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T Huber

Publications and source records attributed to T Huber.

At least 19 recordsLinked to original sources
PubMed1999

Binding of nucleotides by the mitochondrial ADP/ATP carrier as studied by 1H nuclear magnetic resonance spectroscopy.

Nucleotide binding to the cytosolic binding site of the mitochondrial ADP/ATP carrier (AAC) was studied by 1H-nuclear magnetic resonance spectroscopy. Binding (as opposed to translocation) could be identified as a result of the rapid ligand on/off kinetics, using the cytosolic side specific inhibitor carboxyatractyloside (CAT) for the distinction from nonspecific interactions. The off rate constant of the nonhydrolyzable ATP analogue AMP-PCP was more than 3 orders of magnitude larger than the transport rate. The nucleotides adopt an anti conformation in the carrier binding site as shown by measurements of the transferred nuclear overhauser effect (TRNOE). A thermal transition around 14 degreesC that had been previously detected in transport studies [Klingenberg, M., Grebe, K., and Appel, M. (1982) Eur. J. Biochem. 126, 263-269] was reflected by the inhibitor sensitive line broadening, indicating that this transition also affects nucleotide binding. Nucleotide monophosphates were employed to study the relation between nucleotide structure and affinity, using selective excitation, sample spinning with digital suppression of spinning sidebands, and line shape simulation. The binding of purines depends on the distribution of the electrical potential and on the position of ring substituents, while pyrimidines are barely recognized at all by the AAC. It is also shown that the photocleavable "caged" derivatives are more tightly bound than the original nucleotides. A two step model of carrier catalysis will be discussed on the basis of these results.

Adenosine Diphosphate↗
PubMed1998

Protein fold recognition without Boltzmann statistics or explicit physical basis.

We present a fast method for finding optimal parameters for a low-resolution (threading) force field intended to distinguish correct from incorrect folds for a given protein sequence. In contrast to other methods, the parameterization uses information from >10(7) misfolded structures as well as a set of native sequence-structure pairs. In addition to testing the resulting force field's performance on the protein sequence threading problem, results are shown that characterize the number of parameters necessary for effective structure recognition.

Algorithms↗
PubMed1998

Psychological and cardiovascular effects and short-term sequelae of MDMA ("ecstasy") in MDMA-naïve healthy volunteers.

3, 4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational drug reported to produce a different psychological profile than that of classic hallucinogens and stimulants. It has, therefore, been tentatively classified into a novel pharmacological class termed entactogens. This double-blind placebo-controlled study examined the effects of a typical recreational dose of MDMA (1.7 mg/kg) in 13 MDMA-naïve healthy volunteers. MDMA produced an effective state of enhanced mood, well-being, and increased emotional sensitiveness, little anxiety, but no hallucinations or panic reactions. Mild depersonalization and derealization phenomena occurred together with moderate thought disorder, first signs of loss of body control, and alterations in the meaning of percepts. Subjects also displayed changes in the sense of space and time, heightened sensory awareness, and increased psychomotor drive. MDMA did not impair selective attention as measured by the Stroop test. MDMA increased blood pressure moderately, with the exception of one subject who showed a transient hypertensive reaction. This severe increase in blood pressure indicates that the hypertensive effects of MDMA, even at recreational doses, should not be underestimated, particularly in subjects with latent cardiovascular problems. Most frequent acute somatic complaints during the MDMA challenge were jaw clenching, lack of appetite, impaired gait, and restless legs. Adverse sequelae during the following 24 hours included lack of energy and appetite, feelings of restlessness, insomnia, jaw clenching, occasional difficulty concentrating, and brooding. The present findings are consistent with the hypothesis that MDMA produces a different psychological profile than classic hallucinogens or psychostimulants.

Adult↗
PubMed1998

Noninvasive determination of language lateralization by functional transcranial Doppler sonography: a comparison with the Wada test.

BACKGROUND AND PURPOSE: Functional transcranial Doppler ultrasonography (fTCD) can assess event-related changes in cerebral blood flow velocities and, by comparison between sides, can provide a measure of hemispheric perfusional lateralization. It is easily applicable, insensitive to movement artifacts, and can be used in patients with less than perfect cooperation. In the present study we investigated the validity of fTCD in determining the hemispheric dominance for language by direct comparison of fTCD with intracarotid amobarbital anesthesia (Wada test). METHODS: fTCD and the Wada test were performed in 19 patients evaluated for epilepsy surgery. By the Wada test, 13 patients were classified as left-hemisphere dominant and 6 as right-hemisphere dominant for language. fTCD was based on the continuous bilateral measurements of blood flow velocities in the middle cerebral arteries and event-related averaging during a cued word generation task previously shown to activate lateralized language areas in normal adults. RESULTS: In 4 patients fTCD assessment was not possible because of lack of an acoustic temporal bone window. In the remaining 15 candidates, determination of language dominance was concordant with the Wada test in every case. Moreover, the correlation of the lateralization measures from both procedures was highly significant (r=.92, P<.0001). CONCLUSIONS: This strong correlation validates fTCD as a noninvasive and practical tool for the determination of language lateralization that can be applied for clinical and investigative purposes.

