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Biomedical subjects

J Günther

Publications and source records attributed to J Günther.

At least 19 recordsLinked to original sources

Binding and action of insulin-like growth factors and insulin in bovine luteal tissue during the oestrous cycle.

The effect of insulin-like growth factors (IGFs) and insulin on the release of progesterone and oxytocin from bovine corpus luteum was investigated at early (days 5-7), mid- (days 8-12) and late (days 15-18) luteal phases of the oestrous cycle in an in vitro microdialysis system. The expression of specific receptors was evaluated in bovine corpora lutea of the respective luteal stages. A 30 min infusion of IGF-1, IGF-2 (1.3, 13 and 130 nmol l-1) or insulin (13, 130 and 1300 nmol l-1) caused a stimulation of the release of progesterone (P < 0.05). IGF-1 was most effective in releasing progesterone. Oxytocin release from corpora lutea was stimulated by insulin at all doses tested (13-1300 nmol l-1), whereas the IGFs were only effective at the highest dose (130 nmol l-1) applied. The high doses of IGFs (130 nmol l-1) and insulin (1300 nmol l-1) stimulated the release of progesterone and oxytocin throughout the luteal phase (P < 0.05). For all three peptides, greatest stimulation was seen during the late luteal phase (days 15-18 of the oestrous cycle) with the peak of progesterone release directly related to peptide infusion (P < 0.05). In addition, IGF-1 stimulated total release of progesterone (units in 4 h) after the beginning of the stimulation during this phase (P < 0.05). IGF-1 caused a gradual increase of progesterone even beyond the time of peptide perfusion, whereas IGF-2 and insulin stimulated progesterone release only during the peptide perfusion. Distinct receptors for IGF-1 and IGF-2 were present in corpora lutea membrane preparations at all stages investigated. Specific binding for insulin was also seen in all stages of the cycle without any cycle-dependent changes in the amount of binding. The displacement of labelled insulin by unlabelled IGF-1 and IGF-2 did not show the rank of order that has been described as typical for insulin receptors (i.e. insulin > IGF-1 > IGF-2), but comparable binding affinities were observed for the three unlabelled ligands. Specific binding of IGF-2 was markedly higher than that of IGF-1 or insulin throughout the cycle (1.9- and 4.9-fold higher compared with IGF-1 and insulin, respectively). Receptor specificity did not change during luteal development. Binding affinity and capacity of IGF-1 receptor was constant throughout the oestrous cycle. Specific IGF-2 binding increased and showed a positive co-operativity towards the end of the cycle. Specific binding of insulin was not significantly different in the three luteal stages examined.

Animals

Adverse immune reactions to gold. I. Chronic treatment with an Au(I) drug sensitizes mouse T cells not to Au(I), but to Au(III) and induces autoantibody formation.

Upon weekly i.m. injections of disodium gold thiomalate (Na2AuTM) 100% of A.SW mice produced IgG autoantibodies to antinuclear Ag and nucleolar Ag, respectively; about 70% of C57BL/6 mice produced IgG antinuclear Ag, whereas DBA/2 mice were resistant. Moreover, C57BL/6 mice, but not DBA/2 mice, showed increased mesangial deposits of IgG. These alterations were due not to disodium thiomalate, but to the gold ion of Na2AuTM. An assumed T cell reactivity of susceptible mouse strains to Na2AuTM was tested by means of the direct popliteal lymph node (PLN) assay. However, no distinct PLN reaction to Na2AuTM was detectable. Likewise, AuCl did not induce a PLN reaction. Both Na2AuTM and AuCl contain gold in the Au(I) state. The poor PLN responses to Au(I) contrasted with the strong PLN responses to Au(III) compounds. PLN reactions to Au(III) were dose dependent, T cell dependent, and specific. When Au(III) was reduced to Au(I) by addition of Na2TM or methionine before testing in the PLN assay its sensitizing capacity was significantly decreased. Thus, the oxidation state of gold, i.e., Au(III) vs Au(I), plays a major role for its sensitizing capacity. Therefore, we propose that the Au(I) of Na2AuTM is oxidized to Au(III) before T cells are sensitized and adverse immunologic reactions develop. Results obtained with the adoptive transfer PLN assay indicated that, indeed, repeated i.m. injections of Na2AuTM sensitized A.SW and C57BL/6 splenic T cells to Au(III).

Animals

The isometric twitch of rabbit papillary muscle: reflection of the cellular calcium movements?

