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P A Merz

Publications and source records attributed to P A Merz.

32 records · Page 2Linked to original sources
PubMed1984

Infection-specific particle from the unconventional slow virus diseases.

Scrapie-associated fibrils, first observed in brains of scrapie-infected mice, were also observed in scrapie-infected hamsters and monkeys, in humans with Creutzfeldt-Jakob disease, and in kuru-infected monkeys. These fibrils were not found in a comprehensive series of control brains from humans and animals affected with central nervous system disorders resulting in histopathologies, ultrastructural features, or disease symptoms similar to those of scrapie, kuru, and Creutzfeldt-Jakob disease. These fibrils are also found in preclinical scrapie and in the spleens of scrapie-infected mice; they are a specific marker for the "unconventional" slow virus diseases, and may be the etiological agent.

Alzheimer Disease↗
PubMed1984

Alzheimer paired helical filaments: bulk isolation, solubility, and protein composition.

A method has been developed for the bulk isolation of Alzheimer neurofibrillary tangles (ANT) of paired helical filaments (PHF) from histopathologically confirmed cases of Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT). The fresh or frozen autopsied cerebral cortex affected with Alzheimer neurofibrillary changes is dissociated by homogenization and sieving through nylon bolting cloth and the ANT are separated by a combination of sucrose discontinuous density gradient centrifugation, glass bead column chromatography, and sodium dodecyl sulfate (SDS) treatment. The isolated ANT produce red-green birefringence when viewed through polarized light after staining with Congo red. Ultrastructurally, the isolated PHF are well preserved and have the dimensions of the PHF seen in situ. Two major Populations of ANT which exist in different proportions in AD/SDAT brains are identified on the basis of their solubility in SDS. The ANT I and the ANT II are soluble and insoluble respectively on treatment with 2% SDS at room temperature for 5 min. Solubilization of the ANT II requires several repeated extractions with a solution containing 10% each of SDS and beta-mercaptoethanol (BME) at 100 degrees C for 10 min. Sonication of the ANT II greatly facilitates their solubilization. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the isolated ANT reveals the presence of two major polypeptides with molecular weights (MW) of 62,000 and 57,000, several minor polypeptides with MW below 57,000, and a significant amount of material not entering the stacking and the resolving gels. Re-electrophoresis of polypeptides extracted from various areas of the resolving gel or of the material which does not enter the gel generates the same polypeptide profile as on the first gel, suggesting that the PHF material which does not enter the gel may result from the reaggregation of the polypeptides that enter the resolving gel. None of the polypeptides that enter the resolving gel. None of the polpeptides observed in the isolated PHF comigrate in the SDS-PAGE with any of the neurofilament polypeptides, tubulin, actin, or myosin.

Actins↗
PubMed1984

Ultrastructure of paired helical filaments of Alzheimer's neurofibrillary tangle.

Isolated paired helical filaments (PHF) of Alzheimer's disease and senile dementia of the Alzheimer type (AD/SDAT) were studied by negative stain techniques and electron microscopy (EM). The helical structure of the PHF was confirmed by tilt analysis of negatively stained isolated PHF. A substructure of four protofilaments, each 3-5 nm in diameter, was also observed. A comparison of PHF substructure, neurofilaments and microtubules, revealed no similarity among the three structures.

Aged↗
PubMed1984

The effects of detergents on the composition of postsynaptic densities.

A method of purifying postsynaptic densities (PSD) of Cohen et al. (1977) has been modified, primarily by the substitution of octyl glucoside as the detergent used to solubilize synaptosomal fractions. Subsequent extraction with other detergents resulted in the selective removal of specific polypeptides. In particular sulphobetaine 3-14 removed most of the beta-tubulin but not alpha-tubulin. Sodium N-lauroyl sarcosinate completely destroyed the structural integrity of the PSD when the in vitro formation of intermolecular disulphide bonds was minimized. These results suggest that the structure of PSDs is more labile than previously thought and demonstrate a technique for further examining their composition.

Animals↗
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↗
PubMed1981

Abnormal fibrils from scrapie-infected brain.

Abnormal fibrillary structures, designated "scrapie-associated fibrils" (SAF), have been observed using negative stain techniques in subfractions of brains from scrapie-affected animals. SAF have been observed in all combinations of strain of scrapie agent and strain or species of host examined, regardless of their histopathology, in particular the presence or absence of amyloid plaques. SAF consist either of two or four filaments. They are morphologically dissimilar to the normal brain fibrils--microtubules, neurofilaments, glial filaments, and F actin. However, SAF do bear a resemblance to amyloid.

Amyloid↗
PubMed1972

Decreased percentage of polymorphonuclear neutrophils in mouse peripheral blood after inoculation with material from multiple sclerosis patients.

