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Biomedical subjects

G S Merz

Publications and source records attributed to G S Merz.

At least 19 recordsLinked to original sources
PubMed1992

Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils.

The function of microglia associated with beta-amyloid deposits still remains a controversial issue. On the basis of recent ultrastructural data, microglia were postulated to be cells that form amyloid fibrils, not phagocytes that remove amyloid deposits. In this electron microscopic study, we examined the ability of microglia to ingest and digest exogenous amyloid fibrils in vitro. We demonstrate that amyloid fibrils are ingested by cultured microglial cells and collected and stored in phagosomes. The ingested, nondegraded amyloid remains within phagosomes for up to 20 days, suggesting a very limited effectiveness of microglia in degrading beta-amyloid fibrils. On the other hand, we showed that in microglial cells of classical plaques in brain cortex of patients with Alzheimer's disease, amyloid fibrils appear first in altered endoplasmic reticulum and deep infoldings of cell membranes. These differences in intracellular distribution of amyloid fibrils in microglial cells support our observations that microglial cells associated with amyloid plaques are engaged in production of amyloid, but not in phagocytosis.

Amyloid↗
PubMed1990

The mRNA encoding the scrapie agent protein is present in a variety of non-neuronal cells.

PrP 27-30, a unique protease-resistant protein associated with scrapie infectivity, derives from the proteolytic cleavage of a larger precursor encoded by a host gene. To identify sites of PrP biosynthesis, in situ hybridization was done using cloned PrP cDNA as a probe. In rodent brain, PrP mRNA was expressed in neurons, ependymal cells, choroid plexus epithelium, astrocytes, pericytes, endothelial cells and meninges of both scrapie-infected and uninfected animals. PrP mRNA was also detected in vitro in isolated brain microglia cells. Pulmonary cells and heart muscle cells contained high levels of this mRNA. Hybridization was not detected in spleen, confirming earlier RNA blot experiments indicating extremely low levels of PrP mRNA in this tissue. Results indicate that PrP mRNA is a normal component in a variety of non-neuronal tissues and may explain the origin of the amyloid plaques present in the subependymal region of scrapie-infected brain.

Animals↗
PubMed1987

Isolation and characterization of macrophages from scrapie-infected mouse brain.

We have isolated and characterized a population of brain macrophages from normal and scrapie-infected mice. The cells are phagocytic, possess Fc-IgG receptors, Mac-1 surface antigen and proliferate in the presence of macrophage colony stimulating factor. They resemble microglia in that they have a plasmalemmal distribution of the enzyme nucleoside diphosphatase, a property tht is characteristic of microglia in situ. In two of the three combinations of scrapie agent and mouse strain examined, the number of brain macrophages was several fold higher than in normal control mice. The increase was not observed in mice infected intraperitoneally or in control mice inoculated with normal brain homogenate. The increase is detectable as early as 3-5 weeks postinoculation. The agent/host combination that failed to show an increase in brain macrophages is one that develops large numbers of amyloid plaques. These observations suggest that these cells are closely associated with the scrapie pathogenic process in the CNS. The failure of these cells to increase in the plaque forming model of scrapie disease also suggests that they play a role in the control of CNS amyloidogenesis.

Acid Anhydride Hydrolases↗
PubMed1984

Senile dementia of the Alzheimer type: possibility of infectious etiology in genetically susceptible individuals.

The concept that SDAT is caused by an infectious agent acting in a genetically susceptible host was approached from a number of standpoints. The similarities between SDAT and the transmissible encephalopathies are discussed. One of the areas of similarity is the influence of genetic background on the development and expression of both conditions. Evidence is presented showing that genetics plays a role in many cases of SDAT and that there are known genetically controlled phenomena, the incidence of which is positively correlated with SDAT. For human encephalopathies the genetics of CJD and GSS are detailed. In experimental systems with scrapie, the influence of genetic control, operating through both host and agent, on the outcome of infection with scrapie is described. The events controlled include length of incubation period, type of lesions and their distribution and intensity. In the context of the human diseases, scrapie provides a model for the known human encephalopathies and for SDAT.

