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Biomedical subjects

J C Lewis

Publications and source records attributed to J C Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1984

Hemobartonellosis in squirrel monkeys (Saimiri sciureus) in a domestic breeding colony: case report and preliminary study.

Infection with Hemobartonella sp was diagnosed in a colony-born squirrel monkey with normocytic, normochromic anemia and pronounced punctate erythrocytic basophilic stippling on Wright's-Giemsa stained blood films. The diagnosis was confirmed using transmission electron microscopy. Two randomly selected colony-born squirrel monkeys were splenectomized in an effort to activate and detect possible latent hemobartonellosis . One monkey became parasitemic 12 days following splenectomy. The second monkey was inoculated on day 14 with 1 ml of whole blood from an infected, but nonparasitemic monkey and developed overt parasitemia 3 days later (day 17 following splenectomy). Infections in the latter two monkeys were confirmed using scanning electron microscopy.

Anaplasmataceae↗
PubMed1984

Characterization of the effect of influenza virus on polymorphonuclear leukocyte membrane responses.

Depressed chemotactic activity of polymorphonuclear leukocytes (PMNL) infected with influenza virus could be due to changes occurring at the plasma membrane. The present study examined the effect of unopsonized influenza virus on chemotaxis, adherence, receptor binding, shape change, membrane fluidity, and release of specific granules from PMNL. Chemotactic activity of PMNL under-agarose to the chemoattractants, zymosan-activated serum ( ZAS ) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), and adherence of PMNL to a plastic surface were markedly decreased in virus-treated cells as compared to control cells. The binding of fMLP to the PMNL was increased in virus-treated cells compared with control cells. Exposure of cells to virus, ZAS , or fMLP caused 35%-50% of the cells to become bipolar in shape, whereas less than 5% of the cells exposed to buffer became bipolar. Influenza virus did not alter membrane fluidity as measured by electron spin resonance spectroscopy with the probe 5-doxyl stearate. Virus-treated PMNL stimulated with FMLP or Staphylococcus aureus exhibited a marked decrease in the amount of lactoferrin released into phagosomes, onto the cells' outer membrane, and into the extracellular medium as compared to control cells. The possible relationship between inhibition of lysosomal enzyme degranulation and decreased chemotactic activity and adherence of PMNL is discussed.

Cell Adhesion↗
PubMed1984

Early atherogenesis in White Carneau pigeons. I. Leukocyte margination and endothelial alterations at the celiac bifurcation.

The addition of 0.2% or more cholesterol to the diet of young White Carneau pigeons produced atherosclerotic lesions within 10 weeks in a 2-sq mm area of the lower thoracic aorta. Concurrent with lesion development, a shift in the shape of endothelial cells from fusiform to polygonal was noted. This shift changed the ratio of endothelial cell width to length from 0.34 in pigeons receiving a control diet to 0.50 in pigeons receiving cholesterol. In contrast, endothelial cells in an atherosclerosis-resistant region 6 cm superior to the test region retained their fusiform shape despite the addition of cholesterol to the pigeon's diet. Cholesterol diets also increased adherence of leukocytes to the luminal surface of the aorta. This was most prevalent at the edge of large lesions (2430 +/- 180 cells/sq mm) and over small lesions (2240 +/- 150 cells/sq mm). Leukocyte adherence was also increased in the central region of large lesions (960 +/- 140 cells/sq mm). In addition, leukocyte activation, as evidence by crawling or spreading cells, was increased almost twofold over small lesions and the edge of large lesions when compared with adherent cells over nonlesion areas.

Animals↗
PubMed1983

Vincristine and vinblastine lower plasma cholesterol concentrations in rhesus monkeys.

