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Biomedical subjects

C Weiss

Publications and source records attributed to C Weiss.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1999

p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells.

The Ah receptor (AhR), a bHLH/PAS transcription factor, mediates dioxin toxicity in the immune system, skin, testis and liver. Toxic phenomena are associated with altered cell proliferation or differentiation, but signaling pathways of AhR in cell cycle regulation are poorly understood. Here we show that AhR induces the p27(Kip1) cyclin/cdk inhibitor by altering Kip1 transcription in a direct mode without the need for ongoing protein synthesis or cell proliferation. This is the first example of Kip1 being a direct transcriptional target of a toxic agent that affects cell proliferation. Kip1 causes dioxin-induced suppression of 5L hepatoma cell proliferation because Kip1 antisense-expressing cells are resistant to dioxins. Kip1 is also induced by dioxins in cultures of fetal thymus glands concomitant with inhibition of proliferation and severe reduction of thymocyte recovery. Kip1 expression is likely to mediate these effects as thymic glands of Kip1-deficient mice (Kip1(Delta51)) are largely, though not completely, resistant.

Animals↗
PubMed1999

The new chromogranin-like protein NESP55 is preferentially localized in adrenaline-synthesizing cells of the bovine and rat adrenal medulla.

The protein NESP55, a new member of the chromogranin family, is present in large dense-core secretory granules of neuroendocrine tissues. We investigated its cellular distribution in adrenal medulla with immunohistochemistry and in situ hybridization. A preferential co-localization of NESP55 with phenylethanolamine-N-methyltransferase in the adrenergic cell population was found by immunolabelling of consecutive sections. Noradrenergic cells also contained small amounts of NESP55, but the levels as measured by radioimmunoassay were five times lower. The distribution of NESP55 mRNA was similar to preproenkephalin mRNA which previously was shown to be confined to adrenaline-producing cells of the adrenal medulla. The present study indicates that stimulation of adrenergic cells will release significantly higher amounts of NESP55. The functional implications of this preferential secretion, however, have yet to be discovered.

Adrenal Medulla↗
PubMed1999

Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis.

Eph receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, regulate axon guidance and bundling in the developing brain, control cell migration and adhesion, and help patterning the embryo. Here we report that two ephrinB ligands and three EphB receptors are expressed in and regulate the formation of the vascular network. Mice lacking ephrinB2 and a proportion of double mutants deficient in EphB2 and EphB3 receptor signaling die in utero before embryonic day 11.5 (E11.5) because of defects in the remodeling of the embryonic vascular system. Our phenotypic analysis suggests complex interactions and multiple functions of Eph receptors and ephrins in the embryonic vasculature. Interaction between ephrinB2 on arteries and its EphB receptors on veins suggests a role in defining boundaries between arterial and venous domains. Expression of ephrinB1 by arterial and venous endothelial cells and EphB3 by veins and some arteries indicates that endothelial cell-to-cell interactions between ephrins and Eph receptors are not restricted to the border between arteries and veins. Furthermore, expression of ephrinB2 and EphB2 in mesenchyme adjacent to vessels and vascular defects in ephB2/ephB3 double mutants indicate a requirement for ephrin-Eph signaling between endothelial cells and surrounding mesenchymal cells. Finally, ephrinB ligands induce capillary sprouting in vitro with a similar efficiency as angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), demonstrating a stimulatory role of ephrins in the remodeling of the developing vascular system.

Animals↗
PubMed1999

Prospective evaluation of the coronary sinus anatomy in patients undergoing electrophysiologic study.