The cycling of the activator-Ca of the myocardium is mediated by the sarcolemma (SL) and the sarcoplasmic reticulum (SR). Both the extent and the time course of the release as well as of the removal of the activator-Ca by the SL differ from that by the SR. The visualization of these differences in the isometric myograms of isolated myocardium (Bogdanov et al. 1979; Günther et al. 1986; King and Bose 1983; Malecot et al. 1986) prompted the conclusion that distinct cellular Ca movements determine distinct parts of the isometric contraction-relaxation cycle. To test this hypothesis the effects of Ca, isoprenaline and ouabain on the isometric contraction-relaxation cycle of rabbit papillary muscles were re-evaluated. The similarities and differences in the effects of the interventions on the twitch measures could be explained by their effects on the cellular Ca movements.

Animals

Postrest contractions as an example for the regulation of the course of isometric twitch.

Postrest contractions (PRC) of isometrically contracting rabbit papillary muscles are used to analyse how the shape of the twitch can be explained by existing models for the accompanying Ca-regulation. By the change of the extracellular Ca concentration (Cae) potentiated or depressed PRC were produced. The course of the twitch is separated by mechanical indices commonly used. The results fit some biochemical and electro-physiological findings, as the regulatory role of the sarcoplasmic reticulum and the Na-Ca exchange, but do not reflect others. The sharp separation between an early and late phase of the contraction and relaxation, respectively, is limited by the overlapping of different Ca regulating processes.

Animals

The complement membrane attack complex stimulates the prostanoid production of cultured glomerular epithelial cells.

Incubation of cultured rat glomerular epithelial cells (GEC) with sublytic amounts of the purified complement components C5b6, C7, C8 and C9 greatly stimulated the release of the prostanoids prostaglandin E (PGE) and thromboxane B2. Incubation of GEC with C5b-8 was also stimulatory, whereas omission of C7 abolished the enhanced prostanoid production. These effects were dose-dependent. The increased release of PGE was biphasic with peaks at 5 min and 24 h of incubation. The second peak could be prevented by treatment with cycloheximide, suggesting its dependence on protein synthesis. The observations on cultured GEC provide evidence that terminal complement components alter the metabolism of glomerular cells, resulting in increased production of prostanoids. The results are consistent with the concept that deposition of nonlytic amounts of complement in the glomerular capillary wall may affect the GEC in vivo and may indirectly contribute to abnormalities of the glomerular filter as it is seen in glomerular disease.

Animals

Modification of relaxation of isometrically contracting rabbit papillary muscle by calcium, isoprenaline, ouabain and amiloride.

The influence of isoprenaline, ouabain, amiloride, as well as enhanced extracellular Ca on the time course of relaxation of the isometrically contracting papillary muscle was investigated. Under the experimental conditions used the relaxation rate shows different phases, which are modified characteristically. It is concluded that this reflects the different involvement of the Ca transport mechanisms for the relaxation.

Amiloride

Stimulation pattern dependent contractions of myocardial preparations after lipid diets.

Lipid diets modify the electro-mechanical coupling. To characterize the regulation of the supply of Ca for the activation of the contraction the influence of the stimulation pattern on the development of tension was investigated after diets containing cholesterol (Ch), rape oil (RO) and cholesterol-oil (ChO). The sequence of increasing inotropic states produced was compared with a control group (C). In ChO high resting potentiation, low postextrastimulatory potentiation (PEP) and a delayed Ca supply for interpolated extra contractions (EC) are typical features. The positive inotropic effect of rising extracellular Ca grows parallel to the sequence of the inotropic states. The maximum rate of contraction and relaxation correlates linearly with the tension development. Some of the results are similar in RO. In both groups a more pronounced involvement of the sarcoplasmic reticulum in the Ca regulation should be responsible for the effects. Especially in C the Ca loading effect of paired stimulation shortens the latent period and increases the rate of contraction and relaxation. In Ch the highest values of PEP are reached. These results reflect the involvement of a high sarcolemmal fraction of Ca in the activation.

Animals

K-p-nitrophenylphosphatase activity, Na and K content, Na permeability and membrane lipid composition in rabbit myocardium after cholesterol rich diet.

