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Biomedical subjects

I Joris

Publications and source records attributed to I Joris.

At least 19 recordsLinked to original sources
PubMed1995

Cytogenetic biomonitoring of a population of children allegedly exposed to environmental pollutants. Phase 2: Results of a three-year longitudinal study.

Our previous cytogenetic biomonitoring of a group of inhabitants in a village (Mellery, Belgium) where exposure to a mixture of toxic environmental pollutants, (probably originating from a neighbouring chemical waste disposal site) was suspected, showed that difference in the SCE and HFC bioassays was more pronounced for children. The results of follow-up study in 1992 confirmed this surprising conclusion by an even higher incidence. As very few studies have been performed on the levels of children's biomarkers, this group of exposed populations needed to be explored further. Do children residing in the vicinity of hazardous waste sites indeed represent a population at higher risk? In the present study, we compare the performance of various bioassays (SCE, HFC, SSB and MN) in extended exposed and reference children's groups. Simultaneously, in the exposed group, we followed variation in the lymphocyte SCE frequencies as a function of time. Reversibility of the latter biomarker was ascertained subsequent to a preliminary technical remediation of the disposal site. We compared these data with those obtained from a synchronous cross-sectional study on a group of children living near a similar chemical disposal site. The two exposed populations did not differ from the reference population regarding to the SCE and HFC mean levels. Comparisons of the mean levels of the two other biomarkers, SSB and MN, showed no difference between the Mellery exposed children and the reference group from Wavre whereas significant differences appeared when the Hensies group is compared either to the Mellery or to the Wavre reference group.

Adolescent↗
PubMed1995

Apoptosis, oncosis, and necrosis. An overview of cell death.

The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from ónkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage.

Animals↗
PubMed1994

Reversible endothelial cell relaxation induced by oxygen and glucose deprivation. A model of ischemia in vitro.

Endothelial cells (EC) cultured on polymerized silicone deform the underlying substrate, producing microscopically visible wrinkles. This has been interpreted as cellular contraction, and we have previously concluded that EC normally maintain an active contractile tone. Since in ischemic tissues capillaries become "paralyzed" and lose their tone, we decided to examine the effects of glucose and/or oxygen deprivation on EC contractility. Contracting cultures with wrinkled silicone substrates were exposed to complete anoxia with or without exogenous glucose and followed by time-lapse photography. Under either glucose-or oxygen-free conditions, contraction was maintained for up to 4 days. If, however, both oxygen and glucose were removed, cellular contraction was reversed. After a period of 2 to 4 hours substrate wrinkles gradually disappeared, until by 3 to 7 hours, few to no wrinkles remained. Furthermore, within 10 minutes of restoration to normal oxygen (but not glucose) levels, substrate wrinkling reappeared. F-actin microfilament patterns and cell number per unit area were also altered by glucose and oxygen deprivation. Similar results were obtained using large or small vessel EC. We conclude that in the absence of glucose and oxygen EC lose their contractile tone, and that tone can be re-established upon re-exposure to oxygen. These findings should have implications for the pathogenesis of capillary paralysis in ischemia.

Animals↗
PubMed1993

Cytogenetic monitoring of a village population potentially exposed to a low level of environmental pollutants. Phase 1:SCE analysis.

By analogy to the techniques applied for monitoring biological effects of exposure to genotoxic agents in occupational populations, we have carried out cytogenetic monitoring in a group of inhabitants of a village (Mellery, Belgium) suspected to have been exposed to a variety of toxic environmental pollutants. These pollutants probably originated from a neighboring chemical wastes site. A group of 51 environmentally exposed and 52 reference persons (including children) were examined for the frequency of sister-chromatid exchanges (SCE) in their peripheral blood lymphocytes. The technique was further refined by using a high frequency cells (HFC) analysis. Analysis of the reference subgroups showed a significant difference between non-smoking adults and children. The influence of tobacco was clear, too. In the exposed group, no significant differences could be demonstrated between either the smokers or the non-smokers or the children. Furthermore, not only were the mean frequencies of SCE higher than in the respective reference subgroups but comparison between the two groups also showed a higher number of individuals presenting a HFC level above the background in the exposed group. Surprisingly, the difference was more pronounced for the children. A follow-up of the same exposed population carried out 18 months later and after remediation of the atmospheric chemical release, the previously observed tendencies in the exposure parameter remained unmodified.

Adult↗
PubMed1992

Acute endothelial cell contraction in vitro: a comparison with vascular smooth muscle cells and fibroblasts.

