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Biomedical subjects

J M Fenton

Publications and source records attributed to J M Fenton.

7 recordsLinked to original sources

Serologic responses to hepatitis C virus in solid organ transplant recipients.

BACKGROUND: Hepatitis C (HCV) infection is known to have been transmitted by both blood transfusion and donor organs. We sought to determine the historical incidence of donor- and transfusion-acquired HCV infection in kidney transplant (RTx) and heart transplant (HTx) recipients at our center and to study the kinetics of seroconversion to HCV. METHODS: A bank of sera collected from organ donors (388 RTx and 88 HTx) who received allografts between January 1984 and April 1992 was screened for anti-HCV using a third generation enzyme immunoassay. Recipient sera collected before transplant (preTx), at 1 year after transplant, and at last follow-up were tested. Fresh follow-up sera on all surviving anti-HCV-positive (+) RTx and HTx, all anti-HCV-negative (-) HTx, and a subset of 85 anti-HCV- RTx were assayed for HCV RNA using an reverse transcriptase-polymerase chain reaction assay. RESULTS: Twenty-four of 388 RTx (6.2%) and 2 of 88 HTx (2.3%) were anti-HCV+ preTx. Eight of 218 (3.7%) organ donors were anti-HCV+. Six of the seven (85.7%) anti-HCV+ donors with adequate recipient follow-up transmitted HCV infection to one or more recipients. Nineteen of 313 RTx (6.1%) and 8 of 72 HTx (11.1%) with follow-up > or =1 year seroconverted to anti-HCV. One of 85 (1.2%) anti-HCV- RTx and 3 of 44 (6.8%) anti-HCV-HTx were HCV RNA+ when tested at last follow-up. Five cases of de novo HCV infection occurred after the introduction of first generation anti-HCV screening of donors. Persistent viremia (HCV RNA+) at last follow-up was observed in 70.6% (12/17) RTx anti-HCV+ preTx. Fourteen of 15 (93.3%) RTx and 9 of 9 (100%) HTx with de novo HCV infection had persistent viremia. Seroconversion was more delayed in HTx than RTx (P=0.0572, log-rank Mantel-Cox statistic) although both groups demonstrated an impaired humoral response to HCV when compared with the immunocompetent host. CONCLUSIONS: Organ donor- and transfusion-acquired HCV infection was common in RTx and HTx transplanted before the introduction of second generation anti-HCV screening in 1992. Serologic responses to HCV are often delayed and sometimes absent in these patients. Assays for HCV RNA should be considered as a screening test for the detection of HCV infection in this population. Serologic responses to HCV were more impaired in HTx compared with RTx, which may reflect the more intensive immunosuppressive regimens given to HTx at our center.

Heart Transplantation

A knowledge-based method for protein structure refinement and prediction.

The native conformation of a protein, in a given environment, is determined entirely by the various interatomic interactions dictated by the amino acid sequence (1-3). We describe here a knowledge-based approach for protein structure assessment and prediction. Using a well-defined set of high-resolution protein structures, we have derived statistical potentials, in the form of atom-pairwise distance probability density functions. These provide a description of pairwise interatomic interactions of native proteins. When applied to highly randomized and noisy structures of proteins distinct from the basis set, native-like structures were obtained to very high precision (< or = 2A). The examples tested include proteins of all sizes (from 38 up to 461 amino acids long) and diverse topological structures (alpha, beta and alpha-beta classes). The potentials appear to be sensitive enough to recognize subtle distortions from a native packing structure and in optimization of structures drive them consistently to a higher probability. Therefore they provide a powerful tool for refinement of X-ray and NMR derived structures at arbitrary degrees of initial precision.

Crystallography, X-Ray

Effect of bambermycins on quantity, prevalence, duration, and antimicrobial resistance of Salmonella typhimurium in experimentally infected broiler chickens.

Twenty broiler chickens were fed bambermycins (Flavomycin; an antibiotic produced by Streptomyces) at the rate of 3 g/ton (US) for 63 days, and 20 control birds were fed nonmedicated feed. The birds were inoculated (dosed) on the 10th and 11th feeding day with Salmonella typhimurium. The study evaluated the effects of bambermycins on Salmonella incidence, shedding, and antimicrobial resistance. Bambermycins had no effect on body weights, duration of shedding of salmonellae, number of salmonellae shed on postdosing day 3, tissue recoverability of salmonellae, and total number of resistance patterns. Bambermycins resulted in the decrease of salmonellae to be more gradual; however, both treatments were comparable at the end of the study. The majority of S typhimurium from bambermycins-treated birds maintained the original antibiogram of streptomycin, sulfadiazine, and nalidixic acid. The salmonellae isolated from the control birds were more resistant to 2 drugs (varying antibiograms). Bambermycins as a feed additive in broiler diets given at the dose level of 3 g/ton had no detrimental effects based on salmonellae shedding and antimicrobial resistance.

Animals

Comparison of therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin on E. coli infection of young chickens.

Three replicate trials were conducted with broiler male chicks to test the therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin in water against an artifically induced Escherichia coli infection. Mortality, lesion scores (heart, liver and air sac), and performance data were the criteria in evaluating therapeutic efficacy of these drugs. Results indicated the therapeutic efficacy of doxycycline was greater than chlortetracycline and lincomycin-spectinomycin.

Administration, Oral