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J Meyer

Publications and source records attributed to J Meyer.

At least 109 records · Page 6Linked to original sources
PubMed2001

Rhinovirus infection up-regulates eotaxin and eotaxin-2 expression in bronchial epithelial cells.

BACKGROUND: Human rhinoviruses (RVs) are the most common precipitants of asthma exacerbations. RV infection of bronchial epithelium results in local airway inflammation inducing eosinophil recruitment and activation. Induction of eosinophil chemoattractants could represent a central mechanism, as well as a prime target for intervention. OBJECTIVE: To assess the effect of RV infection on mRNA expression and production of eosinophil chemoattractants by bronchial epithelial cells in-vitro. METHODS: BEAS-2B cells were infected with major and minor RVs and the mRNA expression of IL-8, RANTES, MIP-1alpha, eotaxin, eotaxin-2, MCP-2, MCP-3 and MCP-4 was assessed by reverse transcription PCR. In cases where mRNA induction was observed, a fluoroimmunoassay was used to confirm protein production. To assess the virus-specificity of the observed reactions, cells were also exposed to inactivated RVs. RESULTS: RV infection was able to up-regulate mRNA expression of IL-8, RANTES, MIP-1alpha, eotaxin and eotaxin-2, did not affect MCP-4, while MCP-2 and MCP-3 were not expressed either at baseline or after virus infection. Protein production was confirmed for IL-8, RANTES and eotaxin, but not for MIP-1alpha. When RVs were inactivated cytokine up-regulation was almost completely lost. CONCLUSION: Infection of bronchial epithelial cells with RVs results in the production of a wide array of mediators that are able to chemoattract eosinophils. These include the eosinophil-specific molecules eotaxin and eotaxin-2, in addition to IL-8 and RANTES, which are the most abundant. Eosinophil recruitment after RV infection of bronchial epithelium could represent a central event in the pathogenesis of virus-induced asthma exacerbations.

Bronchi↗
PubMed2001

The effects of sepsis on gut mucosal blood flow in rats.

BACKGROUND AND OBJECTIVE: The effects of sepsis on gut mucosal blood flow have not been fully clarified. We designed an experiment to explicitly describe the effects of sepsis on gut mucosal blood flow in rats using an advanced intravital microscopy technique. METHODS: This work was performed as a prospective, controlled laboratory experiment. Twenty-four hours after sham laparotomy or laparotomy and caecal ligation and perforation to create sepsis, rats were anaesthetized and their lungs mechanically ventilated (n=7 per group). Intravital videomicroscopy was performed on 6-12 villi of ileum mucosa. Video recordings were analysed off-line using computerized image analysis. RESULTS: Intercapillary area size (inversely related to capillary density) was increased in sepsis as compared with the control group (941 +/- 92 vs. 669 +/- 79 microm(2), P < 0.05). In the central villus arteriole, blood flow was similar between groups (control: 3.5 +/- 0.4 nL min(-1); caecal ligation and perforation group: 3.6 +/- 0.5 nL min(-1)). There were no relevant changes in arteriolar red cell velocity and diameter. CONCLUSIONS: In the gut mucosa of rats, sepsis resulting from caecal ligation and perforation depressed the perfused capillary density without affecting blood flow in the central villus arteriole. Mucosal hypoperfusion at the level of the capillary networks may occur in the presence of precapillary shunting in the villus microcirculation.

Animals↗
PubMed2001

Defining the nursing contribution to patient outcome: lessons from a review of the literature examining nursing outcomes, skill mix and changing roles.

A review of the evidence to define the nursing contribution to patient outcome is presented. The review relies on work related to nursing sensitive outcomes, skill mix and changing roles. Methodological difficulties associated with these studies are highlighted. Areas requiring further research are discussed. It is suggested that experimental evidence is not always appropriate, when attempting to describe nursing activity. The authors advocate that new methodologies, in particular practitioner-centred research, are needed to unpack the nature of nursing.

Diagnosis-Related Groups↗
PubMed2001

Effect of the atrial blanking time on the detection of atrial fibrillation in dual chamber pacing.

