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Biomedical subjects

C Weiss

Publications and source records attributed to C Weiss.

At least 73 records · Page 4Linked to original sources
PubMed2000

Myocardial ischemia during physical exercise in patients with stable coronary artery disease: predictability and prevention.

AIMS: We assessed whether exercise-induced myocardial ischemia during intensive group exercise sessions can be predicted in patients with coronary artery disease and stable angina pectoris. METHODS AND RESULTS: Twenty-three patients underwent cardiac catheterization, 201-thallium scintigraphy, and exercise testing prior to participation in group training sessions. Heart rates and myocardial ischemia were documented by Holter monitoring. The individual training heart rate was calculated as a percentage of the maximal heart rate achieved during symptom-limited exercise testing. Myocardial ischemia occurred significantly more often during group exercise sessions (15 of 23 patients) than during treadmill testing (4 of 23 patients, P<0.001). Maximal heart rate (145+/-23 vs. 134+/-21 beats/min, P<0.004) and maximal plasma lactate concentrations (6.0+/-2.9 vs. 4.3+/-2.0 mmol/l, P<0.05) were significantly higher than during symptom-limited exercise testing. Ischemic episodes occurred significantly more often during jogging than during competitive ball games or interval training. Myocardial ischemia occurred in patients who exceeded their individual target training heart rates (43 of 44 episodes; P<0.001). Duration of ischemic episodes did not correlate with any marker obtained at the beginning of the study. CONCLUSION: These data demonstrate that routine diagnostic procedures do not sufficiently identify patients at risk for exercise-induced myocardial ischemia. Ischemic events are only effectively prevented by choosing adequate types of exercise and, above all, by the strict adherence to individual target heart rates.

Coronary Angiography↗
PubMed2000

Reconstitution of higher plant chloroplast chaperonin 60 tetradecamers active in protein folding.

Unlike the GroEL homologs of eubacteria and mitochondria, oligomer preparations of the higher plant chloroplast chaperonin 60 (cpn60) consist of roughly equal amounts of two divergent subunits, alpha and beta. The functional significance of these isoforms, their structural organization into tetradecamers, and their interactions with the unique binary chloroplast chaperonin 10 (cpn10) have not been elucidated. Toward this goal, we have cloned the alpha and beta subunits of the ch-cpn60 of pea (Pisum sativum), expressed them individually in Escherichia coli, and subjected the purified monomers to in vitro reconstitution experiments. In the absence of other factors, neither subunit (alone or in combination) spontaneously assembles into a higher order structure. However, in the presence of MgATP, the beta subunits form tetradecamers in a cooperative reaction that is potentiated by cpn10. In contrast, alpha subunits only assemble in the presence of beta subunits. Although beta and alpha/beta 14-mers are indistinguishable by electron microscopy and can both assist protein folding, their specificities for cpn10 are entirely different. Similar to the authentic chloroplast protein, the reconstituted alpha/beta 14-mers are functionally compatible with bacterial, mitochondrial, and chloroplast cpn10. In contrast, the folding reaction mediated by the reconstituted beta 14-mers is only efficient with mitochondrial cpn10. The ability to reconstitute two types of functional oligomer in vitro provides a unique tool, which will allow us to investigate the mechanism of this unusual chaperonin system.

Adenosine Triphosphate↗
PubMed2000

Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation.

This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody causes platelet aggregation and granule secretion. A physiological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen. A pathophysiological role for the F11R was revealed by demonstrating the presence of F11R-antibodies in patients with thrombocytopenia. Adhesion of platelets through the F11R resulted in events characteristic of the action of cell adhesion molecules (CAMs). To determine the structure of this protein, we cloned the F11R cDNA from human platelets. The predicted amino acid sequence demonstrated that it is an integral membrane protein and an immunoglobulin superfamily member containing 2 extracellular C2-type domains. The structure of the F11R as a member of a CAM family of proteins and its activity in mediating adhesion confirm each another. We conclude that the F11R is a platelet-membrane protein involved in 2 distinct processes initiated on the platelet surface. The first is antibody-induced platelet aggregation and secretion that are dependent on both the FcgammaRII and the GPIIb/IIIa integrin and that may be involved in pathophysiological processes associated with certain thrombocytopenias. The second is an F11R-mediated platelet adhesion that is not dependent on either the FcgammaRII or the fibrinogen receptor and that appears to play a role in physiological processes associated with platelet adhesion and aggregation. (Blood. 2000;95:2600-2609)

Amino Acid Sequence↗
PubMed2000

Bovine NAD+-dependent isocitrate dehydrogenase: alternative splicing and tissue-dependent expression of subunit 1.