The contractile responses of cultured rat and calf endothelial cells (EC), vascular smooth muscle cells (VSMC), and fibroblasts (FB) to vasoactive mediators (thrombin, serotonin, bradykinin, and histamine), forskolin, and cytochalasin B were compared. Cells were grown on a pliable silicone membrane, and contraction was assessed, using time-lapse video microscopy, by recording changes in the wrinkling of the silicone as the cells exerted tension on the surface. We found that all cells contracted in the presence of serum or thrombin and that VSMC and FB also contracted with serotonin stimulation. Bradykinin and histamine were not contractants in this system. Discrepancies between these results and reports of changes in permeability of endothelial layers in vitro and in vivo may be due to (1) the vascular segment from which EC were studied or (2) the possibility that certain mediators may provoke a noncontractile response that results in gap formation. Thus changes in vascular permeability, which occur during inflammation, may have both contractile and noncontractile components. Forskolin, known to indirectly inhibit myosin light-chain kinase activity, and cytochalasin B were potent relaxants, suggesting a similar smooth muscle-like contractile mechanism for all three cell types.

Actin Cytoskeleton↗
PubMed1991

Lipid deposition and intimal stress and strain. A study in rats with aortic stenosis.

These experiments were designed to study the topography of lipid deposition in the stenotic aorta of hypercholesterolemic rats, and to correlate it with flow conditions and intimal stresses and strains studied in a scale biophysical model and in a computer model. A 69% +/- 5% stenosis was produced with a U-shaped metal clip. One month to 8 months later, the aorta was studied en face by light microscopy after fixation and lipid staining. The intima in the throat of the stenosis was almost completely free of lipid, whereas symmetric lipid deposits occurred as bands just above and especially just below the stenosis; elsewhere lipid deposits appeared to be random. The flow data obtained from the scale model showed that the intima in the throat of the stenosis was subjected to an increase of as much as 20 times in shear stress, whereas the lipid deposits just above and just below the stenosis were associated with asymmetric flow conditions: the proximal area corresponded to a region of rapidly increasing shear stress, the distal area to a region of low to normal shear stress and separated flow. A finite element computer model based on the aortic deformations indicated that the endothelium at the inlet and outlet of the stenosis is subjected to a symmetric pattern of elevated stresses and strains. These results indicate that 1) the pattern of lipid deposition can not be adequately explained by a hypothesis based solely on flow conditions, and 2) lipid deposits can develop in areas of increased fluid shear stress, decreased fluid shear stress, and increased intimal strains.

Animals↗
PubMed1990

Morphological and physiological characteristics of pancreas-specific venular permeability induced by Monastral blue B.

Leaky blood vessels in the microcirculation can be detected in vivo by injecting an animal with colloidal pigments such as Monastral blue B (MbB) or carbon black. We have previously used the MbB labeling method in the spontaneously diabetic BB/W or rat and detected increased vascular permeability restricted to the venules of the pancreas. We now report the morphological and physiological characteristics of this phenomenon in additional rat strains. Susceptibility to pancreatic labeling with MbB among strains was found to be a highly variable, heritable characteristic, but in no strain did vessels label in any organ other than the pancreas. Pancreatic labeling by MbB was dose dependent, was observed in both inbred and outbred rats, and was not related to major histocompatibility complex haplotype. Enhanced permeability was induced by MbB within minutes of its administration as a result of the formation of gaps between endothelial cells; these gaps then closed within 15 min. Pretreatment with silica or carrageenan, agents known to affect macrophage function, completely blocked pancreatic MbB venular labeling, but the effect was reversible over a period of several days. We hypothesize that presence of MbB in the pancreatic circulation induces organ-specific venular leakage either by a direct effect on pancreatic endothelial cells or via the local release of a mediator.

Animals↗
PubMed1990

Capillary leakage in inflammation. A study by vascular labeling.

The local injection of pure inflammatory mediators induces venular leakage. To test the effect of endogenous mediators from dying tissue on vascular leakage, the authors devised an experimental model simulating an infarct, whereby living vessels would be exposed to fragments of organs undergoing aseptic necrosis. Tissues from donor rats were implanted aseptically in the cremasteric sac. Control rats were implanted with materials deemed to be as close as possible to nonirritating: boiled tissues and spheres of Teflon or glass. At different points the rats were injected intravenously with carbon black and killed an hour later. Whole cremaster mounts showed that vascular labeling was strictly venular up to 8 hours, mixed with capillary labeling between 12 and 24 hours, and mainly or exclusively capillary at 48 hours. Histology showed an acute inflammatory infiltrate in the labeled areas. A similar but weaker labeling pattern accompanied by milder inflammation was seen in controls. These results indicate that the vascular leakage in aseptic inflammation is biphasic, first venular, then capillary; and that the capillary phase is induced by the inflammatory reaction itself, possibly through a form of diffuse angiogenesis.

