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Biomedical subjects

C L Masters

Publications and source records attributed to C L Masters.

At least 271 records · Page 15Linked to original sources
PubMed1979

Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering.

The worldwide epidemiology of Creutzfeldt-Jakob disease (CJD) is presented from an analysis of 1,435 patients. In the United States, the average annual mortality rate is at least 0.26 deaths per million. Temporal-spatial clustering of cases was not found in the United States, but reports from other countries indicate that such clustering does occur. Fifteen percent of the cases were of the familial type, suggesting a genetic susceptibility to infection. Iatrogenic transmission by corneal transplantation and neurosurgical operations has occurred, and the possibility is raised that previous surgery or preexisting neurological operations has occurred, and the possibility is raised that previous surgery or preexisting neurological disease may be associated with an increased risk of developing CJD. It remains to be determined whether the virus of CJD is maintained only by patient-to-patient transmission, has a zoonotic reservoir such as scrapie, or causes widespread latent infection of man that is occasionally activated.

Adolescent↗
PubMed1978

Pathogenesis of the Arnold-Chiari malformation: the significance of hydrocephalus and aqueduct stenosis.

In 24 cases of spina bifida, correlations were made comparing the degree of hydrocephalus with the cross-sectional area of the supratentorial compartment, posterior fossa, hindbrain prolapse, size of myelocele, and degree of fibrovascular reaction at the base of the brain. The size and postion of the aqueduct and fourth ventricle were compared with the degree of hydrocephalus. The results demonstrate that the aqueduct stenosis is usually due to external compression of the mesencephalon. The results also suggest that the size of the posterior fossa and hindbrain prolapse are secondary to hydrocephalus. It is postulated that the hydrocephalic process may be initiated by fibrovascular occlusion of the basal subarachnoid space.

Arnold-Chiari Malformation↗
PubMed1977

Penicillamine-associated myasthenia gravis, antiacetylcholine receptor and antistriational antibodies.

Myasthenia gravis with thymic hyperplasia developed in a patient with Wilson's disease after eight years of penicillamine treatment. Four months prior to the onset of myasthenia, penicillin hypersensitivity was observed. Immunofluorescence on the excised thymus revealed immunoglobulin and complement deposition, but the myasthenia persisted after thymectomy and continuation of penicillamine therapy. Increased antiacetylcholine receptor antibody was demonstrable throughout. This patient subsequently became pregnant, enabling studies to be performed on the transplacental transfer of the immunoglobulin G (IgG) class antiacetylcholine receptor antibody. Eleven cases of rheumatoid arthritis with penicillamine-associated antistriational antibodies have also been observed; in three of these cases there was evidence of myasthenia gravis. These observations extend earlier reports of the association of penicillamine with myasthenia gravis and suggest that antistriational antibody, antiacetylcholine receptor antibody and thymic hyperplasia may be independent effects of penicillamine therapy.

Acetylcholine↗
PubMed1976

Experimental kuru in the gibbon and sooty mangabey and Creutzfeldt-Jakob disease in the pigtailed macaque. With a summary of the host range of the subacute spongiform virus encephalopathies.

The experimental host range for the slow virus infections causing subacute spongiform virus encephalopathies is enlarged in primates to include the gibbon for kuru, the pigtailed macaque for Creutzfeldt-Jakob disease, and the sooty mangabey for both diseases. The report is based on neuropathological evidence of the diseases in animals with preclinical lesions. A table lists all the species to which the subacute spongiform virus encephalopathies have been transmitted.

Animals↗
PubMedDate not supplied

Characterization of the high affinity heparin binding site of the Alzheimer's disease beta A4 amyloid precursor protein (APP) and its enhancement by zinc(II).