Adolescent↗
PubMed1998

Reproducibility of functional transcranial Doppler sonography in determining hemispheric language lateralization.

BACKGROUND AND PURPOSE: Since functional transcranial Doppler ultrasonography (fTCD) allows convenient and fully automated quantification of language lateralization, it seems ideal for longitudinal studies of perfusion changes during deterioration as well as recovery of language functions. However, during serial examinations, the technical, stochastic, and physiological variabilities of cerebral blood flow velocities (CBFV) have to be considered. Therefore, before fTCD is accepted as a tool for evaluation of changes in lateralization in the diseased state, its reliability in healthy subjects needs to be determined. METHODS: We performed fTCD during a word generation task based on a previously validated technique with automated calculation of the averaged CBFV differences in the middle cerebral arteries providing an index of lateralization (LI). RESULTS: (1) The accuracy of the LI as assessed by the confidence interval was better than 1% of the mean hemispheric difference. (2) On repeated examination, LIs obtained from 10 subjects showed a high test-retest reproducibility (Pearson product moment correlation coefficient r = 0.95, P < 0.0001). (3) On 10 repeated assessments of LI in the same subject, no practice effects were detected. CONCLUSIONS: Functional TCD is a suitable and very robust tool for the longitudinal quantitative measurement of cerebral language lateralization.

Adult↗
PubMed1997

Angiotensin II increases the cytosolic calcium activity in rat podocytes in culture.

In the glomerulus, angiotensin II (Ang II) reduces the ultrafiltration coefficient and enhances the filtration of macromolecules. During glomerular injury, inhibition of the renin-angiotensin system by angiotensin-converting-enzyme inhibitors reduces proteinuria and retards the progression to end-stage renal insufficiency. The mechanisms by which Ang II modulates glomerular function are still a matter of investigation. To study whether Ang II may regulate the cytosolic calcium activity ([Ca2+]i) in podocytes, these cells were propagated in short-term culture and the effect of Ang II was examined with the Fura-2 microfluorescence technique in single podocytes. The cellular identity of cultured podocytes was proven by the expression of WT-1 and pp44, specific antibodies against podocytes in vivo. Ang II led to a concentration-dependent, reversible and slow increase of [Ca2+]i with an EC50 of 3 nmol/liter Ang II (N = 229). Ten nmol/liter Ang II increased [Ca2+]i from 41 +/- 9 to 260 +/- 34 nmol/liter (N = 210). In a solution with an extracellular reduced Ca2+ concentration of 10 micromol/liter, Ang II-mediated [Ca2+]i increase was significantly reduced by 60 +/- 20% (N = 12), indicating that the [Ca2+]i increase was due to a Ca2+ influx from the extracellular space and a release of Ca2+ from intracellular stores. Flufenamate, an inhibitor of non-selective ion channels, significantly inhibited Ang II-mediated increase of [Ca2+]i (IC50 = 20 micromol/liter, N = 29), whereas the L-type Ca2+ channel blocker nicardipine even in high concentrations of > 1 micromol/liter had only a small inhibitory effect. The AT1 receptor antagonist losartan inhibited Ang II-mediated [Ca2+]i increase with an IC50 of about 0.3 nmol/liter (N = 35). The data suggest that Ang II increases [Ca2+]i in podocytes by an influx of Ca2+ through non-selective channels and by a release of Ca2+ from intracellular stores. The effect of Ang II is mediated via an AT1 receptor.

Angiotensin II↗
PubMed1997

Development of a gas chromatographic-mass spectrometric drug screening method for the N-dealkylated metabolites of fentanyl, sufentanil, and alfentanil.

A sensitive, specific urinary assay for fentanyl, sufentanil, and alfentanil based on their N-dealkylated metabolites is described. Norfentanyl, norsufentanil-noralfentanil, and 2H5-norfentanyl are synthesized and characterized by standard analytical techniques. Derivatization of these secondary amines to yield the pentafluorobenzamides produces stable products with good gas chromatographic properties and unique, high-mass fragments in their mass spectra. These properties are utilized to develop a drug screening procedure based on gas chromatography-mass spectrometry to detect these major metabolites in human urine. The metabolites are isolated from urine samples by a liquid-liquid extraction procedure. The method allows for detection of metabolite concentrations as low as 0.3 ng/mL.

