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Biomedical subjects

M Böhm

Publications and source records attributed to M Böhm.

At least 343 records · Page 19Linked to original sources
PubMed1993

[Recurrent paroxysmal neck swellings as the primary manifestation of a pheochromocytoma].

A 45-year-old female had been suffering for about 6 months almost daily from paroxysmal neck swellings with occasional difficulties in swallowing and from non-specific abdominal complaints. Hormone analyses, performed because of the marked blood pressure increase up to 210/120 mm Hg during such an attack, revealed an increase in vanillyl mandelic acid and epinephrine concentrations in the 24-hour urine. CT demonstrated a tumour of 4 x 5 x 5 cm size in the region of the right adrenal. The paroxysmal neck swellings and blood pressure increase could be reproduced by means of pressure applied over the tumour range with the ultrasound transducer. The tumour was extirpated and histology revealed a phaeochromocytoma. For more than one year now the patient has been free from complaints. To date, recurrent neck swellings have not been reported in association with a phaeochromocytoma. Possible causes may be an enhanced congestion of the deep neck vessels during paroxysmal blood pressure increase or an enhanced response by the adrenoreceptors of these vessels to the released catecholamines.

Adrenal Gland Neoplasms↗
PubMed1993

Force-frequency-relation in human atrial and ventricular myocardium.

In human heart failure, an increase in frequency of stimulation is followed by a reduced force of contraction in vivo and in vitro. The present study aimed to investigate whether a different origin of the myocardial sample or pretreatment with the cardioprotective agent 2,3-butanedione-monoxime (BDM) influences the force-frequency-relationship in electrically driven muscle strips taken from failing and nonfailing human myocardium. With as well as without pretreatment with BDM, the altered force-frequency-relationship in failing compared to nonfailing human ventricular myocardium can be observed. The effectiveness and the potency to increase force of contraction following an increase in frequency of stimulation was significantly higher in atrial than in ventricular myocardium in nonfailing and failing tissue. The different observations in atrial and ventricular myocardium provide evidence for functionally relevant differences in the electromechanical coupling between the human atrial and ventricular myocardium.

Adult↗
PubMed1993

Correlation of myosin heavy chain expression in the rat with cAMP in different models of hypertension-induced cardiac hypertrophy.

Both genetically determined and artificially-induced hypertension lead to cardiac hypertrophy and shift the myosin heavy chain (MHC) expression to the beta-MHC form. The cause of this change in gene expression is unknown. To contribute to the understanding of this phenomenon, we correlated the MHC expression in the left ventricle with basal, Forskolin- and isoprenaline-stimulated adenylate cyclase activity (cAMP production of membrane fractions). We used two control rat strains [Wistar-Hagemann (WH), Wistar-Kyoto (WKY)] and several rat models of hypertension: one clip-one kidney (1C-1K), desoxycorticosterone-treated rats (DOCA), rats with reduced renal mass (RRM) and spontaneously hypertensive rats (SHR). The level of hypertension correlated positively with the degree of cardiac hypertrophy (P < 0.01) and negatively (P < 0.05) with cAMP production, e.g. the higher the degree of hypertension, the lower both basal and stimulated cAMP levels. In addition we found that the lower the basal, isoprenaline- and Forskolin-stimulated cAMP production the lower was the expression of the alpha-MHC isoenzyme (P < 0.05). Thus, our data suggest that the decreased alpha-MHC expression upon hypertension-induced cardiac hypertrophy could be mediated via decreased adenylate cyclase activity and thus decreased intracellular cAMP production.

Adenylyl Cyclases↗
PubMed1993

Detection of tumor-specific homozygous deletions in human biopsies by polymerase chain reaction.

Cancer is associated with homozygous deletions of specific DNA sequences that are in some instances too small to be detectable by cytogenetic methods or Southern blot analysis. Such small tumor-specific deletions can be detected, however, by the polymerase chain reaction (PCR) provided that tumor cells are meticulously and verifiably isolated from contaminating nontumor cells. Nontumor cells can give positive PCR results and thus obscure the detection of deletions. Using a method that allows accurate and verifiable excision of tumor cells for subsequent PCR analysis, homozygous deletions, one in a putative tumor suppressor gene on chromosome 8 and one in the p53 gene, were detected in two out of 20 human lung carcinomas investigated.