Animals↗
PubMed1989

Quantitation of oil red O staining of the aorta in hypercholesterolemic rats.

A technique is described which provides morphologic and quantitative data on the amount of oil red O (ORO) staining in thoracic aortas of rats fed a high cholesterol diet. Samples are stained with ORO, the dye is extracted, and the concentration of ORO in the extract is measured colorimetrically. Wistar rats fed ad libitum either standard chow (control group: n = 15) or chow supplemented with 4% cholesterol, 1% cholic acid, and 0.5% thiouracil (CCT group: n = 23) were maintained on these diets for 1, 3, 6, 9, or 12 months. Plasma cholesterol levels averaged overall 87 and 737 mg/dl for the control and CCT groups, respectively. Animals were killed under anesthesia by perfusion fixation with formalin or glutaraldehyde, and samples of thoracic aorta were stained with ORO. After microscopic study en face and measurement of surface area, the ORO was extracted in chloroform-methanol (2:1). Concentrations of ORO (microM) were determined from a standard curve and expressed as microM/mm2 of aorta. Aortas of CCT animals showed progressive diet- and time-dependent increases in the amount of ORO staining compared to controls. We conclude that this method yields reliable quantitative data applicable to studying atherosclerosis in small animals.

Animals↗
PubMed1988

Venular endothelium in vitro: isolation and characterization.

The structural and functional properties of the endothelium vary in relation to anatomic site and position along the vascular tree. Cultures of endothelial cells have been obtained so far from large arteries, large veins and capillaries, but not from venules. We now report techniques for culturing not only rat arterial and venous endothelium, but also a special method for obtaining and culturing venular endothelium. The technique is based on the principle of "vascular labeling," whereby an insoluble pigment can be permanently deposited in the wall of the venules, making them easily visible by light microscopy. The venules of a rat cremaster muscle are labeled with a local injection of histamine followed by Monastral blue B intravenously (i.v.); 24 hours later selected venules are isolated by microdissection and either enzymatically dispersed or placed directly into tissue culture wells. The wells are coated with fibronectin and laminin and supplemented with DMEM, 20% fetal calf serum, and endothelial cell growth factor. Polygonal and spindly endothelial cells begin as clusters, grow in sheets, and sometimes form tubes. The cells stain variably for Factor VIII-related antigen, Ulex Europeus I lectin, and non-muscle specific actin. They synthesize angiotensin-converting enzyme, but do not metabolize acetylated LDL. Ultrastructurally, they display pinocytic vesicles, microtendons, and tight junctions, but not Weibel-Palade bodies. We believe that this method will be important for studying the pathophysiology of venules, which are the preferential target of inflammatory mediators and the typical site of inflammatory cell diapedesis.

Actins↗
PubMed1988

Intimal changes in the aorta of prehypertensive rats.

Intimal changes were quantitated in several rat models of arterial hypertension. One kidney-one clip rats drinking water (1K-1C-water), one-kidney rats treated with deoxycorticosterone acetate and drinking 1% NaCl (1K-DOCA-salt), and two-kidney rats drinking 1% NaCl (2K-salt) were studied after 1 to 8 weeks. The thoracic aorta was examined en face and by electron microscopy. Surprisingly, all 2K-salt, most 1K-DOCA-salt (17 out of 19), and two-thirds of 1K-1C-water rats (12 out of 18) had normal arterial pressure at sacrifice. In these normotensive 2K-salt, 1K-1C-water, and 1K-DOCA-salt animals, intimal mononuclear cells (which emigrated from the blood) increased between three- and ninefold. In these same normotensive 1K-1C-water and 1K-DOCA-salt rats, endothelial cell mitoses increased three- to sixfold with a corresponding increase in endothelial cell numbers. In the latter two groups, there was no evidence of endothelial cell denudation or changes in aortic circumference, and the subendothelial space widened mainly with reticular basement membrane presumably synthesized by the endothelium. In normotensive 1K-DOCA-salt rats, most of the endothelial cells were thick and there were several intercellular gaps. Endothelial proliferation, synthesis of macromolecules, and gap formation, as well as increased mononuclear cell emigration, indicate functional changes in mononuclear cells and in endothelial cells. We suggest that the experimental procedures designed to produce hypertension also generate factor(s) which activates mononuclear cells and/or endothelial cells. This cellular activation leads to intimal changes independent of hypertension.

Animals↗
PubMed1988

Endothelial adaptations in aortic stenosis. Correlation with flow parameters.

