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Biomedical subjects

C L Masters

Publications and source records attributed to C L Masters.

At least 253 records · Page 14Linked to original sources
PubMed1984

The sequential development of spongiform change and gliosis of scrapie in the golden Syrian hamster.

The lesion profiles of spongiform change and gliosis in the hamster occurring after intracerebral (IC) inoculation of scrapie virus, are calculated and compared to the lesion profile of spongiform change of scrapie in mice and of scrapie and Creutzfeldt-Jakob disease (CJD) in the squirrel monkey. The profile of scrapie in hamsters differs considerably from that of a closely related strain of scrapie in mice, and both differ from scrapie and CJD in the squirrel monkey. These differences emphasize the effect of the host on the distribution of pathological changes in these unconventional virus infections. The sequential development of the lesions in the hamster shows that the earliest changes are detectable before the onset of clinical disease 49-57 days after inoculation, as assessed by light microscopy. Gliosis is detectable by indirect immunofluorescence 35-39 days after inoculation by use of a monoclonal antibody directed against astrocytes.

Animals↗
PubMed1983

Syndromes of amyotrophic lateral sclerosis and dementia: relation to transmissible Creutzfeldt-Jakob disease.

A review of over 2,000 cases of Creutzfeldt-Jakob disease and related disorders in the literature and our own files yielded 231 cases of dementia with early lower motor neuron signs. The clinical-pathological profiles of the 231 cases were distinctly different from those of cases of transmissible Creutzfeldt-Jakob disease: the patients had a longer illness, and their brains lacked the typical spongiform change. Brain tissue from 33 of these patients has been inoculated intracerebrally into nonhuman primates, but only 2 atypical cases transmitted a spongiform encephalopathy; 23 have been incubating from three to twelve years and can be considered negative transmission experiments. The findings suggest that most cases of dementia associated with early amyotrophy are more closely related to classic amyotrophic lateral sclerosis than to transmissible Creutzfeldt-Jakob disease and do not deserve the label of "amyotrophic Creutzfeldt-Jakob disease." When lower motor neuron involvement occurs in transmissible Creutzfeldt-Jakob disease, it is usually late and accompanied by signs of a more fulminant cerebral and cerebellar involvement.

Adult↗
PubMed1983

Ultrastructural morphology of amyloid fibrils from neuritic and amyloid plaques.

The structure of partially purified, CNS amyloid fibrils from three different sources have been compared by negative stain EM. The fibrils isolated from brains with senile dementia of Alzheimer type were 4-8 nm in diameter, narrowing every 30-40 nm and apparently composed of two 2-4 nm filaments. The fibrils from a Gerstmann-Sträussler syndrome brain were 7-9 nm in diameter, narrowing every 70-80 nm and with a suggestion that they are composed of two 3-5 nm filaments. The fibrils isolated from 87V scrapie-affected mouse brains were 4-8 nm in diameter with a twist every 15-25 nm presumably composed of two 2-4 nm filaments. The fibrils from the scrapie brains were usually observed in pairs. The shape of the clusters of the isolated amyloid fibrils observed in each disease was similar in negative stain and thin section EM preparations and was related to the characteristic morphology of the amyloid fibrils in the neuritic and amyloid plaques in situ. The structural differences between the CNS amyloid fibrils from the various diseases studied by us may reflect differences in the polypeptides which comprise the fibril and/or a different pathogenesis in the formation of the amyloid fibrils.

Alzheimer Disease↗
PubMed1983

A clinico-pathological study of a case of kuru.

Kuru was diagnosed in a 42-year-old Melanesian male from the Eastern Highlands Province of Papua New Guinea. The clinical features indicated predominant cerebellar degeneration together with widespread cortical neuronal dysfunction and involvement of the diencephalon, hippocampus and basal ganglia. Dementia was an early and prominent feature. The duration of clinical illness was about 12 months and atypically he spent the last 7 months in hospital allowing continuous assessment. At autopsy, spongiform encephalopathy was demonstrated, and inoculation of brain tissue into 4 squirrel monkeys and 1 capuchin monkey resulted in the development of kuru. This is the longest continuous study of kuru in a hospital setting to be recorded in the adult human subject. The virus isolated from the brain of this patient has been adopted as a standard reference strain of kuru for future use and repository.

