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Biomedical subjects

David Goldstein

Publications and source records attributed to David Goldstein.

43 records · Page 3Linked to original sources

Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics.

Kuru is an acquired prion disease largely restricted to the Fore linguistic group of the Papua New Guinea Highlands, which was transmitted during endocannibalistic feasts. Heterozygosity for a common polymorphism in the human prion protein gene (PRNP) confers relative resistance to prion diseases. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are, in marked contrast to younger unexposed Fore, predominantly PRNP 129 heterozygotes. Kuru imposed strong balancing selection on the Fore, essentially eliminating PRNP 129 homozygotes. Worldwide PRNP haplotype diversity and coding allele frequencies suggest that strong balancing selection at this locus occurred during the evolution of modern humans.

Adult↗

Multicentric Castleman's disease treated with antivirals and immunosuppressants.

A patient negative for human immunodeficiency virus (HIV) developed multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) associated with active human herpesvirus 8 (HHV-8) infection. He was treated with sequential antiviral therapy, chemotherapy, and corticosteroids. HHV-8 levels were monitored throughout the course of the patient's illness, and were found to rise on relapse. No consistent change in HHV-8 levels was found with antiviral therapy. We demonstrate that in this patient antiviral therapy was clinically ineffective, and did not alter HHV-8 levels, but that corticosteroid and combination chemotherapy led to clinical improvement. Despite the implication of HHV-8 as a cause of MCD, few studies have correlated HHV-8 levels with clinical response.

Aged↗

Genomic microsatellites as evolutionary chronometers: a test in wild cats.

Nuclear microsatellite loci (2- to 5-bp tandem repeats) would seem to be ideal markers for population genetic monitoring because of their abundant polymorphism, wide dispersal in vertebrate genomes, near selective neutrality, and ease of assessment; however, questions about their mode of generation, mutation rates and ascertainment bias have limited interpretation considerably. We have assessed the patterns of genomic diversity for ninety feline microsatellite loci among previously characterized populations of cheetahs, lions and pumas in recapitulating demographic history. The results imply that the microsatellite diversity measures (heterozygosity, allele reconstitution and microsatellite allele variance) offer proportionate indicators, albeit with large variance, of historic population bottlenecks and founder effects. The observed rate of reconstruction of new alleles plus the growth in the breadth of microsatellite allele size (variance) was used here to develop genomic estimates of time intervals following historic founder events in cheetahs (12,000 yr ago), in North American pumas (10,000-17,000 yr ago), and in Asiatic lions of the Gir Forest (1000-4000 yr ago).

Acinonyx↗

Torque Production Using Handwheels of Different Size During a Simulated Valve Operation Task.

Opening and closing valves in industrial facilities often requires operators to use bars and wrenches as levers (cheaters) in order to overcome initial actuation forces. In order to determine more appropriate operational specifications, the maximum torque production capability was measured when 12 male participants used 4 different valve handwheels at 3 different heights and 2 different angles (in relationship to the coronal plane). The results indicate that the participants produced significantly greater torque when the largest of the 4 wheels (40.6 cm diameter) was used than when the medium (22.9 cm), small (20.3 cm), and handled (17.8 cm) handwheels were used. Although the main effect of heights was found to be statistically significant, post-hoc analyses between the heights found them to be, essentially, equal. In addition, the vertical and horizontal wheel orientations were not found to be different. The results are applicable to all industries where handwheels are used and applicable to valve manufacturers for designing operational torque specifications below the values found in this study.

handwheels↗