From sarcomeric mutations to heart disease: understanding familial hypertrophic cardiomyopathy.
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Animals↗
Biomedical subjects
A Maass
Publications and source records attributed to A Maass.
Inferring traits from behaviors versus behaviors from traits: the induction-deduction asymmetry.
It is argued that inductive inferences from behaviors to traits are performed more frequently than deductive inferences from traits to behaviors-a phenomenon referred to as the induction-deduction asymmetry. Two experiments are reported in which behavior-to-trait inferences and trait-to-behavior inferences were compared within the same paradigm: Participants learned a series of descriptions of a target person, half of which were presented in trait form, half in behavior form. A subsequent recognition task was constructed so that some of the items (traits and behaviors) had actually been seen, some were entirely new, and some were new but had been implied by the information given. The 2 experiments provide clear evidence for the hypothesis that traits implied by a behavior are more frequently misidentified as already seen than behaviors implied by a trait. Response-time data in Experiment 2 further suggest that inferences from behaviors to traits are made on-line, whereas inferences from traits to behaviors appear to be memory based.
Adult↗
Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse.
In this paper, we describe the effects of voluntary cage wheel exercise on mouse cardiac and skeletal muscle. Inbred male C57/Bl6 mice (age 6-8 wk; n = 12) [corrected] ran an average of 4.3 h/24 h, for an average distance of 6.8 km/24 h, and at an average speed of 26.4 m/min. A significant increase in the ratio of heart mass to body mass (mg/g) was evident after 2 wk of voluntary exercise, and cardiac atrial natriuretic factor and brain natriuretic peptide mRNA levels were significantly increased in the ventricles after 4 wk of voluntary exercise. A significant increase in the percentage of fibers expressing myosin heavy chain (MHC) IIa was observed in both the gastrocnemius and the tibialis anterior (TA) by 2 wk, and a significant decrease in the percentage of fibers expressing IIb MHC was evident in both muscles after 4 wk of voluntary exercise. The TA muscle showed a greater increase in the percentage of IIa MHC-expressing fibers than did the gastrocnemius muscle (40 and 20%, respectively, compared with 10% for nonexercised). Finally, the number of oxidative fibers as revealed by NADH-tetrazolium reductase histochemical staining was increased in the TA but not the gastrocnemius after 4 wk of voluntary exercise. All results are relative to age-matched mice housed without access to running wheels. Together these data demonstrate that voluntary exercise in mice results in cardiac and skeletal muscle adaptations consistent with endurance exercise.
Acclimatization↗
A role for calreticulin in the adult heart?
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Animals↗
Animal models of hypertrophic cardiomyopathy.
Familial hypertrophic cardiomyopathy (FHC) is an autosomal-dominant disease that is both clinically and genetically heterogeneous. Disease-causing mutations have been found in eight genes encoding structural components of the thick and thin filament systems of the cardiac myocyte; it has therefore been coined a disease of the sarcomere. How each mutation leads to the diverse clinical phenotypes is still obscure, and research in this area is very active. Many approaches have been used to characterize the pathogenesis of the disease. Biochemical characterization of mutant alleles expressed in vitro has shed some insight into the functional deficits of several mutant alleles of myosin heavy chain, troponin-T, and alpha-tropomyosin. Transgenic animal models for FHC have been created to gain further insight into the pathogenesis of this disease. Most of these models have been made in mice; however, recently a transgenic rabbit model has been created. In addition, there are several natural-occurring forms of FHC in animals that will be interesting to explore. The discovery of additional responsible genes and the elucidation of the molecular mechanisms of pathogenesis through the use of animal models promise improved and early diagnosis and the potential for developing specific, mutation-, or mechanism-based therapeutics.
Animals↗
[Significance of calcium detection with electron-beam tomography in coronary disease].
