[Clinical study of sarcoidosis. Part 1 (author's transl)].
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Biomedical subjects
Publications and source records attributed to S Morikawa.
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Two E-rosette (spontaneous rosette with sheep red blood cells)-forming lymphoid cell lines were established. One (HPB-ALL) was derived from a young male Japanese patient with acute lymphoblastic leukemia (ALL), and the other (HPB-MLT) was from a 62-year-old female Japanese patient with a leukemic T-lymphoid malignancy. Formation of E rosettes, absence of any immunoglobulin determinants, absence of EBNA (Epstein-Barr virus associated nuclear antigen) and very limited stimulating ability in mixed lymphocyte culture, were characteristics mostly identical with those of so far established T-cell-derived lymphoid cell lines, MOLT, CCRF-CEM, CCRF-HS-B2, RPMI-8402 and JM. Only HPB-MLT, however, has been derived from an aged patient with T-lymphoid malignancy.
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Delayed hypersensitivity (DH) reaction can be induced in mice by intravenous sensitization with sheep erythrocytes (SRBC). However, as the sensitizing procedure is quite different from a usual mode of sensitization for DH using complete Freund's adjuvant (FCA), the nature of this reaction has been a matter of controversy. In an attempt to characterize this reaction, we placed special interest on two possibilities regarding the nature of this reaction; Jones-Mote reaction or tuberculin type DH. From the kinetics study on the DH after challenge, the DH reaction to SRBC in mice by intravenous sensitization was clearly distinguished from the Arthus reaction. The dose-response pattern of this reaction also suggested that the contribution of Arthus reactivity to delayed reactivity was negligible. Cell reconstitution experiments revealed this DH to be quantitatively thymus cell dependent. Furthermore, this DH required macrophages at its manifestation stage, and appearance of basophil infiltration at the lesion was absent. In addition, strain difference and ageing of host mice influenced the DH reaction in exactly the same fashion in which these factors influence the tuberculin type-DH induced by subcutaneous sensitization with methylated human serum albumin (MHSA) in FCA. Taken collectively, it was concluded that this DH reaction can be categorized as the tuberculin type.
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T-T-cell interactions involved in delayed hypersensitivity (DH) response have been studied by employing delayed foot pad assay to methylated human serum albumin in C57BL/6J mice. The DH response, one of the T-cell manifestations of cell-mediated immune response is suppressively regulated by T cells and such observation was based on studies of age-associated kinetics of foot pad reaction and effects of cell transfer and adult thymectomy on developing DH response. These suppressively regulatory T cells in DH have a life span of less than 4 wk and a constant derivation from the thymus is required. Such cells are numerous in the young mouse thymus and few in the spleen and thymus of old mice. On the one hand, the presence of a long-lived effector T-cell population was suggested in DH. These cells are numerous in the spleen and are low responders to phytohemagglutinin in vitro. It is assumed that these suppressive T cells interact with antigen-reactive cells at their proliferating stage by recognition of the iodiotypic difference through surface receptors. As in the case of graft-vs.-host and humoral response in vivo, three different subsets of immune competent cells participate in the DH response. These cells consist of one specifically antigen-reactive T cell, one suppressive regulatory T cell, and one bone marrow-derived cell, a macrophage that responds to a chemical mediator from sensitized effector T cells and that develops a DH skin lesion nonspecifically.
Variously modified protein antigens were tested by footpad assay to clarify the effect of these medications in producing delayed hypersensitivity in mice. The most potent antigen examined was carboxyl-methylated serum albumins. These antigens were highly basic proteins and hydrophobic compared with native serum proteins. They stimulate humoral antibody response in mice poorly, and remain at the subcutaneous injection site much longer than native serum albumins. In vitro tests of susceptibility of thymus and spleen cells and peritoneal macrophages to the antigens revealed that methylated serum albumins possessed the stimulatory activity to the latter and were toxic to the former. As for macrophage, fluorescein-labelled methylated serum albumin showed an affinity to their membrane and were phagocytosed, but FITC-BSA did not show any affinity to the macrophages. These biological activities to tissue or cells may be contributable to render methylated serum albumins to induce and elicit delayed hypersensitivity preferentially in mice.
Seventeen cases of gastric sarcoidosis have been reported in Japanese literature. Age distribution was from the 3rd decade (6 cases) to the 6th decade (3 cases) and the sex ratio was 2 females to 1 male. Preoperative diagnosis included 10 cases of gastric carcinoma and 6 cases of gastric ulcer. Sites of the granulomas were limited to the mucous membrane in 4 cases, from serosa to the mucous membrane in 9 cases and from the muscle layer to the mucous membrane in 1 case. As there are granulomas in the mucous membrane in all cases, it appears that granulomas may spread from the mucous membrane to outside and they can possibly be detected by biopsy. There were no BHL in any chest X-ray. Kveim test was positive in only 2 out of 11 cases. Prognosis is very good. There has been a question whether the gastric granuloma is a local or a generalized manifestation. From our findings, we will report in detail, it may not be a local reaction, but a gastric manifestation of generalized sarcoidosis.
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