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Biomedical subjects

E Betz

Publications and source records attributed to E Betz.

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

[Effect of dihematoporphyrin derivatives on cultivated human smooth muscle cells from normal and atherosclerotic vascular segments-- Overview of results and implications for photodynamic therapy].

It is little known that photosensitizing porphyrins can be used not only for the localization and photodynamic therapy of tumors, but that they also accumulate in atherosclerotic plaques. This observation might be of interest for the detection and therapy of vascular stenoses. The present study examines whether dihematoporphyrin-ester and -ether, at clinically relevant concentrations, selectively influence cultured smooth muscle cells from human atherosclerotic plaques (primary stenoses and secondary stenoses) in comparison to smooth muscle cells obtained from non-atherosclerotic arteries. The results demonstrate that the drug accumulated to a greater extent in plaque-derived cells than in smooth muscle cells from normal arteries. Even without photoactivation, dihematoporphyrin-ester and -ether significantly decreased the proliferative activity of cells from atherosclerotic plaques. Light exposure of porphyrin-labeled cells resulted in a more pronounced sensitivity of plaque cells when compared with smooth muscle cells from non-atherosclerotic arterial wall. A comparison of the proliferative activity of cells before and after photodynamic reaction demonstrated that this activity was unaltered in surviving smooth muscle cells from non-atherosclerotic arteries, whereas surviving plaque-derived cells exhibited a significantly decreased or even non-proliferative activity. From the in vitro studies, a porphyrin concentration of 1-5 micrograms/ml (= 1-5 mg/kg body weight in vivo after systemic application) seems to be the most suitable dosage. In addition, morphological alterations of the cells caused by photodynamic reaction were documented.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Restenosed growth of plaque cells from restenosed peripheral and coronary plaque material of the human in vitro: a correlation to animal experiment results following angioplasty].

In this study cells were isolated from primary-stenosing and re-stenosing tissue of human peripheral (extraction by Prof. Höfling and Dr. Bauriedel, Munich) and coronary arteries. The vast majority of plaque cells was identified as smooth muscle cells (SMC) by positive reaction with monoclonal antibodies against smooth muscle alpha-Actin. All SMC consisted of two different subpopulations, which were discriminated by different cell diameters: Relatively small cells (diameter: 18.0 +/- 4 microns, mean +/- SD) and large cells (diameter: 26.0 +/- 3 microms, mean +/- SD). Population doublings per day (PD/day) for SMC from re-stenosing lesions were significantly increased (0.60 +/- 0.13 PD/day, mean +/- SD) in comparison to SMC from primary-stenosing lesions (0.15 +/- 0.04 PD/day, mean +/- SD), p much less than 0.001). Thus, the increased growth of SMC from restenosing lesions in vitro might be the equivalent to the rapid progression of restenosing events after angioplasty in vivo. These results are in accordance with data from experimental studies after angioplasty.

Aged↗
PubMed1991

The CARDIA dietary history: development, implementation, and evaluation.

To meet the objectives for dietary assessment in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective study, we developed a dietary history to provide accurate and reliable quantitative data on habitual individual nutrient intakes at baseline. The CARDIA dietary history was an interviewer-administered method that included a short questionnaire regarding general dietary practices followed by a comprehensive food frequency questionnaire about typical intake of foods using the previous month as a reference for recall. For each broad category of foods, participants were questioned in detail about specific foods only if they indicated that they consumed foods from that category. Follow-up questions for selected foods concerned serving size, frequency of consumption, and common additions to these foods. Provision was made for reporting foods not found in the food frequency list. The interview took approximately 45 minutes. Cue cards prompted responses and plastic food models assisted in estimating usual amounts consumed. A precoded format standardized coding for reported items and established the detail needed for recall during the interview. Baseline nutrient analyses from the CARDIA dietary history provided estimates that agreed reasonably well with expected caloric intake for body mass index according to the age- and sex-specific Recommended Dietary Allowances, but were higher than those reported from 24-hour recalls for comparable age, sex, and race groups in the second National Health and Nutrition Examination Survey. The CARDIA dietary history is a comprehensive assessment tool that can provide a dietitian with detailed information regarding habitual eating patterns and nutrient intakes among adults.