Adenocarcinoma↗
PubMed1993

Evidence for an interaction of halothane with the L-type Ca2+ channel in human myocardium.

BACKGROUND: The present study was aimed at investigating the underlying mechanisms for the cardiac depressant effect of halothane. To test the hypothesis, whether there is an interaction of halothane with the L-type Ca2+ channels in human myocardium and whether this interaction has functional consequences for force generation in the human myocardium, effects of halothane were studied in human myocardial membranes and isolated cardiac preparations. METHODS: The experiments were performed on isolated, electrically driven ventricular preparations (1 Hz, 37 degrees C) and cardiac membranes with radioligand binding experiments using 3H-PN 200-110. Myocardium from human failing and non-failing hearts was obtained at cardiac surgery. RESULTS: Halothane produced a negative inotropic effect, which was similar in nonfailing and failing myocardium. Halothane shifted the concentration-response curve for the positive inotropic effect of the L-type Ca2+ channel agonist BayK 8644 to the right. The density of dihydropyridine receptors as judged from 3H-PN 200-110 radioligand binding experiments was similar in nonfailing and failing myocardium, whereas the density of beta-adrenoceptors was reduced. Halothane concentration dependently reduced the binding of 3H-PN 200-110, an antagonist at the 1,4 dihydropyridine receptor site of the Ca2+ channel, to myocardial membranes. Furthermore, halothane produced a rightward shift of the competition curve of BayK 8644 for binding of 3H-PN 200-110 to cardiac membranes. CONCLUSIONS: In human ventricular myocardium, halothane exhibits an interaction with the L-type Ca2+ channel by interfering with its dihydropyridine binding sites. This may explain, at least in part, the observed negative inotropic effect of this agent and could hypothetically play a general role in its anesthetic effects.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Gene expression of cardiac beta 1-adrenergic receptors during the development of hypertension in spontaneously hypertensive rats.

OBJECTIVE: To study adrenergic receptors in the heart tissues of genetically hypertensive rats by evaluating the gene expression and the membrane protein density of beta 1-adrenergic receptors using steady-state messenger RNA (mRNA) levels and a radioligand binding assay, respectively. DESIGN: We compared prehypertensive (5-week-old) and early-hypertensive (13-week-old) spontaneously hypertensive rats (SHR) with age-matched Wistar-Kyoto (WKY) normotensive control rats. METHODS: Polyadenylated RNA was extracted from individual hearts and analysed by the slot-blot technique using a beta 1-adrenergic receptor complementary DNA probe. beta-Adrenergic receptors in myocardial membranes were studied by radioligand binding assay using [125I]-cyanopindolol and the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively. RESULTS: beta 1-Adrenergic receptor mRNA levels were slightly higher, and membrane protein density was similar in prehypertensive SHR and age-matched WKY rats. However, both beta 1-adrenergic receptor mRNA levels and beta 1-adrenergic receptor density were lower in the hypertensive SHR than in the control rats. beta 1-Adrenergic receptor mRNA was significantly reduced in older rats of both strains, and this reduction was most evident in the SHR. CONCLUSIONS: The absence of downregulation of beta 1-adrenergic receptors in young SHR, despite published data indicating a higher cardiac noradrenaline turnover than in WKY rats, may suggest that the cardiac hyperadrenergic activity observed in prehypertensive SHR is maintained, at least in part, by the participation of peripheral, postsynaptic component(s) involving beta 1-adrenergic receptor dysregulation. In addition, the present data suggest that the previously reported evidence of an age-related decrease in cardiac beta 1-adrenergic receptors in rats may be determined at the transcriptional level.

Animals↗
PubMed1993

Effects of halothane on beta-adrenoceptors and M-cholinoceptors in human myocardium: radioligand binding and functional studies.

