Unusual resistance to ionizing radiation of the viruses of kuru, Creutzfeldt-Jakob disease, and scrapie. (1/40)

The titers of several preparations of kuru. Creutzfeldt-Jacob disease, and scrapie viruses were reduced by only 1/10th or less by high doses of gamma radiation of 50 kGy and by only 1/10th-1/1000th or less for 200 kGy. This unusual radiation resistance of the two human viruses further links them with the scrapie virus and suggests that the genetic information of all three viruses is considerably smaller than that of any other known viruses of mammals.  (+info)

Genetic influence on the structural variations of the abnormal prion protein. (2/40)

Prion diseases are characterized by the presence of the abnormal prion protein PrP(Sc), which is believed to be generated by the conversion of the alpha-helical structure that predominates in the normal PrP isoform into a beta-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrP(Sc), type 1 and 2, can be distinguished based on the difference in electrophoretic migration of the PK-resistant core fragment. In this study, protein sequencing was used to identify the PK cleavage sites of PrP(Sc) in 36 cases of prion diseases. We demonstrated two primary cleavage sites at residue 82 and residue 97 for type 1 and type 2 PrP(Sc), respectively, and numerous secondary cleavages distributed along the region spanning residues 74-102. Accordingly, we identify three regions in PrP(Sc): one N-terminal (residues 23-73) that is invariably PK-sensitive, one C-terminal (residues 103-231) that is invariably PK-resistant, and a third variable region (residues 74-102) where the site of the PK cleavage, likely reflecting the extent of the beta-sheet structure, varies mostly as a function of the PrP genotype at codon 129.  (+info)

Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype. (3/40)

Kuru reached epidemic proportions by the mid-twentieth century among the Fore people of New Guinea and disappeared after the abolition of cannibalistic rituals. To determine susceptibility to kuru and its role in the spread and elimination of the epidemic, we analyzed the PRNP gene coding sequences in 5 kuru patients; no germline mutations were found. Analysis of the PRNP 129 methionine (M)/valine (V) polymorphism in 80 patients and 95 unaffected controls demonstrated that the kuru epidemic preferentially affected individuals with the M/M genotype. A higher representation of M/M carriers was observed among the affected young Fore males entering the age of risk, whereas a lower frequency of M/M homozygotes was found among the survivors. M/V and V/V genotypes predisposed to a lower risk of disease development and longer incubation times. These findings are relevant to the current outbreak of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom, because all vCJD patients tested thus far have been M/M carriers.  (+info)

Genetic studies in relation to Kuru. VI. Evaluation of increased liability to Kuru in Gc Ab-Ab individuals. (4/40)

The validity of the reported association between GcAb and kuru is analyzed. Phenotypes with one or more GcAb genes have an increased incidence of the disease at the expense of Gc 1-1 and Gc 2-2. Incidence ratios of kuru associated with various phenotypes examined over the linguistic groups studied indicate that only Gc Ab-Ab persons have a significantly greater chance of dying of kuru. The association X2 for the incidence ratio for those phenotypes possessing only one GcAb gene is significant, but there is significant heterogeneity between groups studied. Those of the Gc Ab-Ab phenotype are six times as likely to contract kuru as the baseline group. Criticisms of this analysis include difficulties defining an adequate control group in such heterogeneous populations, errors in determination of Gc phenotypes, inclusion of persons incubating kuru in the control groups, and questions of validity of statistical tests in isolated inbred populations.  (+info)

Prion diseases: a dual view of the prion hypothesis as seen from a distance. (5/40)

We review the historical background and principles of the prion theory in its current shape. We showed that most of data may be still interpreted dually according to the protein only hypothesis and according to the theory in which additional component is necessary to comprise the infectivity. The enormous impact of structural biological studies is also stressed.  (+info)

Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. (6/40)

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.  (+info)

Human evolution: a legacy of cannibalism in our genes? (7/40)

A new study of genetic variation in the human prion protein gene suggests that balancing selection has operated on an amino acid sequence polymorphism in the gene during the last five hundred thousand years. Is this a legacy of widespread cannibalism by our ancestors?  (+info)

Creutzfeldt-Jakob disease with congophilic kuru plaques: CT and pathological findings of the cerebral white matter. (8/40)

In a patient whose Creutzfeldt-Jakob disease with congophilic kuru plaques that was proved at necropsy, the early brain CT showed low-density areas in the cerebral white matter before cortical atrophy and ventricular enlargement became apparent. Subsequently, there occurred diffuse white matter lucency and severe brain atrophy. At necropsy, there was severe white matter destruction which was more prominent than cortical neuronal loss. Serial CT scans were of great value for demonstrating the early and predominant changes in the cerebral white matter.  (+info)