PURPOSE: Coronary calcium is a powerful indicator of arteriosclerosis and can be detected very precisely with electron beam tomography. The method can be applied in patients with known coronary artery disease or in asymptomatic patients at risk of arteriosclerotic disease. METHODS: The standard protocol of EBT consists of 30 to 40 slices of 3-mm thickness with a scan time of 100 ms, no overlap. No contrast medium is needed. The total scan can be performed within one breathhold. The calcium score is calculated as described by Agatston. Radiation exposure amounts to 0.8 mSv per total screen. We used spiral CT with and without ECG trigger as an alternative. RESULTS: At the University of Munich we performed an EBT scan of the heart in 1100 patients within the last year. In 567 patients coronary angiography was performed also (+/- 3 days). Confirming previous reports in the literature, we found a correlation of the calcium score with the age and gender of the patients. Severe coronary artery disease (stenoses > or = 75%) was associated with significantly more calcium than less severe CAD. The calcium score did not discriminate between one-, two- and three-vessel disease. The site of calcification does not correlate with the localization of stenoses. Thirty-three percent of the patients with significant coronary artery disease showed a normal age-adjusted calcium score; a total of 8.1% of patients with severe stenoses did not reveal any coronary calcification (score = 0). With asymptomatic patients there are only a few studies available. Soft plaques cannot be detected with EBT, but in most patients soft plaques occur together with hard plaques. Our results show that spiral CT of the newest generation may also be used for calcium screening. There was an excellent correlation of the calcium scores of EBT and spiral CT at all levels of calcification. DISCUSSION: Coronary calcium is a sensitive marker of coronary artery disease. In the clinical setting EBT is indicated in patients with known coronary artery disease (to evaluate prognosis), in patients who are unable to perform a stress test, and in patients with atypical chest pain. However, lack of calcification may be associated with severe stenoses in a minority of patients. The clinical value in asymptomatic patients needs to be defined: randomized studies are necessary. We see a possible indication in patients with known risk factors, in whom primary preventive strategies could be performed more selectively and cost-effectively.
Adolescent↗
Expression of the plasma membrane Ca2+-ATPase in myogenic cells.
To study the physiological function of the plasma membrane calmodulin-dependent calcium ATPase (PMCA) in intact cells, L6 myogenic cell lines stably overexpressing the human PMCA isoform 4CI (= human PMCA isoform 4b) were generated. Several independent L6 clones and controls stably transfected with the empty expression vector were analyzed in detail. The resting cytosolic calcium level in hPMCA4CI-overexpressing muscle cells (measured by the Fura-2 method) was significantly reduced by 20-30% compared with controls. This was shown in a cytosolic window of 1322 single cells (p < 0.01). Furthermore, the differentiation process of these cells was remarkably accelerated compared with control myoblasts and parental nontransfected L6 cells as assessed by multinucleated myotube formation and creatine phosphokinase activity elevation. After 4 and 6 days of differentiation, PMCA-overexpressing L6 cells from four independent clones displayed a 3- and 4-fold higher creatine phosphokinase activity compared with controls (n = 5, p < 0.02). These results may extend the concept of the function of the PMCA from simple prevention of calcium overload to an active involvement in intracellular calcium regulation with potentially important consequences for cellular functions.
Animals↗
Opposite effects of alcuronium on agonist and on antagonist binding to muscarinic receptors.
Alcuronium is known to retard allosterically the dissociation of [3H]N-methylscopolamine from muscarinic M2 receptors, thereby augmenting the binding of this antagonist. Functionally, alcuronium behaves as a weak antimuscarinic agent and induces in combination with N-methylscopolamine an overadditive antimuscarinic action with oxotremorine-M as the agonist. The effect of alcuronium on the binding of [3H]oxotremorine-M was studied in porcine heart homogenates. Agonist binding was concentration dependently inhibited with a Ki = 0.48 +/- 0.03 microM (means +/- S.D., n = 3). Under identical conditions [3H]N-methylscopolamine binding was elevated. Alcuronium, 100 microM, which nearly prevented the dissociation of [3H]N-methylscopolamine, retarded the rate of dissociation of [3H]oxotremorine-M only by a factor of two. These findings support the notion that the overadditive antimuscarinic action of alcuronium in conjunction with N-methylscopolamine is based on a shift by alcuronium of the interplay between agonist and antagonist in favour of the antagonist.