BACKGROUND: Previous retrospective studies could find a predominant incidence of coronary sinus (CS) anomalies in patients with accessory pathways and a characteristic anatomy of the CS ostium in patients with atrioventricular nodal reentrant tachycardias (AVNRT). HYPOTHESIS: In the present prospective study, CS angiograms were prospectively performed to analyze the incidence of CS anomalies and to measure the diameters of the CS ostium. METHODS: The study included patients referred for electrophysiologic study and catheter ablation of various tachyarrhythmias. The anatomy of the CS and its side branches was visualized [left anterior oblique (LAO) 30 degrees, right anterior oblique (RAO) 30 degrees] by retrograde angiography in 204 consecutive patients (82 women, 122 men, age 45 +/- 15 years); of these, 120 presented with 123 accessory pathways (45 left-sided, 33 right-sided, 45 septal). The diagnosis in the remaining patients was atrioventricular nodal reentrant tachycardia in 43 cases, atrial tachycardia or atrial fibrillation in 12, and ventricular tachycardia in 15. In 14 patients, the indication for the electrophysiologic study was an unexplained syncope. The CS angiogram was evaluated for anomalies and the size of the CS ostium was manually measured in both projections. RESULTS: Anomalies of the CS defined as diverticula, persistent left superior vena cava, or enlarged CS ostia were found in 18 patients (9%). Of those, CS diverticula were found in nine patients, all with a posteroseptal or left posterior manifest accessory pathway, which was abolished within the neck of the diverticulum in seven patients and at the posteroseptal tricuspid annulus in two patients. Persistence of the left superior vena cava was found in five patients, four had atrioventricular reentrant tachycardia secondary to five accessory pathways (left free wall in four, right midseptal in one), and one patient had atrioventricular nodal reentrant tachycardia (AVNRT). Enlargement of the CS ostium of > 25 mm width was detected in nine patients (5%), of whom four had AVNRT. However, the width of the CS ostium generally did not differ significantly between patients with AVNRT (LAO: 14.4 +/- 5.6; RAO 9.3 +/- 2.4 mm) compared with the control group (LAO 13.4 +/- 4.1; 8.2 +/- 1.9 mm). CONCLUSIONS: Anomalies of the CS as diverticula, persistent superior vena cava, or enlargement of the CS ostium are predominantly found in patients with accessory pathway-related tachycardias. Diverticula of the proximal CS were found in 7% of patients with accessory pathways; in these cases, ablation succeeded mostly by radiofrequency (RF) current delivery in the neck of the diverticulum. Enlargement of the CS ostium was more often seen in patients with AVNRT than in all other patients. However, in general the measurements of the coronary sinus ostium did not significantly differ in patients with AVNRT compared with the control group.

Adult↗
PubMed1999

The classic nail in the therapy of trochanteric fractures.A prospective, controlled study.

In a prospective controlled study we analysed the classic nail, a new intramedullary implant for the fixation of peritrochanteric fractures. By means of lateral bending of 4 degrees, unreamed implantation is generally possible. Our collective of 85 patients was characterized by elderly mean age (82.3 years), a predominance of female patients (4.3 : 1), a minor trauma aetiology without relevant additional injuries, and a high rate of concomitant disease (92%). Only 31A-type femur fractures were treated, with a low specific complication rate of 13%, whereby operative revision was necessary in only two patients (3%). A good anatomic reconstruction and full weight-bearing with the osteosynthesis was achieved in the majority of patients. No secondary shaft fractures and only one case of cutting out was observed. The mortality (30 days: 18%, 6 months: 25%) as well as the high rate of unspecific complications (20%) were caused by the patients' multiple morbidity. Deficits in the Merle d'Aubigne score at follow-up after 6 months can be interpreted within the same context. Nevertheless, 85% could return to their former social environment and only 15% became dependent on a nursing institution in connection with the fracture treatment.

Aged↗
PubMed1999

Cholinergic facilitation of trace eyeblink conditioning in aging rabbits.