Adult↗
PubMed1991

[Transluminal excimer laser angioplasty of experimentally-induced atheromatous plaque: morphologic changes and importance of proliferation of smooth muscle cells].

To determine the time-course of morphological changes after excimer laser treatment of atherosclerotic carotid arteries, laser angioplasty was performed in 34 rabbits after production of an intimal plaque (13 +/- 6 cell layers, 30 +/- 9% stenosis) using electrical stimulations. The animals were sacrificed 3, 7, 14, 21, 28, and 42 days after laser treatment. A total or subtotal thrombotic occlusion was found in four cases. No perforation was observed, but in 10 animals histological examination evidenced a partial ablation of the medial layer with signs of local thrombus formation and local reduction of SMC in the media. In five animals a stenosis of more than 50% of luminal reduction was due to intimal proliferation of smooth muscle cells (SMC), as determined by a monoclonal antibody against alpha-actin. After the initial ablation, a continuous increase of intimal cell layers was found, from 7 +/- 6 cell layers (19 +/- 9% stenosis) at 7 days, to 28 +/- 5 cell layers (45 +/- 18% stenosis) at 28 days following excimer laser angioplasty (p less than 0.01). After 42 days no additional increase of intimal thickening occurred. Our data suggest that incidence and morphology is comparable to the proliferative response of SMC following conventional balloon angioplasty.

Angioplasty, Laser↗
PubMed1990

In vitro growth characteristics of human atherosclerotic plaque cells: comparison of cells from primary stenosing and restenosing lesions of peripheral and coronary arteries.

Cell size distribution and growth rates were studied in vitro in human plaque cells from advanced primary stenosing and fresh restenosing lesions of peripheral and coronary arteries. Cells were isolated either by the explant technique or by enzymatic disaggregation and were identified as smooth muscle cells by their typical growth pattern and their positive reaction with antibodies against smooth muscle alpha-actin. Endothelial cells were found in plaque specimens from coronary arteries but were only present in primary cultures. Smooth muscle cells from primary stenosing tissue (ps-SMC) exhibited a significantly lower growth rate in culture (0.15 +/- 0.04 population doublings per day; means +/- SD) compared with cells from restenosing lesions (re-SMC; 0.60 +/- 0.13 population doublings per day; means +/- SD). ps-SMC usually became senescent in their second passage, i.e., after 5-7 cumultive population doublings. re-SMC retained their high proliferative activity even after five passages (15 cumulative population doublings). Cell populations of both origins consisted of two distinct subpopulations which could be discriminated by cell size measurements: relatively small, predominant cells (cell diameter: 18.0 +/- 4 microns; means +/- SD) and large fibroblast-like cells (cell diameter: 26.0 +/- 3 microns; means +/- SD). The proportion of large cells was higher in cell populations derived from primary stenosing tissue. These results suggest that stenosing plaque tissue from human peripheral and coronary arteries consists of two smooth muscle cell subpopulations. The low proliferative activity of total smooth muscle cell populations of advanced primary stenosing lesions contrasts with the high mitotic activity of smooth muscle cells obtained from secondary stenosing intimal proliferates.

Aged↗
PubMed1990

Responses of cultured smooth muscle cells from human nonatherosclerotic arteries and primary stenosing lesions after photoradiation: implications for photodynamic therapy of vascular stenoses.