NAD+-dependent isocitrate dehydrogenase (IDH), a key regulatory enzyme in the Krebs cycle, is a multi-tetrameric enzyme. At least three of the subunits in the core tetramer of mammals are unique gene products. Subunits 1/beta and 2/gamma are considered to be regulatory, while subunits 3,4/alpha, comprising half the tetramer, are catalytic. The full sequence was obtained for the major subunit 1 cDNA in bovine heart, IDH 1-A. A second cDNA, rare in heart, was also identified (IDH 1-B). Differences in the two were confined to the 3'-region, suggesting alternative splicing. Screening of brain, kidney, and liver RNA showed the presence of IDH 1-A and 1-B and a third major species, IDH 1-C. Amplification of bovine genomic DNA by PCR across the regions of difference produced a single product. Comparison of the genomic and mRNA sequences showed that IDH 1-A resulted from splicing of exon W to exon Y, eliminating intron w, exon X, and intron x. IDH 1-B was formed by splice junctions between exon W, exon X, and exon Y. IDH 1-C resulted from splicing of exon W to exon X and subsequent retention of intron x. The 2 proteins predicted from these 3 mRNAs are identical over their first 357 residues. Protein IDH 1-A, resulting from a termination codon within exon Y, contains an additional 26 residues. Proteins IDH 1-B and 1-C derive from a common termination codon within exon X and contain an additional 28 residues. The two C-terminal regions differ notably in the number and nature of charged residues, resulting in proteins with a charge difference of 3.2 at pH 7.0. Subunit 1 sequences previously reported from other species grouped with one or the other of the bovine proteins. No evidence was found for alternative splicing in subunit 3,4/alpha. The results of the present study, together with recent work on the 2/gamma subunit [Brenner,V., Nyakatura, G., Rosenthal, A., and Platzer, M. (1998) Genomics 44, 8], indicate that the regulatory subunits of the enzyme, but not the catalytic, possess alternatively spliced forms varying in C-terminal properties with tissue-specific expression. The finding is suggestive of a mechanism for modulation of allosteric regulation tailored to the needs of different tissues.

Alternative Splicing↗
PubMed2000

The M1 muscarinic agonist CI-1017 facilitates trace eyeblink conditioning in aging rabbits and increases the excitability of CA1 pyramidal neurons.

The M1 muscarinic agonist CI-1017 was administered intravenously to aging rabbits on a daily basis before and during hippocampally dependent trace eyeblink conditioning sessions. Circulating levels of CI-1017 were significantly related to the drug dose. The drug was found to significantly increase the rate and amount of learning in a dose-dependent manner with no significant effects on the amplitude, area, or latency of conditioned responses. There was no evidence of pseudoconditioning at the highest drug concentration, and the minimally effective dose produced only mild and temporary hypersalivation as a side effect. CI-1017 (10 microM) was also found to increase the excitability of CA1 pyramidal neurons recorded from hippocampal slices from young and aging naive rabbits as measured by changes in spike-frequency adaptation and the postburst afterhyperpolarization. These biophysical changes were reversed with either atropine (1 microM) or pirenzepine (1 microM). These results suggest that M1 agonists ameliorate age-related learning and memory impairments at least in part by reducing the afterhyperpolarization and spike-frequency adaptation of hippocampal pyramidal neurons and that M1 agonists may be an effective therapy for reducing the cognitive deficits that accompany normal aging and/or Alzheimer's disease.

Acoustic Stimulation↗
PubMed2000

fMRI of visual system activation in the conscious rabbit.

A conscious rabbit preparation developed for fMRI, and the results from visual stimulation studies at a 4.7T magnetic field are described. The rabbit is ideal for these experiments because of its natural tolerance for restraint. High spatial and temporal resolution magnetic resonance images, without movement artifacts, were obtained during long periods of restraint. Functional activation in primary visual cortex and lateral geniculate nucleus (LGN) were reproducibly observed in response to light stimulus. In comparison to existing anesthetized animal models, a functional response free of the anesthetic modulation can be recorded with the new approach. The conscious animal model can be applied to functional studies of sensory systems, learning and memory, and drug-induced cerebral activation.

Animals↗
PubMed2000

The cost-effectiveness of different management strategies for type I diabetes: a Swiss perspective.

