Biomedical subjects

M Spindler

Publications and source records attributed to M Spindler.

26 records · Page 2Linked to original sources

PubMed1996

Low concentrations of cis-linoleic acid induce cell damage in epithelial cells from bovine lenses.

As low as 5 micromol/l of cis-linoleic acid proves to be cytotoxic for bovine lens epithelial cells in culture. Albumin eliminates the linoleic acid cytotoxicity completely, presumably by binding the fatty acid. However, the damaging effect appears again when the molar ratio of linoleic acid to albumin exceeds 1:1. The assumption that the linoleic acid-caused cell damage would be mediated by peroxidation products could not be confirmed. The results obtained rather favor the idea that linoleic acid molecules themselves injure lens epithelial cells. Obviously, cell damage even occurs in the presence of albumin if one molecule of albumin binds more than one molecule of linoleic acid. Micromolar concentrations of linoleic acid produce reversible bleb formation as well as cell retraction within 30 min. In primary culture 10 micromol/l linoleic acid damage lens epithelial cells irreversibly within some hours. Trans-linoleic acid, linolenic acid and oleic acid are also harmful to lens cells but to a lesser degree, while saturated fatty acids are without any effect. Bleb formation as a leading early sign hints at the plasma membrane as the primary target for linoleic acid induced cytotoxicity.

Albumins↗

PubMed1995

Interference of angiotensin-converting enzyme inhibition with vasoactive peptides in the coronary circulation of dogs.

The coronary effects of angiotensin-converting enzyme (ACE) inhibitors and their mechanisms of action are not well understood. Because these drugs may interfere with hormone systems other than the reninangiotensin system (RAS), we studied modulation of the coronary effects of neurotensin, neuropeptide Y (NPY), and endothelin-1 (ET-1) by pretreatment with captopril in anesthetized, open-chest dogs. The left anterior descending coronary artery (LAD) was cannulated and perfused at a pressure equal to mean aortic blood pressure. Coronary blood flow (CBF) was measured by an electromagnetic flowmeter, subendocardial segment length by ultrasonic crystals. ACE inhibition (captopril 0.25 mg/kg), as an intracoronary (i.c.) injection, followed by an intracoronary infusion (0.25 mg/kg/h) did not affect the relative vasoconstrictor effects of ET-1 (10(-4)-10(-1) micrograms/kg i.c.) or neuropeptide Y (10(-3)-1 microgram/kg i.c.). However preinjection flow of a second dose-response curve of ET-1 was significantly higher in captopril-treated as compared with control animals. The increase in CBF induced by neurotensin (10(-3)-1 microgram/kg i.c.) was potentiated by captopril (40 +/- 14% after vs. 20 +/- 9% before captopril, p < 0.01, at the highest dose used). Changes in hemodynamics or in regional myocardial function could not explain altered effects of neurotensin. We therefore conclude that ACE inhibition does not interfere with the acute vasoconstrictor effects of ET-1 or NPY in this canine model but may reverse the long-term tonic coronary constrictor effect of ET-1. Potentiation of the neurotensin effect on CBF might be due to prevention of hydrolysis of neurotensin or to a cyclooxygenase-dependent mechanism.

Analysis of Variance↗

PubMed1995

Growth regulation by cell shape alteration and organization of the cytoskeleton.

The correlation between cellular growth and microfilament-dependent morphology was investigated. It was found that the proliferative growth of various nontransformed cell lines does not only depend on cell adhesion to a suitable substratum and cell flattening but also on intact microfilaments. Disintegration of microfilaments by cytochalasin D (CD) as well as lactrunculin (LAT)-A and LAT-B is correlated with a strong decline of the number of DNA-synthesizing cells during a period of 8 to 12 h after application of the drug. RNA and protein synthesis are reduced already after a preincubation time of 2 h. Although microinjected rhodamine-phalloin is colocalized with microfilaments there is no stabilizing effect against CD even at high phaloidin concentrations. Microinjection of DNAse I results in a strong alteration of the microfilament system. The disorganization of microfilaments was correlated with a moderate decrease of protein synthesis 2 h after microinjection, whereas RNA synthesis remained unchanged, if RNase-free DNase I was used. The number of DNA-synthesizing cells was somewhat diminished 24 h after microinjection. Furthermore, the microfilament system is disorganized by microinjection of gelsolin and gelsolin segment 1 + 2, respectively. The severing the microfilaments by gelsolin is correlated with a significant restriction of RNA and protein synthesis during a period of 2 to 4 h after injection, but the labeling index remaining unchanged. Therefore, we assume that inhibition of the G0-G1-S transition is only caused by a disintegration of microfilaments lasting longer than 4 h. The significance of microfilament organization for growth regulation is discussed.

Actin Cytoskeleton↗

PubMed1991

Demonstration of the cytoskeleton of lens epithelial cells with gold sol techniques.

1. The Triton-extraction procedure is well suited for the demonstration of the cytoskeleton by TEM. A good preservation of the fine cytoskeletal network depends on optimal drying. 2. Immunogold-labeling is a useful method for visualization of intermediate filaments (IF) and microfilaments (MF). Labelled and unlabelled filaments are discernible. 3. Various methods were tested for a direct gold-labeling of MF with phallotoxin-gold preparations: The application of phalloidin-gold complexes results in an intensive unspecific staining of cytoskeletal filaments. A modified coupling procedure for the binding of phallacidin to transferrin was necessary to avoid the agglomeration of gold particles. The direct labeling of the cytoskeleton by the application of phallacidin-transferrin-gold complexes to Triton-extracted cells demonstrated an enrichment of gold particles on the both types of filaments, but MF and IF were not discernible. The treatment with phallacidin-polylysin-gold complexes demonstrated labelled filaments, but without sufficient intensity.

Actin Cytoskeleton↗

PubMed1983