invasive cases, tumor cells of invasive lesions and metastases were positive while intraepidermal tumor cells were negative.

Aged↗

T-cell receptor gene rearrangement in cells infiltrating skin eruptions specific to adult T-cell leukemia.

We examined T-cell receptor gene rearrangement in skin lesions and peripheral blood from 6 patients with adult T-cell leukemia (ATL) using the Southern blot method and a c beta 1 probe. A rearrangement signal common to skin lesions of all 6 patients was observed. One patient (Case 4) exhibited another rearrangement signal in the skin lesion and an identical signal was detected in the peripheral blood. This is the first report describing a specific pattern of T-cell receptor gene rearrangement in ATL. The signal obtained is assumed to represent receptors of T cells involved in surveillance of HTLV-I infected T cells.

Aged↗

A case of lupus meningitis treated successfully with methylprednisolone pulse therapy.

A 46-year-old female had suffered from systemic lupus erythematosus (SLE) for 8 years. Headache, vomiting and stiff neck appeared in the active phase of SLE. Findings in the cerebrospinal fluid were consistent with those of lupus meningitis. No pathogenic microbes were detected by microbiological or immunological examinations. She was diagnosed as having lupus meningitis. The method discussed herein which elucidates the cause of fever in SLE using white blood cell count (WBC) and alpha-2 globulin appeared to be useful for examining this case of meningitis. Lupus meningitis seems to preferentially occur in SLE patients with positive anti-ribonucleoprotein (RNP) antibody. Pulse therapy with methylprednisolone appeared to work well in this lupus meningitis patient who had had a long course of corticosteroid therapy.

Female↗

A case of epidermolysis bullosa hereditaria--dominant dystrophic type of Cockayne and Touraine.

We report a patient with the Cockayne and Touraine type epidermolysis bullosa dystrophica domains. A 6-year-old Japanese female developed blisters and erosions on the extremities 3 months after birth. Immunohistology showed a linear binding pattern of the monoclonal antibody against type VII collagen (LH:2) on the epidermal basement membrane. By means of electron microscopy and morphometric analysis, it became apparent that the anchoring fibrils were rudimentary in structure and reduced in number.

Basement Membrane↗

Monoclonal anti-melanoma antibodies IKH-1 and IKH-2 which work on formalin-fixed, paraffin embedded tissues: characterization, clinical trials and comparative studies with HMB-45.

Mouse monoclonal antibodies (MoAbs), IKH-1 and IKH-2, were produced against cloned human melanoma cells, KHm-6, which were cultured with 12-O-tetradecanoylphorbol-13-acetate (TPA) and processed by formalin fixation and alcohol dehydration (FFAD). According to the biochemical analysis, antigenic substances which reacted with IKH-1 were 34.0-60.0 kDa glycoproteins, and those which reacted with IKH-2 were 33.5, 34.5 and 36.0 kDa glycoproteins. Immunoelectron microscopy revealed that reaction products of IKH-1 were seen in some membranous vesicles, premelanosomes and cell membrane of TPA-treated KHm-6 cells, while IKH-2 recognized only premelanosomal structures. Immunohistochemical tests revealed that IKH-1 and IKH-2 have a high sensitivity (94.0% and 85.0%, respectively) to formalin-fixed, paraffin-embedded (FFPE) tissue sections of malignant melanomas. IKH-1 had a high specificity and IKH-2 and 100% specificity to FFPE tissue sections of melanocytic lesions.

Animals↗

Differences in HTLV-I integration patterns between skin lesions and peripheral blood lymphocytes of HTLV-I seropositive patients with cutaneous lymphoproliferative disorders.

We examined HTLV-I integration patterns in nine cases of HTLV-I-seropositive patients with cutaneous lymphoproliferative disorders. The Southern blot on EcoRI digests of DNA revealed a discrete band of HTLV-I provirus (monoclonal integration) in either skin lesions or peripheral blood lymphocytes (PBL). Four cases showed the monoclonal integration of HTLV-I provirus only in skin lesions: one case showed only in PBL and two cases showed in both skin and PBL. The Southern blot on PstI digests of DNA revealed a 2.4 Kb band of the internal construct of HTLV-I provirus (polyclonal integration) in the PBL of EcoRI-negative samples. The difference in HTLV-I integration patterns between skin lesions and PBL in these cases suggests that the monoclonal outgrowth of HTLV-I-infected cells in the skin is causatively associated with the pathogenesis of cutaneous ATL.

Aged↗

Expression of human T-cell lymphotropic virus type-1 gene products in the short-term cultured skin tissues of an adult T-cell leukemia/lymphoma patient with cutaneous manifestations.

