Effect of ex vivo perfusion with anti-Ia monoclonal antibodies on rat cardiac allograft survival.
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Biomedical subjects
Publications and source records attributed to K Sakagami.
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In order to clarify the beneficial effect of donor-specific blood transfusions (DST) on kidney allograft survival, sera from 16 patients treated with DST were studied using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrate that MLC inhibitory factors could be induced in the serum of the recipients after the completion of DST, and that these factors are directed against cells of the recipient but not against cell from the donor. Regarding the correlation with rejection episodes and clinical outcome, a significant improvement in renal transplant survival and reduction in rejection episodes was observed when MLC inhibitory factors were present in post-DST sera. These data suggest that such factors may contain antibodies directed against recognition sites on T lymphocytes, e.g., anti-idiotypic antibodies, and be associated with prolonged graft survival of living-related, high MLC-reactive one-haplotype-mismatched kidney.
An artificial liver support system for plasma exchange and plasma perfusion through BR-601 resin using a membrane separator was applied to 5 patients with postoperative liver failure. Percent absorption of total and direct bilirubin, and of bile acids were 77.1 +/- 6.4, 78.4 +/- 6.1, and 93.4 +/- 3.6%, respectively, when 250 ml of plasma was treated. Percent reductions in total and direct bilirubin, and in bile acids were 24.5 +/- 5.8, 25.5 +/- 5.8 and 30.9 +/- 8.5%, respectively. In contrast, percent reductions in total and direct bilirubin, and in bile acids by plasma exchange were 30.9 +/- 13.3, 34.5 +/- 12.5 and 24.2 +/- 8.5%, respectively. The coma grade was improved in 4 out of 5 cases, but unfortunately the patients did not recover. In conclusion, plasma perfusion through BR-601 resin is expected to play a promising role in artificial liver support systems because of its capacity to absorb bilirubin and bile acids.
The survival rate of 19 patients who underwent living-related kidney transplantation after donor-specific blood transfusions (DST) was compared with that of 32 historical controls receiving transplants without DST. The graft survival rate of the DST group was 82% after two and three years. The graft survival rate of the DST group was significantly better than the 53% rate after two years obtained with the 32 historical controls (p less than 0.05). We tested sera from 16 DST-treated recipients to study the beneficial effect of DST on kidney allograft survival using the mixed lymphocyte culture (MLC) serum inhibition test. The results demonstrated that MLC inhibitory factors were induced in the serum of the recipient after completion of DST. This inhibition of MLC was observed by treatment of responder lymphocytes with serum obtained three weeks after DST plus rabbit complement. The inhibitory effect was also specific for responder cells in anti-donor MLC. Regarding the correlation with rejection episodes, these MLC inhibitory factors were often observed in the non-rejection group (p less than 0.05). The data suggest that such factors may be anti-idiotypic antibodies and be associated with prolonged graft survival.
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A 26-year-old male with renal allograft, who received immunosuppressive treatment with azathioprine, presented marked elevations of serum biliary tract enzymes, such as gamma-glutamyl transpeptidase (5,609 units/l) and alkaline phosphatase (60.5 Bessey-Lowry units), 14 months after transplantation. Two months later the patient became icteric; he died of respiratory failure 19 months after the renal allograft. Postmortem examination revealed intrahepatic cholestasis with minimal inflammatory cell infiltration, indicating drug hepatotoxicity.
Synthesis and antibacterial activities of 7-[2-(2-amino-1,3,4-thiadiazol-5-yl)acetamido]-cephalosporins and their derivatives having the methoxyimino group at the 2-position of the 7-acyl moiety are described. These compounds are of interest as structural analogues of potent antibiotics, 7-[2-(2-aminothiazol-4-yl)acetamido]cephalosporins. 7-[2-(2-Amino-1,3,4-thiadiazol-5-yl)acetamido]cephalosporins showed comparable activity with cefazolin. Introduction of methoxyimino group to the 7-side chain resulted in a lowering of activity.
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1. Three cases of acute rejection were detected by macrophage migration inhibition tests (MIT) conducted directly on seven patients who had received renal allografts. The macrophage migration inhibitory factor (MIF) activity was positive in all cases 1-2 days before the appearance of acute rejection. 2. After the administration of a high dose of Solu-Medrol (1g/day for 3 days) to suppress the acute rejection, MIF activity recovered to its normal level 3 days later. These findings seem to indicate that MIT yields immunologically useful criteria for the early detection of an acute rejection.
In order to formulate an early diagnostic method for acute rejection after kidney transplantation, macrophage migration inhibition test (MIT) was carried out with lapse of time after inbred rat kidney allotransplantation. The mean survival time of rat kidney allograft was found to be 7.07 +/- 1.34 days. On the other hand, in the group treated with rabbit anti-rat lymphocyte serum (ALS) the mean survival time was lengthened to 14.15 +/- 2.14 days (p less than 0.05). The corresponding antigen used for MIT was prepared with donor kidney by ultrasonication, and its protein concentration at 180 mug/ml was the most optimal as not to elicit non-specific inhibition of macrophages. In the control group, activity of macrophage inhibitory factor (MIF activity) turned positive 3 days after the transplantation, and it became strongly positive by 5 or 7 dyas at the period when rejection crisis appeared frequently. ALS-treated group showed a lower MIF activity than the control group (p less than 0.05) and on 7-12 dyas before rejection crisis appeared frequently, MIF activity became strongly positive. These findings suggest that this MIT is simple and will be proved to be useful in predicting the acute rejection as well as in controlling the immunosuppression.
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