We investigated whether a postsynaptic sensitization by halothane for beta-adrenoceptor-mediated effects occurs in diseased human myocardium. In addition, we hoped to achieve further insights into the cellular mechanism and, in particular, the role of M-cholinoceptors and beta-adrenoceptors. The experiments were performed on isolated, electrically driven atrial and ventricular preparations and membranes isolated from human hearts obtained at cardiac surgery. Halothane concentration-dependently reduced binding of [3H]quinuclidinylbenzilate ([3H]QNB) to M-cholinoceptors but had no effect on equilibrium saturation binding of 125-iodocyanopindolol (125I]Cyp) to beta-adrenoceptors. High-and low-affinity states of agonist binding of carbachol to M-cholinoceptors were not affected, but halothane inhibited high-affinity binding of isoprenaline to beta-adrenoceptors. In contrast, halothane augmented the potency and efficacy of the positive inotropic effect of isoprenaline in atrial and ventricular myocardium. The "direct" negative inotropic effect in atrial and the "indirect" negative inotropic effect in ventricular myocardium by M-cholinoceptor stimulation with carbachol was unchanged by halothane. We conclude that in human atrial and ventricular myocardium a sensitization to catecholamines is induced by halothane, the mechanism of which is likely to be located at the postsynaptic level of the sympathetic neuroeffector junction. Facilitated coupling of beta-adrenoceptors or an uncoupling of M-cholinoceptors with reduced negative inotropic effects of agonist does not play a role. We showed that sensitization of this system apparently is due to direct actions of halothane on the G-protein-coupled adenylate cyclase complex.

Catecholamines↗
PubMed1993

Effects of exercise on myocardial adenylate cyclase and Gi alpha expression in senescence.

The present study investigated the influence of physical training on alterations leading to reduced adenosine 3',5'-cyclic monophosphate (cAMP) formation in aged myocardium. Senescent (28-mo-old) rats underwent a moderate treadmill exercise program and were compared with sedentary controls. In myocardial membranes from aged rats, isoprenaline-stimulated adenylate cyclase activity (AC) was reduced compared with that in young animals and was accompanied by an increase of pertussis toxin substrates (17.5%) and an increased amount of immunodetectable inhibitory guanine nucleotide-binding proteins (Gi alpha; 72%). Physical training reduced the amount of Gi alpha proteins (30-35%) in young and old animals and enhanced only isoprenaline-stimulated AC in the aged rats, and basal and 5'-guanylylimidodiphosphate [Gpp(NH)p]- as well as isoprenaline-stimulated AC in young rats. Physical training or aging had no effect on the number of beta-adrenoceptors or m-cholinoceptors or on forskolin-stimulated AC in either group. The amount of immunodetectable stimulatory guanine nucleotide-binding proteins (Gs alpha) using an antiserum raised against the COOH-terminal peptide of Gs alpha (RMHLRQYELL) was unchanged in either condition. It is concluded that enhanced Gi alpha expression might be one mechanism leading to depressed cAMP formation in aged myocardium. Depressed AC and increased Gi alpha can be partially reversed by physical training, especially in young myocardium. Gi alpha might serve as a regulator of cardiac AC in a variety of physiological and pathophysiological situations in the absence of beta-adrenoceptor changes.

Adenylate Cyclase Toxin↗
PubMed1993

Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart.

BACKGROUND: In chronic heart failure, the positive inotropic effects of beta-adrenergic receptor agonists are greatly reduced, in part as a result of two alterations of the cardiac beta-adrenergic receptors: loss of their function (receptor uncoupling) and reduction of their number (downregulation). In vitro studies have shown that a major mechanism leading to beta-adrenergic receptor uncoupling involves phosphorylation of the receptors by the specific beta-adrenergic receptor kinase (beta ARK). METHODS AND RESULTS: We have therefore investigated expression of beta ARK and beta-adrenergic receptors in samples from the left ventricles of patients with dilated cardiomyopathy or ischemic cardiomyopathy and from nonfailing control ventricles. Contractile responses to beta-receptor stimulation were decreased in the failing hearts compared with control hearts, whereas those to forskolin and calcium remained unchanged. The messenger RNA (mRNA) levels of beta ARK, beta 1- and beta 2-receptors, and of glyceraldehyde phosphate dehydrogenase and beta-actin as controls were measured by quantitative polymerase chain reactions. In addition, beta ARK enzyme activity assays were performed, and the levels of beta 1- and beta 2-receptors were determined by radioligand binding. beta ARK mRNA levels were increased almost threefold in both forms of heart failure, and beta ARK activity was enhanced. beta 1-Receptor mRNA levels and beta 1-receptor numbers were decreased by approximately 50% in both failing groups, whereas these levels were unaltered for beta 2-receptors. There were no differences between dilated and ischemic cardiomyopathy for any of these parameters. CONCLUSIONS: In addition to other alterations found in failing hearts, the diminished response to beta-receptor agonists appears to involve the combined effects of enhanced expression of beta ARK and reduced expression of beta 1-receptors.

