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Biomedical subjects

K Wenzel

Publications and source records attributed to K Wenzel.

At least 37 records · Page 2Linked to original sources
PubMed1997

Relationship of polymorphisms in the renin-angiotensin system and in E-selectin of patients with early severe coronary heart disease.

Previous association studies between angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have reported variable results. Therefore we examined the association of the DNA variants of ACE and AGT with early, severe coronary heart disease (CHD). In addition, we compared the genotypes of both polymorphisms and the recently discovered polymorphism in the E-selectin gene in both patients and an unselected population. This study included 113 patients with severe CHD (50 years old or less) and up to 197 control subjects. The frequencies of the ACE I/D variants were 48% I and 52% D in the controls and 46% I and 54% D in the patients. The frequencies of the AGT-M235T polymorphism were 60.8% M and 39.2% T in controls and 49.1% M and 50.9% T in the patients. The frequencies of the S128R polymorphism of the E-selectin were 91.3% S and 8.7% R in controls and 84.5% S and 15.5% R in the patients. In our studies the DD genotype of ACE was not associated with early severe CHD. We found a correlation between the M235T molecular variant of AGT and the S128R variant of E-selectin to early severe CHD.

Adult↗
PubMed1997

Phenotypic analysis of T lymphocytes isolated from non-small-cell lung cancer.

BACKGROUND: The study of the nature of tumor-infiltrating lymphocytes (TIL) may provide insight into the complex issue of tumor-host interactions. METHODS: Cytofluorometric analysis was performed to characterize the phenotypic profiles of TIL from non-small-cell lung cancers (NSCLC) and pulmonal metastases of different primary locations. An extensive panel of antibodies was used specific to different activation-associated molecules on T cells. In 10 patients, findings on the T cell phenotype of TIL were compared with the findings in peripheral blood lymphocytes (PBL) from the same patients. Furthermore, we investigated whether the measurement of the TIL phenotype might serve as a prognostic parameter correlating with survival of patients with NSCLC. RESULTS: In contrast to PBL, T cells infiltrating lung tumors expressed significantly higher amounts of various activation antigens. However, the immunophenotype of TIL hardly differed among different histological subtypes and pulmonal metastases. Addressing the prognostic value of the lymphocytic composition of TIL, we found no significant difference in the survival of NSCLC with high or low percentages of T and natural killer cells, whereas high percentages of B cells were associated with increased survival (p = 0.05). Patients with high percentages of CD13+ tumor-infiltrating T cells had significantly poorer prognosis according to Cox's multivariate analysis. CONCLUSION: Our results indicate that different tumor histologies within the lung are characterized by a 'similar' T cell phenotype, at least with respect to the surface molecules studied by us. The measurement of the expression of activation-associated markers on T cells may have prognostic value in the pathological evaluation of NSCLC.

Adult↗
PubMed1996

DNA polymorphisms in adhesion molecule genes--a new risk factor for early atherosclerosis.

To contribute to the analysis of the genetic background of atherosclerosis, especially endothelial dysfunction, we searched for DNA polymorphisms in the genes encoding E-, P-, and L-selectin, and ICAM-I and VCAM-I. We detected 17 mutations by single-strand conformation polymorphisms analysis and direct sequencing. Five of them resulted in an amino acid substitution. In E-selectin, exchanges from serine to arginine (position 128), from leucine to phenylalanine (position 554), and a DNA mutation from guanine to thymine (position 98) present significantly different allele frequencies in young patients with angiographically established, severe atherosclerosis, compared with an unselected population. Results suggest that these polymorphisms are associated with a higher risk for early severe atherosclerosis.

Adult↗
PubMed1996

Levels of dissociation in detoxified substance abusers and their relationship to chronicity of alcohol and drug use.

This study compared the frequency and types of dissociative experiences reported by detoxified alcoholics and drug abusers, and examined the relationship between dissociation and recent and lifetime use of alcohol, cannabis, cocaine, and heroin. One hundred thirty-eight self-referred male veterans detoxified from alcohol (N=62) and drugs (N=76) on inpatient units at a Veterans Affairs hospital completed questionnaires including the Dissociative Experiences Scale. Three types of dissociative experiences were examined: amnesia, depersonalization/derealization, and absorption. Ninety-one of the patients were also given the Addiction Severity Index interview to determine their histories of recent (past 30 days) and lifetime drug and alcohol use. High levels of dissociation were found in both groups, with alcoholics reporting higher levels of all three types of dissociative experiences than drug addicts. Chronicity (lifetime years) of both alcohol and cocaine use was significantly correlated with dissociation scores. The amnestic effect of chronic cocaine use persisted even after controlling for the effects of chronic alcohol use. In contrast, no dissociative effects of recent (past month) use of alcohol or drugs were found. These findings suggest that dissociation may be a chronic residual effect of long-term substance abuse, including both alcohol and cocaine. Implications are discussed for the treatment of chronic substance abusers.