Cultured smooth muscle cells from human nonatherosclerotic arteries and from primary stenosing lesions were labeled with dihematoporphyrinester and ether, a photosensitizing probe used mainly for the detection and photodynamic therapy of tumors. After labeling for 24 h, cells were irradiated with ultraviolet light (wavelength 365 nm, energy densities ranging from 30 to 1,200 mJ/cm2). Twenty-four hours after photoradiation, 80% of smooth muscle cells from nonatherosclerotic arteries and only 20% of smooth muscle cells from atherosclerotic plaques were viable and still adherent. Moreover, dynamic cell and cytoskeletal alterations in response to irradiation are described. The differential sensitivity of smooth muscle cells from nonatherosclerotic arteries and from atherosclerotic plaques provides evidence that a photodynamic treatment might be a valuable therapeutic approach to vascular stenosis.

Arteriosclerosis↗
PubMed1990

Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty.

Smooth muscle cell (SMC) proliferation is known to be an important factor for the development of restenosis after percutaneous transluminal coronary angioplasty. To determine the time course of intimal and medial SMC proliferation and morphological changes after experimental angioplasty, an intimal atheroma was produced with repeated weak electrical stimulations in the right carotid artery of 45 male New Zealand White rabbits. Angioplasty was subsequently performed in 35 rabbits, and the proliferative responses were analyzed with histomorphological and immunohistological criteria at 3, 7, 14, 21, 28, and 42 days after intervention. A hemodynamic relevant stenosis after angioplasty was found in eight (23%) of 35 dilated arteries. In five rabbits the stenosis was due to a mural thrombus, and in three animals restenosis was caused by intimal SMC proliferation. In all dilated arteries the intimal wall thickness increased from 13 +/- 5 intimal cell layers (after electrical stimulation) to 33 +/- 14 cell layers during 28 days after angioplasty (p less than 0.05). Later than 4 weeks after angioplasty, no additional increase of intimal thickening occurred. Application of bromodeoxyuridine 18 and 12 hours before excision of the vessels allowed determination of the percent of cells undergoing DNA synthesis in the intima and media using monoclonal antibody against bromodeoxyuridine. SMCs were identified by alpha-actin staining. Immunohistological quantification of intimal SMC proliferation showed a maximum of cells undergoing DNA synthesis within the first 7 days after angioplasty (p less than 0.01). In contrast, medial proliferation of SMCs was delayed and showed a small but significant increase 21 days after dilatation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1990

[Migration and proliferation of smooth muscle cells in the vessel wall].

1. Intimal migration and proliferation causing artery stenoses in the course of atherogenesis can be inhibited by various drugs. 2. Secondary stenoses after ballooning of arteries are caused mainly by proliferation of smooth muscle cells. 3. Ballooning of arteries or repeated transmural electrical stimulations of artery walls with weak electrical current is followed by an increased mitotic activity of smooth muscle cells in the ballooned resp. stimulated area which reaches a maximal value about one week following the onset of the experiment. The mitotic activity returns then slowly to initial levels. 4. Adaptations to proliferation-inducing stimuli are possible. The experiments demonstrate that the proliferative phases in atherogenesis can be explained as a sequence of adaptations and deadaptations (= change of disposition) to the proliferation-inducing stimuli. 5. To select qualified drugs for an inhibition of the development of intimal proliferates in the course of atherogenesis makes it necessary to combine in vivo tests in animal experiments with tests on cell cultures of human cells from artery walls.

Arteriosclerosis↗
PubMed1990

Human vascular smooth muscle cells in culture: growth characteristics and protein pattern by use of serum-free media supplements.

This study demonstrates that cultivation of vascular smooth muscle cells from human artery wall is possible under completely serum-free conditions. The effects of attachment factors on cell spreading and cell proliferation are described in detail as well as routine cultivation methods under serum-free conditions (clone cultures, cell migration, subcultivation by use of an exogenous trypsin inhibitor, cryopreservation and readaptation of cells). After a careful adaptation period, only two (BMS and Ultroser G) of the four commercially available serum-free media supplements tested were used successfully for a routine cultivation of the smooth muscle cells over several passages. With both supplements cell proliferation rates were comparable with those obtained in medium containing 10% fetal calf serum. The addition of platelet-derived growth factor or transferrin to serum-free cultures had no growth-stimulating effect. The addition of endothelial cell growth factor isolated from bovine brain caused a significant increase in proliferative activity of cells cultivated with BMS, but not with Ultroser G. Moreover, we report that under the serum-free culture conditions described here, the gamma-actin content of the cells is largely reduced (51% +/- 13% (means +/- SD) for cells cultivated in Ultroser G, and 12% +/- 4% (means +/- SD) for cells cultivated in BMS) when compared with cells cultivated under serum-containing conditions (gamma-actin content = 100%). The alpha-actin content was observed to be unaltered. Even after a careful readaptation of serum-free cultured cells to serum conditions, the gamma-actin content remained reduced.