Adult↗
PubMed1982

Experimental scrapie in golden Syrian hamsters: temporal comparison of in vitro cell-fusing activity with brain infectivity and histopathological changes.

Golden Syrain hamsters were inoculated intracerebrally with the hamster-adapted 263K strain of scrapie virus, and the evolution of in vitro cell fusing activity induced by brain suspensions was compared with brain infectivity titers and histological changes. Cell-fusing activity abruptly appeared 4 weeks after inoculation, 1 week before the earliest detectable histopathological changes, at an infectivity level of 7.6 log 50% lethal doses per g of brain. Cell-fusing activity was sustained throughout the remaining 4 weeks of the incubation period and the subsequent 1- to 3-week stage of clinical illness but did not increase with the logarithmic progression of infectivity, which reached a level of 11 log 50% lethal doses per g in the agonal stage of disease. Gliosis was most sensitively detected by a monoclonal antibody reacting with astrocyte intermediate filaments in an indirect immunofluorescence test, anticipating histological recognition of gliosis and spongiform change by 1 to 2 weeks. In vitro cell-fusing activity is thus one of the earliest known biological markers (apart from infectivity itself) of experimental scrapie infection.

Animals↗
PubMed1981

Transmissible spongiform encephalopathy (Creutzfeldt-Jakob disease). Atypical clinical and pathological findings.

A middle-aged neurosurgeon had an 18-month illness characterized by abnormal sleep patterns, paresthesias, and necrotizing cutaneous lesions with vasculitis and signs of cerebral, brainstem, vestibulocerebellar, and progressive spinal cord involvement. Biopsy specimens of nerve and skin showed an acute vasculitis with endovascular cellular proliferation in the pattern of a Köhlmeier-Degos lesion and focal epidermal necrosis. Mental changes and cranial-nerve signs developed. Myoclonus occurred occasionally during sleep. Akinetic mutism ensued. At autopsy, major abnormalities were limited to the nervous system and skin. Spongiform encephalopathy typical of Creutzfeldt-Jakob disease was found with amyloid kuru plaques. A cribriform change distinct from the spongiform change was seen focally in the white matter. Scarred skin lesions and a healed, partially obliterative arteritis were noted. Inoculation of brain and lung into nonhuman primates resulted in a spongiform encephalopathy.

Brain Stem↗
PubMed1981

Monoclonal antibodies to central nervous system antigens.

Thirty monoclonal antibodies produced by mouse hybrid myelomas which react with antigens in hamster or mouse nervous system tissues were derived. Using these antibodies as probes with indirect immunofluorescence and immunoperoxidase techniques, we can selectively identify by morphological criteria many of the structural components of the brain seen at a light-microscopic level, including the neutrophil, neuronal cytoplasm, nuclei, axons, astrocytes and ependyma. Some of the antibodies display cytoskeletal and filamentous structures, including intermediate filaments, microfilaments, neurofilaments, glial and ependymal filaments. The specificity to neural tissue components of these hybridoma antibodies was assessed by their reactivity to mouse and hamster non-neural tissues and selected mouse, hamster, rat and human cultured cell lines. Of the 30 clones analyzed, specificity ranged from 3 clones reacting only with grey matter of mouse and hamster brain, one clone reacting only with axons in animal and human brain, to 19 clones reactive with both neural and non-neural tissue components.

Animals↗
PubMed1981

The familial occurrence of Creutzfeldt-Jakob disease and Alzheimer's disease.