The Alzheimer's disease beta A4 amyloid precursor protein (APP) has been shown to be involved in a diverse set of biological activities including regulation of cell growth, neurite outgrowth and adhesiveness. The APP and amyloid protein precursor-like proteins (APLP1 and APLP2) belong to a superfamily of proteins that are probably functionally related. In order to characterize the cell adhesion properties of APP the brain specific isoform APP695 was purified and used to assess the binding to heparin, a structural and functional analogue of the glycosaminoglycan heparan sulfate. We show that APP binds in a time dependent and saturable manner to heparin. The salt concentration of 620 mM at which APP elutes from heparin Sepharose is greater than physiological. The apparent equilibrium constant for dissociation was determined to be 300 pM for APP binding to heparin Sepharose. A high affinity heparin binding site was identified within a region conserved in rodent and human APP, APLP1 and APLP2. This binding site was located between residues 316-337 of APP695 which is within the carbohydrate domain of APP. We also demonstrate an interaction between this heparin binding site and the zinc(II) binding site which is conserved in all members of the APP superfamily. We show by using an automated surface plasmon resonance biosensor (BIAcore, Pharmacia) that the affinity for heparin is increased two- to four-fold in the presence of micromolar zinc(II). The identification of zinc-enhanced binding of APP to heparan sulfate side chains of proteoglycans offers a molecular link between zinc(II), as a putative environmental toxin for Alzheimer's disease, and aggregation of amyloid beta A4 protein.

Alzheimer Disease↗
PubMedDate not supplied

A synthetic substrate assay for the gamma-secretase of the beta-A4 amyloid of Alzheimer's disease.

gamma-secretase, the endoprotease which releases the C-terminus of beta A4 amyloid peptide, cleaves within the hydrophobic transmembrane domain of the amyloid precursor protein. In order to obtain a substrate for gamma-secretase, a dodecapeptide which spans the cleavage site was synthesized, labelled with 125-iodine and conjugated to an agarose gel. A radiometric solid-phase assay was developed using this immobilized substrate. Peptide products were separated by reverse-phase HPLC and TLC to allow characterization of the cleavage site(s).

Alzheimer Disease↗
PubMedDate not supplied

Creutzfeldt-Jakob disease in an adolescent.

A 16-year-old boy was stricken with a progressive neurologic disorder characterized primarily by dementia progressing to severe neurologic debility in 12 months and death 28 months following the first symptoms. Pathologic examination showed a spongiform encephalopathy, consistent witha clinical diagnosis of Creutzfeldt-Jakob disease (CJD). The noteworthy features of the case are the age of onset, the somewhat prolonged course an the amount of white matter change. These are discussed within the frame of reference of CJD and the spongiform encephalopathies of infancy and childhood. Animal inoculation studies employing post-mortem embalmed brain as inoculum are currently in progress to determine the transmissibility of this patient's disease.

Adolescent↗
PubMedDate not supplied

Commentary on the consensus recommendations for the post mortem diagnosis of Alzheimer's disease.

The consensus recommendations for the post mortem diagnosis Alzheimer's disease (AD) highlight the difficulties in establishing a pathological diagnosis in brains from clinically demented individuals with both certainty and uniformity. There is, however, a need for diagnostic guidelines that are relatively simple, inexpensive, and adaptable to general pathologists and different laboratories. The current Consortium to Establish a Registry for Alzheimer's disease (CERAD) criteria and the recommendations in the consensus document giving three probabilistic categories for diagnosis go a long way towards establishing a uniform approach for the diagnosis of AD. However, more uniformity could be adopted in the topography of sectioning to enhance diagnostic and future research comparisons. We also recommend that immunohistochemistry for beta A4 (A beta) amyloid and tau-reactive neurofibrillary changes, in addition to hematoxylin and eosin stains, should become the basis for histological diagnosis. We agree with the guidelines concerning documentation of all AD changes. Until a clearer understanding of the early changes of AD is established, strict observation and recording are the pathologists' best diagnostic skills. The ill-defined diagnostic areas of AD continue to prompt the need for a new method of detection of the underlying pathologic process.

Aged↗
PubMedDate not supplied

The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor.

Alzheimer's disease is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles and extracellularly as amyloid plaque cores and in blood vessels. The major protein subunit (A4) of the amyloid fibril of tangles, plaques and blood vessel deposits is an insoluble, highly aggregating small polypeptide of relative molecular mass 4,500. The same polypeptide is also deposited in the brains of aged individuals with trisomy 21 (Down's syndrome). We have argued previously that the A4 protein is of neuronal origin and is the cleavage product of a larger precursor protein. To identify this precursor, we have now isolated and sequenced an apparently full-length complementary DNA clone coding for the A4 polypeptide. The predicted precursor consists of 695 residues and contains features characteristic of glycosylated cell-surface receptors. This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.

