PubMed Health⌕ Search

Biomedical subjects

H Köppel

Publications and source records attributed to H Köppel.

At least 19 recordsLinked to original sources
PubMed2006

The serotonin transporter gene polymorphism is not associated with smoking behavior.

Nicotine increases serotonin release in the brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. The promoter region of the serotonin transporter gene, solute carrier family neurotransmitter transporter member 4 (SLC6A4), contains a functional tandem repeat polymorphism. The long (L) variant is more actively transcribed than the short (S) variant and is associated with a higher serotonin uptake. To investigate the potential role of this polymorphism for smoking behavior, SLC6A4 genotypes were determined in two different studies, the SMOKING GENES case-control study (470 current smokers and 419 subjects who had never smoked) and the cross-sectional Ludwigshafen risk and cardiovascular health (LURIC) study (777 current smokers and 1178 subjects who had never smoked). In the SMOKING GENES case-control study, SLC6A4 genotype frequencies were not statistically different between smokers (LL: 30.9%; LS: 46.8%; SS: 16.4%) and non-smokers (LL: 36.3%; LS: 41.8%; SS: 14.3%; P=0.13). Similar results were obtained in the cross-sectional LURIC study (smokers: LL, 36.5%, LS, 45.6%, SS, 17.9%; non-smokers: LL, 33.6%, LS, 48.9%, SS, 17.6%; P=0.33). SLC6A4 genotypes were furthermore not associated with Fagerstrom Tolerance Questionnaire score, packyears, number of cigarettes smoked per day or previous attempts to quit smoking. We conclude that the SLC6A4 promoter polymorphism is not a major determinant of smoking behavior in Caucasian.

Adult↗
PubMed2005

Remarkable impact of intermode couplings on multimode vibronic dynamics: the photoelectron spectrum of CH3F.

Electronic and nuclear motions on intersecting potential energy surfaces are often intricately mixed and the spectrum can become very complex. Here we choose the strongly coupled Jahn-Teller system CH3F+ as a prototype example, and establish the importance of intermode coupling terms on multimode vibronic dynamics. The theoretical approach consists of a full second-order diabatic vibronic Hamiltonian, constructed from high-quality electronic structure calculations. Our results compare amazingly well with the experimental data. This highlights the success of the present theoretical approach in explaining the complex structure of vibronic spectra, ubiquitous in molecular systems.

Journal Article↗
PubMed2005

On the (Emultiply sign in circlee)-Jahn-Teller conical intersections in the 3p(E') and 3d(E") Rydberg electronic states of triatomic hydrogen.

The static and dynamic aspects of the Jahn-Teller (JT) interactions in the 3p(E') and 3d(E") Rydberg electronic states of H3 are analyzed theoretically. The static aspects are discussed based on recent ab initio quantum chemistry results, and the dynamic aspects are examined in terms of the vibronic spectra and nonradiative decay behavior of these states. The adiabatic potential-energy surfaces of these degenerate electronic states are derived from extensive ab initio calculations. The calculated adiabatic potential-energy surfaces are diabatized following our earlier study on this system in its 2p(E') ground electronic state. The nuclear dynamics on the resulting conically intersecting manifold of electronic states is studied by a time-dependent wave-packet approach. Calculations are performed both for the uncoupled and coupled state situations in order to understand the importance of nonadiabatic interactions due to the JT conical intersections in these excited Rydberg electronic states.

Journal Article↗
PubMed2004

Theoretical study of excitations in furan: spectra and molecular dynamics.

The excitation spectra and molecular dynamics of furan associated with its low-lying excited singlet states 1A2(3s), 1B2(V), 1A1(V'), and 1B1(3p) are investigated using an ab initio quantum-dynamical approach. The ab initio results of our previous work [J. Chem. Phys. 119, 737 (2003)] on the potential energy surfaces (PES) of these states indicate that they are vibronically coupled with each other and subject to conical intersections. This should give rise to complex nonadiabatic nuclear dynamics. In the present work the dynamical problem is treated using adequate vibronic coupling models accounting for up to four coupled PES and thirteen vibrational degrees of freedom. The calculations were performed using the multiconfiguration time-dependent Hartree method for wave-packet propagation. It is found that in the low-energy region the nuclear dynamics of furan is governed mainly by vibronic coupling of the 1A2(3s) and 1B2(V) states, involving also the 1A1(V') state. These interactions are responsible for the ultrafast internal conversion from the 1B2(V) state, characterized by a transfer of the electronic population to the 1A2(3s) state on a time scale of approximately 25 fs. The calculated photoabsorption spectrum of furan is in good qualitative agreement with experimental data. Some assignments of the measured spectrum are proposed.

