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Biomedical subjects

G Zimmer

Publications and source records attributed to G Zimmer.

18 recordsLinked to original sources
PubMed1992

Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.

OBJECTIVES: The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND: The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS: Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS: Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS: These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.

Age Factors↗
PubMed1992

The effects of glucose, insulin and metformin on the order parameters of isolated red cell membranes. An electron paramagnetic resonance spectroscopic study.

Human red blood cell (RBC) membranes (RBC ghosts) were treated with glucose, insulin and metformin. The order parameters of RBC membranes were determined by 5- and 16-doxyl-stearic acid spin labels. Metabolic effects were excluded using an isolated system of RBC membranes. The membranes were incubated with glucose in physiological (5 mM), renal threshold (10 mM) and manifested diabetic (20 mM) concentrations for limited times. High concentrations of glucose (10, 20, 100 mM) increase the order parameters of RBC membranes significantly. Insulin by itself has a similar effect which is, however, not strictly concentration-dependent. By contrast, metformin at therapeutic concentrations (0.5 and 5.0 microM) decreases the order parameters. At 50 microM concentration the metformin effect is expressed less and recurs at 100 microM concentration. The effects are significant with 5-doxyl-stearic acid, but are not significant with the 16-doxyl derivative. When RBC membranes are co-incubated with 20 mM glucose and metformin at 0.5 and 5.0 microM concentrations the order parameters as determined by 5-doxyl-stearic acid remain normal (= control values). Higher concentrations of metformin (50 and 100 microM) cause an overshoot to very low order parameters. Insulin at 10, 100 and 200 mU/L does not influence significantly the effects of metformin. Addition of physiological amounts of bovine serum albumin does not abolish the effects of metformin. Metformin, at therapeutic concentrations (0.5 and 5.0 microM), maintains the normal fluidity at the polar interface of isolated RBC membranes by counterbalancing non-enzymatic glycosylation with 20 mM glucose in vitro.

Cyclic N-Oxides↗
PubMed1992

Reduced capillary density in the myocardium of uremic rats--a stereological study.

Using stereological techniques capillaries, interstitium and myocardial fibers were analyzed in perfusion-fixed hearts of subtotally nephrectomized male Sprague-Dawley rats with uremia of 14 months duration (or their sham-operated controls). Uremic rats had higher systolic blood pressure (140 +/- 20.3 mm Hg vs. 119 +/- 6.61 mm Hg) and left ventricular weight/body weight ratio (3.37 +/- 0.09 mg/kg vs. 2.01 +/- 0.12 mg/kg) than controls, and had slight anemia (Hct 35.0 +/- 3.16% vs. 40.4 +/- 3.3%). Length density (Lv) of capillaries, that is, capillary length per unit myocardial volume, was significantly (P < 0.001) decreased in uremia (2485 +/- 264 mm/mm3 vs. 3329 +/- 194 mm/mm3) versus controls. In parallel, surface density and volume density of the capillary lumina were also reduced (7.95 +/- 1.69 cm3/cm3 vs. 11.4 +/- 1.8 cm3/cm3) in the uremic rats. We conclude that in experimental uremia, cardiac hypertrophy is not accompanied by a commensurate increase in capillaries.

Animals↗
PubMed1992

Electron paramagnetic resonance (EPR) imaging in skin: biophysical and biochemical microscopy.

Electron paramagnetic resonance (EPR) is a spectroscopic technique that allows detection of paramagnetic compounds, e.g., free radicals, in skin, and is used for measuring skin membrane fluidity and polarity. EPR imaging is concerned with spatially resolved EPR spectroscopy. We studied EPR images at X-band frequency (9 GHz) in the skin biopsies of hairless mice. Our particular imaging technique utilized a modulated field gradient to obtain cross-sectional images perpendicular to the skin surface. Employing nitroxide free radicals, this approach allows analysis of skin biophysical and biochemical features at the micrometer resolution level. By spin labeling drugs, pharmacokinetic properties of the labeled compound can be monitored in skin. We suggest that EPR imaging has a broad application potential in dermatologic research. In comparison to other spatially visualizing techniques, such as nuclear magnetic resonance (NMR) imaging and ultrasound, EPR imaging has significant advantages, such as high spatial resolution and providing specific biochemical and biophysical information that cannot be obtained by other methods in skin.

Animals↗
PubMed1992

Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo.

