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L McCardle

Publications and source records attributed to L McCardle.

12 recordsLinked to original sources
PubMed2004

Specificity of lymphoreticular accumulation of prion protein for variant Creutzfeldt-Jakob disease.

BACKGROUND: Immunocytochemical accumulation of prion protein (PrP) in lymphoid tissues is a feature of variant Creutzfeldt-Jakob disease (vCJD) that has been used both to aid in the diagnosis of patients and as a basis of large scale screening studies to assess the prevalence of preclinical disease in the UK. However, the specificity of this approach is unknown. AIM: To assess the specificity of lymphoreticular accumulation of PrP for vCJD by examining a range of human diseases. METHODS: Paraffin wax embedded lymphoreticular tissues from patients with several reactive conditions (58 cases), tumours (27 cases), vCJD (54 cases), and other human prion diseases (56 cases) were assessed. PrP accumulation was assessed by immunocytochemistry using two different monoclonal anti-PrP antibodies and a sensitive detection system. RESULTS: All cases of vCJD showed widespread lymphoreticular accumulation of PrP; however, this was not seen in the other conditions examined. CONCLUSION: Lymphoreticular accumulation of PrP, as assessed by immunocytochemistry, appears to be a highly specific feature of vCJD.

Blotting, Western↗
PubMed2002

Pathological diagnosis of variant Creutzfeldt-Jakob disease.

The neuropathological and biochemical features of the 89 histologically confirmed cases of variant Creutzfeldt-Jakob disease (vCJD) diagnosed up to the end of October 2001 in the UK are reviewed. Histology of the central nervous system, lymphoid tissues and other organs was accompanied by immunocytochemistry and Western blot analysis of the disease-associated form of the prion protein (PrP(RES)). All patients with vCJD were methionine homozygotes at codon 129 of the PrP gene. The pathology of vCJD showed relatively uniform morphological and immunocytochemical characteristics, which were distinct from other forms of CJD. PrP(RES) accumulation was widespread in lymphoid tissues in vCJD, but was not identified in other non-neural tissues. PrP(RES) in vCJD brain tissue showed a uniform glycotype pattern distinct from sporadic CJD. Given the increasingly widespread occurrence of bovine spongiform encephalopathy in Europe and Asia, there is a major need for widespread CJD surveillance. This should be accompanied by a multidisciplinary laboratory approach to the investigation and diagnosis of all forms of CJD, with the need to investigate autopsy tissues from suspected cases by the histological and biochemical techniques described herein.

Autopsy↗
PubMed2000

Laboratory diagnosis of variant Creutzfeldt-Jakob disease.

The neuropathological and biochemical features of 33 cases of variant Creutzfeldt-Jakob disease (vCJD) diagnosed up to the end of 1998 are analysed in relation to the 646 cases of suspected CJD referred to the CJD Surveillance Unit laboratory from 1990 to 1998. Morphological studies of the central nervous system, lymphoid tissues and other organs were accompanied by immunocytochemistry; Western blot analysis of PrPRES was performed on frozen brain tissue. The findings were analysed in relation to clinical and genetic data. The pathology of vCJD showed morphological and immunocytochemical characteristics distinct from other cases of CJD. PrP accumulation was widespread in lymphoid tissues in vCJD, but was not identified in other non-neural tissues. PrPRES accumulation in vCJD brain tissue showed a uniform glycotype pattern distinct from sporadic CJD. All analysed cases of vCJD were methionine homozygotes at codon 129 of the PrP gene. No evidence currently exists to suggest that cases of CJD diagnosed in individuals who are MV or VV at codon 129 of the PrP gene represent 'human bovine spongiform encaphalopathy (BSE)'. Continued surveillance is required to further investigate this possibility, with the need to investigate autopsy tissues from suspected cases by histological and biochemical techniques.

Blotting, Western↗
PubMed2000

Ultrastructural analysis of the florid plaque in variant Creutzfeldt-Jakob disease.

We report here the first description of florid plaques--the hallmark of variant Creutzfeldt-Jakob disease (vCJD). These plaques are composed of broad bundles of amyloid, are highly neuritic and exhibited astrocytes and microglial cells. Collectively, they are more similar to neuritic plaques of Alzheimer's disease than to kuru plaques of kuru--Creutzfeldt-Jakob disease--Gerstmann-Sträussler-Sheinker disease.

Alzheimer Disease↗
PubMed1999

Protection of personnel and environment against Creutzfeldt-Jakob disease in pathology laboratories.

