Genetic diversity of longtail macaques (Macaca fascicularis) on the island of Mauritius: an assessment of nuclear and mitochondrial DNA polymorphisms.

BACKGROUND: Individuals from an introduced population of longtail macaques on Mauritius have been extensively used in recent research. This population has low MHC gene diversity, and is thus regarded as a valuable resource for research. METHODS: We investigated the genetic diversity of this population using multiple molecular markers located in mitochondrial DNA and microsatellite DNA loci on the autosomes and the Y chromosome. We tested samples from 82 individuals taken from seven study sites. RESULTS AND CONCLUSIONS: We found this population to be panmictic, with a low degree of genetic variability. On the basis of an mtDNA phylogeny, we inferred that these macaques' ancestors originated from Java in Asia. Weak gametic disequilibrium was observed, suggesting decay of non-random associations between genomic genes at the time of founding. The results suggest that macaques bred in Mauritius are valuable as model animals for biomedical research because of their genetic homogeneity.

Mechanism of action of imiquimod 5% cream in the treatment of anogenital warts.

Objective: The objective of this randomized, double-blind, placebo-controlled trial was to evaluate the mechanism of action of imiquimod cream in the treatment of anogenital warts, and to apply the findings to the results of previously conducted safety and efficacy trials.Methods: Imiquimod (16 patients) or placebo (3 patients) cream was applied 3 times a week for up to 16 weeks; cream remained on the skin overnight for 8 +/- 2 hours. Wart biopsies were taken at prestudy, week 6, and the end of treatment (just prior to clearance or at week 16) and analyzed using PCR for HPV/DNA and RT-PCR for mRNA to identify cytokines, cellular markers, markers of proliferation and differentiation, and viral gene products. Efficacy was assessed based on wart area regression as documented by wart area measurements and photographs.Results: All patients enrolled in the trial had HPV type 6/11. All imiquimod-treated patients experienced a >/=75% clearance in baseline/target wart area. Imiquimod treatment stimulated significant increases in mRNA for IFN-alpha, 2'5' AS and IFN-gamma. Increases in mRNA for CD4, CD8, and TNF-alpha were also observed, suggesting activation of a T-helper type-1 cell mediated response. During the trial one of the vehicle treated patients also experienced spontaneous wart clearance; comparisons of the cytokine levels for this patient were similar to those observed for the imiquimod treated patients.Conclusions: The results of this mechanism of action trial indicate that the stimulation of local cytokines and cellular infiltrates by imiquimod leads to a reduction of HPV types 6 and 11 viral load with subsequent wart regression and normalization of keratinocyte proliferation without evidence of scarring. In two previous randomized vehicle-controlled trials evaluating patients with anogenital warts, the majority of patients had HPV-DNA types 6 or 11 as assessed by in situ hybridization. These results provide additional insight into the mechanism of total clearance for these otherwise healthy patients. The Th1 response demonstrated in this trial also explains the lower total clearance rates demonstrated in HIV-positive and AIDS patients.