Patients with paroxysmal atrial fibrillation (PAF) and dual chamber pacemakers frequently have short postventricular atrial blanking times and sensitive atrial sensing thresholds used to provide reliable detection and mode switching during AF. However, short atrial blanking times increase the risk of atrial sensing of ventricular far-field signals. We evaluated if the length of the atrial blanking time influences the detection of AF. The study included ten patients with a VDDR (n = 7) or DDDR system (n = 3), who presented with AF at 18 follow-up visits. Bipolar atrial sensing was programmed to the most sensitive value. Atrial blanking times were programmed from 100 to 200 ms in 25-ms steps in each patient. Using marker annotation, the following parameters were measured at ten consecutive ventricular beats: VAF = the interval between ventricular stimulus and first sensing of AF; AFS = the number of atrial-sensed events between two ventricular events; and XAF = the interpolated number of atrial-sensed events during atrial blanking time. The intervals between ventricular events and between atrial-sensed event markers showed no significant differences for the five blanking times tested. There was no significant influence of the atrial blanking time onto the measured parameters (least square means +/- standard error) with VAF between 281 +/- 12 and 300 +/- 12 ms (P = NS), AFs between 3.4 +/- 0.2 and 3.6 +/- 0.2 beats (P = NS) and XAF between 1.84 +/- 0.12 and 2.03 +/- 0.12 beats (P = NS). At ventricular rates < 100/min, the atrial sensing of AF in dual chamber pacemakers demonstrated no evidence for deterioration by an increase of the atrial blanking time from 100 to 200 ms. Thus, the risk of ventricular far-field sensing may be reduced without compromising atrial sensing.

Aged↗
PubMed2001

Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA.

BACKGROUND: Fibrinolytic therapy increases the risk of bleeding events. TNK-tPA (tenecteplase) is a variant of rt-PA with greater fibrin specificity and reduced plasma clearance that can be given as a single bolus. We compared the incidence and predictors of bleeding events after treatment with TNK-tPA and rt-PA. METHODS AND RESULTS: In the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 trial, 16 949 patients with acute myocardial infarction were randomly assigned a single weight-adjusted bolus of TNK-tPA or a 90-min infusion of rt-PA. A total of 4.66% of patients in the TNK-tPA group experienced major non-cerebral bleeding, in comparison with 5.94% in the rt-PA group (P=0.0002). This lower rate was associated with a significant reduction in the need for blood transfusion (4.25% vs 5.49%, P=0.0003) and was consistent across subgroups. Independent risk factors for major bleeding were older age, female gender, lower body weight, enrolment in the U.S.A. and a diastolic blood pressure <70 mmHg. Females at high risk (age >75 years and body weight <67 kg) were less likely to have major bleeding when treated with TNK-tPA even after other risk factors were taken into account. A total of 0.93% of patients in the TNK-tPA and 0.94% of patients in the rt-PA group experienced an intracranial haemorrhage. Female patients >75 years of age who weighed <67 kg tended to have lower rates of intracranial haemorrhage when treated with TNK-tPA (3/264, 1.14% vs 8/265, 3.02%). CONCLUSIONS: The increased fibrin specificity and single bolus administration of TNK-tPA do not increase the risk of intracranial haemorrhage but are associated with less non-cerebral bleeding, especially amongst high-risk patients.

Adult↗
PubMed2001

Diagnosis of culture-negative endocarditis: the role of the Duke criteria and the impact of transesophageal echocardiography.

BACKGROUND: The Duke criteria have been shown to be more sensitive than the von Reyn criteria in the diagnosis of culture-positive endocarditis but to date have not been fully validated for culture-negative endocarditis (CNE). The aim of this study was (1) to compare the diagnostic accuracy of the Duke criteria versus clinical judgment and the von Reyn criteria in CNE and (2) to assess the diagnostic impact of transesophageal echocardiography (TEE) on the Duke criteria in CNE. METHODS: The study group consisted of 49 patients with suspected CNE in whom the presence (n = 32) or absence (n = 17) of endocarditis was confirmed by surgery, autopsy, or both. All patients underwent transthoracic echocardiography (TTE) and TEE. They were classified into a Duke category initially with TTE data only, and then the Duke categories were reevaluated with the additional TEE data. RESULTS: The Duke criteria demonstrated a significantly higher sensitivity (72%) than the von Reyn criteria (28%; P =.0008) and a higher specificity (100%) than clinical judgment (76%; P =.02). No major differences were noted between sensitivities of the Duke criteria and clinical judgement. TEE significantly augmented the capacity to diagnose CNE by Duke criteria versus TTE (P <.05). CONCLUSIONS: The Duke criteria are of high diagnostic validity for the conduction of clinical studies on CNE. They have the potential to affect clinical decision-making, based on the higher specificity versus clinical judgment. TEE appears to be crucial for the diagnosis of CNE when the Duke criteria are applied. The diagnostic differentiation between CNE, sclerotic valve degeneration, and nonbacterial thrombotic endocarditis remains a challenge.

