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Biomedical subjects

M Shamoto

Publications and source records attributed to M Shamoto.

At least 37 records · Page 2Linked to original sources

Human glioma-specific antigens detected by monoclonal antibodies.

Three murine monoclonal antibodies, designated GA-17, GB-4, and GC-3, were prepared by the hybridization of murine myeloma cells (NS-1) and spleen cells of BALB/c mice immunized with the crude membrane fraction of cultured human gliosarcoma cells (GI-1). Two of them (GA-17 and GB-4) reacted exclusively with the membrane of glioma cells, and the other (GC-3) reacted with the membrane of glioma cells and a T cell line (MOLT-4). Although these antibodies reacted with almost all of the gliomas, the reactions differed. GA-17 reacted equally well with all glioblastoma (17 cases) and low-grade astrocytoma (10 cases), whereas GB-4 reacted poorly with 7 cases of glioblastoma and GC-3 did not react with 7 cases of low-grade astrocytoma. The antigens, exclusively expressed on the cell surface, were analyzed by surface labeling with 125I followed by a cell lysis and immunoprecipitation with these antibodies. The findings obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that GA-17, GB-4, and GC-3 reacted with Mr 140,000-145,000, Mr 160,000, and Mr 145,000-150,000 proteins, respectively. Some evidence has been obtained indicating that these antigens are composed of the same polypeptide chain (Mr 120,000) with the carbohydrate chains being different.

Animals↗

A new rat mutant with chronic conjugated hyperbilirubinemia and renal glomerular lesions.

A new mutant strain of inbred Sprague Dawley rats with autosomal recessive hyperbilirubinuria, were studied by biochemical, histologic, and ultrastructural methods. The plasma bilirubin concentration in the homozygote was significantly higher than that of the heterozygote, and about 80% of the bilirubin was conjugated. Plasma BSP and ICG clearance were both severely delayed in the homozygote. Plasma BSP elimination kinetics suggested that the pathophysiologic defect was not hepatic uptake or storage but rather in secretion into bile. Histopathology of the liver demonstrated brown pigment in the hepatocytes that appeared to be lipofuscin. The electron microscopic features of the hepatic pigment resembled those of the Dubin-Johnson syndrome. Homozygote histopathology also revealed glomerular lesions with mesangial expansion and proliferation in the kidneys. Immunohistologic studies disclosed mesangial granular deposition of IgG, IgA, and to a lesser degree, IgM and C3. These renal changes resembled those of IgA nephropathy. The spontaneous hyperbilirubinuric rat (EHBR) may be a useful animal model for studying constitutive conjugated hyperbilirubinemia, bilirubin metabolism, cholestasis, and glomerulonephropathy subsequent to hepatic dysfunction.

Animals↗

Ascorbic acid and adriamycin toxicity.

Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.

Animals↗

Cytogenetic characterization of a T-cell line, ATN-1, derived from adult T-cell leukemia cells.

A T-cell line, ATN-1, was established by culturing peripheral blood mononuclear cells derived from a patient with adult T-cell leukemia/lymphoma (ATL/L). Identities of the patterns of chromosomal abnormalities, cell surface phenotypes, morphologic findings, rearrangement patterns of T-cell receptor beta chain gene, and an integration site of human T-cell leukemia virus I proviral genome indicated that ATN-1 was derived from original leukemic cells. Both ATN-1 and the original leukemic cells showed a variety of patterns of chromosomal abnormalities that include 3q-, 6q-, rearrangements involving 2q31, 7q11.2, 8q11, 8q24, 19p13.3, and also 14q11 and 14q32, where genes for the T-cell receptor alpha chain and the immunoglobulin heavy chain are located. Availability of a genuine ATL/L cell line with these chromosomal abnormalities may greatly facilitate the biologic analysis of ATL/L.

Antibodies, Monoclonal↗

A monoclonal antibody detecting a novel antigen expressed in the HTLV-I-infected cells.

A monoclonal antibody, FTF 148, was prepared by hybridizing murine myelomal cells (NS-1) and spleen cells of BALB/c mice immunized with cultured cells derived from an adult T cell leukemia (ATL) patient (KUT-2 cells). This monoclonal antibody reacted with all of the human T cell leukemia virus I (HTLV-I)-infected cell lines tested but did not react with other T cell lines derived from acute lymphocytic leukemia, Epstein-Barr virus-transformed B cell lines, or an erythroleukemic cell line. This monoclonal antibody was not directed to viral antigens because it reacted equally well with almost all KUT-2 and MT-1 cells, only 1% to 3% of which were ATL-associated antigen-positive. In contrast to interleukin 2 receptors expressed on both ATL cells and normal phytohemagglutinin-stimulated blasts, this antigen was not expressed on the latter cells. The antigen, mainly expressed on the cell membrane, was analyzed by metabolic labeling with 3H-leucine and surface labeling with 125I followed by cell lysis and immunoprecipitation with the FTF 148 antibody. The findings obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that p50 and p74 proteins were specifically precipitated and the antigen was also different from the product of the Xs gene of HTLV-I.

Antibodies, Monoclonal↗

Hepatoid adenocarcinomas of the stomach. An analysis of seven cases.