Adult↗
PubMed1993

Effect of inotropic stimulation on the negative force-frequency relationship in the failing human heart.

BACKGROUND: In severe human heart failure, an increase in frequency of stimulation is accompanied by a reduced force of contraction in vivo and in vitro. The present study was aimed to investigate whether inotropic stimulation influences the inverse force-frequency relationship in failing human myocardium. METHODS AND RESULTS: The effects of the cAMP-independent positive inotropic agents ouabain (0.01 mumol/L) and BDF 9148 (0.1 mumol/L) as well as the beta-adrenoceptor agonist isoprenaline (0.01 mumol/L and 0.1 mumol/L) on the force-frequency relationship in electrically driven papillary muscle strips from nonfailing (brain death, n = 5) and terminally failing (NYHA class IV, heart transplants, dilated cardiomyopathy, n = 22) human myocardium were studied. For comparison, we examined the effect of elevation of the extracellular Ca2+ concentration (3.2 mmol/L and 6.2 mmol/L). In nonfailing myocardium, force of contraction, peak rate of tension rise, and peak rate of tension decay increased, whereas time to peak tension and time to half relaxation decreased following an increase of stimulation frequency. In NYHA class IV, force of contraction gradually declined followed by changes of other parameters of isometric contraction. Moderate stimulation of contractility by isoprenaline (0.01 mumol/L) partly reversed the negative force-frequency relationship in NYHA class IV and preserved the positive force-frequency relationship in nonfailing myocardium. The addition of ouabain and BDF 9148 together restored completely the force-frequency relationship in NYHA class IV. In contrast, high concentrations of isoprenaline (0.1 mumol/L) and an elevation of the extracellular Ca2+ concentration enhanced the decline in force of contraction in the presence of higher stimulation frequencies. CONCLUSIONS: It is concluded that functionally important changes occur in the intracellular Ca2+ handling, leading to the negative force-frequency relationship in terminally failing human myocardium. Interestingly, the negative force-frequency relationship can be restored by agents producing positive inotropic effects by elevation of the intracellular Na+ concentration. These findings suggest that hitherto unknown changes in the intracellular ionic homeostasis occur in the failing human heart. Even though increasing [Ca2+]i in failing heart cells may be detrimental, increasing [Na+bdi may be beneficial through a mechanism independent of an increase in [Ca2+]i.

Adult↗
PubMed1993

Circadian blood pressure variation in transgenic hypertensive rats.

Automatic, around-the-clock blood pressure measurements have increased our understanding of hypertension in humans. Patients with essential hypertension display patterns similar to those observed in normotensive subjects, whereas those with secondary hypertension frequently show abnormal circadian rhythms characterized by a failure to reduce blood pressure at night. We have modeled this situation in rats. Normotensive Wistar-Kyoto and Sprague-Dawley rats, spontaneously hypertensive rats, and rats made hypertensive by transgenic implantation of the mouse salivary gland renin gene (TGR[mRen-2]27) underwent chronic implantation of a device that telemetrically monitored their blood pressures, heart rates, and motor activities. In either normotensive or hypertensive rats, motor activity peaked during the dark phase, indicating that animals from all strains were nocturnal. In both normotensive and spontaneously hypertensive rats, the 24-hour blood pressure and heart rate profiles showed peak values during the rats' active phase at night, ie, between midnight and 3 AM. In the transgenic rats, on the other hand, blood pressure values were at maximum during the day around noon, when the rats were in their resting phase. The heart rate of the transgenic rats nevertheless still peaked around midnight. These data suggest that normotensive rats and those with primary and secondary hypertension display circadian rhythms of blood pressure and heart rate analogous to those observed in normotensive and primary or secondary hypertensive humans, respectively. The TGR(mRen-2)27 strain may be a useful model with which to investigate the mechanisms responsible for alterations in circadian rhythms of blood pressure and heart rate in forms of secondary hypertension.

