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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 19 recordsLinked to original sources
PubMed1998

Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin.

BACKGROUND: A threshold concept for ischemic preconditioning (IPc) has been proposed. It is unclear, however, whether IPc, above a certain threshold, is an all-or-nothing or a graded phenomenon. METHODS AND RESULTS: In 71 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 minutes followed by 2 hours of reperfusion resulted in an infarct size (IS, by triphenyltetrazolium chloride) of 16.7+/-3.4% (SEM) of the area at risk. IPc by 2 minutes of low-flow ischemia and 15 minutes of reperfusion before the 90-minute target ischemia did not reduce IS (21.9+/-7.0%). IS was decreased to 9.0+/-2.6% (P<0.05) by 3 minutes of IPc and reduced further to 1.9+/-0.9% (P<0.05) by 10 minutes of IPc. The interstitial adenosine concentration (microdialysis, high-performance liquid chromatography) was unchanged with 2 and 3 minutes of IPc but increased with 10 minutes of IPc (by 573+/-144%). The interstitial bradykinin concentration (microdialysis, radioimmunoassay) remained unchanged with 2 minutes of IPc but increased to a similar extent with 3 minutes (by 198+/-32%) and 10 minutes (by 224+/-30%) of IPc. The IS reduction by 3 minutes of IPc was abolished by blockade of the bradykinin B2 receptor with intracoronary HOE 140 (16.6+/-4.3%) but not with intracoronary infusion of adenosine deaminase (8.4+/-2.5%, P<0.05). HOE 140, however, did not affect the IS reduction (3.5+/- 1.1%, P<0.05) by 10 minutes of IPc. Combined infusion of HOE 140 and adenosine deaminase abolished the IS reduction by 10 minutes of IPc (15.4+/-6.7%). CONCLUSIONS: IS reduction by IPc is a graded phenomenon. Whereas bradykinin is essential during preconditioning ischemia of shorter duration, adenosine is more important during preconditioning ischemia of longer duration.

Adenosine↗
PubMed1998

Beta-blocker therapy of severe congestive heart failure in infants with left to right shunts.

We report on the clinical and neurohumoral effects of adding low-dose propranolol to conventional therapy with digoxin and diuretics in 6 infants with severe congestive heart failure due to large left-to-right shunts. A significant decrease in heart failure scores and a decrease of the highly activated renin-angiotensin-1 aldosterone system by approximately 70% strongly suggests a beneficial effect of this new therapeutic approach.

Adrenergic beta-Antagonists↗
PubMed1998

Translocation of phosducin in living neuroblastoma x glioma hybrid cells (NG 108-15) monitored by red-shifted green fluorescent protein.

Activation of G protein-coupled receptors triggers translocation of certain proteins from cytoplasm to cell membrane located targets. One of these cytosolic proteins is phosducin (Phd) which has been described to compete with G protein-coupled receptor kinases for Gbetagamma dimers attached to the cell membrane, thereby attenuating desensitization of activated receptors. These features of protein redistribution prompted us to examine whether stimulation of membrane associated E-prostaglandin receptors coupled to Gs causes Phd to migrate towards the plasma membrane. We made use of enhanced green fluorescence protein (EGFP), a reporter protein, to follow redistribution of Phd both by means of confocal microscopy and biochemical techniques in living neuronal NG 108-15 hybrid cells challenged with prostaglandin E1 (PGE1). The cells were transiently transfected to express Phd fused to the C-terminus of EGFP, or to express EGFP only. Overexpression of the proteins is implied by FACS analysis as well as by western blot technique, and the functional integrity of EGFP-tagged Phd was confirmed by its ability to elevate cAMP accumulation. Time-lapse imaging of single living cells by means of confocal microscopy revealed that exposure to prostaglandin causes EGFP/Phd, which is evenly spread throughout the cell, to relocate towards the membrane within few minutes. Fluorescence associated with the cell nucleus displayed little rearrangement. The principle finding that prostaglandin triggers translocation of Phd from cytosol to the cell periphery was verified with membranes prepared from EGFP/Phd expressing cells. We found maximal concentrations of membrane associated fluorescent material 5 to 7 min upon prostaglandin exposure. The present study reports for living NG 108-15 hybrid cells that PGE1 stimulation causes cytosolic Phd to translocate towards the membrane, where it is believed to bind to G protein subunits such as Gbetagamma and Galphas.

