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Biomedical subjects

J C Lewis

Publications and source records attributed to J C Lewis.

At least 91 records · Page 5Linked to original sources
PubMed1987

Monoclonal antibodies specific for human platelet membrane glycoproteins bind to monocytes by focal absorption of platelet membrane fragments: an ultrastructural immunogold study.

The membrane labeling of monocytes by monoclonal antibodies directed against platelet glycoproteins Ib (AN51), IIb (Tab), IIIa (C17), IIb-IIIa complex (J15) and to antigens common to platelets and monocytes (anti-monocyte platelet antigen and FA6 152) has been investigated by an ultrastructural immunogold method. Only with FA6 152, which identifies a structure shared by erythroblasts, platelets, and monocytes, was labeling obtained on membranes of both platelets and monocytes from normal blood. With all the other monoclonal antibodies, platelets were highly labeled but monocytes lacked quantitatively significant label; however, focal microparticles which exhibited gold particles were adherent to the membrane of monocytes. This localized labeling, interpreted as resulting from the fragmentation of platelet membranes during monocyte isolation with adhesion of the fragments to monocyte surfaces, was verified by two approaches. First, double staining with C17 visualized by an anti-IgG coupled to 40 nm gold particles and MO2 recognizing exclusively a surface monocyte antigen, as visualized by an anti-IgG coupled to 15 nm gold particles, was performed. The absence of colocalization of large and small gold particles either on monocytes or on microparticles confirmed the exclusive cell origin. Second, when analyzed by quantitative x-ray analysis, monocyte associated gold following C17 treatment was restricted to platelet pseudopods and fragments on whole mount spread cells. Finally, when monocytes were spread immediately after blood collection in the absence of sedimentation and centrifugation to prevent platelet activation, platelet rosetting was avoided and the number of microparticles markedly decreased. Thus, the attachment to monocyte membranes of microparticles originating from platelets may be confused with true labeling of monocytes by antibodies to platelet glycoproteins if analysis is limited to immunofluorescence.

Adsorption↗
PubMed1987

Monocyte chemoattractants in pigeon aortic atherosclerosis.

Atherosclerosis occurs in the aorta of White Carneau pigeons proximal to the celiac bifurcation, where monocyte adhesion and migration into lesions have been demonstrated. This study documents chemoattractants that might be responsible for monocyte adherence and migration. Ten-week-old pigeons were fed either a cholesterol-free (normal) diet or a 0.4% cholesterol diet for 12 or 24 weeks. Birds with a normal diet did not have lesions in the lesion-prone area of the aorta, whereas birds fed a cholesterol-containing diet had simple intimal foam-cell lesions (12 weeks) or foam-cell lesions complicated with extracellular lipid and fibrillar matrix material (24 weeks). Plasma cholesterol levels in birds on the cholesterol-containing diet were 780-1080 mg/dl versus 140-240 mg/dl in the normal diet control group(s) at necropsy. To assay for chemoattractants, tissue was collected from lesion-prone and nonsusceptible (nonlesion) areas of the aortas. Samples from the two types of regions were separately pooled, then homogenized and tested for chemoattractant activity for pigeon peripheral blood monocytes. Monocyte chemoattractants were demonstrated in lesion area homogenates from pigeons fed cholesterol for 12 or 24 weeks and also in analogous homogenates from pigeons fed a normal diet. Monocyte migration to lesion-prone homogenates was significantly greater than that to nonlesion area homogenates. The chemoattractants in homogenates were monocyte-specific. The chemoattractant activity in the birds fed cholesterol for 12 weeks was confined to the aqueous phase of lipid extracts. This activity was abolished by pronase but unaffected by heat (100 C, 30 minutes), which indicated that the chemoattractant(s) in these homogenates was heat-stable protein(s). Activity in lipid extracts of lesion area homogenates from birds fed a cholesterol-containing diet for 24 weeks was found in both the aqueous and organic phases, suggesting that these samples contained lipid as well as proteinaceous chemoattractants.

Animals↗
PubMed1986

Diet and vasectomy: effects on atherogenesis in cynomolgus macaques.

