Biomedical subjects
Publications and source records attributed to D Rand.
A new pair of papers reports the complete coding sequences for 28 mitochondrial DNAs in Drosophila. By examining the patterns of polymorphism and divergence among functionally distinct classes of synonymous and nonsynonymous nucleotide sites, Bill Ballard provides a comprehensive whole-genome picture of how mtDNA sequence evolution can depart from the strictly neutral and nearly neutral models of molecular evolution.
BACKGROUND/AIMS: Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. METHODS: We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. RESULTS: Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five patients developed graft re-infection with lamivudine-resistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus. CONCLUSIONS: Our observations suggest that the resistant species may be present in the viral quasispecies in the serum and liver of patients with high-level replication prior to lamivudine exposure. The resistant species can persist during lamivudine treatment prior to transplantation, and emerge following transplantation. These observations suggest strategies which might prevent the emergence of drug-resistant species, and imply that graft re-infection may be a preventable phenomenon.
The latitudinal cline in P transposable element-associated characteristics in eastern Australian populations of Drosophila melanogaster has changed between 1986 and 1991-1994. New collections were made in 1991-1994 from localities along the eastern coast of Australia. P element-associated properties of 256 isofemale lines from 43 localities were evaluated using gonadal dysgenesis and/or singed-weak hypermutability assays. The overall results indicate that both P activity and P susceptibility have declined, with all populations showing a tendency towards a state with little P activity potential but with P repressor function (neutral or 'Q'). P repressor function is strong in all populations except some of the most southernly. P activity potential peaks at about 27 degrees SLat, and drops off to the south (as in 1983-1986 collections) and to the north (in contrast to 1983-1986 collections); thus the cline is no longer a simple P-to-Q-to-M pattern from north to south, but is now Q-P-Q-M. A mtDNA RFLP that putatively distinguishes North American and European populations varies in frequency among the populations but the frequency does not vary clinically with latitude, ruling out massive introductions from North America and Europe as causing the cline.
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Six slow loris were exposed to air temperatures between 10 degrees C and 40 degrees C. Rectal temperature was stable (mean, 34.8 degrees C) at air temperatures between 17 degrees C and 31 degrees C; at higher air temperatures, the animals became hyperthermic. Oxygen consumption was minimal at air temperatures of 31.4-36.6 degrees C; the mean value (0.250 ml O2 g-1 h-1) was only 36% of the expected level for a eutherian Mammal. The slow loris increased its heat production at lower air temperatures. Thermal polypnea occurred in response to heat, and some of the animals were able to dissipate their entire metabolic heat production at lower air temperatures. Thermal polypnea occurred in response to heat, and some of the animals were able the combined thermal conductance of the tissues and haircoat was 73% of the predicted values. It was concluded that, in spite of its low metabolic rate, the slow loris had effective responses to moderate cold, and that, in addition, it was well adapted to a hot climate.