Alzheimer Disease↗
PubMedDate not supplied

Cerebral changes and cerebrospinal fluid beta-amyloid in Alzheimer's disease: a study with quantitative magnetic resonance imaging.

Pathological and biochemical studies indicate that beta-amyloid (betaA4) deposition is a hallmark in the pathogenesis of Alzheimer's disease (AD). Neuroimaging studies demonstrate that the respective cerebral changes primarily strike the temporal lobe and the amygdala-hippocampus complex and may be reliably assessed using quantitative magnetic resonance imaging (MRI). Therefore one may expect that reduced betaA4-levels are significantly correlated with measures of the temporal lobe rather than global cerebral atrophy in AD patients. To test this hypothesis in a clinical study, cerebrospinal fluid concentrations of total betaA4 and its major C-terminal variations betaA4 1-40 and betaA4 1-42 were compared with cerebral changes as assessed by quantitative magnetic resonance imaging (MRI). Significantly (P< 0.05) reduced betaA4 1-40 and betaA4 1-42 levels were found in the AD patients (17 female; six male; AD/NINCDS-ADRDA-criteria) in comparison to the patients with major depression (seven female; two male; DSM-III-R). Within the AD group, betaA4 and betaA4 1-42 levels were significantly correlated with the volume of the temporal lobes (r= 0.46 and r= 0.48, respectively) but none of the other volumetric measures. These findings indicate that changes in cerebral betaA4 levels contribute to temporal lobe atrophy in AD and support the possibility that betaA4 is central to the etiology of AD.

Aged↗
PubMedDate not supplied

Preclinical lesions and their progression in the experimental spongiform encephalopathies (kuru and Creutzfeldt-Jakob disease) in primates.

Creutzfeldt-Jakob disease and kuru were studied in experimental primates. Eight animals with clinical disease lasting from 1/2 to 12 1/2 months were evaluated for histological evidence of progression of the pathological triad of neuronal vacuolation, neuronal loss and fibrous astrocytosis. The first change to appear was neuronal vacuolation, in both the body of neurones and in the neuropil. Fibrous astrocytosis was found subsequent to neuronal damage and necrosis. Neuronal loss was apparent when clinical signs were present. As the clinical disease progressed, so did the severity of neuronal loss and astrocytosis. Five animals, 1 1/2-10 1/2 months after intracerebral inoculation, before they had shown any signs of clinical disease, had histological evidence of neuronal vacuolation and astrocytosis.

Animals↗
PubMedDate not supplied

An analysis of the morphology of senile plaques in Down's syndrome patients of different ages using immunocytochemical and lectin histochemical techniques.

The morphology of the senile plaque (SP), within the hippocampus and the temporal cortex, has been examined in 21 patients with Down's syndrome (DS), dying between the ages of 13 and 65 years, using immunocytochemical and lectin histochemical methods, as well as with a conventional silver staining technique. The earliest changes detectable within these areas of brain in the younger patients involved a fine diffuse deposition of amyloid (A4) protein and a uniform granular accumulation of an oligosaccharide recognized by the lectin from Canavalia ensiformis (ConA). At this stage, these 'pre-plaque' areas are unrecognizable using silver staining. Later the conventional SP morphology becomes apparent; the A4 protein aggregates into the usual plaque core and neurites appear with silver staining. The fine ConA positive material concentrates into large clumps and becomes recognizable by other lectins such as PSA, WGA and ePHA, which bind to mannose containing structures in an increasingly complex form. It is suggested that the development of the pathological changes of Alzheimer's disease, in patients with DS (and also in AD itself) involves a primary deposition of amyloid protein in conjunction with the accumulation of an as yet unidentified oligosaccharide. These changes precede the neuronal response that is characterized by the formation of neurites and the accumulation of neurofibrillary tangles that ultimately leads to cell death.

Adolescent↗