Actins↗
PubMed1990

Effect of etofibrate on the development and the regression of atheromas in a rabbit model of atherosclerosis.

The study presents the effect of 2-[2-(p-Chlorophenoxy)-2-methylproprionoxy]ethyl nicotinate (Etofibrate, Lipo-Merz) on progression and regression of experimentally induced atheromas. The atheromas (intimal proliferates) were produced in carotid arteries of rabbits fed for 4 weeks a diet containing 1% cholesterol. One carotid artery was stimulated transmurally with weak electrical pulses via chronically implanted electrodes during the 4 weeks in which the animals received the cholesterol-enriched food. The standardized stimulus induced an atheroma in the stimulated region of the artery in all animals. Quantitation was carried out by counting cell layers in serial sections of the stimulated artery region. Lipid accumulation was measured in oil red stained histological sections with a semiquantitative technique. Additionally serum cholesterol, serum triglycerides, and HDL-cholesterol were determined. Addition of 200 mg Etofibrate/kg body weight per day to the cholesterol-enriched food caused a significant inhibition of the proliferation of the smooth muscle cells in the intimal proliferate which consequently resulted in a less pronounced plaque. Stainable lipids were found in all controls and all Etofibrate-treated animals. HDL-cholesterol levels were higher in the treated animals than in the controls while the other lipid parameters were not influenced by Etofibrate. In another set of experiments two groups of rabbits were treated as described above. After the production of an atheroma (4 weeks) they were fed normal food. One of the groups received daily 200 mg Etofibrate/kg body weight, the other not. After the regression period of one year the arteries were excised and sectioned for histology and lipid levels were measured as above.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Intimal thickenings of jugular veins after application of a stimulus known to be sclerogenic in arteries.

The present study examined the intimal reactions of rabbit jugular veins to a stimulus known to elicit arteriosclerotic alteration in the artery wall. Repeated transmural electrical stimulation was applied to external jugular veins of both normo- and hypercholesterolaemic rabbits. Endothelial permeability, as well as changes in intimal architecture, were investigated by electron microscopy. Initially, the veins responded to electrical stimulation with an increased transendothelial transport of horseradish peroxidase (40,000 daltons). After application of the stimulation program for 4 weeks, intimal fibrous thickening (33%), cellular fibrous proliferation (50%), and organized mural thrombi were observed. The fibrous thickening was characterized by an abundance of connective tissue matrix and paucity of subendothelial cells. The cellular fibrous proliferate predominantly consisted of myocytes with few interspersed monocytes/macrophages and granulocytes. It resembled intimal plaques induced in carotid arteries by the same method. However, the venous thickenings showed limited size and a more pronounced fibrous response when compared with the arteriosclerotic lesions. The morphological similarities between the observed venous intimal thickenings and the different types of phlebosclerotic manifestations described in the literature, especially intimal proliferations in vein grafts, render the model of electrical stimulation suitable for the elucidation of underlying pathogenic mechanisms.

Animals↗
PubMed1989

Freeze-fracture analysis of endothelial cell membranes in rabbit carotid arteries subjected to short-term atherogenic stimuli.