Mice inoculated with brain homogenates from multiple sclerosis (MS) cases showed marked changes in their leukocyte differential counts, with a decrease in per cent polymorphonuclear neutrophils (PMN) and an increase in the per cent lymphocytes. These changes were based upon an absolute decrease in the number of circulating PMN. The decrease in PMN percentages was apparent at 16 hr after infection and persisted for at least 11 months. The factor responsible for the decrease in PMN was (a) recoverable from 12 hr to 8(1/2) months after inoculation, (b) present in human brain homogenate at a concentration of 3 x 10(12), and (c) between 25 and 50 nm in diameter. Inoculation of 100 units of factor into mice and subsequent titration showed that the factor had undergone a net increase in the mouse of at least 10(9)-fold. The factor causing the PMN decrease was found in all MS material thus far tested: three brains, one spleen, three sera, and two cerebrospinal fluid (CSF) from nine cases of MS. The factor was not found in normal human material that included two brains, one spleen, two sera, and two CSF.

Animals↗
PubMed1972

Scrapie-induced changes in the percentage of polymorphonuclear neutrophils in mouse peripheral blood.

A decrease in the percentage of polymorphonuclear neutrophils (PMN) in the peripheral blood of mice appeared 3 days after intracerebral (IC) inoculation with scrapie mouse brain homogenate. Mice inoculated IC with normal mouse brain had PMN percentages similar to those found for uninoculated mice. This difference between normal and scrapie-inoculated mice continued throughout the preclinical phase of the disease. In the clinical phase of the disease, the percentage of PMN was either higher or lower than that found in normals. The factor causing the decrease in PMN percentages was found in the filtrates from 220-, 100-, and 50-nm filters, but not in the filtrates from a 25-nm filter. Sodium periodate treatment of the scrapie brain samples eliminated their ability to cause the decrease in PMN percentages, whereas sodium iodate had no effect. In addition to two genetically different scrapie mouse brain isolates, homogenates of mouse spleen, sheep brain, and sheep spleen from scrapie-affected animals caused a decrease in percent PMN, whereas the corresponding normal tissue homogenates did not.

Animals↗
PubMedDate not supplied

Scrapie-associated fibrils in Creutzfeldt-Jakob disease.

Scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of man belong to a group of transmissible encephalopathies which have been successfully transmitted to a variety of hosts. In susceptible hosts, these diseases are characterized by progressive degeneration of the central nervous system leading inevitably to death. The agents responsible for these diseases have not yet been identified, but they exhibit similar physicochemical characteristics. Abnormal fibrils designated 'scrapie associated fibrils' (SAF) have been observed in synaptosomal preparations of scrapie infected brain. They have never been observed in various types of control animals. We report here that SAF are present in CJD brain fractions in the experimentally transmitted disease as well as in a few naturally occurring human cases of CJD. SAF are also present in spleen extracts of animals experimentally infected with scrapie or CJD. This close association of SAF with these two diseases and two different tissues (brain and spleen) known to contain titres of infectivity, suggest that the SAF are: (1) a unique pathological response to the disease or (2) the infectious agent of these diseases.

Animals↗
PubMedDate not supplied

The nature of the unconventional slow infection agents remains a puzzle.

Unconventional slow infections are progressive transmissible degenerative disorders of the central nervous system. The human diseases belonging to this group are Creutzfeld-Jakob disease, kuru, and Gerstmann-Straussler syndrome. Scrapie, transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, and the recently discovered bovine spongiform encephalopathy are similar diseases found in animals. Unusual characteristics of the unconventional slow infections clearly distinguish these disorders from conventional infections. These include: unusually long incubation periods (from months to years); progressive CNS degeneration with characteristic histopathological lesions; the lack of an immune or inflammatory response; unconventional biological and physical properties of the etiologic agents. There has been considerable controversy concerning the nature of the causative agent. The 3 main hypotheses, virus, virino, and modified host protein, are reviewed relative to their ability to explain the properties of the agent and the unusual characteristics of the disease process. The discovery of an abnormal structure, termed scrapie associated fibrils (SAF) and an abnormally modified 33-37 kDa host-encoded glycoprotein unique to unconventional slow infections opened new areas of intense interest and investigation. SAF are abnormal filamentous structures which copurify with infectivity and possess characteristics of "amyloids." The major component of SAF is the host-encoded scrapie-specific protease resistant glyco-protein. Considerable data has accumulated on the biochemistry, immunology and molecular biology of this host coded scrapie protein. The relationship of SAF and the scrapie-specific protein to the infectious agent is discussed in the context of each of the "nature of the agent" hypotheses.

Animals↗