AIMS/HYPOTHESIS: A computer model was developed to determine the health outcomes and economic consequences of different combinations of diabetes interventions in newly diagnosed patients with Type I (insulin-dependent) diabetes in Switzerland. METHODS: We modelled seven complications of diabetes: hypoglycaemia, ketoacidosis, acute myocardial infarction, stroke, lower extremity amputation, nephropathy, and retinopathy. Transition probabilities and costs were taken from published literature. The Swiss health insurance payer perspective was taken. Various combinations of diabetes management strategies, including intensive or conventional insulin therapy and screening and treatment strategies for renal and eye disease were defined. Life expectancy, cumulative incidences of complications, and mean expected total lifetime costs per patient were calculated under six different management strategies. Incremental cost-effectiveness ratios were calculated in terms of costs per life-year gained compared with conventional insulin therapy alone. RESULTS: The addition of screening for microalbuminuria and retinopathy followed by appropriate treatment, if detected, were cost saving, with reduction in cumulative incidence of end stage renal disease and blindness respectively, and, in the case of microalbulminuria screening and treatment, an improvement in life expectancy. Intensive therapy improved life expectancy but increased total lifetime costs. CONCLUSION/INTERPRETATION: Optimal management of Type I diabetic patients, including secondary and tertiary prevention, leads to reduced complications and improved life expectancy, with the increased costs of prevention offset to varying degrees by cost savings due to complications avoided.

Albuminuria↗
PubMed2000

Outline of a diabetes disease management model: principles and applications.

A complex interactive computer model was developed to determine the health outcomes and economic consequences of different diabetes interventions for user-defined observation periods. The interventions include intensive or conventional insulin therapy, different oral hypoglycaemic medications, different screening and treatment strategies for micro-vascular complications, different treatment strategies for end-stage complications, or multi-factorial interventions. The analyses can be performed on different sub-groups of type 1 and 2 diabetic patients, defined in terms of age, gender, baseline risk factors and pre-existing complications. The model performs real-time simulations. Full on-screen documentation of the model structure, logic, calculations and data sources is available to maximize the model's transparency. Economic and clinical data used in the disease management model are editable by the user, allowing the input of new data as they become available, the creation of country-specific, HMO-specific, or provider-specific versions of the model, and the exploration of new hypotheses ('what-if' analyses). The approach used allows maximum flexibility, adaptability, and transparency within the model structure. For the user-defined patient cohorts and intervention strategies the diabetes disease management model compares life expectancy, expected incidence and prevalence of complications as well as expected life-time (or shorter) treatment cost. Diabetes and complication management strategies can be compared in different patient populations in a variety of realistic clinical settings. The model allows extrapolation of results obtained from relatively short-term clinical trials to longer-term medical outcomes, and from trial populations to real-life populations providing a tangible yardstick to judge the quality of diabetes care. The model was used to evaluate diabetes care options in Germany, France, Switzerland, UK and US.

Computer Simulation↗
PubMed2000

Catheter ablation of atrial flutter guided by electroanatomic mapping (CARTO): a randomized comparison to the conventional approach.

INTRODUCTION: Three-dimensional electroanatomic (CARTO) activation mapping of the cavotricuspid isthmus can be helpful to guide atrial flutter ablation, but to date has not been investigated in comparison to conventional strategies. The aim of the present study was to assess the efficacy of the CARTO navigation system, especially with respect to the fluoroscopy time required for successful atrial flutter ablation. METHODS AND RESULTS: Eighty patients with recurrent common-type atrial flutter were randomly assigned to temperature-controlled radiofrequency (RF) catheter ablation, either guided by conventional criteria (group 1) or additionally oriented on electroanatomic mapping (group 2). In all patients, similar multipolar catheters were inserted into the coronary sinus and placed at the tricuspid annulus, respectively. In group 2, positioning of the mapping electrode and delivery of RF pulses within the cavotricuspid isthmus was mainly oriented on the CARTO map to achieve the most linear and continuous RF lesions. Abolition of intra-atrial conduction verified by conventional criteria (group 1) and electroanatomic mapping (group 2) could be verified in all patients. The overall number of RF pulses (group 1: 16.7+/-6.5; group 2: 13.2+/-5.3) and mean procedure duration (group 1: 172.5+/-47.4 min; group 2: 169.3+/-47.3 min) were not different between the two groups, but mean fluoroscopy time was significantly shorter when the CARTO technology was used (group 1: 29.2+/-9.4 min; group 2: 7.7+/-2.8 min; P = 0.0001). Recurrence of atrial flutter was observed in 3 (9%) patients in each group after a mean follow-up of 8.5+/-2.8 months. CONCLUSION: Atrial flutter can be abolished effectively using the conventional technique as well as oriented on electroanatomic mapping. However, overall X-ray exposure can be significantly reduced by the CARTO-guided approach without prolongation of procedure duration.

Aged↗
PubMed2000

Hemostasis and fibrinolysis in patients with intermittent claudication: effects of prostaglandin E1.