The influence of alpha-lipoic acid (CAS 62-46-4) on the amount of intracellular glutathione (GSH) was investigated in vitro and in vivo. Using murine neuroblastoma as well as melanoma cell lines in vitro, a dose-dependent increase of GSH content was observed. Dependent on the source of tumor cells the increase was 30-70% compared to untreated controls. Normal lung tissue of mice also revealed about 50% increase in glutathione upon treatment with lipoic acid. This corresponds with protection from irradiation damage in these in vitro studies. Survival rate of irradiated murine neuroblastoma was increased at doses of 100 micrograms lipoic acid/d from 2% to about 10%. In agreement with the in vitro studies, in vivo experiments with whole body irradiation (5 and 8 Gy) in mice revealed that the number of surviving animals was doubled at a dose of 16 mg lipoic acid/kg. Improvement of cell viability and irradiation protection by the physiological compound lipoic acid runs parallel with an increase of intracellular GSH/GSSG ratio.

Animals↗
PubMed1992

Treatment of chronic active hepatitis and primary biliary cirrhosis with ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA) improves liver function tests in patients with chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC). UDCA will reduce biochemical parameters of both cholestasis and hepatocellular damage. The effects may be less beneficial in patients with advanced stages of chronic liver disease: in PBC we found the improvement of laboratory parameters in stage I and II very impressive, in stage III and IV it was less marked. Data of two controlled trials in PBC showed an improvement in liver histology, in one study the improvement was statistically significant. UDCA can be administered for at least 10 years without any adverse effects, the treatment is safe and improves life quality. The mode of action of UDCA seems to be in its displacement of toxic hydrophobic bile salts from the bile acid pool and the hepatocellular membrane. In in-vitro investigations a direct protective effect of UDCA on isolated sinusoidal hepatocyte membranes against toxic bile salts has been shown. This protective effect of a more general nature may explain the efficacy of UDCA in different chronic, especially cholestatic liver diseases.

Adult↗
PubMed1992

[Plasma-membrane fluidity studies of murine neuroblastoma and malignant melanoma cells under irradiation].

Murine neuroblastoma (C-1300 NMB) and malignant melanoma (B16) cells were radiated in presence of radiopharmaceutics. Sensibilization was carried out with BSO and protection with TMX. Changes in fluidity of the plasma membrane, in cellular GSH contents and cell cycle were observed. After radiation fluidity of the plasma membrane is increased, whereas intracellular GSH decreased. These changes were intensified by BSO and reduced by TMX. Fluidity of the plasma membrane correlates with intracellular GSH and also with cell cycle. It is suggested that changes in plasma membrane fluidity can be used as an additional parameter for the determination of sensitivity towards radiation.

Animals↗
PubMed1979

ATP contents and condensed configuration of rat liver mitochondria induced by rising ionic strength.

Experiments using shifts in ionic strength between 0.15 and 0.8 mol/l revealed that from 0.3 mol/l KCl onward toward higher concentration condensed mitochondria are observed. Parallel with increasing condensation, the ATP contents were found to rise up to 0.6 mol/l KCl. At 0.8 mol/l KCl already destroyed mitochondria were found. Also, at this concentration of KCl, ATP contents did not rise any longer. The SH reagent 2-mercaptopropionylglycine was effective at about physiological ionic strength only. Up to concentrations of 0.6 mol/l KCl H+/O ratios were not different from the controls at physiological ionic strength, but the effect of valinomycin was effectively reduced by high concentrations of KCl. It is suggested that condensation of mitochondrial structure is correlated with increases in ATP content.

Adenosine Triphosphate↗
PubMed1978

[Biochemical and clinical studies on the influence of 2-mercaptopropionylglycine on liver cell function (author's transl)].

2-Mercaptopropionylglycine was used for the treatment of chronic hepatitis. The drugs showed very good clinical results. In biochemical studies it was found that there was no effect on phosphate transport. Instead, there was an increase of reactive SH-groups sensitive to oligomycin in the membrane of rat liver mitochondria. The ATPase activity in mitochondria was diminished, while ATP-contents of the mitochondrial suspensions were increased by the drug. In the presence of ATP-MG++ there was an increase of oligomycin-sensitive contraction of the mitochondria. In aged mitochondria, the P/O ratios were improved. Reversal of electron transport with formation of NADH by succinate in the presence of rotenone and ATP was, concentration dependently, improved by MPG. Thus, MGP obviously acts at some specific sulfhydryl groups of the mitochondrion. It is concluded that the action of the drug in chronic hepatitis may be interpreted via an improvement of mitochondrial function.