A 69 +/- 5% stenosis was produced in the rat aorta, with the purpose of correlating endothelial changes with local flow patterns and with levels of shear stress; the hydrodynamic data were obtained from a scaled-up model of the stenosed aorta. In the throat of the stenosis, where shear stress values were 15-25 times normal, the endothelium was stripped off within 1 hour. It regenerated at half the rate of controls but modulated into a cell type that could withstand the increased shear stress. Adaptations included changes in cell orientation, number, length, width, thickness, stress fibers, and anchoring structures, as well as changes in the length, argyrophilia, and permeability of the junctions. Areas of either elongated or "polygonal" cells consistently developed at the same sites in relation to the stenosis, but the hydrodynamic data showed that they did not always correspond (as had been anticipated) to high and low shear, respectively. It is concluded that endothelial cell shape in the living artery must be determined by some other factor(s) in addition to shear stress.

Actins↗
PubMed1987

The mechanism of vascular leakage induced by leukotriene E4. Endothelial contraction.

This study identifies the microvascular target of leukotriene E4 (LTE4) by vascular labeling with carbon black and establishes the mechanism of its action at the cellular level by electron microscopy. LTE4 and its tripeptide precursor, leukotriene C4 (LTC4) were injected subcutaneously in guinea pigs. With LTE4, venular labeling was intense at 1000 and 100 ng and slight at 10 ng, with extinction at 1 ng. LTC4 induced a ring of labeled venules around a blank central area, suggestive of vasospasm. The nonpeptidyl leukotriene LTB4 induced no labeling. Histamine (1000 ng) induced an area of vascular labeling about equal to that by 1000 ng LTE4, but the labeling of individual venules was more intense. By electron microscopy, LTE4 was found to induce gaps in the endothelium of the venules; the endothelial cells adjacent to the gaps bulged into the lumen and showed wrinkled nuclei, consistent with cellular contraction. This ultrastructural evidence suggests that LTE4 increases vascular permeability by contraction of endothelial cells selectively, in the postcapillary venules, as was previously demonstrated for other inflammatory mediators, including histamine, serotonin, and bradykinin.

Animals↗
PubMed1987

Focal arteriolar insudation. A response of arterioles to chronic nonspecific irritation.

The subcutaneous insertion of sterile, inert plastic pellets over the cremaster muscles of rats induces characteristic focal lesions of the arterioles at a distance from the pellets. These lesions appear with a delay of about 6 hours; by light microscopy they are characterized by a focal dilatation accompanied by endothelial damage and increased permeability. They are more severe if the pellets are loaded with histamine and are inhibited if the pellets are loaded with serotonin. Electron microscopy shows interendothelial gaps; the media is massively infiltrated with blood components and fibrin. The medial smooth muscle cells are stretched and at times necrotic; inflammatory cells are scarce. On the basis of these features the lesion was named focal arteriolar insudation (FAI). Although its pathogenesis is not yet clear, the data at hand suggest that it is caused by endogenous mediators affecting the smooth muscle cells and/or the endothelium. FAI appears to be a specific arteriolar response to chronic nonspecific irritation.

Animals↗
PubMed1987

A pancreatic venular defect in the BB/Wor rat.

BB rats develop spontaneous autoimmune diabetes mellitus characterized morphologically by insulitis, an inflammatory lymphocytic infiltration of the islets of Langerhans. To investigate the role of the vascular endothelium of the pancreas in this destructive process, the authors injected diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats as well as other nondiabetic strains of rats with Monastral blue B, a colloidal pigment that identifies leaky microvasculature. They found evidence of a venular defect limited to the pancreas that is specific to the BB rat. Light- and electron-microscopic evidence suggests that this defect is due to a population of trapped (marginating) intravascular monocytes, which may be activated by the colloidal pigment and release vasoactive mediators.

Animals↗
PubMed1986

Cellular changes during hypertension: a quantitative study of the rat aorta.

Using rats made hypertensive by aortic ligation or by the one kidney--one clip method, we searched the aorta for morphologic clues that could explain why hypertension aggravates atherosclerosis. Both atherosclerosis and hypertension are characterized by an increased migration of mononuclear cells into the aortic intima; we therefore quantitated this phenomenon and studied its time course. In the thoracic aorta of hypertensive rats intimal cells (emigrated mononuclear cells) increased up to 15 times 2 weeks after surgery and remained stationary thereafter. In both control and experimental rats, leukocyte emigration was heavier in the thoracic aorta than in the abdominal region. A two- to threefold increase in medial smooth muscle herniae into the intima (myointimal herniae) was also found at 8 weeks, indicating a smooth muscle cell dysfunction. Electron microscopic study of the intima showed that its thickening was due to blood-borne material and also to extracellular matrix synthesized by the endothelium. Heightened secretion reflects cell activation, a condition that (in the endothelium) leads also to leukocyte adhesion. These data suggest that, in renovascular hypertension, the aortic endothelium is in an activated state, possibly through a hormonal stimulus.

Animals↗