There is evidence that the coagulation system is activated in patients with peripheral arterial occlusive disease (PAOD). The beneficial effects of the vasoactive drug prostaglandin E1 (PGE1) may rely in part on the modulation of the coagulation system. The study was designed to evaluate the effects of PGE1 on hemostatic and fibrinolytic variables in patients with intermittent claudication. Therefore molecular markers of thrombin (prothrombin fragment 1+2, PTF 1+2; thrombin-antithrombin III complexes, TAT) and fibrin formation (fibrinopeptide A, FPA) and markers of the fibrinolytic activity (fibrin degradation products, D-dimers) were determined before and immediately after the first PGE1 dose (60 microg in 100 ml NaCl over 2 h i.v.) as well as after 4 weeks of daily infusion therapy in 12 PAOD patients and in eight control patients before and after a single placebo infusion. Plasma levels of PTF1+2, TAT, FPA and D-dimers tended to decrease after the initial dose of PGE1. Infusion therapy with PGE1 for 4 weeks led to a decrease of all hemostatic and fibrinolytic parameters with most pronounced changes for PFT1+2, D-dimers and plasminogen activator inhibitor-1 decreasing by 11% (P<0.05), 20% (P<0.05), and 7% (P<0.05), respectively. These variables remained unchanged in controls with placebo infusion. In summary, infusion therapy with PGE1 in patients with PAOD reduces thrombin formation and results in a decrease of fibrin degradation. PGE1 may thus reduce fibrin deposition involved in the pathogenesis of atherosclerosis.

Aged↗
PubMed2000

Do we need MR images for diagnosing tendon ruptures of the distal biceps brachii? The value of ultrasonographic imaging.

AIM: To assess the usefulness of ultrasound in the diagnosis of rupture of the distal biceps brachii muscle by demonstrating the clear differentiation between the distal biceps muscle and the surrounding soft tissue in a standardized section of the elbow. METHOD: Under sonographic guidance five biceps muscles of three cadavers were marked with a needle in the region of the elbow joint. Thereafter an anatomical preparation of the distal biceps brachii muscle followed to verify the correct positioning of the needle. Real time ultrasound was performed with a 7.5 MHz linear array transducer. The standard section of the elbow and the images on the screen correspond to the guidelines provided by the German Society of Ultrasonography in the Locomotor Apparatus (DEGUM). RESULTS: In all five cases the needle tip could be found in the middle of the distal biceps muscle. It was possible to perform a sonographically guided puncture of the muscle and to differentiate between distal biceps brachii and surrounding soft tissues using a high resolution transducer of the newest generation in ultrasound technology. CONCLUSION: Our investigation confirmed our clinical ultrasound findings in distal biceps tendon ruptures. The echo-intense signal is replaced by a hypoechogenic signal representing the haematoma in the area of the distal biceps brachii muscle. In addition to the clinical examination in case of a ruptured distal biceps muscle ultrasound of the elbow is a valuable and reliable imaging method to support the diagnosis. MRI of the elbow is not always necessary to confirm the diagnosis.

Female↗
PubMed2000

Sonographic imaging of a spinoglenoid cyst.

Spinoglenoid cysts can be the reason for suprascapular nerve entrapment syndrome resulting an isolated atrophy of the infraspinatus muscle. The syndrome usually presents painless and is frequently observed in professional volleyball players. The incidence of these cysts in volleyballplayers is still unknown. Diagnosis is made by neurological examination using electromyography and magnetic resonance imaging. Our case shows the potential of ultrasound as a possible imaging method of ganglion cysts that could be used as a screening method to prevent suprascapular neuropathy.

Female↗
PubMed2000

[Endocardial mapping and high frequency catheter ablation of ventricular tachycardia after myocardial infarction].

Recurrent ventricular tachycardia in the setting of remote myocardial infarction are frequently resistant to antiarrhythmic drug treatment. Endocardial mapping and ablation is feasible in case of hemodynamically tolerable and reproducibly inducible forms. Identification of critical components of the reentrant circuit is mainly guided by entrainment mapping and the analysis of the post-pacing interval. The emergence of multiple types of ventricular tachycardia is a common limitation of the procedure. Ventricular tachycardia can be acutely abolished by radiofrequency current ablation in 60-70% of cases when only single forms are present. This success rate is substantially lower in case of multiple tachycardia morphologies. The incidence of tachycardia recurrences varies from 20-30%. The overall mortality during follow-up is increased due to progressive heart failure and the occurrence of rapid ventricular tachyarrhythmias. Catheter ablation has been shown to be a useful tool for the treatment of clusters of ventricular tachycardia following implantation of a cardioverter-defibrillator. Furthermore, this method can be life-saving in the setting of incessant forms. Currently, catheter ablation represents an adjunctive treatment to antiarrhythmic drugs and the implantation of a cardioverter-defibrillator. Improvement of mapping and ablation technologies may help to further increase the efficacy of this treatment strategy in the near future.