Alprostadil↗
PubMed1998

Positron emission tomography analysis of [1-(11)C] acetate kinetics in short-term hibernating myocardium.

BACKGROUND: Modeling of the time-[1-(11)C]acetate activity curve assumes a constant concentration of labeled tricarboxylic acid cycle intermediates and associated metabolites, such as glutamate and aspartate, which may, however, decrease in short-term hibernating myocardium. METHODS AND RESULTS: In 12 anesthetized pigs, [1-(11)C]acetate was injected as a bolus into the cannulated left anterior descending coronary artery during normoperfusion, inotropic stimulation, and early (5 to 45 minutes) and prolonged ischemia (60 to 90 minutes). Regional myocardial oxygen consumption (MVO2, microliters per minute per gram) was measured, and the absence of necrosis was verified by triphenyl tetrazolium chloride staining. Inotropic stimulation increased MVO2 from 52.5+/-7.4 to 195.4+/-36.2 (mean+/-SD) and the rate constant (kmono, minutes[-1]) of [1-(11)C]acetate clearance from 0.094+/-0.018 to 0.322+/-0.076. During early ischemia, MVO2 and kmono were decreased to 24.3+/-8.5 and 0.061+/-0.011, respectively. Kmono closely correlated to MVO2 during normoperfusion, inotropic stimulation, and early ischemia. In short-term hibernating myocardium, however, at an unchanged MVO2, kmono increased toward control values (0.080+/-0.014). Myocardial glutamate and aspartate concentrations (biopsies) decreased to 47+/-26% and 77+/-18%; the peak count rate decreased to 66+/-22% of its respective control value. After correction for the decreases in glutamate and aspartate or in peak count rate, kmono was again decreased (0.050+/-0.016 or 0.052+/-0.014, respectively), and a close relationship to MVO2 was restored. CONCLUSIONS: Kmono correlates to MVO2 in short-term hibernating myocardium when the decreases in aspartate and glutamate or in peak count rate are considered.

Acetates↗
PubMed1998

Thiols protect the inhibition of myocardial aconitase by peroxynitrite.

Peroxynitrite (ONOO-) is a potent inhibitor of myocardial aconitase. Because ONOO- reacts with sulfhydryl moieties, we investigated whether thiols protect against ONOO(-)-mediated inhibition of aconitase. Aconitase activity was examined in ventricular homogenates prepared from freshly isolated rat hearts. Peroxynitrite, but not the nitric oxide donor S-nitroso-N-acetyl-d,l-penicillamine (0.03-300 microM), inhibited aconitase activity (IC50 = 47 +/- 6 microM). L-Cysteine (0.03-3 mM), glutathione (0.03-3 mM), and N-(2-mercaptoproprionyl)-glycine (MPG, 0.1-3 mM) protected against the inhibitory effect of ONOO- (100 microM) with the rank order of potency of MPG > glutathione > L-cysteine. D-Cysteine (3 mM) had a protective effect similar to L-cysteine, but L-cystine, the oxidized form of L-cysteine, offered no protection. Ferrous ammonium sulfate (1 mM) markedly enhanced the protection provided by L-cysteine, but not by glutathione or MPG. Thiols protect myocardial aconitase against inhibition by ONOO- in a manner which is sulfhydryl group dependent and not stereospecific. The protection is related to the maintenance of the redox state of the iron-sulfur cubane cluster and cysteine residues at the active site of the enzyme. Both naturally occurring thiols and thiol-based drugs may be useful to protect the heart during ischemia-reperfusion injury where there is an excessive production of ONOO-.

Aconitate Hydratase↗
PubMed1998

Rat beta-adrenergic receptor kinases 1 and 2 in mouse neuroblastoma X rat glioma NG 108-15 hybrid cells.