We report here the effect of a moderately atherogenic diet on the progression of atherosclerosis among cynomolgus macaques that were either vasectomized or sham vasectomized. Both groups were compared to sham vasectomized monkeys fed a control Monkey Chow diet. As expected, slight hyperlipoproteinemia induced by the moderately atherogenic diet increased endothelial cell replication rates and resulted in the development of intimal lesions among sham vasectomized monkeys. Unexpectedly, vasectomy resulted in reduced leukocyte adherence to arterial surfaces, reduced endothelial cell replication rates in response to the moderately atherogenic diet, and at most arterial sites, smaller intimal lesions were produced. These data suggest that with slight hyperlipoproteinemia vasectomy may result in a small protective effect against atherosclerosis, while other studies have shown that marked hyperlipoproteinemia in cynomolgus macaques along with vasectomy results in exacerbation of atherogenesis.

Animals↗
PubMed1986

Production of hypoprothrombinaemia by cefazolin and 2-methyl-1,3,4-thiadiazole-5-thiol in the rat.

Recent findings have suggested that the 1-methyltetrazole-5-thiol (MTT) group contained in several beta-lactam antibiotics may be responsible for the hypoprothrombinaemia associated with these drugs. In order to determine if the hypoprothrombinaemia associated with cefazolin is due to the presence of the structurally related 2-methyl-1,3,4,-thiadiazole-5-thiol (MTD) group which it possesses, the ability of MTD and cefazolin to produce hypoprothrombinaemia in rats was examined. Female rats maintained on a vitamin K-deficient diet for ten days developed hypoprothrombinaemia after the intravenous administration of cefazolin for two subsequent days. Hypoprothrombinaemia was also produced by the oral administration to vitamin K-deficient rats of either cefazolin or MTD, while the oral administration of cefotaxime, which does not contain a thiol group, had no effect. In a rat liver microsomal system, MTD was found to be a much more potent inhibitor than cefazolin of the vitamin K-dependent step in clotting factor synthesis, the gamma-carboxylation of glutamic acid. These results suggest that the hypoprothrombinaemia associated with cefazolin may be due to the MTD group.

Administration, Oral↗
PubMed1986

Cytoskeletal disruption during human cytomegalovirus infection of human lung fibroblasts.

Human cytomegalovirus (HCMV) infection causes a rapid, progressive disruption of the host cell cytoskeleton that correlates with actin depolymerization. Whole-mount (3D) electron microscopy was used to analyze the cytoskeleton of uninfected and HCMV-infected human lung fibroblast cells. Within 2 min of HCMV infection, localized areas of cytoskeletal disruption were observed. Disruption extended throughout the cytoplasm during the ensuing 45 to 90 min of infection and resulted in generalized cytoskeletal disorganization. Actin depolymerization occurred, as indicated by an increase in DNase I inhibition and alteration in the fluorescence pattern with rhodamine-conjugated phalloidin. Thus, actin appears to be the primary cytoskeletal target involved during HCMV infection. Fractionation of the virus seed inoculum showed that development of DNase I inhibitory activity in infected cells was associated only with the virus-containing fractions. Cytochalasin B treatment at early times of HCMV infection stimulated progeny virus production. This study demonstrates that rapid cytoskeletal disruption occurs during early periods of HCMV infection and indicates that actin depolymerization facilitates viral infectivity.

Actins↗
PubMed1986

Cytoskeletal changes during adhesion and release: a comparison of human and nonhuman primate platelets.

The organization of cytoskeletal proteins in whole-mount adherent platelets from African green monkeys and normal human volunteers has been studied by SEM, high vacuum electron microscopy (HVEM) and conventional (120 kV) electron microscopy. We describe three distinct organizational zones, the Central Matrix, the Trabecular Zone and the Peripheral Web in spread platelets from both sources. The Central Matrix is an ill-defined superstructure of 80-100 A filaments of short length which enshrouded the granules, dense bodies, mitochondria and elements of the open-channel and dense-tubular systems. The latter, identified through the use of peroxidase cytochemistry with the whole mounts, is an anastomosing network of elongate saccules having diameters of 600-1200 A. The Trabecular Zone, which encircles the Central Matrix, contains 165, 80-100 and 30-50 A filaments in an open lattice of irregular lattice spacing. The outermost region of the cells, the Peripheral Web, is comprised of 70 A filaments organized in a honeycomb lattice with center to center spacing in the range 150-300 A. This pattern for the spread cells is not consistently observed in cells during the early stages of adhesion; therefore, correlations of SEM and TEM observations are made for the various stages of adhesion/activation.

Animals↗
PubMed1986

Endothelial cell proliferation and monocyte adhesion to atherosclerotic lesions of white carneau pigeons.