Alcuronium↗
Lack of evidence of areas of slow conduction early after radiofrequency current application at porcine atrial myocardium.
Electrophysiological sequelae after creation of atrial myocardial lesions by radiofrequency current (RFC) application have not been studied in vitro. During general anesthesia, a steerable 6 French electrode catheter, equipped with a thermistor at the 4-mm tip electrode, was positioned at the lateral atrial aspect of the tricuspid valve annulus in 5 piglets (German Landrace, mean body weight 12.5 kg). Temperature-guided (75 degrees C) RFC (500 kHz) was delivered over 30 seconds. Forty-eight hours later, the hearts were removed and placed in ice-cold Turner's solution. The right atria were dissected, and the RFC lesions with surrounding tissue were cut out and transferred to an organ bath according to Steiert. Preparations were superfused with Turner's solution at 37 degrees C. Pacing of the viable tissue at the border of the preparations was accomplished at a cycle length of 500 ms. Whole atrial preparations were impaled (76 to 150 impalements per specimen) with KCl capillary microelectrodes containing 3 MKCl. In the surrounding viable tissue of the five preparations, mean maximum diastolic transmembrane potential ranged from -61.3 to -63.7 mV, mean action potential duration at 90% repolarization ranged from 135.2 to 156.1 ms, and mean maximum upstroke velocity of phase 0 of the action potential was between 104.7 and 112.9 V/sec. Statistical analysis revealed no significant differences among all 3 variables. No intracellular action potential was recorded from the surface of all 5 lesions. The surrounding tissue was sharply demarcated, with unaltered transmembrane action potential characteristics in the vicinity of the lesions. Areas of slow conduction were not observed. Lack of evidence of areas of slow conduction after RFC application to the atrial myocardium may imply that this technique is safe regarding occurrence of atrial tachyarrhythmias.
Action Potentials↗
Potentiation by alcuronium of the antimuscarinic effect of N-methylscopolamine in guinea pig left atria.
Alcuronium is known to stabilize allosterically the binding of the muscarinic antagonist N-methylscopolamine to muscarinic M2 receptors and thus to elevate the equilibrium binding of N-methylscopolamine in homogenized cardiac tissue. In order to check for a functional consequence of this effect, the action of alcuronium alone and in combination with N-methylscopolamine was determined in contracting guinea pig left auricles with oxotremorine-M as the negative inotropic agonist. For sake of comparison, the allosteric modulator W84 = hexane-1,6-bis(dimethyl-3'- phthalimidopropyl-ammonium bromide) was included. Alcuronium displayed a weak antimuscarinic action (pA2 = 5.7). In conjunction with 10(-7) M N-methylscopolamine, alcuronium (> or = 10(-6) M) induced a more pronounced antimuscarinic effect than expected for a combination of competitive antagonists. The extent of overadditivity with combinations of W84 and 10(-7) M N-methylscopolamine was smaller. In conclusion, alcuronium potentiates the antimuscarinic effect of N-methylscopolamine in contracting cardiac preparations with high effectivity.
Alcuronium↗
Linguistic intergroup bias: differential expectancies or in-group protection?
The linguistic intergroup bias describes the tendency to communicate positive in-group and negative out-group behaviors more abstractly than negative in-group and positive out-group behaviors. This article investigated whether this bias is driven by differential expectancies or by in-group protective motives. In Experiment 1, northern and southern Italian participants (N = 151) described positive and negative behaviors of northern or southern protagonists that were either congruent or incongruent with stereotypic expectancies. Regardless of valence, expectancy-congruent behaviors were described more abstractly than incongruent ones. Experiment 2 (N = 40) showed that language is used in an equally biased fashion for individuals as previously demonstrated for groups. Experiment 3 (N = 192) induced expectancies experimentally and found greater abstraction for expectancy-congruent behaviors regardless of valence. All experiments confirmed the differential expectancy approach.