Most neuropathology laboratories have been faced with the question of dealing with cases of Creutzfeldt-Jakob disease (CJD) which is a rare neurodegenerative disorder. Neuropathologists have been long aware of the transmissibility and unique properties of the agent which make it resistant to conventional inactivating reagents. The emergence of iatrogenic cases and of the bovine spongiform encephalopathy (BSE) crisis has induced anxiety among laboratory staff and raised questions about the efficiency of safety measures and procedures hitherto applied in pathology laboratories. This article aims at presenting an overview of the risk involved in handling CJD material. It gives practical advice and a key to more detailed procedures, guidelines and recommendations available in scientific literature and through government agencies. Neuropathologists and biochemists are at a higher potential risk than others since the diagnosing of CJD involves the handling of nervous tissue which contains the highest levels of infectivity.

Animals↗
PubMed1997

Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent.

There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains. We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species. This BSE 'signature' has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant, providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt-Jakob disease (CJD), referred to as 'new variant' CJD (vCJD), have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France. This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.

Animals↗
PubMed1997

Prion protein immunocytochemistry--UK five centre consensus report.

Creutzfeldt-Jakob disease (CJD) and other prion diseases are associated with the deposition of insoluble prion protein (PrPCJD) in the central nervous system (CNS). Antibodies raised against PrPCJD also react with its precursor protein, a soluble form of PrP (PrPC), which is widely distributed in the normal CNS. This cross-reactivity has in the past raised doubts as to the specificity and diagnostic reliability of PrP immunolocalization, especially in familial cases which are atypical clinically and which lack characteristic pathology findings. Following an MRC-funded workshop which focused on this problem, a multicentre prospective study was set up to identify a reliable protocol for PrPCJD immunocytochemistry. Five UK centres took part in this study and demonstrated consistent staining of plaques, vacuolar deposits in severe spongiform change, and perineuronal deposits using a variety of antibodies and enhancement procedures. A protocol using formic acid, guanidine thiocyanate, and hydrated autoclaving pre-treatment in conjunction with a monoclonal PrPCJD antibody produced the clearest immunochemical results and is presented as the consensus UK recommendation for PrPCJD immunocytochemical procedures.

Brain↗
PubMed1997

Human prion diseases.

Explore the source record for details and available documents.

Creutzfeldt-Jakob Syndrome↗
PubMed1994

Neuropathological phenotype and 'prion protein' genotype correlation in sporadic Creutzfeldt-Jakob disease.

A systematic study of 'prion protein' genotype in cases of sporadic Creutzfeldt-Jakob disease showing amyloid plaques staining with anti-prion protein antibody has been performed. This revealed a relative excess of cases with valine at position 129 of the gene's open reading frame. The observation emphasises the importance of this site of common polymorphism in influencing the neuropathological phenotype in human spongiform encephalopathy.

Aged↗
PubMed1993

Ubiquitin immunocytochemistry in human spongiform encephalopathies.

The distribution of ubiquitin was studied by immunocytochemistry in eight cases of human spongiform encephalopathy and compared with the findings in seven age- and sex-matched cases of Alzheimer's disease and six non-demented control cases. The results were also compared with the immunocytochemical distribution of prion protein and the lysosomal aspartic protease cathepsin D. In the human spongiform encephalopathies, ubiquitin immunoreactivity was found in a punctate distribution at the periphery of prion protein amyloid plaques and in a finely granular pattern in the neuropil around and within areas of spongiform change. Cortical nerve cells contained scanty ubiquitinated dot-like inclusions, and occasional microglia around the areas of spongiform change also gave a positive staining reaction for ubiquitin, as did multiple irregular thread-like structures in the neuropil and white matter. The ubiquitin-containing structures at the plaque periphery in human spongiform encephalopathies resemble the neuritic processes at the periphery of the senile plaque in Alzheimer's disease. The granular positivity for ubiquitin associated with areas of spongiform change closely resembles the pattern of immunostaining seen with the antibodies to the prion protein and cathepsin D, consistent with the reported accumulation of ubiquitinated proteins and prion protein in lysosomes in the murine scrapie model. Further studies are required to investigate the role of lysosomes in this group of disorders, and to study the localization of other cell stress proteins and prion protein in spongiform encephalopathies.

Adult↗
PubMed1989

The self-reported effects of PCP on human aggression.

The elicitation of violent of psychotic behavior by phencyclidine (PCP) administration is well documented. There are indications, however, that behavioral responses to PCP may differ among PCP users as a function of background or personality characteristics. The present study examined 35 male jail inmates with histories of PCP use. Estimates of the nature and extent of drug use and self-reports of previous psychiatric hospitalizations were obtained in these subjects. The Buss-Durkee Hostility Inventory was modified to reflect behaviors under the two simulated conditions of "No PCP" and "PCP" use. Results showed that PCP use was related to increased levels of hostility in our subjects when present age, age of first use, the frequency of use and suspicion and assaultive behavior when not using PCP was considered. Also, subjects with a history of psychiatric hospitalizations reported higher levels of assault when using PCP than those without psychiatric histories. These data suggest that the self-reported behavioral results of PCP use are associated with certain personality traits and background features.

Adolescent↗