[Early discovery and nursing of adverse effects associated with administration of massive dosages of MTX].
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Biomedical subjects
Publications and source records attributed to N Shinohara.
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Genomic DNA fragments carrying the genes, I-A alpha k and I-A beta k, encoding the class II major histocompatibility complex (MHC) molecule I-Ak were inserted into a transducing vector pRSVneo. This vector was introduced into a B lymphoma line expressing the class II molecules (H-2d). The resultant transformants expressed I-Ak molecules on the membrane surface. These transformants were capable of presenting antigen to I-Ak restricted helper T (Th) cells and were susceptible to lysis by class II specific killer T cells. The vector pR-A alpha kA beta k which contains both I-A alpha k and I-A beta k genes will provide a useful tool to analyze function of Ia molecules in cellular interaction, recognition, regulations and stimulation.
This clinicopathologic study concerns 17 cases of intramuscular myxoma, including an immunohistochemical survey of 10 cases and an electron microscopic examination of 4. There was a female preponderance in a ratio of 14:3. The most common sites of tumors were the large muscles of the thigh (seven cases), followed by those of the buttock (three) and the lower leg (three). The size of the tumor ranged from 1.5 to 20 cm (median, 6 cm) in the greatest diameter. Neither recurrence nor metastasis was seen in any of 15 patients for whom information was available. In addition to the conventional microscopic features, such as hypocellularity, absence of a plexiform capillary network, and no detection of typical glycogen-rich lipoblasts, the following findings were regarded as helpful to differentiate an intramuscular myxoma from myxoid liposarcoma: hypovascularity of the tumor, demonstrated by angiography; a homogeneous computed tomography appearance with low density, absence of S-100 protein immunoreactive cells such as lipoblasts; and electron microscopically, the constituent cells were predominantly fibroblast-like cells with a prominent secretory activity, together with a small number of primitive mesenchymal cells and histiocyte-like cells, but with no lipoblasts. After simple excision, the 15 patients who could be followed are well with no recurrence during various periods of follow-up.
Cloned CTLs QM3 and QM7 isolated from a bulk CTL line B10.QBR anti-B10.MBR recognized a combination of the H-2Kb molecule and an I-Ak subregion gene product. Such a combinatorial specificity was revealed by complementation of the target antigen in F1 animals between two negative parental strains carrying H-2Kb and I-Ak, respectively. We confirmed the involvement of the H-2Kb molecule by blocking killing with anti-Kb mAb and failure of certain mutant H-2Kb genes to complement with I-Ak to generate the determinant in F1 animals. Although the nature of the I-Ak subregion gene product is not definitive, there was a correlation between the expression of Ia antigens on the cell surface and susceptibility of the cells to lysis by these CTLs, suggesting that it is the classical I-Ak class II antigen.
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Giant-cell reparative granuloma occurring in the thoracic vertebra of a 16-year-old girl is presented, and the literature concerning the subject is reviewed. This report is of the second documented case with this essentially rare lesion arising in the vertebra. Microscopically, the lesion was characterized by a reactive granulation tissue with formation of reactive osteoid, collagenization and vascularization, and focal accumulations of giant cells, particularly around hemorrhagic portions. The patient is doing well without further recurrence 38 months after the second therapeutic curettage. The authors describe the clinicopathologic features of this particular case because of its rarity in location, and briefly discuss the difference from other giant-cell lesions of bone mainly in view of differential diagnosis.
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The relationship between the requirement for Ia+ accessory cells (IaAC) and the differentiation of the precursor of CTL (PCTL) in the primary in vitro induction of allogeneic CTL was studied. The following observations were made PCTL can complete the antigen recognition step in the absence of IaAC. This process probably does not involve cell division. The sensitized PCTL require additional signals, which are provided through an IaAC-dependent process to differentiate into the effector CTL. IaAC from any of the responder, the stimulator, or even the third-party strains can fulfill the requirement. However, IaAC of the responder strain failed to generate the helper signal in the absence of allogeneic antigens. The cellular events taking place in the induction of CTL are discussed.