Hepatoid adenocarcinomas of the stomach are gastric carcinomas with both adenocarcinomatous and hepatocellular differentiations. They usually produce large amounts of alpha-fetoprotein (AFP) with a Concanavalin A-binding property of hepatic type. In this study, these carcinomas occurred in older persons, with the antrum being a common site. Observed grossly, growth of the tumors was nodular and massive. Prognosis was poor because of frequent liver metastases. In the cytoplasms of tumor cells, various serum proteins were identified, including AFP, alpha-1 antitrypsin (AAT), alpha-1 antichymotrypsin (ACT), albumin, and prealbumin. Localizations of ferritin, prothrombin, and transferrin were demonstrated with less frequency. Adenocarcinomatous foci were composed of well-differentiated, intestinal-type epithelial cells and often contained carcinoembryonic antigen. These adenocarcinomatous and hepatoid areas were often intermingled with each other. There were extensive venous involvements by tumor cells. The poor prognosis of the tumors may be attributed to these involvements as well as to production of AFP and presence of AAT/ACT, which have immunosuppressive and protease-inhibitory properties, respectively.

Adenocarcinoma↗

The effect of phototherapies on cutaneous lesions of histiocytosis X in the elderly.

The effect of therapeutic ultraviolet light (UV) radiation on the skin lesions of histiocytosis X (HX) was studied in two old patients. Histiocytosis X cells in the biopsy specimens were strongly reactive with OKT-6, OK-Ia1, an anti-S-100 protein antibody, and were weakly stained with Leu-3a. Some HX cells outgrown from the explants bore immunoglobulin G receptors (Fc-IgG) and C3 receptors. In accordance with clinical improvement after repeated topical 8-methoxypsolaren (8-MOP) plus UV-A (PUVA) or UV-B radiation, the density of infiltrating HX cells gradually was decreased. The PUVA therapy seemed to be more effective than UV-B radiation in our treatment schedule. Even after repeated phototherapies, however, the reactivity of surface and cytoplasmic antigens related to OKT-6, OK-Ia1, and S-100 protein in the remaining HX cells were the same as in untreated HX cells. Although the exact mechanism remains obscure, satisfactory therapeutic results were obtained in response to the phototherapies. New skin lesions eventually recurred after cessation of the treatments, but such eruptions resolved when additional PUVA was resumed. These studies confirm that HX cells share a battery of cytologic characteristics with epidermal Langerhans' cells (LC) and that repeated phototherapies provide a beneficial effect for skin lesions of HX without adverse reactions.

Aged↗

Immunoelectron-microscopic localization of Tac antigen in adult T-cell leukemia/lymphoma.

The localization of Tac antigen in adult T-cell leukemia-associated antigen (ATLA)-positive lymphomas was studied ultrastructurally with the use of the immunoperoxidase technique. The antigen was observed on the plasma membranes of a portion of the characteristic cells with convoluted nuclei and a majority of the cells with less irregular nuclei, which were larger than the former. In addition, the cisternae of the rough endoplasmic reticulum, perinuclear cisternae, and Golgi cisternae of the latter cells were also positively stained with anti-Tac antibody. It is thought that the positive reaction of the plasma membranes may correspond to interleukin 2 (IL 2) receptors, the cytoplasmic and perinuclear reaction sites may well correspond to the precursor of IL 2 receptors, and Tac antigen may be produced in the cytoplasm of the ATLA-positive lymphoma cells.

Antigens, Surface↗

Immunoelectron microscopic studies on peripheral T-cell lymphomas using monoclonal antibodies.

Ultrastructural comparison between helper/inducer and suppressor/cytotoxic type cells in peripheral T-cell lymphomas was made using the immunoperoxidase technique. The nuclei of T4 positive cells were more irregular in outline than those of T8 positive cells, and nuclear irregularity was further pronounced in the cells of the adult T-cell leukemia/lymphoma which were of helper/inducer type cells. The suppressor/cytotoxic type cells possessed in their cytoplasm scattered dense bodies encircled by distinct membranes, although they also contained clustered dense bodies. On the other hand, the helper-inducer type cells had only clustered dense bodies. No other significant differences were observed regarding other cytoplasmic organelles between T4 positive cells and T8 positive cells. The existence of the peripheral T-cell lymphomas with "double-markers" which possessed surface antigens for both helper/inducer and suppressor/cytotoxic subsets was also demonstrated.

Antibodies, Monoclonal↗

A thymic tumor with massive proliferation of myoid cells.

A case of thymic tumor, composed of both epithelial and myoid cells, was presented. The myoid cells occurred in clusters, and showed prominent proliferation between the nests of epithelial cells. The myoid cells had intracytoplasmic myofibrils, and there were foci of electron dense Z-lines along the course of these fibrils. Some of these cells possessed sarcomeres identical to those of striated-muscle cells. Histochemically, a significant amount of glycosaminoglycans was observed on the surface of the myoid cells.

Cell Division↗

Epidermoid carcinoma arising in parotid adenolymphomatous lesion with microdeposit of amyloid substance.

A case of an epidermoid carcinoma which arose in a cystic adenolymphoma-like lesion of the parotid gland is presented. Histologically, in the major part, the tumor tissue showed a papillary cystadenoma lymphomatosum-like pattern with the stroma consisting of mainly plasma cells and lymphocytes, but the epithelial element was mostly multilayered, showing a keratinous differentiation. In some areas, sebaceous-like cells and oxyphilic cells were found in the epithelial component. In the surrounding fibrous tissue, the invasive growth of the epithelial cells could be observed. Microdeposit of amyloid substance was found in the lymphoid stromal tissue and also in the intercellular space of the epithelial element. A mass of epithelioid cells and cholesterol crystal clefts were observed in the granulomatous tissue which proliferated around the tumor tissues. About 4 months after surgical excision, a recurrent tumor, which was well differentiated squamous cell carcinoma, appeared on the same site as the primary tumor.

Adenolymphoma↗