3-4 days after a single clinical dose of vincristine or vinblastine in rhesus monkeys there was a marked decrease in plasma low-density lipoprotein cholesterol concentrations. There was also a concomitant increase in plasma triacylglycerol concentrations. Plasma lipid levels returned to normal concentrations within 7-10 days after injection. Plasma high-density lipoprotein cholesterol concentrations were unaltered by the drugs. Electron micrographs of the hepatocytes from monkeys treated with vincristine or vinblastine showed an accumulation of glycogen particles and proliferation of smooth endoplasmic reticulum, which was accompanied by an increase in the number of lipoprotein-containing vesicles. These results indicate that vincristine and vinblastine alter plasma cholesterol and triacylglycerol concentrations in part by interfering with hepatic lipid and lipoprotein metabolism. These studies further suggest the possibility that other less cytotoxic alkaloids from Catharanthus species with clinically useful hypocholesterolemic activity may be discovered.

Animals↗
PubMed1983

Recurrent diarrhoea in a dog associated with Clostridium perfringens type A.

A case of chronic intermittent diarrhoea in a dog is reported. Large numbers of Clostridium perfringens type A were recovered from the faeces. A toxin neutralised by C perfringens type A antitoxin was demonstrated in the same samples. No clear predisposing factors contributing to the condition could be determined. The dog recovered following a 10 day course of metronidazole at 20 mg/kg/day per os and a change to a bland diet.

Animals↗
PubMed1983

Three-dimensional organization of the platelet cytoskeleton during adhesion in vitro: observations on human and nonhuman primate cells.

Adhesion of platelets in vitro resulted in rapid polymerization of the amorphous cytoplasmic ground substance into an organized cytoskeletal superstructure. This cytoskeleton, characterized through the use of whole-mount and stereo (3-D), high-voltage microscopy in conjunction with morphometrics and cytochemistry, comprised four major size classes of filaments organized in distinctive zones. The central matrix, or granulomere, at the center of the cell mass, was an ill-defined meshwork of 80-100-A filaments which enshrouded granules, dense bodies, and elements of the dense tubular system as identified through peroxidase cytochemistry. Demarcating this central matrix was a trabecular zone containing 30-50, 80-100, and 150-170 A filaments in an open and rigid-appearing lattice. Circumscribing the trabecular zone and extending to the margins of the hyalomere was the third region, the peripheral web, in which 70-A filaments were arranged in a tight honeycomb lattice. This organizational pattern was retained in cytoskeletons prepared by Triton x-100 extraction of the adherent cells, and was observed in basally located cells of aggregates which formed subsequent to adhesion. Our observations are consistent with biochemical studies of cytoskeletons prepared from suspended platelets and suggest a contractile protein composition for the superstructure during adhesion.

Animals↗
PubMed1983

Platelet-activating factor effects on pulmonary ultrastructure in rabbits.

Morphometric analysis of endothelium in rabbit lungs demonstrated a dramatic effect of platelet-activating factor (PAF) on the ultrastructure of pulmonary vasculature. Plasmalemmal vesicles in capillaries were increased both in size (638 A PAF vs 538 A control) and in number (386/micrograms 3 cytoplasm PAF vs 125/micrograms 3 cytoplasm control) when PAF was administered as a single acute low dose (chi less than 3 micrograms/kg). High concentrations of PAF (chi greater than 3 micrograms/kg) as a single acute dose also increased vesicle number (203/micrograms 3 cytoplasm), but frequently precipitated the respiratory distress syndrome. Chronic administration of PAF with daily doses over periods of either 3.5 or 7 weeks resulted in changes paralleling the acute observations, but did not lead to more extensive lung disease.

Animals↗
PubMed1983

The immunogenicity of carcinoembryonic antigen (CEA) in athymic nude mice.

Experiments were carried out to determine whether athymic nude (nu/nu) mice are capable of producing circulating antibodies to carcinoembryonic antigen (CEA). By a double antibody radioimmunoassay technique, no antiCEA activity was detected in the sera of normal nude mice, nude mice bearing any one of four types of CEA positive human colonic tumour xenografts or nude mice immunized with a purified CEA preparation. Conversely, we were able to demonstrate antiCEA activity in the sera of euthymic (+/+) Balb/c and heterozygote nude (nu/+) mice immunized by the same schedule. We conclude that nude mice do not produce significant amounts of circulating antiCEA in response to CEA, whether present in colorectal tumour xenografts or in the immunization schedule used. The immunogenicity of CEA in other xenograft systems and man is compared and contrasted to that in the nude mouse, and the significance of differences discussed with respect to the use of the nude-mouse-human-xenograft system as a model for human colonic cancer.