Adult↗
PubMed1995

Redesigning patient care delivery: being at the bleeding edge!

Processes for total quality management, redesigning of patient care delivery and differentiated practice in nursing were developed and implemented simultaneously on two nursing units. This article describes the activities of the steering team and three work groups through the first nine months of implementation.

Hospital Restructuring↗
PubMed1994

Polymorphism in the human E-selectin gene detected by PCR-SSCP.

By using the non-isotopic single-strand conformation polymorphism (SSCP) technique to analyse products of the polymerase chain reaction (PCR), we detected a 561-adenine to cytosine substitution resulting in an amino acid exchange from serine to arginine at position 128 of the E-selectin gene. If this amino acid substitution has an effect on the adhesion of blood cells to the endothelium, the polymorphism could be of interest with respect to association studies in a number of pathological conditions, such as cardiovascular diseases.

Base Sequence↗
PubMed1994

E-selectin polymorphism and atherosclerosis: an association study.

Adhesion molecules like the members of the selectin family participate in the interaction between leukocytes and the endothelium. They are also involved in the pathogenesis of atherosclerotic processes. To contribute to the analysis of the genetic background of atherosclerosis we searched for DNA polymorphisms in the genes encoding adhesion molecules especially E-selectin which seems to be expressed only in activated endothelium. An adenine to cytosine substitution for cDNA position 561 resulting in an amino acid exchange from serine to arginine (position 128) was detected in the epidermal growth factor like domain. A significantly higher mutation frequency (P = 0.02) was observed in 97 patients aged 50 years or less with angiographically proven severe atherosclerosis (allele frequency of arginine 0.155) compared with an unselected population (allele frequency of arginine 0.088) as well as in 40 patients aged 40 years or less (allele frequency of arginine 0.21, P = 0.0025). These data suggest that the 128-serine/arginine polymorphism is associated with a higher risk for early severe atherosclerosis.

Adult↗
PubMed1994

Initial reliability and validity of a new retrospective measure of child abuse and neglect.

OBJECTIVE: This report presents initial findings on the reliability and validity of a new retrospective measure of child abuse and neglect, the Childhood Trauma Questionnaire. METHOD: Two hundred eighty-six drug- or alcohol-dependent patients were given the Childhood Trauma Questionnaire as part of a larger test battery, and 40 of these patients were given the questionnaire again after an interval of 2 to 6 months. Sixty-eight of the patients were also given a structured interview for child abuse and neglect, the Childhood Trauma Interview, that was developed by the authors. RESULTS: Principal-components analysis of responses on the Childhood Trauma Questionnaire yielded four rotated orthogonal factors: physical and emotional abuse, emotional neglect, sexual abuse, and physical neglect. Cronbach's alpha for the factors ranged from 0.79 to 0.94, indicating high internal consistency. The Childhood Trauma Questionnaire also demonstrated good test-retest reliability over a 2- to 6-month interval (intraclass correlation = 0.88), as well as convergence with the Childhood Trauma Interview, indicating that patients' reports of child abuse and neglect based on the Childhood Trauma Questionnaire were highly stable, both over time and across type of instruments. CONCLUSIONS: These findings provide strong initial support for the reliability and validity of the Childhood Trauma Questionnaire.

Adult↗
PubMed1992

Potassium channel activation in vascular smooth muscle.

1. Numerous compounds and changes in physical state functions shift the membrane potential of vascular smooth muscle to more negative values. The consequence is a vasodilatation because Ca2+ channels are closed. K+ channel opening frequently causes the hyperpolarization. 2. Acidification of the blood substitute solution and a fall in O2 partial pressure dilate arterial vessels. Acidosis is associated with a rise in K+ permeability and a simultaneous fall in Na+ permeability. Prostacyclin has a 20-30% share, and EDHF a 70-80% share, in hypoxic vasodilatation. Experiments with iloprost (PGI2 analogue) confirmed the K+ channel opening properties of this drug. A voltage-dependent K+ channel and a Ca(2+)-activated K+ channel, via the influence of cA-PK or cG-PK, are responsible for the hyperpolarization with iloprost and with oxygen deficiency. 3. Cicletanine and ajoene cause a concentration-dependent membrane hyperpolarization and are potent vasodilators. A cicletanine concentration, which is attained by the dosage given to patients, is sufficient to produce these effects. Ajoene exerts a hyperpolarizing and vasodilating influence even in a concentration which may occur in the extracellular space by the administration of a single garlic clove. 4. The stationary activation curve 'developed force vs. membrane potential' satisfactorily explains the effects of K+ channel openers. The tight electromechanical coupling expressed by this curve comprises a 50% vasorelaxation for a 2.5 mV hyperpolarization. In the linear part of the curve, the coupling ratio is 5.1 mV/g. 5. In the vascular smooth muscle, vasorelaxation can be evoked by membrane hyperpolarization which is linked to a simultaneous increase in K+ outward current and 42K+ efflux. In the case of substances whose influence is solely or partially receptor-mediated, cyclic nucleotides may be involved in vasorelaxation. Since cyclic nucleotides also hyperpolarize through an increase in K+ conductance, the resulting dilatation often cannot be divided into its single components. Therefore, it is sensible not to give the term "K+ channel opener" too fine a definition. The term should be applied to all substances and changes in physical states which predominantly increase the open probability of K+ channels finally via a conformational change in the cell membrane. For example, giving an acidic blood substitute solution (acidosis) is an intervention opening K+ channels. Which K+ channel and which single channel conductance is concerned in a particular case, and which 'mediator' may participate, become secondary questions.

