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Biomedical subjects

E Kagan

Publications and source records attributed to E Kagan.

At least 37 records · Page 2Linked to original sources
PubMed1991

Coronary artery ultrastructural changes in cardiac transplant atherosclerosis in the rabbit.

Accelerated coronary atherosclerosis is the limiting factor for long-term survival of cardiac transplant recipients, but its pathogenesis is poorly understood. Morphologic and ultrastructural changes in suitable models may help explain the underlying mechanisms. In this study, early (3, 7, 14, and 21 days) and late (42 days) ultrastructural changes of the coronary artery were characterized in rabbit cardiac allografts. Thirty-four New Zealand white male rabbits (3.0-4.0 kg) served as donors and recipients. All recipients received cyclosporine (10 mg/kg/day i.m.) as immunosuppressant. In order to increase the normally very low cholesterol levels in rabbits, both the donor and recipient animals were fed a 0.5% cholesterol diet. Recipient animals were sacrificed between 3 days and 6 weeks after transplantation. The specimens from both donor and recipient were examined by transmission electron microscopy, immunohistochemistry, and morphometry. Our data indicate that intimal thickening was initiated with smooth muscle cell migration within 1 week after transplantation, and occurrence of macrophage-derived foam cells and vacuolized smooth muscle cells 3 weeks after transplantation. These changes occurred in the presence of an ultrastructurally intact endothelium. Platelets were only seldom seen adhering to the endothelium. In contrast, lymphocytes and monocytes were frequently found adhering to the endothelium at 2 and 3 weeks posttransplantation. From 3 weeks posttransplantation, lymphocytes were seen only occasionally in the intima but not in the media. This study suggests that early events elicit a change in the smooth muscle cells in the media to the secretory phenotype that migrates to the intima and proliferate. Lymphocyte and monocyte adhesion to the endothelium may enhance smooth muscle migration and proliferation. The large macrophage involvement may relate to the high serum cholesterol levels induced by the cholesterol diet. All these changes occurred in the presence of a structurally normal endothelium and without apparent platelet involvement.

Animals↗
PubMed1991

Mesothelial cells produce a chemoattractant for lung fibroblasts: role of fibronectin.

Pleural fibrosis may complicate several types of non-exudative pleural injury. Although the pathogenesis of such lesions is poorly understood, it is conceivable that mesothelial cells may recruit fibroblasts to sites of pleural damage. In order to test this possibility, conditioned medium from cultured rat mesothelial cells was tested for chemoattractant activity towards RL-87 rat lung fibroblasts. For this purpose, rat pleural or pericardial mesothelial cells were maintained in vitro for 6 to 96 h. Conditioned medium from each source was obtained at defined culture times and tested for chemotactic activity in a 48-well microchemotaxis assembly. A progressive, time-dependent increase in fibroblast chemoattractant activity was detected in both pleural and pericardial mesothelial cell conditioned medium samples. This effect was maximal in 96-h cultures. Checkerboard analysis revealed that the conditioned medium was truly chemotactic for lung fibroblasts. Characterization of the chemoattractant demonstrated that it was a nondialyzable (greater than 16 kD), thermolabile (100 degrees C for 15 min), acid-stable (pH 2.5), trypsin-sensitive, and pepsin-sensitive protein. The chemotaxin was shown to be fibronectin, since activity was abolished, in a dose-dependent manner, by treatment with anti-rat fibronectin antiserum as well as by passage through a gelatin agarose affinity column. This product consisted of two bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis of apparent molecular masses 250 and 220 kD. The secretion of a mesothelial cell-derived fibroblast chemoattractant may play a role in the response of the pleura to injury and in the pathogenesis of pleural fibrosis.

Animals↗
PubMed1989

Fatal adenovirus pneumonia in a newborn identified by electron microscopy and in situ hybridization.

A male infant born at 25 weeks' gestation died at 2 weeks of age from progressive respiratory insufficiency, metabolic acidosis, and renal failure. Autopsy revealed extensive hemorrhage and necrosis in the lungs, as well as hyaline membrane disease. Alveolar and bronchiolar lining cells contained frequent intranuclear inclusions visible by light microscopy that corresponded to arrays of icosahedral particles suggestive of adenovirus by electron microscopy. Confirmation of overwhelming adenovirus infection was made with in situ DNA hybridization. This case demonstrates the advantage of DNA probe analysis for retrospective diagnosis when no adequate specimen is available for culture or antigen detection. This case is also unusual in that a premature newborn had severe adenovirus infection.

Adenoviridae Infections↗
PubMed1988

Current issues regarding the pathobiology of asbestosis: a chronologic perspective.