Animals↗
PubMed1983

A comparison of the content and immunohistochemical patterns of CEA-like activity in human colorectal tumours and nude mouse xenografts.

The immunohistochemical pattern of CEA-like material was examined in sections of five human colonic tumour xenograft lines in nude mice and in the primary tumours from which these lines were derived. Conventional tissue sections were stained by a PAP immunoperoxidase technique, using affinity purified goat anti-CEA as the primary reagent. Normal human and nude mouse tissues were also examined. Saline extracts were made from three of the human tumours and from examples of the respective xenograft lines. The CEA content of extracts was determined by radioimmunoassay. The pattern of CEA-like material was similar in primary tumours and xenografts, but in 3/5 xenograft lines the intensity of specific staining was reduced when compared to that of the respective primary tumour. The three xenograft lines from which extracts were made contained mean values of 22%, 63% and 68% of the CEA activity found in the respective primary tumours, and the data suggested that reduced immunoperoxidase stain intensity seen in some xenografts resulted from the presence of far less antigen than in the corresponding primary tumour. We suggest that some xenograft lines represent subpopulations of cells in the primary tumour which produce less CEA than those of the primary tumour sample examined, although histologically no differences can be identified. No CEA-like activity was detected in normal nude mouse tissues.

Animals↗
PubMed1983

Concurrent endothelial cell turnover and leukocyte margination in early atherosclerosis.

Leukocyte margination and migration into nascent atherosclerotic lesion have been suggested as two early events in aortic atherosclerosis. It has also been suggested that altered endothelial cell function may mediate the margination process. In this paper we present quantitative data on leukocyte adherence to the luminal aspect of the aortic endothelium and correlate it with severity of atherosclerosis and extent of endothelial cell turnover. Both naturally occurring and cholesterol induced atherosclerotic lesions were studied. The sites of endothelial cell turnover were determined by scanning electron microscope whole mount autoradiography of 3H-thymidine labeled aortas. Morphometric analysis of atherosclerosis severity and leukocyte adhesion was accomplished by stereological analysis of conventional SEM preparations. Leukocyte adherence was localized in atherosclerosis susceptible areas of the aorta and increased dramatically over atherosclerotic lesions. Endothelial cell turnover also increased in atherosclerotic areas as indicated by an increase in the number of labeled nuclei found over lesions. Both leukocyte adherence and endothelial cell turnover occurred over the entire extent of the lesions studied, but were particularly prevalent at the growing edge of the lesions.

Animals↗
PubMed1982

Inhibition of neutrophil lysosome-phagosome fusion associated with influenza virus infection in vitro. Role in depressed bactericidal activity.

The present study examined the effect of various unopsonized strains of influenza A virus on release of myeloperoxidase (MPO) and acid phosphatase in polymorphonuclear leukocytes (PMNL). These results were correlated with the effect that these same viruses had on bactericidal activity in PMNL. Several strains of virus inhibited the fusion of azurophil granules with phagosomes containing Staphylococcus aureus. These same strains inhibited the extracellular release of MPO from PMNL (39-59%) and caused depressed killing (42-77%). In contrast, one of the influenza viruses (X-47a) did not inhibit PMNL MPO release or killing. The data indicate a close relationship between the ability of influenza virus to ablate normal intracellular lysosome-phagosome fusion with subsequent depression of bactericidal functions of PMNL.

Blood Bactericidal Activity↗
PubMed1982

Platelet aggregation and electron microscopic studies of platelets in preleukemia.

Platelet aggregation and electron microscopic studies of platelets were carried out at the time of diagnosis in 11 patients thought to have preleukemia. The clinical course confirmed the diagnosis of preleukemia in seven, of whom platelet aggregation had been performed in six and the results were abnormal in all. Electron microscopic studies were performed in six of the seven, and showed abnormal morphologic structure in five. One patient was unavailable for follow-up, and aplastic anemia developed in another. In time, two patients were seen to have nonmalignant blood disorders. Results of platelet aggregation studies were normal in both of these, but electron microscopy showed morphologic abnormalities. Platelet aggregation is useful in confirming the diagnosis of preleukemia. Electron microscopy of platelets is not so clearly helpful.