The aim of the present study was to investigate the effects of a cholesterol-rich diet on membrane function and lipid composition in rabbit myocardium. The activity and the ouabain sensitivity of the K-p-nitrophenylphosphatase (K-pNPPase), a partial reaction of the Na, K-ATPase, were diminished after a cholesterol/oil or pure cholesterol diet. The content of cholesterol, cholesterol esters and of several classes of phospholipids was enhanced in microsomes. A causal relationship is assumed between cholesterol accumulation and a decrease in membrane fluidity as well as in Na, K-ATPase activity. The intracellular Na content and the Na-Li-exchange rate were higher after the cholesterol diet. The increase in the Na content is supposed to be induced by a lower Na transport and a higher Na permeability. An enhanced Ca flux via the sarcolemma could be the consequence.

4-Nitrophenylphosphatase

[Time dependence of Ca supply in rat and rabbit myocardium].

The time dependence of Ca supply in rat (R) and rabbit myocardium (K) for the activation was analyzed by the action potential area up to 50% of repolarization (APA50) of the action potential (AP) during the electrical restitution as well as by extra contractions (EC) during the mechanical restitution and subsequent postextrastimulatory contraction (PEC) or potentiation (PEP) in isometrically contracting papillary muscle at different extracellular Ca concentrations (Cae). In K a considerable increase in APA50 of the EC-AP during the electrical restitution within the interval of rhythmical contraction (T) strongly correlates with the subsequent PEP. In R both the alteration of the APA50 and the PEP are smaller than in K. Compared with K in R the mechanical restitution is delayed, but accelerated by rising Cae as demonstrated by increasing EC/T. The course of mechanical restitution and the low PEP are regarded to be connected with the fact that the sarcoplasmic reticulum is the main source of activator Ca in R. Differences in both electrical and mechanical restitution and, especially the higher PEP, agree with the sarcolemma as the main source of activator Ca in K.

Action Potentials

[Fatty acid patterns of triglycerides in serum and skeletal muscles of rabbits on a cholesterol diet].

In 18 rabbits a hypercholesterolaemia was produced by a 12-week dietetic load with cholesterol. The hypercholesterolaemic rabbits had increased proportions of saturated and simply unsaturated fatty acids in the triglycerides of the serum and the skeletal muscle. The content of eicosapentaenic acid was lowered. The alterations in the fatty acid pattern are equal to those of patients with hyperlipoproteinaemia and arteriosclerosis. On the basis of these findings rabbits seems to be a suitable model, in order to investigate the connections between fatty acid patterns and the development of arteriosclerosis by experiments on animals.

Animals

Changes in sarcolemmal K+ -p-nitrophenylphosphatase activity induced by atherogenic cholesterol--rapeseed oil diet in rabbit myocardium.

A high level of plasma lipids may possibly modify the composition and function of cardiac cell membranes and the activity of membrane-bound enzymes. Therefore, the activity of K+ -p-nitrophenylphosphatase (pNPPase) as a part of the Na+ -K+ ATPase was determined in myocardial homogenates to indicate sarcolemmal function after an atherogenic diet. After feeding of a cholesterol--rapeseed oil diet, the total and ouabain-sensitive activities of pNPPase were decreased significantly compared with controls. This decrease in pNPPase activity can be reproduced completely by a pure cholesterol diet. A rapeseed oil diet increases the total and ouabain-insensitive activity of pNPPase. Changes in enzyme activity may be caused by alterations in the lipid surroundings of this membrane-bound enzyme. The inhibition of pNPPase activity by 10(-6) M ouabain was smaller after cholesterol--rapeseed oil and pure cholesterol diets but greater after a pure oil diet. This indicates changes in ouabain sensitivity of pNPPase after various lipid diets.

4-Nitrophenylphosphatase

The influence of atherogenic diet on electromechanical coupling in rabbit myocardium.

To characterize the role of the SR in the electromechanical coupling process in rabbit myocardium after a 12-week-long atherogenic diet containing cholesterol and oil, the influence of changes in Ca2e+ on isometric force, relaxation rate, and resting potentiation of isolated trabeculae were compared with 45Ca2+ binding and uptake by the SR. The diet produces a more strongly expressed resting potentiation of force at 1.25 and 2.5 mM Ca2e+ and an increase in the Vmax equivalent, the contractility index [(dF/dt)max/F'] and the relaxation index [-(dF/dt)max/F]. A higher Ca2e+-accumulating activity of heart microsomes from animals was observed after the diet. It is concluded that changes of SR function are involved in the mechanism responsible for modification of electromechanical coupling induced by cholesterol- and oil-containing diet.

Animals

[Diet induced changes of Ca-regulation in rabbit papillary muscle. 1. Contraction and relaxation following a cholesterol diet].