Adult↗
PubMed2001

Treatment of stage II cutaneous T-cell lymphoma with interferon alfa-2a and extracorporeal photochemotherapy: a prospective controlled trial.

BACKGROUND: Both interferon alpha and extracorporeal photochemotherapy have been shown to be effective in primary cutaneous T-cell lymphomas (CTCLs). However, no prospective trial has been published on the combination of both treatments, although retrospective investigations suggested a better efficacy than for either interferon or extracorporeal photochemotherapy. OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of combined interferon alfa-2a with extracorporeal photochemotherapy in a prospective controlled trial. METHODS: A prospective controlled study was performed. Fourteen patients (all male) aged 38 to 72 years with CTCL of the mycosis fungoides type, stage IIa/IIb, and a 72-year-old male patient with a Ki-1 lymphoma were treated twice a month for 6 months with extracorporeal photochemotherapy using oral 8-methoxypsoralen as photosensitizer in combination with interferon alfa-2a subcutaneously 3 times a week in the maximal tolerable dosage (ie, up to 18 x 10(6) U). The effects were investigated by a skin score, staging, histologic score (density of the T-cell infiltrate; from 0 = absent to 3 = heavy), immunohistology, and laboratory investigations including total peripheral T-cell count, CD4/CD8 ratio, and soluble interleukin 2 receptor (sIL-2R). RESULTS: After 6 months, best response was a complete response (CR) in 4 patients, a partial response (PR) in 3, and a stable disease (SD) in 7 of 14 patients (overall response rate [CR + PR] 50%). In responders the time to best response was 4.3 +/- 1.4 months. The skin score decreased from 22.5 +/- 8.1 to 15.1 +/- 11.0 (P <.001), the histologic score decreased from 2.57 +/- 0.51 to 1.21 +/- 0.80 (P <.001). In the lesional skin the percentage of CD4 cells decreased from 75% to 51% (P =.038) and Ki-67-positive cells decreased from 6.7% to 2.4% (P =.001). The total T-cell count/microL decreased from 1018.9 +/- 557.1 to 667.9 +/- 417.9 (P =.012), and the CD4/CD8 ratio also decreased from 1.88 +/- 0.92 to 1.51 +/- 0.67 (P =.038). The sIL-2R levels did not change significantly during the first 4 months of treatment. Among patients of stage IIa the response rate was 60% in contrast to only 25% of those in stage IIb. Side effects were seen temporarily, ranging from grade 0 to grade 3. There was no need for additional therapy, but interferon dose was decreased because of side effects. After 1 year of follow-up the total response rate was 46.2% (6 of 13 patients): 5 of 9 with stage IIa(55.6%) and 1 of 4 with stage IIb (25.0%). CONCLUSION: These results indicate that patients with CTCL stage IIa can achieve a total response rate of 56% with combined interferon alfa-2a and extracorporeal photochemotherapy. Responders seem to experience their best response within the first 6 months of treatment. The treatment is well tolerated and does not cause severe side effects.

Administration, Oral↗
PubMed2001

Alanyl-glutamine dipeptide does not affect hemodynamics despite a greater increase in myocardial heat shock protein 72 immunoreactivity in endotoxemic sheep.

The possible beneficial effect of supplemental glutamine (Gln) in critically ill patients has been suggested to be mediated by the induction of the cytoprotective heat shock proteins (HSP)32 and HSP72. There is evidence that HSP72 and HSP32 have opposite effects on the hemodynamic situation during endotoxemia. Therefore, the effect of Gln supplementation on the cardiovascular system is not clear. We investigated the effect of alanyl-Gln (Ala-Gln) dipeptide on cardiovascular function in healthy and endotoxemic sheep. Ten sheep catheterized for chronic studies received Ala-Gln 700 mg/(kg x d) [equal to 470 mg/(kg x d)Gln] on 4 consecutive days, and 10 sheep received NaCl (9 g/L) as the control solution. On d 4, four sheep of each group were killed and myocardial samples were taken for immunohistochemistry. The remaining sheep received a continuous infusion of endotoxin [Salmonella typhosa, 10 ng/(kg x min)]. Hemodynamic parameters were measured before application of Ala-Gln or the control solution, and during endotoxemia. Myocardial HSP72 immunoreactivity was determined by immunohistochemistry. After 24 h of endotoxemia, the sheep exhibited a hyperdynamic circulation. No difference was found in the hemodynamic parameters between treatment and control group. Ala-Gln treated sheep had a greater increase in myocardial HSP72 immunoreactivity compared with controls after (P < 0.05) but not before endotoxemia. In summary, Ala-Gln increased HSP72 immunoreactivity after endotoxemia, but did not alter hemodynamic parameters. Thus, Ala-Gln supplementation does not seem to aggravate the hyperdynamic circulation in endotoxemic shock.

