Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perforin and granzyme B are 2 cytolytic proteins specific to activated killer cells, particularly CTL. We have studied the mRNA expression of these 2 proteins by a reverse transcriptase polymerase chain reaction method in a unidirectional model of rat small intestine transplant rejection. The allograft group consisted of Lewis x Brown Norway F1 donors into Lewis recipients. The isograft controls were Lewis donors into Lewis recipients. Grafts were placed heterotopically and no immunosuppression was given. Five animals in each group were killed at postoperative days (POD) 3, 5, 7, 8, 9, 10, 12, and 14. mRNA was extracted and a semiquantitative reverse transcriptase polymerase chain reaction was performed. For the semiquantitative analysis, we compared scintillation counts from excised bands. Results were expressed as a percent activity compared with beta-actin. From the same tissue samples, a histologic evaluation was made and rejection was graded according to severity. The isograft controls showed no evidence of histologic rejection and a very low expression of mRNA for perforin and granzyme B from POD 3-14. In contrast, the allograft group began to show histologic evidence of mild rejection on POD 5. By day 7, rejection was moderately severe and associated with a significant up-regulation of perforin and granzyme B in the allografts compared with the controls (P < 0.01), which persisted through POD 14. Peak expression for perforin and granzyme B was on POD 10 and 8, respectively. We conclude that the up-regulation of perforin and granzyme B in rat small intestine transplant allografts is a useful marker of clinically important rejection.
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PMID:Perforin and granzyme B. Cytolytic proteins up-regulated during rejection of rat small intestine allografts. 788 5

Curcumin (CCM; diferuoylmethane) is a dietary pigment in curry with known antineoplastic and anti-inflammatory effects. The immunosuppressive effects of CCM were studied in (1) rat heterotopic cardiac transplant models, using Brown-Norway (BN, RT1(n)) hearts to WKY (RT1(u)) hosts or Buffalo (BUF, RT1(b)) hearts to Wistar-Furth (WF, RT1(u)) hosts, (2) reverse transcriptase-polymerase chain reaction analysis of cytokines from transplanted specimens, and (3) mixed lymphocyte reactions (MLR). In the BN-to-WKY model, CCM alone significantly increased the mean survival time (MST) to 20.5 to 24.5 days, as compared to 9.1 days among nontreated controls. The combination of CCM and subtherapeutic doses of CsA produced further prolongation of the MST to 28.5 to 35.6 days, better than that of CCM or CsA alone (P <.05). In a BUF-to-WF model, CCM alone did not increased the MST, unless it was combined with subtherapeutic doses of CsA, wherein two thirds of the grafts survived for more than 60 days (P <.05 as compared to either treatment group). Cytokine analysis revealed significantly reduced expression of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and granzyme B in the day 3 specimens of the CCM and CCM CsA-treated allografts compared with the nontreated allograft controls. MLRs using the two MHC-incompatible rat strains (BNxWKY) showed an effect of increasing concentrations of CCM and/or CsA, which by combination index (CI) analysis showed a synergistic effect (CI = 0.22 to 0.81). This study for the first time demonstrates the effectiveness of CCM as a novel adjuvant immunosuppressant with cyclosporine both in vivo and in vitro.
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PMID:Curcumin enhances the immunosuppressive activity of cyclosporine in rat cardiac allografts and in mixed lymphocyte reactions. 1282 32