To characterize consequences of cholesterol induced increases of the Na content on the Ca regulation in rabbit myocardium the influence of increasing extracellular Ca (Cae) on isometric contraction and relaxation of papillary muscles has been investigated after a 12 weeks lasting cholesterol-rich diet. After cholesterol-rich diet increasing Cae caused a higher augmentation in peak tension T, accompanied by a decreased index in contractility [Formula: see text], an insignificantly prolonged time to peak tension TPT, and a decrease in the refractory period, which was extended compared with the control group. A delay in relaxation is demonstrated by the maximum relaxation rate [Formula: see text], the half time of relaxation RT 1/2 and more pronounced by a prolonged relaxation time RT. The results correspond with changes in the Na content published earlier and are in agreement with the assumption that a Na-Ca exchange is involved in beat-to-beat regulation in rabbit myocardium; thereby the cholesterol component of atherogenic diet promotes Ca enhancement in rabbit cardiac cells.

Animals

[Diet-induced changes on Ca-regulation in rabbit papillary muscle. 2. Contraction, relaxation and rest potentialization following a rapeseed diet].

To characterize consequences of rape oil-induced changes on the Ca regulation in rabbit papillary muscle, the influence of increasing extracellular Ca (Cae) on contraction, relaxation and resting potentiation of tension has been investigated after a 12 weeks lasting rape oil-diet. After oil diet increasing Cae caused a similar augmentation in peak tension T accompanied by an increased index in contractility [Formula: see text], a significantly shortened time to peak tension and a decline in refractory period. A higher relaxation rate is demonstrated by the maximum relaxation rate [Formula: see text], the half time of relaxation RT 1/2 and relaxation time RT. The resting potentiation of the isometric contraction was enhanced. The results are in agreement with the assumption that the sarcoplasmic reticulum (SR) is more involved in Ca regulation after the oil diet than in the control group. This may be related to differences in the phospholipid content of SR membranes.

Animals

[Defects in cell-mediated and humoral immunity in tumor-bearing mice. Evidence and characterization of suppressor cells ].

The immune response of mice bearing a transplantable tumor which was induced by Benzyprene was studied. The humoral response to sheep red blood cells (hemolytic plaque assay) is increased until the day 18 after inoculation of the tumor if calculated in relation to the total number of spleen cells, but it is decreased related to 10(6) spleen cells after day 9. Because the weight of the spleen increases during this time this result suggests that the relation between antibody producing and nonproducing cells becomes smaller, despite the total number of antibody producing cells is higher. The unspecific suppression of the cell-mediated immune response in vivo was was studied by the adoptive transfer of spleen cells from tumor bearing mice and allografting of the recipients. The rejection of the grafts is delayed. The stimulation of spleen cells with PHA is smaller with cells from tumor animals than in controls. The fraction which is nonadherent on glass beads has a higher reactivity than the total population, this difference is more distinct in tumor animals. The suppressor cells from tumor mice are glass adherent and their activity is negatively influenced by treatment of the tumor mice with Carageenan.

Animals

On the influence of hydrocortisone on the stimulation of mouse spleen cells by PHA. Evidence for the involvement of suppressor cells.

The stimulation rate with PHA of murine spleen cells increases after removal of glass-adherent cells from the total spleen population. Unfractionated spleen population from HC treated mice suppresses the response to PHA of glass non-adherent cells from untreated animals only 24-48 h after HC treatment. From the third day on after the treatment the suppressive effect disappears.

Animals

[Cytotoxic lymphocytes after allostimulation in vivo: kinetic, reproducibility and specificity after primary stimulation (author's transl)].

After allogeneic skin grafting and allogeneic sensibilization with spleen cells in the mouse system cytotoxic lymphocytes are induced, which can be shown in an vitro assay. The maximum of the cytotoxicity appears 2 to 3 days after transplantation. Cytotoxicity during graft rejection is clearly lower than the maximum cytotoxicity. After 3 to 4 weeks no cytotoxic lymphocytes can be detected. A similar time course is seen after sensibilization with allogeneic spleen cells. The cytotoxic lymphocytes do not react only against the stimulator haplotype if tumor cells are used as target cells. Common specificities between the stimulator and target cells may be responsible for this cytotoxicity. On the other side we found a specific cytotoxic reaction with thymocytes as target cells and in vivo no cross reaction for a second-set graft rejection.

Animals