Adolescent↗
Hormonal induction of an immediate-early gene response in myogenic cell lines--a paradigm for heart growth.
Cardiac hypertrophy is characterized by growth of myocardial cells without proliferation. Many endo- paracrine stimuli such as angiotensin II, endothelin, alpha 1-adrenergic agonists, and insulin have been shown to be able to induce cardiac hypertrophy either in vivo or in vitro. We have used the myoblast model of differentiation and proliferation to determine nuclear signal transduction mechanisms in muscle and (by analogy) cardiac growth. The first nuclear event known to occur when a growth stimulus acts upon a cell is induction of a family of immediate-early genes. Our group focused on the role of one of these genes, the early growth response gene-1 (Egr-1). We have shown that this gene is induced in isolated adult cardiac myocytes in the presence of endothelin. An anti-sense oligonucleotide complementary to the first six codons of the Egr-1 mRNA abolishes the stimulation of protein synthesis induced by endothelin. In the present study we further characterized paracrine growth stimuli in the myogenic cell line Sol8, which was used as a paradigm to further investigate mechanisms of paracrine growth induction. We demonstrated that a variety of candidate endo- paracrine stimuli for the induction of cardiac hypertrophy induced the Egr-1 messenger RNA in the myogenic cell line Sol8. Among these are endothelin, insulin, basic fibroblast growth factor, and platelet-derived growth factor BB (PDGF BB). We conclude: (1) In analogy to the myocardium, these growth factors act upon myoblasts. (2) This line appears to be a suitable model for the molecular characterization of Egr-1 target genes.
Cell Differentiation↗
Mitogenic signals control translation of the early growth response gene-1 in myogenic cells.
Muscle is a major site of expression of the early growth response gene-1 (Egr-1). To investigate its role in muscle proliferation and/or differentiation we studied the effect of a variety of growth factors on cultured mouse muscle Sol8 cells. Three groups of responses could be distinguished: 1. AII, endothelin, phenylephrine, and PMA induced Egr-1 mRNA accumulation, but the message remained untranslated. These factors induced neither differentiation nor proliferation. 2. Insulin induced differentiation. It stimulated Egr-1 mRNA accumulation, but no translation into the Egr-1 protein was seen. 3. bFGF, PDGF BB, and FCS strongly induced DNA- and protein synthesis (i.e. proliferation) and Egr-1 mRNA accumulation. Only under these conditions was the message translated into protein. We conclude: 1. AII, endothelin, phenylephrine, and PMA elicit a nuclear response in Sol8 muscle cells which may lead to reprogramming of genes unrelated to differentiation or proliferation. 2. Differentiation induces a translational block of the Egr-1 mRNA which is only relieved by mitotic stimuli. 3. These results strongly suggest a pivotal role of Egr-1 in muscle proliferation and define translational control as a new mechanism of Egr-1 regulation.
Angiotensin II↗
Use of positron emission tomography with fluorodeoxyglucose in patients with extracranial head and neck cancers.
