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Biomedical subjects

E Betz

Publications and source records attributed to E Betz.

137 records · Page 8Linked to original sources

Growth characteristics and cytoskeletal organization of cultured smooth muscle cells from human primary stenosing and restenosing lesions.

Growth characteristics of human plaque cells selectively extracted from advanced primary stenosing and fresh restenosing lesions by percutaneous transluminal atherectomy were studied in vitro. Cells were isolated either by explant technique or by enzymatic disaggregation, and they were identified as smooth muscle cells (SMC) by positive reaction with antibodies against alpha-smooth muscle actin. Endothelial cells were not found in the atherectomized tissue. The cells of primary stenosing tissue (ps-SMC) exhibited a significantly low growth rate (0.16 +/- 0.04 population doublings per day) in comparison to the cells of restenosing lesions (re-SMC, 0.64 +/- 0.15 population doublings per day). Furthermore, ps-SMC became senescent and remained quiescent after two passages, whereas re-SMC retained a high proliferative activity and became quiescent by passage 8 to 10. Both types of cells responded to increasing serum concentrations in a dose-dependent manner. Ps-SMC failed to respond to purified platelet-derived growth factor (PDGF) and a mitogen mixture isolated from bovine brain (ECGF), but their proliferative activity was increased by the addition of re-SMC-conditioned culture medium. Despite their high basic growth rate, the proliferative activity of re-SMC was significantly stimulated by PDGF and ECGF in a dose-dependent manner. PS-SMC and re-SMC populations consisted of two distinct subpopulations, which could be discriminated by cell size measurements and cell adhesion: 1) relatively small (cell diameter, 18.6 +/- 5 microns), low-adhesive, predominant cells, and 2) enlarged (cell diameter, 27.1 +/- 3 microns), high-adhesive, fibroblast-like cells with abundant microfilaments. Neither ps-SMC or re-SMC stained with antibodies against desmin, but did express vimentin. The organization patterns of vimentin and tubulin were unaltered in comparison to each other and to smooth muscle cells cultured from the media of nonatherosclerotic human arteries.

Arteriosclerosis↗

Differential effect of Photofrin II on growth of human smooth muscle cells from nonatherosclerotic arteries and atheromatous plaques in vitro.

The effect of dihematoporphyrin-ester or -ether (DHE), a photosensitizing porphyrin with different amounts of aggregates, on the growth of cultured smooth muscle cells obtained from nonatherosclerotic arteries and from atheromatous plaques (primary stenosing and restenosing lesions) was examined without photoactivation of the drug. Clinically relevant DHE concentrations ranging from 0.1 to 25 micrograms/ml were used. In all proliferation studies with cells of second and third passage (approximately 10 cumulative population doublings in vitro), the growth rates decreased in a dose-dependent manner. Smooth muscle cells from atherosclerotic lesions were significantly more sensitive than smooth muscle cells from normal arteries. Cells derived from restenosing lesions retained their increased sensitivity even after eight passages in culture (approximately 20 cumulative population doublings). Cell size measurements showed that the decreased proliferative activity mainly occurred in smooth muscle cell subpopulations consisting of small cells. A cytotoxic effect of DHE was observed at concentrations above 5 micrograms/ml, causing cytoplasmic protrusions, vacuoles, and even complete cell lysis. At a DHE concentration of 5 micrograms/ml, the number of viable cells was 73% +/- 14% (means +/- SD) for smooth muscle cells from nonatherosclerotic arterial media and only 38% +/- 11% (means +/- SD) for smooth muscle cells from atherosclerotic plaques. In all experiments, no significant difference in response to DHE treatment was observed between cells from primary stenosing and restenosing lesions, suggesting a specific mechanism for plaque-derived cells causing an increased sensitivity in comparison to smooth muscle cells from nonatherosclerotic arteries. The pronounced sensitivity of plaque cells against DHE treatment suggests that this drug--even without photoactivation--is potentially valuable in vivo as a therapeutic approach to vascular stenoses.

Arteriosclerosis↗

Influence of severe hypercapnia upon cerebral cortical metabolism, CSF electrolyte concentrations and EEG in the cat.

The interconnections between EEG, intermediary and energy metabolism of the brain cortex and CSF potassium level are studied during severe hypercapnia in anaesthetized, artificially ventilated cats. Hypercapnic animals were ventilated with 40 to 50% to CO2 in oxygen. During severe hypercapnia the EEG becomes isoelectric. The CSF potassium concentration is raised and the changes in metabolism suggest an acidosis-induced inhibition of phosphofructokinase and, probably, of hexokinase. The energy charge potential remains unchanged whereas the cortical ATP concentration increases slightly. It is assumed that the changes in P-creatine and creatine levels are related to the pH-dependency of creatine phosphokinase. Recovery animals were ventilated with 40% CO2 in O2 and subsequently with room air. After termination of CO2 inhalation the EEG reappears, the CSF potassium concentration normalizes, and the inhibition of the glycolytic enzymes disappears. The energy charge potential shows a small decrease. It is not possible to trace back the disappearance of the EEG to only one of the recorded parameters. Cortical P-creatine levels, CSF potassium concentration, changes in membrane permeability and cortical amino acid concentrations are considered in this context.

Animals↗

Enhanced endothelial permeability and invasion of leukocytes into the artery wall as initial events in experimental arteriosclerosis.

The temporal sequence of the very early events in arteriosclerosis, as induced by electrical stimulation in carotid arteries of rabbits, was examined by combined light microscopy and transmission electron microscopy. After one session (30 min) of DC impulses, the endothelial permeability to horse-radish peroxidase was increased mainly beneath the anode, judging from the massive accumulation of reaction products of peroxidase in the subendothelium. After a further stimulation period, some of the endothelial cells displayed alterations in pattern and size and heavy cytoplasmic deposition of silver salt. However, the endothelium was maintained as a continuous lining. During this initial phase, a considerable number of granulocytes and monocytes was found adhering to the endothelium of the stimulated region and also within the subendothelial space. The invasion of the leukocytes preceded the migration of smooth muscle cells from the media into the intima, a process which began after two days of the electrical stimulation schedule. These initial phases of plaque development may represent a special form of an inflammatory response.

Animals↗