Adult T-cell leukemia/lymphoma (ATLL) is recognized as a disease etiologically associated with human T lymphotropic virus type-1 (HTLV-1) infection, but, neither viral replication nor specific virus antigen expression have been detected on ATLL cells distributed in organs, including skin. To examine the latent expression of HTLV-1 in the cutaneous lesions of ATLL patients, we cultured the lesional skin tissues in vitro and applied immunofluorescence staining with mouse monoclonal antibodies Lt-4, GIN-14, and F10, which react with p40tax, p19 and gp21, respectively. We recognized HTLV-1 specific antigens on clustered ATLL cells only in the deeper dermis of the skin after 24 hrs cultivation of the lesional skin tissue from an ATLL patient in RPMI-1640 medium supplemented with 20% fetal calf serum. In the electron microscope, we observed HTLV-1 like particles, 80-140 nm in diameter with envelope and core structures, in the same tissue specimen. These findings suggest that HTLV-1 gene products may be expressed in the skin lesions of ATLL patients and involved in the pathogenesis of skin eruptions in cutaneous type ATLLs. To our knowledge, this is the first report that envisages the potency of intracutaneous HTLV-1 expression in vivo.

Aged↗

A case of intravascular malignant lymphomatosis (angiotropic large-cell lymphoma) presenting memory T cell phenotype and its expression of adhesion molecules.

A case of intravascular malignant lymphomatosis (angiotropic large cell lymphoma), T cell type was reported. The patient, a 59-year-old woman, had reddish or violaceous indurated macules scattered over the entire body surface. Neither lymphadenopathy nor hepatosplenomegaly was recognized. A chest Roentgenogram, whole body CT scan, and 67Ga-citrate scintigraphy yielded normal findings. Serum anti-HTLV-1 antibody was negative. Histopathologically, lesions showed intravascular large mononuclear cell proliferation associated with occasional fibrin thrombi formation in the dermis to subcutis. Immunohistochemically, the large mononuclear cell immuno-phenotype had a memory T cell character. Also, both lymphocyte function-associated antigen-1s, CD11a and CD18, and intercellular adhesion molecule-1 were demonstrated on the tumor cells and vascular walls in the lesions. To our knowledge, the present case is the fourth case of intravascular malignant lymphomatosis in the T cell lineage.

Cell Adhesion Molecules↗

[A case of insulin receptor abnormality (type A)].

A sixteen year old woman came to the hospital for glucosuria and amenorrhea. Physical examination demonstrated that she had hirsutism, deepening of voice, and pigmented skin in her axillary lesion which was histologically diagnosed as acanthosis nigricans. Ultrasonography showed polycystic ovaries. A diabetic pattern of 75 g oral glucose tolerance test, very high levels of serum insulin (fasting: 320, peak: 1,220 microU/ml), and hyperandrogenism characterized by increases of urine 17-KS, serum testosterone and DHEA-S were found. Both serum insulin and insulin-receptor antibodies were found to be negative. Insulin binding to both erythrocytes and cultured skin fibroblasts were significantly decreased (about 30% of normal controls). Scatchard plot analysis demonstrated decreased number of insulin receptors to about 30% of the normal controls. We therefore diagnosed that she had insulin receptor abnormality, Type A in Kahn's classification.

Acanthosis Nigricans↗

Crystalloid inclusion bodies of the endothelial cells in human fetal skin blood vessels and human umbilical cord vessels: a possible relationship to Weibel-Palade bodies?

Crystalloid inclusion bodies (CIB) of the endothelial cells (EC) were investigated in blood vessels of human fetal skin and the umbilical cord by electron- and immunoelectron microscopy. They were found in up to 15% of the investigated EC in various types of vessels. Their sizes ranged from 0.2 microns to 0.6 microns in the largest diameter. Most frequently we observed a laminated pattern of the crystalloid structure with a regular periodicity of dark and light bands. Additionally a honeycomblike pattern was also seen. Measurement of the CIB laminated structure revealed similar dimensions to Weibel-Palade bodies (WPB). In EC of all vessel types we found numerous WPB differing in electron density, shape and size from those of WPB found in adult blood vessels. WPB were found much less frequently in EC with CIB, suggesting that CIB is a precursor of WPB. After incubation with monoclonal antibody against von Willebrand factor (vWf) both WPB and large organelles were labeled. Because of their shape and size the labeled large organelles seemed to represent inadequately preserved CIB. After incubation with anti-lysozyme only the large organelles were labeled. A possible relationship of CIB to WPB is thus suggested. The presence of lysosomal enzymes such as lysozyme suggest that CIB are lysosomal organelle and participate in the uptake of vWf. The crystalloid pattern of CIB may represent an accumulation of a highly condensed form of vWf.

Endothelium, Vascular↗