BACKGROUND: The purpose of this study was to evaluate the utility of positron emission tomography- (PET) 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) imaging in extracranial head and neck cancers. METHODS: Sixty patients with biopsy-proven cancers were studied using PET-FDG. Thirty-four patients were studied before therapy (staging), of which 15 patients received primary radiotherapy and serial PET-FDG imaging (monitoring). Seven patients with advanced disease had laser excision (monitoring), and 19 patients were evaluated for recurrent disease (recurrence). RESULTS: Four patients had unknown primary lesions. PET-FDG imaging located the primary tumor in two of four patients, and magnetic resonance imaging (MRI) in none of four. In the remaining patients (staging), PET-FDG imaging detected the primary tumor in 29 of 30 patients, and MRI in 23 of 30. In the staging group, PET-FDG imaging identified the presence or absence of lymph node involvement in 32 of 34 patients, and MRI in 31 of 34. PET-FDG imaging was helpful in evaluating tumor response to radiation therapy or laser excision. Ten patients evaluated for recurrent disease had biopsy-confirmed recurrences, and 7 had no recurrence. PET-FDG imaging results were positive for primary tumor recurrence in 9 of 10 patients, and MRI results were positive in 6 of 10. MRI results were negative for lymph node disease in one of these patients with recurrent primary tumor where PET-FDG imaging and biopsy demonstrated nodal involvement. PET-FDG results were negative for recurrent disease in seven of seven patients, and MRI results were negative for recurrent disease in in four of seven. CONCLUSION: In this series, the authors found that PET-FDG is a useful diagnostic modality for evaluating the patient with an unknown primary, monitoring response to therapy, and in detecting recurrent tumors.
Adult↗
Immediate-early gene induction by repetitive mechanical but not electrical activity in adult rat cardiomyocytes.
Mechanical factors are thought to play an important role in the induction of myocardial hypertrophy. Yet, it is not known whether active contraction induces genes that probably represent initial steps in the hypertrophic response in the adult myocardium--and if so, whether the mechanical or the electrical component of the twitch governs this response. We therefore investigated whether electrical stimulation of contraction was able to induce the immediate-early genes (IEGs) egr-1 and c-fos in adult rat cardiomyocytes. Cyclical contraction led to an increase in egr-1 and c-fos mRNA levels within 30 min. Full inhibition of contraction during electrostimulation by the Ca(2+)-desensitizer 2,3-butanedione monoxime (BDM) totally blocked this IEG-response without altering membrane potential. These data suggest that in adult myocardium, the mechanical rather than the electrical activity is responsible for the IEG-response during active twitch.
Animals↗
Hyperosmotic stress induces immediate-early gene expression in ventricular adult cardiomyocytes.
Mammalian cells possessing osmosensors have long been described in brain and kidney. The genetic basis of the response to hyperosmotic stress has been well characterized in prokaryotes. In contrast, the genetic response of eukaryotic cells is poorly understood. Therefore we investigated the effect of hypertonic NaCl and sucrose solutions on the transcriptional activation of the immediate-early genes (IEGs) egr-1 and c-fos in isolated ventricular adult rat cardiomyocytes. We observed that even small increases in osmolarity to 315 +/- 5 mosmol/l and 370 +/- 8 mosmol/l by hypertonic NaCl solution resulted in dose-dependent induction of egr-1 (4-and 5-fold) and c-fos (3-and 4-fold), respectively. Hypertonic sucrose solution had the same effect on egr-1 and c-fos mRNA levels while increased sucrose concentration under isotonic conditions had no effect. Cardiomyocytes exposed to hypertonic media did not significantly shrink as shown by a cell length measurement. We conclude that isolated adult cardiomyocytes possess an osmoreceptor mechanism which is able to sense even slight changes in osmolarity and to translate these into a transcriptional response of the myocardial IEG program.
Animals↗
Language use in intergroup contexts: the linguistic intergroup bias.
Three experiments examine how the type of language used to describe in-group and out-group behaviors contributes to the transmission and persistence of social stereotypes. Two experiments tested the hypothesis that people encode and communicate desirable in-group and undesirable out-group behaviors more abstractly than undesirable in-group and desirable out-group behaviors. Experiment 1 provided strong support for this hypothesis using a fixed-response scale format controlling for the level of abstractness developed from Semin and Fiedler's (1988a) linguistic category model. Experiment 2 yielded the same results with a free-response format. Experiment 3 demonstrated the important role that abstract versus concrete communication plays in the perpetuation of stereotypes. The implications of these findings and the use of the linguistic category model are discussed for the examination of the self-perpetuating cycle of stereotypes in communication processes.
Aggression↗