Asbestosis is a pneumoconiosis that results from the inhalation of asbestos fibers. There is a body of evidence that implicates the alveolar macrophage in the pathogenesis of asbestosis because of its prominence in asbestos-related histologic lesions. Injury to the alveolar epithelium also may contribute to the pathogenesis of asbestosis. Evidence is presented to suggest that pulmonary fibrosis may result from the persistent release of inflammatory mediators (chemoattractants, lysosomal enzymes, toxic oxygen radicals, arachidonic acid metabolites, interleukins, and fibroblast growth factors) at sites of asbestos deposition. Histologic features of asbestosis can be detected within months after the initial contact with asbestos. In contrast, the stigmata of asbestos-related disease usually are not radiologically detectable, even by the most sensitive imaging techniques, until after a latency period of at least a decade, and often considerably longer. There is, therefore, a long diagnostic delay between the time when asbestosis is histologically detectable and when it is radiographically detectable.

Asbestos↗
PubMed1987

Visceral pleural thickening in asbestos exposure: the occurrence and implications of thickened interlobar fissures.

We evaluated fissural (ie, visceral pleural) thickening on radiographs in two asbestos-exposed study populations and a control group. Asbestos workers had an incidence of fissural thickening of 54.5% compared with 16.0% in the unexposed control group, with a strong positive statistical effect due to asbestos exposure beyond that attributable to age. Fissural thickening occurred in 85% of workers with parietal plaques and in 36% without pleural plaques. Fissural thickening occurred in 45% without radiographic evidence of pulmonary fibrosis, but it was very common (85%) in those with pulmonary fibrosis. Data analysis showed that fissural thickening responds more strongly to asbestos exposure than does plaque formation, with 21 years of asbestos exposure needed for a 50% chance of developing fissural thickening, while 31 years of exposure were needed for a 50% chance of forming pleural plaques. From a second group of 57 asbestos workers evaluated clinically, 8 were diagnosed as having asbestosis with radiographically clear lungs and fissural thickening. We conclude that visceral pleural thickening is common in asbestos exposure, that it is related to the years since first asbestos exposure, and that its presence may indicate the presence of pulmonary asbestosis, even with radiographically normal lungs.

Asbestosis↗
PubMed1984

Intrapulmonary distribution of inhaled chrysotile and crocidolite asbestos: ultrastructural features.

Although all commercial types of asbestos can cause pulmonary fibrosis, little is known about ultrastructural differences in the evolution of pulmonary lesions induced by amphiboles and serpentines. The present study was designed to compare the histological and ultrastructural effects produced by chronic inhalation of either crocidolite (amphibole) or chrysotile (serpentine) asbestos in the rat. Animals, exposed by intermittent inhalation for 3 months, were killed after 2 to 16 months. When inhaled, both types of asbestos caused thickened alveolar duct bifurcations associated with macrophage aggregates. Crocidolite inhalation also produced subpleural collections of alveolar macrophages and lymphocytes. Electron microscopy revealed some similarities, but also distinct differences, in the pulmonary distribution of inhaled chrysotile and crocidolite. Whereas both asbestos varieties were identified within the pulmonary interstitium, only crocidolite was detected inside alveolar macrophages. Chrysotile fibres were seen infrequently within the vascular compartment. Microcalcifications were noted after chrysotile inhalation, but were never observed following crocidolite exposure. Both asbestos types induced slight pulmonary fibrosis. These findings indicate that crocidolite and chrysotile produce different pathogenetic features, although both are fibrogenic.

Animals↗
PubMed1984

Enhanced interleukin activity following asbestos inhalation.

Asbestos inhalation can cause pulmonary fibrosis and is associated with a variety of immunological abnormalities. The purpose of this study was to evaluate the effects of asbestos inhalation on interleukin-1 (IL-1) and interleukin-2 (IL-2) production in a rodent model. Two groups of rats were exposed, by intermittent inhalation, to either amphibole (crocidolite) or serpentine (chrysotile) asbestos. A third (control) group of rats was sham exposed to clean air. Animals from the three exposure groups were thereafter immunized (or not immunized) with fetal calf serum antigens. In order to assay interleukin activity, supernatants were generated from cultures containing alveolar macrophages and autologous splenic lymphocytes, and from cultures containing alveolar macrophages alone. Using assay systems designed to detect IL-1 and IL-2 functional activity, the supernatants were evaluated for their capacity to stimulate lymphoproliferation and fibroblast DNA synthesis. Macrophage-lymphocyte co-culture supernatants, when obtained from immunized, asbestos exposed rats, contained greater IL-1 and IL-2 activity than identical supernatants from immunized, sham exposed animals. These between group differences were not, however, observed in supernatants from unimmunized rats, or when supernatants were generated in the absence of immune lymphocytes. These observations suggest that asbestos exposure is associated with enhanced activation of lymphocytes by antigens. The possible relevance of these findings to asbestos related fibrogenesis and immunological stimulation is discussed.

Animals↗
PubMed1983

Prophylactic antibiotics in elective colorectal surgery.

