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J Collinge

Publications and source records attributed to J Collinge.

At least 73 records · Page 4Linked to original sources
PubMed1996

Hippocampal slices from prion protein null mice: disrupted Ca(2+)-activated K+ currents.

The intrinsic properties of hippocampal CA1 pyramidal cells were examined in mice lacking prion protein (PrP-null). The resting potentials, time constants, amplitude of the medium afterhyperpolarization (AHP) and spike firing accommodation did not differ from the control group. The PrP-null group differed in having lower input resistances, a lack of the late AHP and of a charybdotoxin-sensitive summated AHP. We propose that CA(2+)-activated K+ currents, in particular IAHP, are disrupted in PrP-null mice.

Action Potentials↗
PubMed1996

Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene.

Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disorder characterized by the accumulation of aggregates of a cellular protein, PrP, in the brain. In both human and animals, genetic alterations to the gene encoding PrP (PRNP in human) modulate susceptibility to CJD. The recent epidemic of bovine spongi-form encephalopathy in the UK has raised the possibility of transmission from animal produce to humans. To provide a baseline against which to assess possible risk factors, we have determined the frequencies of predisposing mutations and allelic variants in PRNP and their relative contributions to disease. Systematic PRNP genotype analysis was performed on suspected CJD cases referred to the National Surveillance Unit in the UK over the period 1990-1993. Inspection of 120 candidate cases revealed 67 patients with definite and probable CJD, based on clinical and neuropathological criteria. No PRNP mutations were detected in any of the remaining 53 patients assessed as "non-CJD". A disease-associated mutation in the PRNP gene was identified in nine (13.4%) definite and probable cases of CJD, a reliable estimate of the incidence of PRNP-related inherited CJD based on a prospective epidemiological series. Within the group of sporadic CJD patients (lacking PRNP mutations), we confirmed that the genotype distribution with respect to the common methionine/valine (Met/Val) polymorphism at codon 129 within PRNP was significantly different from the normal Caucasian population. The incidence of Met homozygosity at this site was more than doubled and correlated with increased susceptibility to the development of sporadic CJD. Unlike other recent studies, Val homozygosity was also confirmed to be a significant risk factor in sporadic CJD, with the relative risks for the three genotypes Met/Met: Val/Val:Met/Val being 11:4:1.

Alleles↗
PubMed1996

A prion disease with a novel 96-base pair insertional mutation in the prion protein gene.

There are coding mutations in the prion protein gene in familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease, and other phenotypes that make up the inherited prion diseases. Insertional mutations consisting of two, five, six, seven, eight, and nine additional octapeptide repeat elements are seen in the inherited prion diseases and usually present as atypical dementias with considerable intrafamilial phenotypic variability. A four-octarepeat insertion was reported previously in an individual without neurodegenerative disease who died of hepatic cirrhosis. Here we report a novel four-octarepeat insertional mutation in a case with classical clinical, electroencephalographic and histopathologic features of CJD with the unusual finding of pronounced prion protein immunoreactivity of the molecular layer of the cerebellum.

Amino Acid Sequence↗
PubMed1996

[Consensus report: tissue handling in suspected Creutzfeldt-Jakob disease and other spongiform encephalopathies (prion diseases) in the human. European Union Biomed-1 Concerted Action].

Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion diseases) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. The autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for safe performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories experienced in handling tissue from transmissible spongiform encephalopathies. In essence, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potentially infectious material must be adequately decontaminated by specific means. The full English text of this Consensus Report was published in Brain Pathology 5: 319-322 (1995).

Autopsy↗
PubMed1995

Rescue of neurophysiological phenotype seen in PrP null mice by transgene encoding human prion protein.

The prion protein (PrP) is central to the aetiology of the prion diseases, transmissible neurodegenerative conditions of humans and animals. PrP null mice show abnormalities of synaptic neurophysiology, in particular weakened GABAA receptor-mediated fast inhibition and impaired long-term potentiation in the hippocampus. Here we demonstrate that this PrP null phenotype is rescued in mice with a high copy number of a transgene encoding human PrP but not in low copy number mice, confirming the specificity of the phenotype for loss of function of PrP. The ability of human PrP to compensate for loss of murine PrP will allow direct study of the functional consequences of the 18 human PrP mutations, which cause the inherited prion diseases; this phenotype can now form the basis of the first functional assay for PrP.

Animals↗
PubMed1995

Familial non-specific dementia maps to chromosome 3.

A significant minority of degenerative dementias lack distinctive inclusion bodies, plagues or tangles on pathological examination. Half of these cases have a positive family history of dementia. We have studied the largest published family with such a dementia and mapped the disease locus to a 12 cM region of chromosome 3 spanning the centromere. Haplotype analysis demonstrates a common region shared between all affected individuals between the markers D3S1284 and D3S1603. Like a number of other late onset neurodegenerative diseases, the disease presents at an earlier age when paternally inherited.

Chromosome Mapping↗
PubMed1995

Tissue handling in suspected Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases)

Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion disease) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. Autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories with experience in handling tissue from transmissible spongiform encephalopathies. In particular, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potential infectious material must be adequately decontaminated by specific means.

Autopsy↗