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Mechanisms underlying the maintenance of long-term heart allografts were analyzed in rats treated with Cyclosporine. It was shown that acceptance of allografts after cyclosporine did not involve the attenuation of immunogenicity of the grafts. This conclusion was drawn from two observations: (1) Pretreatment of the donors with cyclosporine did not cause prolongation of graft survival time; and (2) cyclosporine stabilized allografts were normally rejected by secondary recipients when retransplanted on day 30. Studies of the acceptance of skin grafts from the heart donor strain indicated the existence of a mechanism to maintain donor-specific unresponsiveness in the presence of a stable allograft in a time-dependent manner. Thus, the mean rejection time of F344 skin grafts on WKA rats bearing F344 hearts was more than 80 days when transplanted on day 210, but it was 32 days when they were transplanted on day 30. Active participation of specific suppressor cells in the maintenance of unresponsiveness was suggested because data obtained in the cell transfer experiments was statistically significant. Transfer of lymphocytes from rats bearing long-term grafts showed a tendency to delay rejection of skin grafts by sublethally irradiated hosts, but it failed to delay the rapid rejection by normal lymphocytes cotransferred to the same recipients.
The species-specific and the interspecies cross-reactive melanoma antigenic determinants are defined by the monoclonal antibodies raised by syngeneic immunizations. The two types of monoclonal antibodies (M562 or M622 and M2590) were obtained by the fusion of P3U1 murine myeloma cell lines and spleen cells of C57BL/6 mice hyperimmunized with MMC-treated syngeneic B16 melanoma cells. The M2590 antibody recognizes the cross-species melanoma determinant commonly shared among at least mouse, hamster, and human, while the M562 or M622 antibody reacts with the mouse (B16) melanoma antigenic determinant. The immunochemical and physiochemical characteristics of the melanoma antigens on SDS-PAGE analyses show that these two characteristic determinants are present on the same molecule (molecular weight of 31,000) of a glycoprotein. Furthermore, the interspecies cross-reactive melanoma antigenic determinants are possibly composed of the sugar moiety, whereas the species-specific determinants seem to be proteinaceous in nature.
In an attempt to solve the conflict concerning the correlation between the Lyt-2 phenotype of T cells subsets and the type of the MHC antigens involved in the recognition by T cells, class 2 (I region) antigen-specific CTL were studied for their Lyt phenotypes and the sensitivity to the blocking effects of anti-Lyt-2,3 antibodies. To avoid contamination by CTL to class 1 antigens such as Qa antigens, A.TH anti-A. TL attackers and A.TH anti-A attackers were tested on LPS blasts of the A strain and the A.TL stain, respectively. By using these combinations, it was shown that the majority of I region-specific killers were Thy-1+, Lyt-1+23+. Specific target cell lysis by these cells were, however, found to be far less sensitive to the blocking effects of various monoclonal antibodies to the Lyt-2,3 antigens than conventional class 1-specific CTL. This conclusion was drawn by directly comparing the sensitivity of the I region-specific and K region-specific killing by identical numbers of the same attacker cells (A.TH anti-A). No significant difference was seen between the primary and the hyperimmune CTL. Lyt-2-, Thy-1+ killer cells with I region specificity could be induced when Lyt-2-depleted A.TH responder cells were stimulated in vitro. Such Lyt-2- killer cells were not induced to the H-2K alloantigen.
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Interspecies cross-reactive antibodies were detected in a mouse alloantiserum, A.TH anti-A. TL raised against products of the I region genes of the H-2 complex. The cross-reactions were found to extend not only to all mammalian species tested but even to avian and amphibian species. Genetic mapping studies of the cross-reactive antibodies in the mouse indicated that the cross-reaction in all cases were attributable to the antibodies to the I-E subregion gene product, i.e. alpha-chain of the I-E molecule. These results probably indicate that the cross-reactive genes are the homologues of mouse I-E gene and share the common ancestral origin. Possible basis for such unusual interspecies cross-reactions of anti-Ia alloantibodies will be discussed.
Certain anti-Ia murine alloantibodies react with the Ia-positive B cells of almost all mammalian species. In this report, the effect of such murine alloantibodies on the function of accessory cells in induction of human immune responses was studied by using human peripheral blood lymphocytes pretreated with anti-Iak murine alloantibodies and complement. The induction of allogeneic mixed lymphocyte reactions and allogeneic cytotonic T cells was drastically reduced by means of pretreatment of the stimulator population with anti-Ia and complement. When both responder and stimulator were pretreated with these reagents, inductions of the residual responses were completely eliminated. Cells with quite similar characteristics (i.e., adherence to the petri dish and crossreaction with the anti-Ia murine alloantibodies) were also found to be essential in the induction of in vitro T cell proliferative responses to purified protein derivate and concanavalin A. These results seem to indicate that the interspecies crossreactive anti-Ia murine alloantibodies react with the human homologue of murine Ia-positive macrophagelike cells that are recognized as antigen-presenting cells. It is also concluded that, in induction of alloimmunity, Ia-positive adherent cells of the stimulator population are the major source of the stimulation.