We have analysed the familial occurrence of Creutzfeldt-Jakob disease (CJD) in 27 families selected from a total of 73 families. Fifteen per cent of all cases of CJD have a family history of disease consistent with autosomal dominant transmission. The onset of disease in familial cases is significantly earlier than in sporadic cases. A maternal effect was not found, nor was there evidence for prenatal vertical transmission of the virus. Temporal and spatial separations between affected members demonstrates that incubation periods ranging at least from one to four decades are to be expected. Affected siblings tend to die at the same age, and not at the same time, which is consistent with some form of vertical transmission (either prenatal or early postnatal), assuming rather uniform incubation periods. CJD occurred in four families in members related by marriage, evidence in favour of horizontal or common source transmission in occasional cases. The familial occurrence of CJD and Alzheimer's disease (AD) were compared using data on 52 families with AD. The age at death and duration of disease in familial AD is greater than in familial CJD. Familial AD also occurs in a pattern of autosomal dominant transmission, without maternal effect. There were four families with AD in which one or more members died from CJD. There were an additional 17 families with AD in which one or more members presented with clinical features resembling CJD. Although virus causing an experimental spongiform encephalopathy was isolated from the brain of two cases of familial AD, most cases of sporadic and familial AD tested failed to cause disease when brain tissue was inoculated into nonhuman primates. The precise mechanism of spread of the virus in familial CJD remains unknown. The results of the present study are consistent with the hypothesis of a genetically inherited susceptibility to infection which is acquired in early infancy or childhood. Other proposed mechanisms such as prenatal vertical transmission or a common environmental source of infection seem less likely.

Adult↗
PubMed1981

Golgi and electronmicroscopic studies of spongiform encephalopathy.

Golgi impregnations of cerebral biopsies from two patients suffering from Creutzfeldt-Jakob disease (subacute spongiform encephalopathy) revealed striking loss of dendritic spines of pyramidal neurons and unusual focal spherical distensions of dendritic and axonal processes. Light and electronmicroscopic studies disclosed spongiform changes, which seemed to be caused by intracytoplasmic vacuoles and expansion of the plasmalemmal membranes of neurons and astrocytes. Although the diagnostic biopsies were performed at a markedly symptomatic stage of the disease, there was no evidence of neuronal cell loss. Neuronal changes in Golgi impregnations of cerebral cortex from hamsters infected with scrapie were essentially identical to those in the human biopsies. The loss of dendritic spines of pyramidal cells and spherical swellings of axons and dendrites thus seem to be characteristic of spongiform encephalopathies, and probably account in part for the clinical neurologic manifestations, which may be severe in the relative absence of neuronal death.

Adult↗
PubMed1981

Neuropathology of the cortical lesions of the Parkinsonian-dementia (PD) complex of Guam.

The Guam amyotrophic lateral sclerosis and Parkinsonian-dementia (ALS and PD) complex still presents a challenge to research. Previous papers have highlighted the lesions in the hippocampus and basal nuclei to explain the bizarre clinical syndrome. In our study of 20 to 62 cases of PD with or without ALS, significant widespread and often severe lesions were found throughout the entire cerebral cortex. These changes included variable degrees of nerve cell loss, spongy change, gliosis, increased lipofuscin content of nerve cells, the presence of granulovacuolar bodies and neurofibrillary tangles within neurones and, less frequently, Hirano bodies. The lesions show a characteristic topographical distribution. The global involvement of the cerebral cortex correlated well with the loss of higher mental function which was present in the patients.

Adult↗
PubMed1980

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

Animals↗
PubMed1980

Evidence for and against the transmissibility of Alzheimer disease.

Nonhuman primates were inoculated intracerebrally with brain tissue from 52 patients with confirmed Alzheimer disease (AD) in order to investigate the possibility of an infectious etiology. Animals inoculated with brain tissue from two patients with familial AD developed a spongiform encephalopathy that was indistinguishable from Creutzfeldt-Jakob disease (CJD). Seventeen other cases of AD on test for more than 50 months failed to produce similar changes, and 33 cases have not been incubating for a sufficient period of time to ascertain the presence of a transmissible agent. The initial transmission of spongiform encephalopathy with brain tissue from the two familial cases of AD has not been reproduced and the association between AD and an infectious agent has not yet been demonstrated with any reasonable degree of certainty. The frequent overlap of clinical symptoms of AD and CJD, and the occurrence of cases of CJD and AD in the same families indicate the need for continuing research on the relationship between the two diseases.

Alzheimer Disease↗