Beta-adrenergic receptor kinase (betaARK, EC 2.7.1.-) has been implicated in the phosphorylation of G protein-coupled receptors, including opioid receptors. Since delta-opioid receptors of mouse neuroblastoma x rat glioma hybrid cells (NG 108-15) desensitize upon activation, this investigation was designed to find out whether NG 108-15 cells contain betaARK activity. Using the reverse transcription polymerase chain reaction technique, we identified two mRNAs, one coding for rat betaARK1 and the other for rat betaARK2. No hint was found for the presence of mouse betaARK. Examining the cytosolic betaARK activity in these hybrid cells using rhodopsin as substrate, we found a strict functional dependence on the presence of exogenous G protein subunit Gbetagamma. This relationship reflects a characteristic for betaARK1 and 2 out of the known G protein-coupled receptor kinases. Finally, highly purified recombinant betaARK1 proved active to phosphorylate enriched delta-opioid receptor preparations in an opioid agonist-dependent manner. The results reported here provide the basis to study more closely the molecular function of G protein-coupled receptor kinases in a cell line (NG 108-15) most frequently used to investigate acute and chronic opioid actions.

Animals↗
PubMed1998

Prevention of ischemic preconditioning only by combined inhibition of protein kinase C and protein tyrosine kinase in pigs.

In rabbits, inhibition of either protein kinase C or protein tyrosine kinase abolishes the infarct size reduction achieved by ischemic preconditioning. In pigs, however, inhibition of protein kinase C does not attenuate ischemic preconditioning. The present study tested whether inhibition of protein tyrosine kinase alone or in combination with inhibition of protein kinase C interferes with ischemic preconditioning in pigs. In 29 enflurane-anesthetized pigs, the LAD was cannulated and perfused from an extracorporeal circuit. Protein tyrosine kinase and protein kinase C were inhibited by continuous intracoronary infusion of genistein (5x10(-6) mol/l) and staurosporine (10(-7) mol/l), respectively. Subendocardial blood flow (ENDO) was measured with microspheres. Infarct size was analysed by TTC staining (% of LV area at risk) following 90 min low-flow ischemia and 120 min reperfusion. In the presence of genistein, 90 min ischemia at an ENDO of 0.06+/-0.01 (+/-s.e.m.) ml/min/g resulted in an infarct size of 16.7+/-4.2% (n=8). With genistein, ischemic preconditioning by 10 min ischemia and 15 min reperfusion still reduced infarct size to 6.5+/-2.7% (ENDO: 0.05+/-0. 01 ml/min/g, n=7, P<0.05). In the presence of both genistein and staurosporine, infarct size following 90 min ischemia was 14.1+/-3. 6% (ENDO: 0.06+/-0.01 ml/min/g, n=7). With genistein and staurosporine, ischemic preconditioning no longer reduced infarct size significantly (11.5+/-3.1%, ENDO: 0.06+/-0.01 ml/min/g, n=7). The effective attenuation of ischemic preconditioning only by simultaneous inhibition of both, protein kinase C and protein tyrosine kinase, suggests a complex signal cascade involving both protein kinases.

Animals↗
PubMed1998

Expression of calcium regulatory proteins in short-term hibernation and stunning in the in situ porcine heart.

BACKGROUND: Myocardial hibernation and stunning are characterised by a reversible contractile dysfunction during and after ischaemia, respectively. Calcium homeostasis might be disturbed in hibernation and stunning due to altered expression of cardiac proteins involved in calcium handling. METHODS: In enflurane-anaesthetised swine the coronary blood flow through the left anterior descending coronary artery was decreased to reduce regional contractile function (microsonometry) by approximately 50%. In transmural biopsies obtained during ischaemia and reperfusion creatine phosphate as well as the expression of sarcoplasmic reticulum calcium ATPase (SERCA), phospholamban (PLB), calsequestrin (CSQ), and troponin inhibitor (TnI) were determined. RESULTS: During ischaemia creatine phosphate, after an initial reduction, recovered back to control values, and necrosis was absent (hibernation). After 90 min of ischaemia the myocardium was reperfused for 120 min but regional contractile function continued to be depressed (stunning). PLB, SERCA, CSQ, and TnI proteins were unchanged during ischaemia as well as reperfusion. Likewise, levels of PLB and SERCA mRNAs were unchanged. CONCLUSION: It is concluded that other mechanisms than altered expression of these regulating proteins underlie the contractile dysfunction observed during acute ischaemia, short-term hibernation and stunning.

Animals↗
PubMed1998

Phosducin expression in NG 108-15 hybrid cells enhances prostaglandin E1 stimulated adenylate cyclase activity.