The hippocampus is importantly involved in learning and memory, and is severely impacted by aging. In in vitro hippocampal slices, both the post-burst afterhyperpolarization (AHP) and spike-frequency accommodation are reduced in hippocampal pyramidal neurons after hippocampally-dependent trace eyeblink conditioning, indications of increased cellular excitability. The AHP results from the activation of outward potassium currents, including sI(AHP) and muscarine-sensitive I(M). The AHP is significantly increased in aging hippocampal neurons, potentially contributing to age-associated learning deficits. Compounds which reduce the AHP and spike-frequency accommodation could facilitate learning in normal aging or in age-associated dementias such as Alzheimer's disease. The cholinesterase inhibitor metrifonate enhances trace eyeblink conditioning by aging rabbits and reduces the AHP and accommodation in hippocampal CA1 neurons in a dose-dependent manner. These reductions are mediated by muscarinic cholinergic transmission as they are blocked by atropine. Hippocampal neurons from metrifonate treated but behaviorally naive rabbits were more excitable and not desensitized to the effects of metrifonate since the AHP and accommodation were further reduced when metrifonate was bath applied to the neurons. These observations suggest that the facilitating effect of chronic metrifonate on acquisition of hippocampally dependent tasks is mediated at least partially by increasing the baseline excitability of CA1 pyramidal neurons. The issue of whether learning can be facilitated with muscarinic cholinergic agonists, in addition to cholinesterase inhibitors, was addressed by training aging rabbits during intravenous treatment with the M1 agonist CI1017. A dose-dependent enhancement of acquisition was observed, with rabbits receiving 1.0 or 5.0 mg/ml CI1017 showing comparably improved learning rates as those receiving 0.5 mg/ml or vehicle. Sympathetic side effects, mainly excess salivation, were seen with the 5.0 mg/ml dose. Post-training evaluations suggested that the effective doses of CI1017 were enhancing responsivity to the tone conditioned stimulus. These studies suggest that muscarinic cholinergic neurotransmission is importantly involved in associative learning; that learning in aging animals may be facilitated by enhancing cholinergic transmission; and that the facilitation may be mediated through actions on hippocampal neurons.

Acetylcholine↗
PubMed1999

IL-9 pathway in asthma: new therapeutic targets for allergic inflammatory disorders.

BACKGROUND: Asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of allergic inflammation and bronchial hyperresponsiveness (BHR). The incidence of asthma continues to rise in industrialized countries despite advances in the identification of cellular and molecular mediators that are associated with the disease. Because of its importance in human health, additional research and alternative therapeutic strategies are justified to create more effective treatments for this debilitating disease. OBJECTIVE: Studies use recombinant inbred mice to demonstrate that BHR in mouse models of asthma is associated with a genetic alteration at the IL-9 locus, where IL-9 expression in lung is strongly associated with bronchial responsiveness. We have investigated the ability of intratracheal instilled IL-9 to induce asthmatic-like responses in naive C57BL/6 (B6) mice, which express very low levels of IL-9. METHODS: IL-9 or vehicle was intratracheal instilled in naive B6 mice for 10 days. Mice were analyzed for effects on BHR, lung eosinophilia, and serum total IgE levels. RESULTS: Phenotypic effects of B6 mice instilled with IL-9 were increased eosinophils in the bronchoalveolar lavage and significantly elevated serum total IgE. Moreover, IL-9 was found to induce IL-5Ralpha in vivo and in vitro, suggesting a potential mechanism for the novel actions described for IL-9 on eosinophils. CONCLUSION: Increased levels of IL-9 in the airway of naive B6 mice induced lung eosinophilia and serum total IgE levels, which are 2 clinical features of asthma. These data support a central role for the IL-9 pathway in the complex pathogenesis of allergic inflammation.

Animals↗
PubMed1999

Hippocampal lesions prevent trace eyeblink conditioning in the freely moving rat.

The effect of hippocampal aspiration lesions on trace eyeblink conditioning was examined in young, freely-moving F1 hybrid rats (Fisher 344 x Brown Norway). Rats which received either bilateral neocortical or bilateral hippocampal aspiration lesions were compared with each other or with sham lesioned control rats. The rats were trained with a 250 ms tone conditioning stimulus (CS), a 250 ms stimulus free trace interval and a 100 ms corneal airpuff unconditioned stimulus (US). Rats with lesions of the hippocampus were significantly impaired relative to the neocortical and sham lesioned control rats. Analyses of different behavioral parameters (e.g. percent conditioned responses, amplitude, and area of response) indicated that all of the measures for the conditioned response were significantly impaired by the hippocampal lesion. The unconditioned response was not significantly affected by the lesion, and there was no significant difference among the groups after 2 days of subsequent conditioning with the delay paradigm (zero trace interval). We conclude that the hippocampus is required for rats to learn the association between a tone CS and an airpuff US when a 250 ms trace interval is interposed between the two stimuli.

Adaptation, Physiological↗
PubMed1999

Trace eyeblink conditioning in the freely moving rat: optimizing the conditioning parameters.