Animals↗
PubMed2001

Thoracic, but not lumbar, epidural anesthesia improves cardiopulmonary function in ovine pulmonary embolism.

UNLABELLED: We hypothesized that sympathetic stimulation is the main mechanism contributing to hemodynamic failure in pulmonary embolism. We investigated the effects of epidural anesthesia-induced sympathetic blockade, restricted to thoracic and lumbar levels, during pulmonary embolism. Two experiments were performed in chronically instrumented ewes. In the first experiment, six sheep received 6 mL bupivacaine 0.175% (Thoracic Epidural Anesthesia [TEA] group), and six sheep received 6 mL saline 0.9% (TEA-Control group), respectively, via an epidural catheter (T3 level). In the second experiment, six sheep received 2.8 mL bupivacaine 0.375% (Lumbar Epidural Anesthesia [LEA] group), and six sheep received 2.8 mL saline 0.9% (LEA-Control group) epidurally (L4 level). Embolization was performed by IV injection of autologous blood clots (Experiment 1, 0.75 mL/kg; Experiment 2, 0.625 mL/kg). TEA was associated with significantly slower heart rates, decreased mean pulmonary artery pressures and central venous pressures, and significantly higher stroke volume index and oxygenation in comparison with the TEA-Control group. By contrast, LEA was associated with significantly faster heart rates and increased central venous pressures and with a significantly lower stroke volume index in comparison with the LEA-Control group. TEA significantly reduced, and LEA significantly increased, hemodynamic deterioration, suggesting beneficial effects of TEA on cardiopulmonary function during pulmonary thromboembolism. IMPLICATIONS: Thoracic (but not lumbar) epidural anesthesia was associated with beneficial cardiopulmonary effects during experimental pulmonary thromboembolism in sheep.

Anesthesia, Epidural↗
PubMed2001

Hemodynamic effects of terlipressin (a synthetic analog of vasopressin) in healthy and endotoxemic sheep.

OBJECTIVE: Hypotension, vasodilation, and vasoplegia are characteristic signs of septic shock. The vasoconstrictive response to catecholamines typically is reduced. A decreased vasopressive effect of catecholamines can be observed in the late phase of hemorrhagic shock. Interestingly, an unaltered vasopressive response to vasopressin can be demonstrated in hemorrhagic shock. In this study, we investigated the vasoconstrictive response to an agonist of the vasopressin receptor, terlipressin, in healthy sheep as well as in ovine hyperdynamic endotoxemia. DESIGN: Prospective controlled trial. SETTING: University research laboratory. SUBJECTS: Six female adult sheep. INTERVENTIONS: Healthy sheep, instrumented for chronic study, received terlipressin (15 microg/kg) as a bolus; 30 mins later, norepinephrine was continuously given for 30 mins. Three hours later, a continuous infusion of endotoxin (Salmonella typhosa, 10 ng x kg(-1) x min(-1)) was started in the same sheep and given for the next 23 hrs. After 20 hrs of endotoxemia, terlipressin and norepinephrine were given as described previously. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were measured before and 30 mins after application of terlipressin and after 30 mins of continuous infusion of norepinephrine. Terlipressin significantly increased systemic vascular resistance index in healthy and endotoxemic sheep (p <.05). The increase was higher in endotoxemic compared with healthy animals (p <.05). Only during endotoxemia, terlipressin increased pulmonary vascular resistance index. This was accompanied by a significant decrease in cardiac index, whereas mean pulmonary arterial pressure did not change after application of terlipressin. Additional treatment with norepinephrine did not further increase systemic vascular resistance index or pulmonary vascular resistance index. CONCLUSIONS: Terlipressin reversed the hemodynamic changes in ovine endotoxemia. However, its pulmonary vasopressive effect might limit its therapeutic use in septic shock.