Aging↗
PubMed1980

Blood group frequencies in multiple sclerosis populations in the United States.

Multiple sclerosis (MS) patients (332) and controls (305) selected from Caucasian populations in the New York City area and in Tucson, Arizona, were tested for ABO blood group factors A and B, and Rh factors C, D, E, c, and e. There was no significant difference in the distribution frequencies of these factors in MS patients and controls.

ABO Blood-Group System↗
PubMed1976

Scrapie in vitro: agent replication and reduced cell yield.

Exposure of PAM cells, a spontaneously transformed mouse cell line, to brain homogenates from mice infected with scrapie caused a relative decrease in total cell yield, which persisted from passage 2 or 3 to passage 18 after treatment. The effect was elicited by each of the eight independent scrapie isolates tested. Lysates prepared from cultures 16 passages after treatment with scrapie caused the decrease when applied to fresh PAM cultures. Mice inoculated with passage 14 and 18 lysates developed a reduced percentage of polymorphonuclear neutrophils by 5 weeks and scrapie disease by 6 to 9 months after inoculation. Based on the total dilution from treatment of the PAM cultures with scrapie material to the preparation of the lysates, we conclude that the agent(s) responsible for the reduced PAM cell yield, the decreased percentage of polymorphonuclear neutrophils, and the induction of scrapie disease had replicated in the PAM cells. By filtration, the diameter of the agent causing the reduction in cell yield was estimated to be between 25 and 50 nm.

Animals↗
PubMed1975

Multiple sclerosis-induced reduction in the yield of a mouse cell line.

Cultures of a mouse cell line (PAM) were treated with 71 multiple sclerosis (MS) and 45 non-MS samples. Of the cultures treated with MS material, 80 percent (58) showed a reduction in cell yield (compared to untreated controls) of at least 20 percent by the third passage after inoculation. The MS samples were from 40 MS cases, and a total of 36 cases yielded at least one positive sample. The agent responsible for the decrease was not limited to nervous tissue, but was also found in serum, cerebrospinal fluid, spleen, kidney, and lymph node of MS patients. Positive samples were present at every stage of the disease. None of the non-MS samples yielded cell counts significantly different from untreated controls. The non-MS category included 12 samples from healthy individuals, 13 assorted non-central nervous system disease samples, and the following central nervous system disease samples: six subacute sclerosing panencephalitis, three Huntington's chorea, two Parkinsonism, six amyotrophic lateral sclerosis, one stroke, one encephalopathy, and one epilepsy. Brain homogenates from mice inoculated with MS tissues elicited the decrease, whereas brain homogenates from mice inoculated with non-MS samples did not.

Animals↗
PubMed1974

Reduced cell yields of mouse cell line cultures after exposure to homogenates of multiple sclerosis tissues.

The total cell yields in cultures of a mouse cell line termed "PAM" were reduced markedly after exposure to multiple sclerosis (MS) homogenates. The reductions were noted as early as the second subcultivation. The effect was produced by eight of eight MS brain homogenates and three of three MS spleen homogenates; the samples were from 10 MS cases. The reduction in total cell yields (compared to medium-treated cultures) was not observed after exposure to homogenates, six brain and two spleen, from eight non-MS cases. The effect was produced by the 50-nm filtrate of a pool of MS brain homogenates. Five of the MS-inoculated cultures were maintained for 18 subcultivations, and the reduction in total cell yields persisted throughout the series. The capacity to induce the reduction in cell yields was present in cell-free lysates from five of five MS cultures at passage 18, as was the capacity to cause a decrease in the polymorphonuclear neutrophils in the peripheral blood of mice. Calculation of the dilution effect (at least 10(18)-fold) that had occurred by the end of the passage series proved that the factor(s) causing the cell change in culture and the polymorphonuclear neutrophil change in mice had replicated in PAM cells.

Animals↗
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↗