Journal Article↗
PubMed2004

Regularized diabatic states and quantum dynamics on intersecting potential energy surfaces.

The importance of diabatic electronic states for a quantum-dynamical treatment of conically intersecting potential energy surfaces is well known. An efficient construction scheme of approximately diabatic states is discussed which focuses on the removal of the singular derivative couplings and often relies on information from the potential energy surfaces alone. Thus an accuracy is achieved which is comparable to that of the Born-Oppenheimer approximation for widely spaced electronic states. New applications are presented for nitrogen dioxide and acetylene.

Journal Article↗
PubMed2004

Diminished response to activated protein C is not correlated with severity of peripheral arterial occlusive disease.

INTRODUCTION: Poor response to activated Protein C (APC) is a well established risk factor for venous thromboembolism. More recently, the hypercoagulable state which results from diminished response to APC has also been associated with arterial thrombosis. Some studies showed a clear association between low response to APC with advanced arterial disease, others, however, failed to support these data. Thus, there is ongoing dispute about the impact of a hypercoagulable state upon progression of atherosclerosis. MATERIAL AND METHODS: We investigated APC ratios and the existence of Factor V Leiden in 800 patients with documented peripheral arterial occlusive disease (PAD). Clinical symptoms according to Fontaine stages II (intermittent claudication), III (rest pain) and IV (gangrene) and the ankle/brachial index served as parameters for the severity of PAD. RESULTS: There was no association between low response to APC or existence of Factor V Leiden and the clinical stage of PAD or ankle/ brachial index. CONCLUSION: Our data suggest that poor response to APC is not correlated with the severity of peripheral arterial occlusive disease.

Activated Protein C Resistance↗
PubMed2003

Nongenomic effects of aldosterone on human renal cells.

The development of chronic renal insufficiency may be partially mediated by the nongenomic action of aldosterone. Here we investigate whether aldosterone could evoke a nongenomic action in primary cultures of human renal cells. Intracellular Ca(2+) ([Ca(2+)](i)) and cAMP were measured in human mesangial cells (MC), glomerular visceral epithelial cells (GVEC), and proximal and distal tubular epithelial cells (Ptec and Dtec) in the presence of aldosterone (10-100 nmol/liter) by fura-2 fluorescence and RIA, respectively. In MC, Ptec, and Dtec, aldosterone increased [Ca(2+)](i) within 1 min, whereas in GVEC, only a minor effect was found. Preincubation of cells with spironolactone did not blunt this effect. Hydrocortisone, used at a concentration 100-fold higher than that of aldosterone, did not affect [Ca(2+)](i.) In MC, Ptec, and Dtec, a dose-dependent increase ( approximately 1.3- to 1.5-fold) in intracellular cAMP levels was found. These data demonstrate a nongenomic action of aldosterone in human MC, Ptec, and Dtec. As these effects occur at concentrations close to free plasma aldosterone levels in man, they may be of physiological relevance and may contribute to renal injury.

Aldosterone↗
PubMed2002

G-455A polymorphism of the fibrinogen beta gene and deep vein thrombosis.

BACKGROUND: Elevated fibrinogen levels have been linked to increased risk for deep venous thrombosis, although it is not clear whether fibrinogen is causal or rather a marker for the presence of other risk factors. A common G/A polymorphism in the gene for the fibrinogen beta-chain (FGB G-455A) is associated with elevated fibrinogen levels. The present study was designed to analyze the role of this genetic marker for deep venous thrombosis. MATERIALS AND METHODS: We performed a case-control study including 307 patients with documented deep venous thrombosis and 316 control subjects. beta-fibrinogen genotypes were determined by allele-specific polymerase chain reaction. RESULTS: GG, GA and AA genotype frequencies were similar among the patients (53.1%, 41.0, 5.9) and controls (51.6%, 42.1, 6.3; P = 0.92). Fibrinogen levels of the patients (median 3.72 g l-1; range 1.93-11.6) did not differ significantly from those of the controls (3.76; 2.17-9.99). Carriers of the homozygous AA genotype had significantly higher fibrinogen levels than noncarriers (patients: 5.32 vs. 3.59; P = 0.024; controls: 6.29 vs. 3.72; P = 0.048). CONCLUSION: Our data suggest that the fibrinogen-elevating FGB G-455A gene polymorphism is not linked to an increased risk for deep venous thrombosis.

Alleles↗
PubMed2001

The PlA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with deep venous thrombosis.