Trace eyeblink conditioning (EBC) parameters, with an airpuff unconditioned stimulus, were examined in male Fischer 344 X Brown Norway F1 rats. Integrated electromyographic activity from the upper eyelid was recorded. An 8-kHz tone was superior to white noise as a conditioning stimulus. Rats trained with 30 or 50 trials per session showed similar learning. Reversal of environmental lighting had no significant effect. Trace intervals of 0 and 250 ms yielded well-timed conditioned responses (CRs); intervals of 500 ms or more did not. These experiments provide parameters that reliably yield CRs and suggest limits on the temporal processing capabilities of the rat. EBC can thus be used as part of a comprehensive test battery for learning and memory in this species. Physiological recording and pharmacological manipulations may also be done easily. This combination of approaches should facilitate a more complete understanding of learning mechanisms and age-related memory impairments.

Animals↗
PubMed1999

Histochemical changes in muscle of individuals with spinal cord injury following functional electrical stimulated exercise training.

STUDY DESIGN: Longitudinal training. OBJECTIVES: To determine the effects of functional electrical stimulated (FES) leg cycle ergometer training on muscle histochemical characteristics in individuals with motor-complete spinal cord injury (SCI). SETTING: University of Alberta, Edmonton, Alberta, Canada. METHODS: Six individuals with motor-complete SCI (age 31-50 years; 3-25 years post-injury) trained using FES leg cycle ergometry for 30 min, 3 days per week for 8 weeks. Biopsies of the vastus lateralis muscle were obtained pre- and post-training and analyzed for fibre composition, fibre size and capillarization. RESULTS: The majority of muscle fibres were classified as type 2 pre- and post-training. Average fibre area increased 23% (P<0.05) and capillary number increased 39% (P<0.05) with training. As a result of these proportional increases, capillarization expressed relative to fibre area was unchanged with training. CONCLUSIONS: FES leg cycle ergometer training results in proportional increases in fibre area and capillary number in individuals with SCI.

Adult↗
PubMed1999

Impact of the ECG for detection of intraatrial conduction block after atrial flutter ablation.

Induction of complete bidirectional conduction block via the posterior isthmus of the right atrium is introduced as a standard endpoint for catheter ablation of atrial flutter. The present study sought to investigate the impact of changes in P wave duration and morphology detected by the surface ECG during coronary sinus and posterolateral right atrial stimulation as a marker for conduction block. Morphology and duration changes of the paced P wave before and after radiofrequency catheter (RFC) ablation were estimated in 22 patients referred for ablation of atrial flutter. We looked for a morphology change of the terminal portion in the 12-lead ECG and an increment of P wave duration. In 16 of 22 patients in whom atrial flutter ablation resulted in a complete bidirectional block, the conduction block was unidirectional in 4 patients and conduction times remained unchanged in 2 patients. After induction of complete bidirectional block a change of the terminal portion of the P wave towards a more positive morphology in one or more inferior leads was detected in 14 (88%) of 16 patients during coronary sinus stimulation and in 15 (94%) of 16 patients during posterolateral right atrial stimulation. These changes were predominantly observed in the inferior leads. Positive morphology changes of the terminal P wave portion in the inferior leads indicating conduction block with a sensitivity of 86% and a specificity of 100% were observed. An increment of 10 ms or more in P wave duration indicates conduction block with a specificity of 100% and a sensitivity of 67%. There was a significantly larger increment of P wave duration during coronary sinus (CS) stimulation compared to posterolateral right atrial stimulation (38 +/- 21 vs 16 +/- 21 ms). The analysis of P wave duration and morphology in the inferior leads of the surface ECG is a reliable tool to assess the intraatrial conduction after atrial flutter ablation. Different conduction during coronary sinus and posterolateral right atrial pacing may cause a different P wave duration after ablation.

Aged↗
PubMed1999

Atrial flutter ablation using a technique for detection of conduction block within the posterior isthmus.