Adenosine Triphosphatases↗
PubMed1978

ATP contents and structure of rat liver mitochondria in the presence of 2-mercaptopropionylglycine.

2-Mercaptopropionylglycine was found to be efficient in the treatment of chronic hepatitis. Interest was focussed on the possible mode of action of that reagent at the subcellular level. ATP contents in mitochondria were increased after anaerobic preincubation and after addition of ADP and 2-mercaptopropionylglycine. Concomitantly, we found an increase in condensed configuration of mitochondria. If the reagent was added before ATP-Mg2+ (ADP) the mitochondrial structure was well preserved, though, throughout of orthodox configuration. In comparison the control specimens were grossly swollen. It is proposed that the reagent may act at the level of mitochondrial energy coupling.

Adenosine Triphosphate↗
PubMed1977

Oligomycin sensitivity of mitochondrial sulfhydryl groups.

Dithionitrobenzoate has been used to titrate sulfhydryl groups of rat liver mitochondria in glutamate buffer, pH 7.4. Reaction with oligomycin and different SH reagents preceded the SH titration. Under these conditions it was found that 2-mercaptopropionylcne and N-ethylmaleimide reacted in an oligomycin-sensitive manner, so that the control values (in the absence of SH reagent) were obtained. Similar concentrations of mersalyl and of N-(N-acetyl-4-sulfamoylphenyl) maleimide, in the presence of oligomycin, enhanced reactivity toward Nbs2. The concentration range of oligomycin-sensitive SH groups was thus defined between approx. 5 and 9 nmol reagent/mg mitochondrial protein. In this way, a differentiation between SH grops, which are implicated in phosphate transport antd those, which react in an oligomycin-sensitive manner, and which are probably connected with the coupling mechanism was achieved.

Animals↗
PubMed1976

Conformation and reactivity of DNA in the complex with protein. IV. Circular dichroism of poly-L-histidine model complexes with DNA polymers and specificity of the interaction.

The CD study of the DNA-poly-L-histidine complex at high degree of protonation revealed that complex formation is already observable at 2 M NaCl. The influence of salt together with 5 M urea suggests that in addition to electrostatic interactions probably hydrogen bonding may favour specific complexes. Affinity of protonated histidines to AT-rich regions is strongly supported by the complexes formed with (dA.dT)-containing polymers. The psi-type structure occurs with poly(dA-dT)-poly(dA-dT) while poly(dA)-poly(dT) is restricted to form a similar psi-state on interaction with highly protonated poly-L-histidine. Differences in the helix winding properties due to variation in the sequence is suggested as a possible factor in the formation of the psi-type complexes. The mechanism of interaction including hydrogen bonding of histidine side-chains with an AT pair at high degree of protonation and with GC-regions at lower degree of protonation in the polypeptide structure is discussed.

Binding Sites↗
PubMed1975

Lipid-protein interactions at the erythrocyte membrane. Different influence of glucose and sorbose on membrane lipid transition.

When observed over a temperature range, erythrocyte membrane lipids undergo a transition at 18-20 degrees C (Zimmer, G. and Schirmer, H. (1974) biochim. Biophys. Acta 345, 314-320). This observation has prompted an investigation of the effects that substrate binding has on the transition of the red cell membrane. Glucose and sorbose were compared, since transport kinetics of these sugars still pose unresolved questions. In membranes, preloaded with glucose, the break at the transition temperature was intensified, while it was abolished or reversed in membranes preloaded with sorbose. These results were corroborated using different solubilization procedures (sonication, sodium dodecyl sulfate treatment) of the membranes, and also different techniques (viscosimetry, 90 degrees light scattering, 1-anilino-naphthalene-8-sulfonate fluorescence). In extracted membrane lipids, viscosimetry indicated a break at transition temperature after preloading with either glucose or sorbose. Disc electrophoresis revealed a different binding pattern of the two sugars. It is suggested, that the amplification of the discontinuity in red cell membranes by glucose and the abolition or reversal of the break by sorbose are mediated by membrane protein- and/or membrane lipid-protein interaction.

Blood Proteins↗