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa, a fibrinogen and von Willebrand factor binding membrane receptor, has an important role in platelet aggregation. A common leucine33-proline polymorphism (PlA1/A2) of the gene encoding the GP IIIa subunit is associated with platelet reactivity and has been proposed as a risk factor for atherothrombotic disease. The aim of this study was to investigate the role of this polymorphism for deep venous thrombosis (DVT). METHODS: We performed a case-control study including 206 patients with documented DVT and a sex- and age-matched group of 310 control subjects. GP IIIa genotypes were determined by restriction fragment analysis of amplimers containing the polymorphic site. RESULTS: A1/A1, A1/A2 and A2/A2 genotypes were found in 67.0, 31.6 and 1.5 percent of patients and 72.3, 25.8 and 1.9 percent of controls (p=0.35), PlA2 allele frequencies were 0.17 in patients and 0.15 in controls (p=0.92). Odds ratio of the PlA2 allele for DVT was 1.21 (95 percent CI 0.85-1.71, p=0.29) and remained insignificant after adjustment for factor V Leiden and prothrombin 20210A genotypes (1.22, 95 percent CI 0.86-1.75, p=0.27). CONCLUSIONS: Our data suggest that the PlA1/A2 polymorphism of GP IIIa is not associated with DVT.

Adult↗
PubMed2000

Prothrombin G20210A, factor V Leiden, and factor XIII Val34Leu: common mutations of blood coagulation factors and deep vein thrombosis in Austria.

Mutations in the gene for prothrombin (F2 20210A) and factor V (F5 1691A, factor V Leiden) are established risk factors for deep venous thrombosis (DVT). Recently, a mutation in the gene for factor XIII (F13 100T) leading to a Valine-Leucine exchange at amino acid position 34 has been reported to be protective against DVT. To analyze the role of these mutations for DVT in Austria, we analyzed their prevalence in 154 patients with documented DVT and 308 sex- and age-matched control subjects. Allele frequencies of F2 20210A, F5 1691A, and F13 100T were 0.018, 0.039, and 0.274 among controls, and 0.045, 0.120, and 0.211 among patients, respectively. Odds ratios for DVT associated with F2 20210A, F5 1691A, and F13 100T alleles were 2.5 (95% CI: 1.1-5.7), 3.4 (95% CI: 1.9-5.8), and 0.7 (95% CI: 0.5-1.0). We conclude that F2 20210A, F5 1691A, and F13 100T are common mutations in the Austrian population. F2 20210A and F5 1691 increase the risk for DVT, whereas F13 100T is associated with a decreased risk for DVT. Routinely, analysis of these mutations may help to analyze the individual risk for DVT.

Adolescent↗
PubMed2000

Factor II G20210A and factor V G1691A gene mutations and peripheral arterial occlusive disease.

BACKGROUND: G to A mutations at positions 20210 of the prothrombin gene (F2) and 1691 of the factor V gene (F5) are established risk factors for venous thrombosis. Several factors associated with coagulation and/or fibrinolysis have been associated with arterial occlusive disease, but the role of F2 20210A and F5 1691A for arterial occlusive disease remains unclear. OBJECTIVE: To investigate if F2 20210A and F5 1691A are associated with peripheral arterial occlusive disease (PAOD). METHODS AND RESULTS: We analyzed the prevalence of F2 20210A and F5 1691A alleles in 336 patients with documented PAOD at Fontaine stage II-IV and 300 controls without vascular disease. Allele frequencies in patients and controls were 0.013 and 0.022 for F2 20210A, and 0.042 and 0.045 for F5 1691, respectively, both differences being not statistically significant. CONCLUSION: Our data suggest that mutations F2 G20210A and F5 G1691A are not associated with PAOD.

Aged↗
PubMed2000

[Free intracellular magnesium in myocardium--measurement and physiological role--state of the art].

Magnesium is an important intracellular cation which is known to participate in over 300 biochemical reactions of the cell. Most of the cell's Mg2+ is bound to intracellular structures, and only 5% of the total Mg2+ are unbound and thus biologically active. Clinical data concerning the therapeutic value of Mg2+ in various conditions like myocardial infarction are conflicting, experimental support for a specific therapy is still lacking, because values of free intracellular myocardial Mg2+ as well as behaviour of (Mg2+)i during ischemia or changes of extracellular ion-concentrations have not been elucidated as yet. Various techniques like Mg2+ sensitive dyes, nuclear magnetic resonance spectroscopy or Mg2+ selective microelectrodes have been employed, each of these techniques, however, harbours serious limitations.

Coloring Agents↗
PubMed1999

Inhibition of vascular K(ATP) channels by U-37883A: a comparison with cardiac and skeletal muscle.