Alfentanil↗
PubMed1996

[Severe complications in diagnostic laparoscopy. 9 years experience in 747 examinations].

BACKGROUND: Despite the introduction of non-invasive imaging procedures, diagnostic laparoscopy is still indicated in suspected liver cirrhoses, cancer staging and ascites or fever of unknown origin. Although the use of laparoscopy decreased over the last decade, some centers still have much experience and their complication rates are of special interest. PATIENTS AND METHODS: The complication rate of 747 patients undergoing a diagnostic laparoscopy in our clinic during the last 9 years is listed retrospectively, and the respective therapy is examined. RESULTS: Severe complications were found in 11 cases (1.5%): 6 bleeding complications, 2 bowel perforations and 3 other complications. Five of these 11 patients had to be operated on (45%). One patient with metastatic gastric cancer died of a multiple organic failure following a lararoscopic tumor biopsy (0.13%). CONCLUSION: The diagnostic laparoscopy is of significant value and has still a low complication-rate in centers with special experience.

Abdominal Neoplasms↗
PubMed1996

Successive activation of both cerebral hemispheres during cued word generation.

Most humans have a left hemispheric dominance for language. However, during diagnostic language testing there also is activation of the right hemisphere, which is probably related to attention. To investigate further the role of attention during language production we monitored cerebral blood flow velocities in the middle cerebral arteries by continuous bilateral transcranial Doppler ultrasonography (TCD) in nine right-handed subjects. During cued word generation, a successive activation of the right hemisphere in the preparatory phase, and of the left hemisphere during word searching was demonstrated. These findings indicate that attentional processes precede verbal activation and that the two procedures can be separated by comparative blood flow velocity measurement.

Acoustic Stimulation↗
PubMed1994

[Differences between women and men in the dipyridamole test. Symptomatic and electrocardiography findings in patients with coronary heart disease].

BACKGROUND: Problems are often encountered in evaluating the exercise stress ECG in women due to frequent false pathological findings. Besides the exercise ECG in the noninvasive diagnosis of coronary heart disease (CHD), the dipyridamole test is often used. As yet little is known about, whether a similarly high incidence of false positive test results occur under provocation with dipyridamole in women as in the exercise stress ECG. PATIENTS: In the present study the results of the dipyridamole test and of the coronary angiography in 218 patients, diagnosed as suspected of having CHD, were compared, especially allowing for specific sex differences. RESULTS: The prevalence of CHD in women was 17.8% and 56.1% in men. Under provocation with dipyridamole allowing for the indicator angina pectoris, the incidence of a false positive test results in relation to a significant coronary stenosis is higher in women with 80.5% than in men with 36.4% (p < 0.001). By contrast, men have a significantly higher rate of false negative test findings (40.9% to 11.1%; p < 0.001). Whereas the women obtained a sensitivity of 87.5%, the rating for men was 70.1%. Specificity was 21.6% for women and 48.7% for men. Test efficiency for men was 60.7% whereas for women 33.3% were calculated. The reaction of heart rate (significant increase of 33%) and systolic and diastolic blood pressure (no significant changes) did not reveal any relevant differences between men and women during the dipyridamole test. CONCLUSION: For patients with CHD similar diagnostic uncertainties occurred relating to specific sex differences in the results of the dipyridamole test, just like those known from the exercise ECG.

Adult↗
PubMed1994

Local elevation: a method for improving the searching properties of molecular dynamics simulation.

The concept of memory has been introduced into a molecular dynamics algorithm. This was done so as to persuade a molecular system to visit new areas of conformational space rather than be confined to a small number of low-energy regions. The method is demonstrated on a simple model system and the 11-residue cyclic peptide cyclosporin A. For comparison, calculations were also performed using simulated temperature annealing and a potential energy annealing scheme. Although the method can only be applied to systems with a small number of degrees of freedom, it offers the chance to generate a multitude of different low-energy structures, where other methods only give a single one or few. This is clearly important in problems such as drug design, where one is interested in the conformational spread of a system.

Algorithms↗
PubMed1994

Coupling constants again: experimental restraints in structure refinement.

Utilization of coupling constants as restraints in computational structure refinement is reviewed. In addition, we address the effect of conformational averaging and examine different approaches to apply the restraints when the experimental observable is obviously a result of averaging. Here, two different computational methods are compared. The simulation of a single structure with time-dependent restraints produces results very similar to those obtained with the calculation of numerous copies of the molecule (an ensemble of structures) and ensemble averaging. The advantages and disadvantages of the two methods are illustrated with simulations of cyclosporin A, for which 117 NOEs and 62 homo- and heteronuclear coupling constants have been measured.

Chemical Phenomena↗