Blood Platelets↗
PubMed1982

Endothelial surface characteristics in pigeon coronary artery atherosclerosis. I. Cellular alterations during the initial stages of dietary cholesterol challenge.

The early events in coronary artery atherosclerosis in White Carneau pigeons were studied by combined scanning and transmission electron microscopy. Endothelial cells throughout the right coronary artery were elongate in shape, having an axial ratio (width + length) of 0.48 +/- 0.03, and were oriented with the long axis parallel to the direction of blood flow. Deviation in both orientation and morphology were found in control birds in zones of high probability for disease. Endothelial cells in the high predilection zones were less elongate in shape, having an axial ratio of 0.69 +/- 0.04, and had poorly defined margins and a paucity of microvilli. These less elongate cells were on the average 50 per cent larger (surface area of 147.9 +/- 13.3 versus 93.4 +/- 5.5 sq. microns for the typical cell) than the normal endothelial cell. Upon cholesterol challenge, the percentage of elongate cells decreased in the high propensity zones within the first few weeks, and following 8 weeks of cholesterol challenge the less elongate cells were associated with nascent atherosclerotic lesions. In addition to these large irregularly shaped endothelial cells, the early lesions characteristically were encircled by small cells having prominant nuclei and a large number of microvilli clustered over the nuclear area. Continuation of the cholesterol diet beyond 36 weeks resulted in progressive lesion enlargement and the selective binding of blood cells to the lesion periphery. This margination of blood cells was maximal at 36 weeks when the process was evident in 60 per cent of the cholesterol-fed animals. With further prolongation of cholesterol challenge, adherent cells were found in only 25 per cent of the birds. The surface events observed by scanning electron microscopy were correlated with ultrastructural changes in the endothelial glycocalyx. Cholesterol challenge resulted in a significant reduction in both the amount of ruthenium red stain and the number of cationized ferritin particles which were bound to luminal surfaces. In control diet animals, the glycocalyx thickness was in the range of 700 to 1000 A, with the thinnest areas being those in zones of high disease predilection and numerous nonelongate endothelial cells. When analyzed on an individual cell basis, the villus portions of the endothelial surface (glycocalyx thickness, 436 A) averaged 64 per cent thinner than the nonvillus portions of the cell. Upon cholesterol challenge, the glycocalyx was reduced in all arterial zones to 450 A, which approximated the thickness found for microvilli. Our results clearly document changes in endothelial morphology during the early stages of coronary atherosclerosis. These morphologic features are discussed with respect to the role the altered cells may play in disease progression.

Animals↗
PubMed1982

The distribution of parenterally administered antibody to CEA in colorectal xenografts. Preliminary findings.

Autoradiography was used to identify the distribution of parenterally administered anti-CEA in human colorectal tumours xenografted to nude mice. Four xenograft lines were studied: three mucinous adenocarcinomas of various degrees of differentiation and one undifferentiated tumour. 125Iodine-labelled, affinity purified goat anti-CEA was given intravenously to xenograft-bearing mice, who were killed at intervals thereafter up to 7 days. Autoradiograms were prepared by both conventional methods and the Appleton 'diffusible compound' technique which is designed to avoid possible translocation and extraction of labelled antibody tracer during tissue processing. Control experiments were done using a non-specific goat gamma-globulin. By combining autoradiography with a PAP-immunoperoxidase method of demonstrating CEA, anti-CEA was found to be preferentially retained at extracellular sites of CEA-positive material within viable tumour areas. Cell surface retention was not observed. At all times following administration more antibody was detected within necrotic areas, extracellular spaces and stromal connective tissue than within the tumour cell compartment. These preliminary results are discussed in relation to the possibility of using anti-CEA as a carrier to deliver chemotherapeutic agents into colorectal tumours. The suitability of diffusible compound and conventional autoradiography for studies of this nature are also examined.

Animals↗