1 The aim of this study was to investigate the selectivity of the ATP-sensitive potassium (K(ATP)) channel inhibitor U-37883A (4-morpholinecarboximidine-N-1-adamantyl-N'-1-cyclohexyl). Membrane currents through K(ATP) channels were recorded in single muscle cells enzymatically isolated from rat mesenteric artery, cardiac ventricle and skeletal muscle (flexor digitorum brevis). K(ATP) currents were induced either by cell dialysis with 0.1 mM ATP and 0.1 mM ADP, or by application of synthetic potassium channel openers (levcromakalim or pinacidil). 2 U-37883A inhibited K(ATP) currents in smooth muscle cells from rat mesenteric artery. Half inhibition of 10 microM levcromakalim-induced currents occurred at a concentration of 3.5 microM. 3 Relaxations of rat mesenteric vessels caused by levcromakalim were reversed by U-37883A. 1 microM levcromakalim-induced relaxations were inhibited at a similar concentration of U-37883A (half inhibition, 1.1 microM) to levcromakalim-induced KATP currents. 4 K(ATP) currents activated by 100 microM pinacidil were also studied in single myocytes from rat mesenteric artery, skeletal muscle and cardiac ventricle. 10 microM U-37883A substantially inhibited K(ATP) currents in vascular cells, but had little effect in skeletal or cardiac myocytes. Higher concentrations of U-37883A (100 microM) caused a modest decrease in K(ATP) currents in skeletal and cardiac muscle. The sulphonylurea K(ATP) channel antagonist glibenclamide (10 microM) abolished currents in all muscle types. 5 The effect of U-37883A on vascular inward rectifier (KIR) and voltage-dependent potassium (KV) currents was also examined. While 10 microM U-37883A had little effect on these currents, some inhibition was apparent at higher concentrations (100 microM) of the compound. 6 We conclude that U-37883A inhibits K(ATP) channels in arterial smooth muscle more effectively than in cardiac and skeletal muscle. Furthermore, this compound is selective for K(ATP) channels over KV and KIR channels in smooth muscle cells.

Adamantane↗
PubMed1998

EDRF does not mediate coronary vasodilation secondary to simulated ischemia: a study on KATP channels and N omega-nitro-L-arginine on coronary perfusion pressure in isolated Langendorff-perfused guinea-pig hearts.

Several authors have alluded to the possible involvement of EDRF (NO) in ischemia-induced coronary artery dilation. Alternatively, it has been suggested that opening of ATP-dependent K channels could play a key role in this context. We studied the effects of sulfonylureas and NG-nitro-L-arginine (LNNA), a specific inhibitor of endothelial NO (EDRF) synthesis, on ischemia-induced coronary vasodilation in isolated Langendorff-perfused guinea pig hearts arrested with 15 mM KCl in normal Tyrode, and isolated pig coronary arteries precontracted with 43 mM KCl. In Isolated Langerdorff-perfused guinea pig heart, when hypoxia was simulated by switching 100% O2 in the perfusate to 100% N2, coronary perfusion pressure (CPP) fell from 90 cm H2O by 45 +/- 5 cm H2O. In the presence of LNNA, a specific inhibitor of NO synthetase in endothelial cells, CPP dropped by 44 +/- 6 cm H2O (n = 6; +/- SEM, no statistically significant). On biochemical simulation of ischemia (addition of iodoacetate [IAA]), CPP dropped 40 +/- 6 cm H2O, and in experiments performed under the same conditions but in the presence of LNNA, CPP dropped by 38 +/- 5 cm H2O (n = 6; +/- SEM; not statistically significant). When ischemia was simulated metabolically by equimolar replacement of 10 mM glucose with 2-deoxyglucose (DOG), an inhibitor of glycolysis CPP decreased by 24 +/- 1 cm H2O (n = 6; +/- SEM) after 15 minutes. This fall in CPP was almost prevented by 20 microM glibenclamide, whereas in the presence of 20 microM LNNA the DOG-induced decrease in CPP was not significantly inhibited, and CPP decreased by 22 +/- 2.6 cm H2O (n = 6; +/- SEM). In isolated pig coronary artery rings, maximal tension, achieved by depolarizing the smooth muscle cells by 43 mM KCl, decreased by 37 +/- 7% upon simulated hypoxia by replacing 100% O2 with 100% N2 in the perfusate (n = 6; +/- SEM) in arteries with intact endothelium. In arteries without endothelium, maximal tension also dropped by 35 +/- 6% (not statistically significant). In the same experiments the decrease in tension could be largely inhibited in the presence of 50 microM glibenclamide. Our results clearly show that in isolated perfused guinea pig hearts, as well as in isolated pig coronary arteries, EDRF does not play a decisive role in the coronary dilatory response to hypoxia and ischemia.

Adenosine Triphosphate↗