In an effort to determine whether or not the addition of parenteral antibiotics to orally administered erythromycin and neomycin would diminish postoperative septic complications in elective colorectal operations, a randomized, double-blind, controlled trial was conducted comparing three groups. All patients received vigorous preoperative mechanical bowel preparation, 3 g erythromycin and 3 g neomycin orally, the day prior to operation. Patients in Group O received three doses of saline intravenously as placebo, patients in Group C received cefazolin, 1 g, immediately preoperatively and 1 g every 6 hours postoperatively, intravenously, for two doses, and patients in Group T received a single immediate preoperative dose of 6 g of ticarcillin intravenously and two saline placebo doses intravenously, postoperatively. The patients' progress was followed in the hospital and for one month postoperatively. Septic complications occurred in 35 per cent of patients in Group O, 7 per cent of patients in Group C, and 5 per cent of patients in Group T. Wound infections comprised most of these complications, occurring in 29 per cent of Group O, 4.7 per cent of Group C, and 2.3 per cent of Group T patients. Thus, the addition of either parenteral cefazolin or ticarcillin in this study significantly reduced wound infections in elective colorectal surgery.

Aged↗
PubMed1983

The effects of chrysotile and crocidolite asbestos on the lower respiratory tract: analysis of bronchoalveolar lavage constituents.

This study was designed to evaluate the effects of amphibole and serpentine asbestos inhalation on the constituents of the lower respiratory tract. Bronchoalveolar lavage (BAL) analyses were performed on three groups of rats: one group was exposed to chrysotile (serpentine) asbestos, another group was exposed to crocidolite amphibole asbestos, while a third group was sham-exposed. Intermittent inhalational exposures lasted three months. The total BAL cell yields and the macrophage content of BAL cells were significantly lower after asbestos exposure, especially in the chrysotile-exposed group. These effects persisted for as long as 1 year after the cessation of exposure. Multinucleated macrophages were seen in BAL cells from both asbestos-exposed groups. Striking ultrastructural alterations of macrophage morphology were noted in BAL cells from both groups of asbestos-exposed rats. Chrysotile fibers were not seen in any BAL cells from chrysotile-exposed animals. However, 15 months after terminating the exposure regimen, a sizeable proportion of BAL macrophages from crocidolite-exposed rats contained phagocytosed asbestos fibers. Significantly higher beta-glucuronidase and lactate dehydrogenase activity was found in BAL fluids from both asbestos-exposed groups and was detected 17-18 months after exposure had ceased. These observations have served as useful correlates of asbestos-mediated injury to the lower respiratory tract. They have also provided evidence of continual pathological sequelae occurring long after withdrawal from asbestos exposure.

Animals↗
PubMed1983

Cytotoxicity of a short-fiber chrysotile asbestos for human alveolar macrophages: preliminary observations.

Studies were performed to compare the cytotoxicity for human alveolar macrophages of a naturally occurring short-fiber chrysotile asbestos (RG 144) to that of a standard reference mixed-fiber (long and short) chrysotile asbestos (UICC chrysotile A. Rhodesian). Parallel studies were also performed with quartz (Min-U-Sil 15), a known macrophage toxin. On a mass basis, and after 24 hr incubation, RG 144 was more cytotoxic than the UICC standard reference fiber and less toxic than quartz (silica). The cytotoxic potential of RG 144 chrysotile was further enhanced after size reduction by milling. These findings may have important biologic implications with respect to the use of short-fiber asbestos in industry.

Adult↗
PubMed1983

Lymphoid and plasma cell malignancies: asbestos-related disorders of long latency.

We have identified 13 asbestos workers with lymphoplasmacytic neoplasms: six with chronic lymphocytic leukemia, four with IgG myeloma, two with IgA myeloma, and one with histiocytic lymphoma. The subjects' occupations were varied, but all had experienced protracted asbestos exposure (ranging from 3-37 years). Tumor latency periods were similar to other known asbestos-related malignancies and ranged from 16-41 years. Stigmata of asbestos-related pulmonary disease were evident in 12 subjects. Malignant pleural mesotheliomas co-existed with IgG myelomas in two individuals, an association which seems unlikely to be fortuitous. It has been speculated previously that asbestos may be a lymphoid system carcinogen. Our findings strongly support this view and indicate that patients presenting de novo with lymphoproliferative neoplasms should be investigated for previous occupational or environmental exposure to asbestos.

Aged↗
PubMed1983

Enhanced release of a chemoattractant for alveolar macrophages after asbestos inhalation.

Alveolar macrophage supernatants from 2 groups of asbestos-exposed rats and a group of sham-exposed rats were tested for chemoattractant activity towards rat alveolar macrophages. Enhanced chemotaxin release was observed in culture supernatants from both crocidolite and chrysotile asbestos-exposed rats when compared with supernatants from sham-exposed rats. These between-group differences persisted for as long as 15 months after exposure had ceased. Chemotactic factor release was maximal after 24 h of culture in all animal groups. Partial characterization of the chemoattractant from each of the 3 rat groups revealed that it was thermolabile, nondialyzable, and trypsin-sensitive. Separation on SDS-polyacrylamide gel electrophoresis revealed 3 major peaks of activity. The production of the chemotaxin in supernatants from asbestos-exposed rats was partially inhibited by both actinomycin D and puromycin. These agents had no appreciable effect on the production of chemoattractant in cultures from sham-exposed animals. The enhanced release of an alveolar macrophage chemoattractant after asbestos inhalation may explain why macrophages accumulate at sites of asbestos deposition in the lungs.

Aerosols↗