Animals↗
PubMed1991

Influence of ion-pair formation on the pharmacokinetic properties of drugs. Pharmacokinetic interactions of bretylium and hexylsalicylic acid in rabbits.

The simultaneous i.v. administration of equimolar doses of bretylium and hexylsalicylic acid results in an increase in plasma area under the curve value of both substances in comparison with their separate administration. The higher plasma levels of both compounds were associated with a reduced renal excretion and an increased biliary elimination. However, the increase in biliary excretion did not compensate for the reduced elimination of bretylium and hexylsalicylic acid via the kidney. The results presented in this paper give further evidence that ion-pairing in-vivo may result in altered pharmacokinetics of drugs particularly due to changes in biliary or renal excretion.

Animals↗
PubMed1989

Purine and pyrimidine nucleotides potentiate activation of NADPH oxidase and degranulation by chemotactic peptides and induce aggregation of human neutrophils via G proteins.

Whereas the chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), induced NADPH-oxidase-catalyzed superoxide (O2-) formation in human neutrophils, purine and pyrimidine nucleotides per se did not stimulate NADPH oxidase but enhanced O2- formation induced by submaximally and maximally stimulatory concentrations of fMet-Leu-Phe up to fivefold. On the other hand, FMet-Leu-Phe primed neutrophils to generate O2- upon exposure to nucleotides. At a concentration of 100 microM, purine nucleotides enhanced O2- formation in the effectiveness order adenosine 5'-O-[3-thio]triphosphate (ATP[gamma S]) greater than ITP greater than guanosine 5'-O-[3-thio]triphosphate (GTP[gamma S]) greater than ATP = adenosine 5'-O-[2-thio]triphosphate (Sp-diastereomer) = GTP = guanosine 5'-O-[2-thio]diphosphate (GDP[beta S] = ADP greater than adenosine 5'-[beta, gamma-imido]triphosphate = adenosine 5'-O-[2-thio]triphosphate] (Rp-diastereomer). Pyrimidine nucleotides stimulated fMet-Leu-Phe-induced O2- formation in the effectiveness order uridine 5'-O-[3-thio]triphosphate (UTP[gamma S]) = UTP greater than CTP. Uracil (UDP[beta S]) = uridine 5'-O[2-thio]triphosphate (Rp-diastereomer) (Rp)-UTP[beta S]) = UTP greater than CTP. Uracil nucleotides were similarly effective potentiators of O2- formation as the corresponding adenine nucleotides. GDP[beta S] and UDP[beta S] synergistically enhanced the stimulatory effects of ATP[gamma S], GTP[gamma S] and UTP[gamma S]. Purine and pyrimidine nucleotides did not induce degranulation in neutrophils but potentiated fMet-Leu-Phe-induced release of beta-glucuronidase with similar nucleotide specificities as for O2- formation. In contrast, nucleotides per se induced aggregation of neutrophils. Treatment with pertussis toxin prevented aggregation induced by both nucleotides and fMet-Leu-Phe. Our results suggest that purine and pyrimidine nucleotides act via nucleotide receptors, the nucleotide specificity of which is different from nucleotide receptors in other cell types. Neutrophil nucleotide receptors are coupled to guanine-nucleotide-binding proteins. As nucleotides are released from cells under physiological and pathological conditions, they may play roles as intercellular signal molecules in neutrophil activation.

Cell Aggregation↗
PubMed1975

[In-vitro and in-vivo studies on the percutaneous absorption of systemic P 32-labelled insecticide organophosphorus compounds in cattle].

The influence of chemical composition and formulation on the absorption of radiophosphorus-labelled trichlorphon, butonate and dimethoate was investigated with isolated strips of bovine skin. Other factors studied were polarity of the solvent, concentration of pesticide, and effect of surface-active agents and dimethyl sulphoxide. Absorption experiments were also carried out on cattle and sheep, and the results were compared with those of the in vitro tests.

Animals↗