Catheter Ablation↗
PubMed1999

Vasorelaxation by new hybrid compounds containing dihydropyridine and pinacidil-like moieties.

The synthesis and pharmacological properties of a novel type of vasorelaxant hybrid compounds are described. The investigated compounds originate from fluorinated 4-aryl-1,4-dihydropyridines, which are known calcium channel blockers, and/or from fluorinated analogues of pinacidil, which is an opener of ATP-sensitive potassium channels. In particular, we studied the most potent hybrid, 2,6-dimethyl-3,5-dicarbomethoxy-4-(2-difluoromethoxy-5-N-(N' '-cyano-N'-1,2,2-trimethyl-propylguanidyl)-phenyl)-1, 4-dihydropyridine (4a), together with its parent compounds, the dihydropyridine 1b and the pinacidil analogue 3. In isolated rat mesenteric arteries, micromolar concentrations of 4a relaxed contractions exerted by K(+)-depolarization or by norepinephrine. The latter effect was sensitive to the potassium channel blocker glibenclamide. Micromolar 4a also inhibited [(3)H](+)-isradipine and [(3)H]P1075 binding to rat cardiac membranes, and it blocked L-type calcium channels expressed in a mammalian cell line. The respective parent compounds 1b and 3 were always more potent and more selective regarding calcium channel or potassium channel interaction, respectively. In contrast, 4a combined both effects within the same concentration range, indicating that it may represent a lead structure for a novel class of pharmacological hybrid compounds.

Animals↗
PubMed1999

Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker.

We report the amino acid sequence, genomic organization, tissue expression, and alternative splice patterns for the human kinase related protein (KRP) gene, as well as the discovery of a new CA repeat sequence polymorphic marker in an upstream intron of the myosin light chain kinase (MLCK) gene. The KRP/MLCK genetic locus is a prototype for a recently discovered paradigm in which an independently regulated gene for a non-enzymic protein is embedded within a larger gene for a signal transduction enzyme, and both classes of proteins are involved in the regulation of the same cellular structure. The MLCK/KRP gene cluster has been found only in higher vertebrates and is localized to human chromosome 3q21. The determination of the human KRP amino acid sequence through cDNA sequence analysis and its comparison to the exon/intron organization of the human KRP gene revealed an alternative splice pattern at the start of KRP exon 2, resulting in the insertion of a single glutamic acid in the middle of the protein. Examination of tissue distribution using Northern blot analysis revealed that the human expression pattern is more similar to the well-characterized chicken KRP gene expression pattern than to rodent or rabbit. Unexpected differences of the human gene from other species is the apparent expression of the human gene products in adult cardiac muscle, an observation that was pursued further by the production of a site-directed antiserum and immunohistochemistry analysis. The results reported here provide insight into the conserved and variable features of this late evolving genetic paradigm, raise new questions about the molecular aspects of cardiac muscle regulation, and provide tools needed for future clinical studies. The comparative analysis of the MLCK/KRP locus, combined with the recent discovery of a similar genomic relationship among other signal transduction proteins, suggest a diverse distribution of this theme among signal transduction systems in higher vertebrate genomes and indicate the utility of comparative genomics in revealing late evolving genetic paradigms.

Adult↗
PubMed1999

Domain structure and lipid interaction of recombinant yeast Tim44.

Tim44 is an essential component of the machinery that mediates the translocation of nuclear-encoded proteins across the mitochondrial inner membrane. It functions as a membrane anchor for the ATP-driven protein import motor whose other subunits are the mitochondrial 70-kDa heat-shock protein (mhsp70) and its nucleotide exchange factor, mGrpE. To understand how this motor is anchored to the inner membrane, we have overexpressed Tim44 in Escherichia coli and studied the properties of the pure protein and its interaction with model lipid membranes. Limited proteolysis and analytical ultracentrifugation indicate that Tim44 is an elongated monomer with a stably folded C-terminal domain. The protein binds strongly to liposomes composed of phosphatidylcholine and cardiolipin but only weakly to liposomes containing phosphatidylcholine alone. Studies with phospholipid monolayers suggest that Tim44 binds to phospholipids of the mitochondrial inner membrane both by electrostatic interactions and by penetrating the polar head group region.

Cardiolipins↗