Toxic shock syndrome toxin-1 (TSST-1)-binding assay using 125I-labeled TSST-1 showed the presence of specific TSST-1 binding in a B cell fraction of human peripheral blood mononuclear cells and L cells transfected with DR2 genes or DR4 genes but not in a T cell fraction and control L cells. Fixation with paraformaldehyde, an inhibitor of antigen processing, did not remove TSST-1-binding activity of the transfectants. Binding of 125I-labeled TSST-1 to the transfectants was reduced by an anti-DR monoclonal antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of a single band with TSST-1-binding activity and the same migration pattern as DR heterodimers. TSST-1-induced T cell responses, proliferation and interleukin 2 (IL2) production were observed in the presence of the transfectants but not in the presence of control L cells, while concanavalin A-induced IL2 production was observed in the presence of either the transfectants or control L cells. Presence of an anti-DR monoclonal antibody inhibited the TSST-1-induced responses. Paraformaldehyde-fixed Daudi cells were effective in supporting TSST-1-induced IL2 production by T cells. These results indicate that HLA class II molecules directly bind intact TSST-1 and perform an essential role as the TSST-1-binding structures on accessory cells in T cell activation by the toxin.
During the 12 years since homotransplantation of the whole canine liver was first described by Welch, there have been reports of several techniques of hepatic homograft preservation in dogs. Goodrich and his colleagues showed that livers removed at normal temperatures became unsuitable for transplantation within 20 or 30 minutes. The first protective device used in our laboratories (15) and by Moore and his associates was hypothermia, induced first by whole body cooling of the donor to 30 degrees C. and then perfusing the excised liver with a chilled electrolyte solution. With a fall in the hepatic core temperature to approximately 15 degrees C., these organs could support the life of recipient dogs if revascularized as orthotopic homografts within 2 hours. After longer times, there was a high rate of acute failure due to outflow block of the transplants, a hemorrhagic diathesis, and acute liver failure. Almost identical conclusions about the efficacy of this simple approach were reached by Ono and his co-workers in experiments which did not involve homotransplantation.Subsequent efforts to extend the acceptable storage time have been disappointing. In dogs, Marchioro and his associates reported a method of hypothermic cadaveric perfusion with the use of an extracorporeal heart-lung apparatus into which a heat exchanger was incorporated. Either the entire corpse or the lower half of the dog was perfused. Orthotopic homotransplantation was performed with livers removed from 2 to 8 hours after the sacrifice of the donors. Eight of the 10 recipients which were treated with azathioprine survived NIH Public Access Author ManuscriptSurg Gynecol Obstet. Author manuscript; available in PMC 2010 December 23. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscriptoperation, but all died within 1 to 5 days thereafter. Mikaeloff and Kestens and their associates used a similar principle in which hypothermic perfusion in situ was limited to the liver. They were able to obtain long term recipient survival after homotransplantation of canine livers removed as long as 6 hours after death. Their technique was an application of a method described several years earlier by Kestens and McDermott.More complex methods have been tried. Brown and his colleagues have evaluated a combination of freezing to − 6 degrees C., immersion into a dimethylsulfoxide or glycerol bath, and dehydration. After 1 to 5 days, the organs were viable but severely damaged and apparently incapable of supporting life as orthotopic homografts. When Moss and his coworkers cooled livers to −20 to −60 degrees C. for 1 to 14 days without dehydration, there was almost no function after the homografts were transplanted to the pelvis. Furthermore, all of the recipients died in 6 hours or less.Recently, there have been 2 reports of conservation of hepatic homografts for 8 to 24 hours, a combination of perfusion, hypothermia, and hyperbaric oxygenation being used. Slapak and his associates placed puppy livers preserved in this way in the neck of adult...
103 adult patients with biopsy-proved IgA nephropathy were typed for HLA-A and HLA-B antigens and 80 of these cases were typed for HLA-DR antigens. A significant association with HLA-DR4 was clearly noted (pc < 0.04). The high phenotype frequency (PF) of BW35 was observed in the patients, but not statistically significant (pc < 0.2). Two groups, the stable group and progressive group, were selected from all patients according to their clinical courses. The PF of HLA-DR4 was significantly higher in the stable group than the progressive group (pc = 0.005). The PF of BW35 was also higher in the stable group, but this difference was not statistically significant (pc = 0.6). The frequency of the combination of HLA-BW35 and DR4 increased significantly as compared to that in the control group. Further, the patients who had both of these antigens showed favorable courses. These results suggest that the HLA-DR4 antigen, especially a combination of HLA-BW35 and DR4 antigens are related to the occurrence of benign IgA nephropathy.
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