Analysis of Variance↗
PubMed1993

Cardiac adenylyl cyclase, beta-adrenergic receptors, and G proteins in salt-sensitive hypertension.

The present study investigated whether high salt intake (8%) in Dahl salt-sensitive and salt-resistant rats with and without hypertension produces a heterologous desensitization of cardiac adenylyl cyclase as observed in various types of hypertension and human heart failure. In membranes from Dahl salt-sensitive rats on a high-salt diet (8%) basal, isoproterenol-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylyl cyclase was reduced compared with the low-salt (0.4%) group and Dahl salt-resistant rats on either 0.4% or 8% sodium chloride. The activity of the catalyst was depressed, and the expression of the immunodetectable inhibitory G proteins Gi alpha was increased in Dahl salt-sensitive rats on 8% sodium chloride, whereas the density of beta-adrenergic receptors and the activity of the stimulatory G protein Gs alpha reconstituted into Gs alpha-deficient S49 cyc- mouse lymphoma cell membranes were unchanged in any condition studied. We conclude that high salt intake in salt-sensitive hypertensive Dahl rats produces hypertension, cardiac hypertrophy, and heterologous desensitization of cardiac adenylyl cyclase. The latter alteration is due to an increase of Gi alpha proteins and a depressed catalyst activity of adenylyl cyclase. The results demonstrate that heterologous adenylyl cyclase desensitization can precede the development of contractile dysfunction in later stages and can occur independently of changes in beta-adrenergic receptors.

Adenosine Diphosphate Ribose↗
PubMed1993

Cellular localization of endothelial alkaline phosphatase reaction product and enzyme protein in the myocardium.

Myocardial capillary endothelial cells, arteriolar endothelial cells, and the arterial adventitia show positive alkaline phosphatase (AP) enzyme reaction and immunoreactivity in both rat and human hearts. In guinea pigs, however, capillary endothelial staining is discontinuous and arterial adventitia is negative. The ultrastructural correlate of discontinuous capillary staining is a pronounced labeling of pericytes in guinea pig heart and relatively weak endothelial staining. In rat and human heart, enzyme reaction products are localized mainly on plasma membranes and cytotic vesicles of endothelial cells. Comparison of two strains of rat reveals a more dense deposition of enzyme reaction product along the luminal and particularly along the abluminal plasma membrane of Sprague-Dawley rats than of Wistar rats. Quantitative analysis of immunogold labeled anti-AP antibody density confirms the pronounced polarity of capillary endothelial cell labeling in Sprague-Dawley rats. More than 80% of total endothelial AP protein in Sprague-Dawley rats is localized over the abluminal plasma membrane and basal lamina, as compared with less than 30% in Wistar rats. Moreover, the total endothelial cell labeling is almost sixfold higher in Sprague-Dawley than in Wistar rats. Total endothelial labeling and proportion of labeling on the abluminal endothelial plasma membrane in human hearts is intermediate between the two strains of rat. The strain and species differences in enzyme distribution could provide important information concerning enzyme function.

Adolescent↗
PubMed1993

Effects of the alpha 1-adrenoceptor agonist phenylephrine in pig heart. Study of the direct action on contractile proteins.

The effects of the alpha 1-adrenoceptor agonist phenylephrine (CAS 59-42-7) on Ca++ sensitivity of the contractile proteins and on force of contraction of the heart were studied in right ventricular preparations isolated from pigs. In contracting trabeculae phenylephrine (3-100 mumol/l) increased force of contraction in the presence of propranolol maximally by 91.8 +/- 36.2% (n = 5). The effect of phenylephrine was antagonized by prazosin, indicating an alpha-adrenoceptor-mediated positive inotropic effect. Glycerol- and Lubrol WX-extracted trabeculae ("chemically skinned") were activated by Ca(++)-concentrations between 0.01 and 47.7 mumol/l. Phenylephrine (0.1-100 mumol/l) did not affect the Ca++ activated force in these preparations. A direct intracellular action of phenylephrine on contractile proteins is thus rather unlikely to contribute to the positive inotropic effect of phenylephrine.

Adrenergic alpha-Agonists↗