Animals↗
PubMed2001

Plasma protein loss during surgery: beneficial effects of albumin substitution.

Plasma protein loss during abdominal surgery is a known phenomenon, but its possible pathophysiological relevance has remained unknown. The present study evaluates the effects of albumin substitution on systemic and local hemodynamics and cellular interactions in the mesenteric microcirculation. Rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Plasma protein concentrations, systemic and local hemodynamics were recorded during the follow up period, with or without albumin substitution. Depending on the time course of plasma protein loss in control experiments, 80% of the calculated protein loss was infused during the first 2 h of surgery, and the other 20% over the following 5 h of intravital microscopy. The control group received a continuous infusion of normal saline. Plasma protein loss was mainly due to loss of albumin. A significant increase in adherent and rolling leukocytes was observed during the course of mesenteric exteriorization, which was almost entirely reversed by albumin replacement. Albumin substitution led to stabilisation of mean arterial pressure and abdominal blood flow and also attenuated reductions in arterial base excess. Albumin infusions to replace plasma protein loss may be a simple and effective measure to attenuate microcirculatory disturbances and may be of benefit in patients undergoing abdominal surgery.

Abdomen↗
PubMed2001

Mutational analysis of the neuronal cadherin gene CELSR1 and exclusion as a candidate for catatonic schizophrenia in a large family.

The cadherin gene CELSR1 is specifically expressed in the brain and located on chromosome 22q13.33, a region that has recently been shown to be involved in the etiopathogenesis of familial catatonic schizophrenia. The gene is a strong positional candidate and was considered for mutational analysis. A total of 17 allelic variants of CELSR1 was found by sequencing all 35 exons, intron-exon junctions, and the putative promoter region by screening two patients from a large family mainly supporting this locus, and three control subjects in a first step. No variant exclusively co-segregates with the disease in the large pedigree, providing evidence that CELSR1 is not causative for the pathogenesis of catatonic schizophrenia in this family.

Alleles↗
PubMed2001

Isolation of Desulfomicrobium orale sp. nov. and Desulfovibrio strain NY682, oral sulfate-reducing bacteria involved in human periodontal disease.

The species of sulfate-reducing bacteria that prevail in sites affected by periodontal disease may be different from those commonly occurring in the digestive tracts of healthy individuals. Ten strains of mesophilic sulfate-reducing bacteria (SRB) were isolated from subgingival plaque in periodontal lesions of ten patients with periodontitis. Characterization on the basis of morphological, physiological and phylogenetic properties demonstrated two distinct types of oral SRB. One strain was a curved rod with high motility. For dissimilatory sulfate reduction, lactate or pyruvate was oxidized incompletely to equimolar amounts of acetate. Desulfoviridin and cytochrome c3 were present in this mesophilic vibrio and the cellular lipid profile was similar to that from members of the genus Desulfovibrio. The 16S rDNA sequence was similar to that of the proposed 'Desulfovibrio fairfieldensis'. Cells of the nine other strains were straight, rod-shaped, exhibited a low growth rate and oxidized substrates incompletely to acetate. These SRB, like members of the genus Desulfomicrobium, lacked desulfoviridin. Analysis of the 16S rDNA sequences of seven of the nine isolates showed a high degree of similarity among these oral strains, forming a distinct lineage within the genus Desulfomicrobium. The cellular lipid profile of a representative oral strain, NY678T, was in accordance with that of other Desulfomicrobium species, but also showed dissimilar features. The phenotypic and phylogenetic analyses indicate that these rod-shaped SRB from the oral cavity could be regarded as a new species, for which the designation Desulfomicrobium orale sp. nov. is proposed.

Bacterial Infections↗
PubMed2001

Substantial reduction of platelet adhesion by heparin-coated stents.

Although optimized antiplatelet medication has improved the clinical outcome after coronary stenting, vessel occlusion and restenosis still remain a relevant clinical problem. Platelets play a key role in this process. Therefore, the authors compared the platelet adhesion on different stent surface modifications (electropolished without coating or coated with carbon, carbon and additional heparin, silicon carbide, or heparin alone) to investigate their role in reducing platelet adhesion. All stents and additional stainless steel plates were incubated in heparinized whole blood with radiolabeled platelets. After washing the stents and plates four times, radioactivity caused by the adhesion of radiolabeled platelets was measured. The adhesion of radiolabeled platelets, compared to uncoated, electropolished stents, was reduced through silicon carbide coating to 58.6%, by carbon coating with additional heparin to 32.9%, and heparin coating alone to 7.7%. Stent coating with heparin is the most effective among the examined coatings in reducing platelet adhesion in vitro.

