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Biomedical subjects

James D Perkins

Publications and source records attributed to James D Perkins.

At least 19 recordsLinked to original sources
PubMed2006

Impact of cytomegalovirus in organ transplant recipients in the era of antiviral prophylaxis.

BACKGROUND: Antiviral prophylaxis has been shown to decrease the incidence of cytomegalovirus (CMV) disease in organ transplant recipients, but whether CMV disease that occurs despite prophylaxis is associated with mortality remains unknown. METHODS: The clinical features and risk factors for CMV disease in a cohort of liver transplant recipients who received antiviral prophylaxis were assessed retrospectively. Cox proportional hazard regression was used to assess the relationship of CMV to mortality during the first posttransplant year. RESULTS: CMV disease developed in 37 of 437 (8.5%) recipients at a median of 4.5 (range, 2.5 to 12) months posttransplant and was associated only with donor-seropositive/recipient-seronegative serostatus in multivariate analysis (P<0.0001). Mortality at 1 year was 12% (51 of 437) and was infection-associated in 49% of cases. In multivariate analysis, CMV disease was independently associated with overall mortality at 1 year (HR, 5.1, P=0.002) and even more strongly with infection-associated mortality (HR 11, P=0.002). There was no association of CMV with noninfection-associated mortality (P>0.05). CONCLUSIONS: Late CMV disease is an important clinical problem in liver transplant recipients who receive antiviral prophylaxis, and is strongly and independently associated with mortality. Strategies to prevent late CMV disease are warranted.

Antiviral Agents↗
PubMed2006

Enhancement of NKT cells and increase in regulatory T cells results in improved allograft survival.

BACKGROUND: Natural killer T (NKT) cells can serve as regulatory cells important in peripheral tolerance. In an experimental colitis model, it was shown that FK506 enhances the tolerizing effect of regulatory NKT cells induced by oral tolerance. We explored whether a subtherapeutic dose of FK506 could enhance the tolerizing effect of NKT cells induced by oral administration of donor spleen cells (SCs) in the pre-transplant period to prolong heart allograft survival. METHODS: Heterotopic heart transplantation was performed from BALB/c to B6 mice. The B6 recipients were pre-treated with either BALB/c SCs (2 x 10(7)/mouse), or FK506 (1.0 mg/kg/d), or BALB/c SCs + FK506 by gavage every other day for a total of five feedings before transplantation. RESULTS: Heart allograft survival was only significantly prolonged in the BALB/c SC + FK506 pre-fed mice. This was associated with a marked increase of NKT cells in both the liver and spleen of the recipients, and most importantly, 7 days after transplantation, an increase in CD25+CD4+ T cells expressing CTLA4 in the spleen. CONCLUSIONS: In our model it appears that a subtherapeutic dose of FK506 enhanced the tolerizing effect of NKT cells induced by oral tolerance, prolonging allograft survival by generating CD25+CD4+ CTLA4 T cells. This appears to be an excellent in vivo model to generate regulatory T cells to allospecific transplant antigens.

Animals↗
PubMed2006

Saying "Yes" to obese living liver donors: short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation.

BACKGROUND: The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. METHODS: Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. RESULTS: The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean+/-SEM], P=0.0028). Body weight and BMI were significantly reduced (73.7+/-3.2 kg vs. 66.9+/-2.9 kg, P=0.0033, 26.4+/-0.7 kg/m(2) vs. 24.1+/-0.8 kg/m(2), P=0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n=7) and donor liver without hepatic steatosis (n=37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. CONCLUSIONS: The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.

Bezafibrate↗
PubMed2006

Productive replication of hepatitis C virus in perihepatic lymph nodes in vivo: implications of HCV lymphotropism.

BACKGROUND & AIMS: The pathogenesis of chronic hepatitis C is poorly understood. This study examines the ability of hepatitis C virus (HCV) to infect, replicate in, and produce progeny virus from perihepatic lymph nodes in vivo. METHODS: Lymph node (LN) biopsy specimens were taken from 20 patients with HCV genotype 1 infection and end-stage liver disease and 20 noninfected negative controls. Sections were probed with HCV RNA strand-specific riboprobes and antibodies specific for HCV core and nonstructural region 3 antigens plus B-cell (CD20) and T-cell (CD2) antigens. In a selected case, HCV quasispecies in serum, peripheral blood mononuclear cells, liver, and perihepatic lymph nodes were analyzed by clonal frequency analysis and sequencing. RESULTS: HCV infection was confirmed in 17 of 20 (85%) of lymph node specimens by in situ hybridization, and HCV replication was confirmed in 50% of cases by detection of HCV replicative intermediate RNA. HCV core and nonstructural 3 antigens were detected in lymph nodes by immunocytochemistry. Infected cell phenotypes were primarily CD20 B cells, although other cell types were positive for HCV replication markers. Quasispecies analysis in one case indicated that 68% of variants circulating in serum were also present in lymphoid tissues, and only 40% of serum variants were identified in liver, documenting a major contribution of lymphoid replication to HCV viremia. CONCLUSIONS: HCV lymphotropism provides new insights into the complex pathobiology of chronic hepatitis C in humans. We demonstrate for the first time a major contribution of extrahepatic HCV replication to circulating virus in serum (viremia).

Antigens, CD20↗