Catheter ablation orientated on the induction of a functional intraatrial block within the posterior isthmus of the tricuspid annulus has been shown to effectively abolish atrial flutter. In order to improve and simplify the current technique, a strategy based on an electrode catheter for combined right atrial and coronary sinus mapping and stimulation was explored prospectively. Twenty-four consecutive patients referred for catheter ablation of recurrent type I atrial flutter were included. A steerable 7 Fr catheter (Medtronic/Cardiorhythm) composed of two segments with 20 electrodes was used for right atrial and coronary sinus activation mapping and stimulation. Multiple steering mechanisms allowing intubation and positioning of the distal part within the coronary sinus were incorporated into the device. Adequate positioning of the mapping catheter was achieved solely via a transfemoral approach in all patients after 7.7 +/- 4.6 minutes, providing stable electrogram recordings during the entire ablation procedure. Radiofrequency current ablation (16.3 +/- 9.6 pulses) caused a significant bidirectional increase of the mean intraatrial conduction times via the posterior isthmus irrespective to the stimulation interval. Significant changes of intraatrial conduction properties were induced during ablation in 22 of 24 patients (bidirectional block: n = 18, unidirectional block: n = 3, conduction delay: n = 1, unchanged conduction: n = 2). Following ablation atrial flutter was noninducible in all patients. Twenty-two of 24 patients (92%) remained free of atrial flutter episodes during a follow-up of 12.5 +/- 5.7 months. Two of six patients without a bidirectional conduction block had a recurrence of atrial flutter. Atrial flutter ablation guided by the induction of an intraatrial conduction block can be effectively performed with this novel strategy for combined mapping of the posterior tricuspid isthmus, including coronary sinus and right atrial free wall. This transfemoral approach has a high accuracy with respect to the detection of radiofrequency current-induced changes of intraatrial conduction patterns.

Atrial Flutter↗
PubMed1998

Two wavelength femtosecond laser induced DNA-protein crosslinking.

Nucleic acid-protein interactions are essential for storage, reproduction and expression of genetic information. Biochemical methods, such as dimethyl sulfate genomic footprinting, have been developed to study stable protein-DNA interactions in vivo and chemical crosslinking has been used for less stable interactions, but the chemical agents are slow, damage cells and perturb native equilibria. To avoid these perturbations, UV laser crosslinking offers an alternative, although the energies required for significant crosslinking cause extensive DNA damage. We find that a combination of femtosecond laser pulses at two different wavelengths, in the UV and the visible range, increases the crosslinking efficiency while minimizing DNA damage. This technique also allowed us to directly measure the singlet S1lifetime of native DNA (tauS1 = 3.2 +/- 0.2 ps), which is mainly determined by the lifetime of thymine [tauS1 = 2.8 +/- 0.4 ps for (dT)16], the photochemically most reactive base. Our results suggest that two wavelength femtosecond laser pulses are well suited for the identification of transcription factors interacting with defined sequences and for studying the kinetics of protein-nucleic acid interactions in intact cells.

DNA↗
PubMed1998

Activation of coagulation and fibrinolysis after rehabilitative exercise in patients with coronary artery disease.

It has been suggested that blood coagulation be activated and fibrinolytic activity be impaired in patients with coronary artery disease (CAD). With regard to the activation of coagulation and fibrinolysis occurring during exercise in healthy individuals, we examined the hypothesis that rehabilitative exercise in patients with CAD might give rise to an exaggerated activation of coagulation. In 12 patients with angiographically documented CAD without myocardial infarction within the preceding 6 months (male, age 55+/-9 years [SD]) and in 12 healthy controls (male, 52+/-7 years), molecular markers of thrombin, fibrin, and plasmin formation were determined before and after a rehabilitative group exercise session lasting 1 hour. Resting levels of prothrombin fragment 1+2 were lower in patients with CAD (0.67+/-0.2 [SE] vs 1.04+/-0.2 nmol/L, p <0.001) and remained unchanged after exercise, whereas a significant increase was noted in controls (p <0.01). After exercise, plasma levels of thrombin-antithrombin III complexes and of fibrinopeptide A increased significantly in both groups, although there were more pronounced changes in controls. Exercise resulted in a marked generation of plasmin as indicated by plasmin-alpha2-antiplasmin complexes increasing 2.5-fold in patients (p <0.001) and threefold in controls (p <0.001). Repeated experiments in control subjects after administration of aspirin (day 1: 500 mg; days 2 to 5: 100 mg) documented that differences between groups could not be attributed to aspirin medication (100 mg/day) in patients with CAD. We concluded that rehabilitative exercise in patients with CAD beyond the immediate postinfarction period has no detrimental effects on thrombin, fibrin, and plasmin formation.

Adult↗