Phosducin (Phd), a cytosolic protein, has been proposed to compete with certain receptor kinases for Gbetagamma of heterotrimeric G proteins, and may inhibit GTPase activity of G alpha s. These suggestions together with the enhancing effect of Phd on odorant-induced cAMP accumulation let us assume a stimulatory action of the protein on intracellular signaling. Therefore, this investigation was designed to examine the excitatory effect of PGE1 on signal transmission in neuroblastoma x glioma hybrid cells (NG 108-15) overexpressing Phd. The neuronal cells stably expressing Phd were found to display a 3 to 4-fold increased sensitivity to PGE1 as compared to wild type cells, using cAMP accumulation as measure. Examination of membranes prepared from Phd-overexpressing cells revealed an elevated GTPase activity as indicated by the formation of 32Pi upon PGE1 challenge. This activity was inhibited by exogenous Phd. In addition, receptor independent stimulation of adenylate cyclase by forskolin reveals an increased formation of cAMP in Phd expressing cells, which is accompanied by an increased binding of [3H]forskolin. The findings let us propose that Phd elevates intracellular levels of functional G alpha s which accounts for the increased response to PGE1.

Adenylyl Cyclases↗
PubMed1998

A qualitative field method for monitoring pesticides in the edge-of-field runoff.

A field method is described, which allows the qualitative estimation of pesticide contamination in the edge-of-field runoff. The method employs cheap and easy-to-use runoff sampling bottles, which were installed in an agricultural stream catchment over a period of three growing seasons. During this time 18 runoff events were detected, in nine of which insecticide contamination was measured (maximum concentrations: lindane 0.7 microgram l-1 and 12.7 micrograms kg-1, parathion 20 micrograms l-1 and 728 micrograms kg-1, fenvalerate 18.4 micrograms l-1 and 924 micrograms kg-1). These insecticides were detected mainly as particle-bound chemicals. On about 80% of the occasions the presence or absence of runoff measured in the field was in agreement with a simulation of runoff presence or absence using the runoff model KINEROS.

Agriculture↗
PubMed1998

Disinhibition in the gamma motoneuron circuitry: a neglected mechanism for understanding myofascial pain syndromes?

Dysregulation in the gamma motoneuron circuitry is proposed as one mechanism to explain the development of trigger point activity in myofascial pain syndrome. Dysregulation in this context is defined operationally as significantly (and functionally) different levels of electrical activity detected in the same muscle on the left and right sides of the body that is persistently present with movement of that muscle. Neurophysiological concepts as they pertain to muscles and motor control principles are reviewed. Research is integrated that ties together material from diverse fields of psychology and medicine. Dysregulation in the gamma motoneuron circuitry may lead to disinhibition of muscle that causes it to remain hyperactive after contraction, generate excessive electrical activity during movement, and/or inappropriately coactivate with other muscles during movement. Any or all of these phenomena may occur with dysregulation. Such dysregulation may be corrected by learning. Immediate clinical implications are discussed, including the addition of specifically targeted neuromuscular retraining procedures via surface electromyography, as well as some conceptual and research issues that require further clarification.

Facial Muscles↗
PubMed1998

Activity restriction and prior relationship history as contributors to mental health outcomes among middle-aged and older spousal caregivers.

In a sample of cancer patients (n = 75) and spousal caregivers (24 men and 51 women), restriction in caregiver routine activities mediated associations between caregiving stress (patient symptom severity) and caregiver depressed affect and resentment. Moreover, the antecedents and affective consequences of caregiver activity restriction were consistent with the theory of communal relationships (e.g., M. S. Clark & J. Mills, 1979, 1993). If a relationship had been communal in the past (i.e., characterized by mutual concern for and responsiveness to one another's needs), activity restriction was predicted by intimacy and affectional loss (rather than by the severity of patient symptoms) and in turn predicted caregiver depressed affect. Among caregivers in less communal relationships, activity restriction was predicted by severity of patient symptoms (rather than by intimacy and affectional loss) and in turn predicted resentment of care recipients and the caregiving role.

Adaptation, Psychological↗
PubMed1998

Caregiving from the recipient's perspective: negative reactions to being helped.

This study investigated predictors of negative reactions to assistance provided to a physically disabled spouse (n = 276, M age: 76.6 years) and the consequences that negative reactions may have for the mental health of the care recipient. Nearly 40% of recipients reported some emotional distress in response to help they received. Fatalistic attitudes, perceived control, and lower self-esteem predicted greater helping distress, whereas lower self-esteem, fatalistic beliefs, and marital conflict were especially likely to lead to helping distress for those who received higher levels of assistance. Helping distress was also found to predict depression as much as 1 year later, suggesting that there may be long-term consequences of negative reactions to assistance. These findings have important implications for the study of caregiving and the relationship between physical impairment and depression.