Two of the early changes that occur at sites of developing atherosclerotic lesions in pigeon aortas are monocyte adhesion and endothelial proliferation. We characterized these events in the abdominal aortas of lesion-free young pigeons and in mature birds that developed either naturally occurring or cholesterol-induced atherosclerosis. Compared with mature animals, very young (7-day-old) pigeons had elevated endothelial cell labeling with 3H-thymidine in normal regions of aorta as quantitated by scanning electron microscopy. All regions of atherosclerosis exhibited at least a fivefold increase in both monocyte adhesion and endothelial proliferation. Adhesion and proliferation were highest at the developing edge of lesions. When naturally occurring lesions of 5-year-old birds were compared with lesions of younger birds fed a 0.5% cholesterol-supplemented diet for either 15 or 52 weeks, monocyte adhesion and endothelial cell proliferation were found to be similar. The same parameters were studied after regression of atherosclerosis in pigeons fed 0.5% cholesterol-supplemented diet for 1 year, followed by cholesterol-free diet for 2, 6, or 11 months. The regression regimen resulted in significant reduction in both monocyte adhesion and endothelial proliferation at lesion sites. It is concluded that progressing atherosclerotic lesions, whether occurring naturally or exacerbated by cholesterol feeding, have similar and significant increases in monocyte adhesion and endothelial cell proliferation. Regression of atherosclerotic lesions is accompanied by a decrease in these two cellular events.

Animals↗
PubMed1985

The effects of severe zinc deficiency on intestinal permeability: an ultrastructural study.

Evidence suggests that intestinal transport of water and electrolytes may be altered in zinc deficiency. We examined the structural features of intestinal epithelial cells of zinc-deficient rats using electron microscopy and assessed the integrity of the junctional complexes using a heavy metal tracer, lanthanum hydroxide. The absorptive cells, as well as Paneth cells and chromaffin cells, were not found to have ultrastructural changes of a consistent nature in zinc deficiency. Moreover, the integrity of the junctional complexes was found to be preserved. These findings suggest that the abnormalities in intestinal transport previously reported are not secondary to increased tight junction permeability in zinc deficiency.

Animals↗
PubMed1985

Organ procurement.

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Allied Health Personnel↗
PubMed1985

Platelets interact with fibrin only after activation.

Interactions between platelets and fibrin have been visualized by phase contrast, epifluorescence, and scanning electron microscope examination of clots formed with dansylcadaverine-labeled fibrin and gel-filtered platelets. After thrombin activation, the platelets appeared as fluorescent aggregates with bridging strands of fibrin; formaldehyde-fixed platelets were not fluorescent under the same experimental conditions. Scanning electron micrographs demonstrated that thrombin-activated cells had numerous pseudopods to which the fibrin strands adhered; fixed platelets exhibited a smooth discoid appearance and did not interact with the clot. Platelets trapped in clots formed with Batroxobin (Pentapharm) (platelets are not activated by Batroxobin as confirmed by light-scattering aggregometry measurements) remained as nonfluorescent, discoid cells, whereas platelets first activated by adenosine diphosphate formed brightly fluorescent aggregates. Light-scattering data of thrombin activation (0.2 U/mL) indicated that preincubation of platelets with 0.1 mmol/L prostaglandin E1 (PGE1) prior to addition of thrombin decreased the extent and rate of platelet shape change and resulted in 100-fold slower aggregation. Clots formed in the presence of PGE1 revealed decreased fluorescence intensity and fewer platelet-fibrin contacts. Gly-Pro-Arg-Pro, which blocks fibrinogen binding and fibrin assembly, was also effective in blocking platelet-fibrin interactions. These results indicate that platelet activation is a prerequisite for attachment of platelets to fibrin.

Adenosine Diphosphate↗
PubMed1985

Early atherogenesis in White Carneau pigeons. II. Ultrastructural and cytochemical observations.

The addition of cholesterol (0.5%) to the diet of White Carneau pigeons induces site specific, temporally predictable, atherosclerotic lesions. The earliest lesions, which occurred after 3 weeks, were small (less than 2500 sq mu in surface area) and were composed primarily of macrophage foam cells (94% of lesion volume). With a prolonged time on the diet the lesions expanded due to increases in the number and size of foam cells, increases in the amount of extracellular space, and influx of smooth muscle cells. Macrophage foam cells in advanced lesions composed 61% of the lesion volume, smooth muscle cells 25%, and extracellular space 14%. Concurrent with the alteration in the constituency of the lesion, redistribution of lipid within foam cells was noted. Lipid in small lesions was primarily cytoplasmic (88%), with the remaining 12% in acid-phosphatase-positive secondary lysosomes. In more advanced lesions, 34% of the lipid was cytoplastic and 66% was lysosomal. The changes in large lesions appeared to be a function of lesion age, because at the growing edge of large lesions both composition and lipid distribution resembled those of small early lesions.