Anticoagulants↗
PubMed2001

Classification and phylogeny of hydrogenases.

Hydrogenases (H2ases) catalyze the reversible oxidation of molecular hydrogen and play a central role in microbial energy metabolism. Most of these enzymes are found in Archaea and Bacteria, but a few are present in Eucarya as well. They can be distributed into three classes: the [Fe]-H2ases, the [NiFe]-H2ases, and the metal-free H2ases. The vast majority of known H2ases belong to the first two classes, and over 100 of these enzymes have been characterized genetically and/or biochemically. Compelling evidence from sequences and structures indicates that the [NiFe]- and [Fe]-H2ases are phylogenetically distinct classes of proteins. The catalytic core of the [NiFe]-H2ases is a heterodimeric protein, although additional subunits are present in many of these enzymes. Functional classes of [NiFe]-H2ases have been defined, and they are consistent with categories defined by sequence similarity of the catalytic subunits. The catalytic core of the [Fe]-H2ases is a ca. 350-residue domain that accommodates the active site (H-cluster). A few monomeric [Fe]-H2ases are barely larger than the H-cluster domain. Many others are monomeric as well, but possess additional domains that contain redox centers, mostly iron-sulfur. Some [Fe]-H2ases are oligomeric. The modular structure of H2ases is strikingly illustrated in recently unveiled sequences and structures. It is also remarkable that most of the accessory domains and subunits of H2ases have counterparts in other redox complexes, in particular NADH-ubiquinone oxidoreductase (Complex I) of respiratory chains. Microbial genome sequences are bringing forth a significant body of additional H2ase sequence data and contribute to the understanding of H2ase distribution and evolution. Altogether, the available data suggest that [Fe]-H2ases are restricted to Bacteria and Eucarya, while [NiFe]-H2ases, with one possible exception, seem to be present only in Archaea and Bacteria. H2ase processing and maturation involve the products of several genes which have been identified and are currently being characterized in the case of the [NiFe]-H2ases. In contrast, near to nothing is known regarding the maturation of the [Fe]-H2ases. Inspection of the currently available genome sequences suggests that the [NiFe]-H2ase maturation proteins have no similar counterparts in the genomes of organisms possessing [Fe]-H2ases only. This observation, if confirmed, would be consistent with the phylogenetic distinctiveness of the two classes of H2ases. Sequence alignments of catalytic subunits of H2ases have been implemented to construct phylogenetic trees that were found to be consistent, in the main, with trees derived from other data. On the basis of the comparisons performed and discussed here, proposals are made to simplify and rationalize the nomenclature of H2ase-encoding genes.

Amino Acid Sequence↗
PubMed2001

Involvement of PKC and NF-kappaB in nitric oxide induced apoptosis in human coronary artery smooth muscle cells.

Apoptosis of vascular smooth muscle cells is critically involved in progression of atherosclerosis and may prevent intimal hyperplasia in restenosis and vascular remodeling. Nitric oxide (NO) is known to induce apoptosis, but the signaling pathways still remain unclear. We investigated p53 accumulation, protein kinase C (PKC) activation and nuclear transcription factor (NF-kappaB) binding activity as possible signaling mechanisms of NO-induced apoptosis. Apoptosis was induced dose-dependently with the NO-donors sodiumnitroprusside (SNP: 232+/-48%) and SIN-1 (241+/-90% of actinomycin D induced apoptosis; means +/- SEM, *p< or =0.05 vs. control) in HSMC. Inhibition of PKC significantly attenuated NO-induced apoptosis. Staurosporine reduced SIN-1/SNP-mediated DNA fragmentation by 55.3+/-13.8% and 38.3+/-13.9% respectively. Comparable results were obtained for calphostin C. However, NO-mediated induction of apoptosis was not preceded by p53 accumulation. SNP decreased NF-kappaB binding activity in HSMC. These results suggest that induction of apoptosis by exogenous NO in HSMC is not dependent on p53 accumulation but involves protein kinase C signaling and regulation of NF-kappaB binding activity. This opens a new therapeutical approach in preventing restenosis after angioplasty.

Apoptosis↗
PubMed2001

Association between P-selectin gene polymorphisms and soluble P-selectin levels and their relation to coronary artery disease.

P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.

Cohort Studies↗