Activities of Daily Living↗
PubMed1998

K(ATP)-channel activation: effects on myocardial recovery from ischaemia and role in the cardioprotective response to adenosine A1-receptor stimulation.

1. Optimization of myocardial energy substrate metabolism improves the recovery of mechanical function of the post-ischaemic heart. This study investigated the role of K(ATP)-channels in the regulation of the metabolic and mechanical function of the aerobic and post-ischaemic heart by measuring the effects of the selective K(ATP)-channel activator, cromakalim, and the effects of the K(ATP)-channel antagonist, glibenclamide, in rat fatty acid perfused, working hearts in vitro. The role of K(ATP) channels in the cardioprotective actions of the adenosine A1-receptor agonist, N6-cyclohexyladenosine (CHA) was also investigated. 2. Myocardial glucose metabolism, mechanical function and efficiency were measured simultaneously in hearts perfused with modified Krebs-Henseleit solution containing 2.5 mM Ca2+, 11 mM glucose, 1.2 mM palmitate and 100 mu l(-1) insulin, and paced at 300 beats min(-1). Rates of glycolysis and glucose oxidation were measured from the quantitative production of 3H20 and 14CO2, respectively, from [5-3H/ U-14C]-glucose. 3. In hearts perfused under aerobic conditions, cromakalim (10 microM), CHA (0.5 microM) or glibenclamide (30 microM) had no effect on mechanical function. Cromakalim did not affect glycolysis or glucose oxidation, whereas glibenclamide significantly increased rates of glycolysis and proton production. CHA significantly reduced rates of glycolysis and proton production but had no effect on glucose oxidation. Glibenclamide did not alter CHA-induced inhibition of glycolysis and proton production. 4. In hearts reperfused for 30 min following 30 min of ischaemia, left ventricular minute work (LV work) recovered to 24% of aerobic baseline values. Cromakalim (10 microM), administered 5 min before ischaemia, had no significant effect on mechanical recovery or glucose metabolism. CHA (0.5 microM) significantly increased the recovery of LV work to 67% of aerobic baseline values and also significantly inhibited rates of glycolysis and proton production. Glibenclamide (30 microM) significantly depressed the recovery of mechanical function to < 1% of aerobic baseline values and stimulated glycolysis and proton production. 5. Despite the deleterious actions of glibenclamide per se in post-ischaemic hearts, the beneficial effects of CHA (0.5 microM) on the recovery of mechanical function and proton production were not affected by glibenclamide. 6. The data indicate that the cardioprotective mechanism of adenosine A1-receptor stimulation does not involve the activation of K(ATP)-channels. Furthermore, in rat fatty acid perfused, working hearts, stimulation of K(ATP)-channels is not cardioprotective and has no significant effects on myocardial glucose metabolism.

Adenosine↗
PubMed1998

D alpha3, a new functional alpha subunit of nicotinic acetylcholine receptors from Drosophila.

Nicotinic acetylcholine (ACh) receptors (nAChRs) are important excitatory neurotransmitter receptors in the insect CNS. We have isolated and characterized the gene and the cDNA of a new nAChR subunit from Drosophila. The predicted mature nAChR protein consists of 773 amino acid residues and has the structural features of an ACh-binding alpha subunit. It was therefore named D alpha3, for Drosophila alpha-subunit 3. The d alpha3 gene maps to the X chromosome at position 7E. The properties of the D alpha3 protein were assessed by expression in Xenopus oocytes. D alpha3 did not form functional receptors on its own or in combination with any Drosophila beta-type nAChR subunit. Nondesensitizing ACh-evoked inward currents were observed when D alpha3 was coexpressed with the chick beta2 subunit. Half-maximal responses were at approximately 0.15 microM ACh with a Hill coefficient of approximately 1.5. The snake venom component alpha-bungarotoxin (100 nM) efficiently but reversibly blocked D alpha3/beta2 receptors, suggesting that D alpha3 may be a component of one of the previously described two classes of toxin binding sites in the Drosophila CNS.

Amino Acid Sequence↗