Endothelial cell membranes of rabbit carotid arteries were examined by the freeze-fracture technique. In the normal endothelium the mean densities of membrane-bound vesicles were 75 vesicles/microns 2 on the luminal cell membrane and 102 vesicles/microns 2 on the abluminal membrane. Whilst the vesical openings on the luminal membrane were randomly distributed those on the abluminal membrane were typically ordered in a macular pattern with lines free of vesicles. Tight and gap junctions between endothelial cells were numerous. After stimulating the carotid arteries with weak electrical impulses, a technique used to induce enhanced endothelial permeability and the formation of atheromatous plaques after repeated stimulations (Betz et al. 1985), vesicle openings were reduced to 78 vesicles/microns 2 on abluminal membranes. Membranes on the luminal side and intercellular tight and gap junctions remained unchanged.

Animals↗
PubMed1989

Cell constitution and characteristics of human atherosclerotic plaques selectively removed by percutaneous atherectomy.

The Simpson atherectomy device used for the recanalization of severely stenosed peripheral arteries is able to collect plaque material which can be further characterized. This study reports histological, immunohistochemical and transmission electron microscopic findings on advanced human primary atherosclerotic plaques of peripheral arteries percutaneously removed by a Simpson atherectomy catheter. Material from stenosing plaques consisted of dense connective tissue with abundant amounts of concentrically arranged elastic fibers and lamellae. This meshwork contained numerous cells, often arranged in clusters and oriented with their longer axis parallel to the direction of blood flow. The vast majority of these cells could be easily identified as vimentin-positive and desmin-negative smooth muscle cells containing lipid deposits in the perinuclear region and numerous glycogen particles. Monocytes/macrophages were observed only very infrequently. Plaque tissue contained a range of smooth muscle cell phenotypes. Most of the cells were of an intermediate phenotype, i.e. sparsely filled with myofilament bundles at the cell periphery and a high amount of organelles such as mitochondria, rough endoplasmic reticulum and Golgi cisterns. An intact lining of pieces of intimal tissue with endothelial cells was not observed. Two-dimensional gel electrophoresis of plaque tissue showed the presence of alpha-, beta- and gamma-actin isoforms with a clear predominance of the beta-isoform.

Arteriosclerosis↗
PubMed1989

Densitometric measurement of increased endothelial permeability in arteriosclerotic plaques and inhibition of permeability under the influence of two calcium antagonists.

A densitometric technique was established to investigate quantitative changes in endothelial permeability for horseradish peroxidase (HRP), mol. wt. 40,000 daltons, in rabbit carotid artery. Repeated weak electrical stimulations of rabbit carotid arterial walls with implanted electrodes lead to fibromuscular plaques mainly beneath the anode. It could be demonstrated that there exists a typical growth curve of the plaques dependent on the number of days of electrostimulation, with a fast proliferation rate of smooth muscle cells in the first 2 weeks of electrostimulation, and an increasing retardation of proliferation during the next 4 weeks. Endothelial permeability for HRP increases in close relation to the plaque development. Intravenous applications of single doses of the calcium entry blockers flunarizine or nimodipine are able to inhibit the increased permeability of the endothelial lining covering arteriosclerotic plaques. The intensity of the inhibitory action of these calcium antagonists correlates with the size of the arteriosclerotic plaques in inverse proportion, but nevertheless in large plaques an inhibitory effect is seen.

Animals↗
PubMed1989

Structural alterations in vascular endothelial tight junctions in the course of their gradual degradation in vitro.

Rabbit aorta explants in organ culture maintained their endothelium as a confluent cell layer for 1-6 days. Depending on culture time, interendothelial tight junctions underwent gradual morphological changes in their substructure, as seen in freeze-fracture replicas. The formation of a P-face associated groove and concurrent confluence of tight junction particles on E-faces after 24 hr in vitro was followed by a rarefaction of particles and shortening of tight junctional strands. By day 6 in vitro, almost all tight junctions have disappeared. We interpret these findings as signs of a degradation of tight junctions in vitro, involving three different substructural components: a component facing the protoplasm, tight junction particles and a component facing the extracellular space. The degradation was inhibited by culturing under increased ambient pressure (910 mmHg).

Animals↗