Acid Phosphatase↗
PubMed1984

A preliminary study on the use of carbenicillin in snakes.

The results of a 10 year survey on the in vitro antibiotic resistance patterns of Pseudomonas spp. isolated from clinically ill reptiles, showed a high degree of sensitivity to carbenicillin. On the basis of sensitivity testing, carbenicillin was used to treat nine snakes of four different species, with confirmed Pseudomonas infections. Plasma carbenicillin levels were assayed, by a microbiological agar diffusion technique, at intervals of time after a single intramuscular injection at a dose rate of 400 mg/kg. Peak plasma levels of 177 and 270 micrograms/ml were reached 1 h after the initial injection and therapeutic levels persisted for at least 12 h. This initial study indicated that a suggested dose regime in snakes, derived by extrapolation from mammalian dosages, of 100-125 mg/kg daily was insufficient to produce plasma levels of sufficient magnitude and duration to effectively treat Pseudomonas infections in snakes.

Animals↗
PubMed1984

Production of hypoprothrombinemia by moxalactam and 1-methyl-5-thiotetrazole in rats.

To determine whether the hypoprothrombinemia associated with antibiotics containing a 1-methyl-5-thiotetrazole (MTT) group is a result of the presence of the MTT group, rats were maintained on a vitamin K-deficient diet for 10 days and then received either intravenous moxalactam or cefotaxime or oral MTT for two additional days. MTT and moxalactam, which contains the MTT group, prolonged prothrombin time. Cefotaxime, which lacks the MTT group, had no effect.

Administration, Oral↗
PubMed1984

Choriocarcinoma xenografts in the nude rat.

The transplantation of a human choriocarcinoma xenograft (CC3) in the nude rat is reported. The tumours grew progressively for up to 5 weeks but subsequently regressed. Our preliminary results suggest that regression of the tumours appears to be dependent on host age.

Age Factors↗
PubMed1984

Sterile shunt malfunction. A scanning electron microscopic perspective.

Recently, a delayed hypersensitivity reaction to silicone plastics has been demonstrated in some patients with breast and joint implants and subcutaneously injected silicone. In this study, the authors examined the internal surface of shunting systems to evaluate the cellular response to implanted silicone plastic. The distal peritoneal tubing from 20 patients with ventriculoperitoneal shunts was examined with a scanning electron microscope. Twelve tubes were removed because of documented distal shunt malfunction and eight for an elective lengthening procedure. Cultures of all tubing were negative. The catheters removed for malfunction contained a variety of cells: sometimes in clumps, sometimes associated with platelets and densely adherent to the silicone tubing wall. In several shunts, giant cells were seen with multiple foot processes adherent to the internal silicone surface. The internal surface of the tubing of two malfunctioning shunts was embedded in electron microscopy plastic and studied with transmission electron microscopy. The cells proved to be neutrophils with no evidence of silicone granules inside the cell bodies. The shunts removed for elective revision showed only a few cells, and those were never associated with platelets. There was proteinaceous material scattered on the internal surface of the tubing, but the cellular response was markedly different from that in malfunctioning shunts. The authors postulate that the findings in malfunctioning shunt tubing represent a delayed hypersensitivity to silicone similar to that seen with other types of silicone implants.

Adolescent↗
PubMed1984

The comparative distribution of monoclonal antibodies to CEA in colorectal xenografts.

The in vivo distribution of three different, parenterally administered, monoclonal antibodies to CEA was studied in MAWI human colorectal tumour xenografts. By the use of conventional autoradiography, more antibody was generally detected within necrotic areas, extracellular spaces and stromal connective tissue than within tumour cells. However, some peripheral tumour cell groups markedly accumulated anti-CEA. The number of such groups involved and the degree to which antibody was internalised varied widely with the antibody studied. Immunoperoxidase staining of the same preparations showed that antibody accumulation did not necessarily correspond to CEA-positivity. These findings are compared with results of previous work with polyclonal anti-CEA, and discussed in relation to the use of anti-CEA's as carriers to deliver cytotoxic agents into colorectal tumours.

Adenocarcinoma↗