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W Schwarz

Publications and source records attributed to W Schwarz.

At least 19 recordsLinked to original sources
PubMed2025

Ion-selective channels in K562 cells: a patch-clamp analysis.

Four types of ion-selective channels were found by the patch-clamp technique in the human erythroleukemia K562 cells. I) in cell-attached configuration at potentials less negative than -40 mV an 8 ps channel was detected. The potential dependence of channel activity suggests that this is the TTX-sensitive Na+ channel. II) A cation-selective channel was observed with equal permeability for Na+ and K+ and a potential-independent single-channel conductance of 19 pS. The channel is activated by intracellular Ca2+ and inhibited by TEA, III) A predominantly anion-selective channel was identified with the selectivity sequence NO3- > J- > Cl- = Br- >> SO4(2-). The single-channel conductance shows outward rectification, and is in symmetrical NaCl solution 19 pS at -60 mV and 54pS at +50 mV. The open- and closed-time distributions suggest one open and at least four closed states. At submicromolar concentrations, the open state is blocked by H2DIDS leading to channel flicker between open and blocked channel; higher concentrations (apparent KI = 6.8 uM) lead to a longer-lasting blocked state. Both components of inhibition are reversible. IV) In addition, an 8 pS, Na(+)- and K(+)- selective channel could be induced by application of palytoxin. For channel activity, the presence of extracellular Na+ is essential. It is assumed that the Na+, K(+)-pump molecule is involved in the channel formation. Similarly, it is discussed whether the anion-selective channel represents a pore conformation of an electrically silent anion exchanger.

Acrylamides↗
PubMed1996

Cardiac Na+ pump current-voltage relationships at various transmembrane gradients of the pumped cations.

Thermodynamic considerations predict changes of the Na+ pump current (Ip)-voltage (V) relationship of animal cells upon variations of the electrochemical gradients against which cations must be pumped. Experimental data in support of the predictions are sparse. Therefore, the effect on the Ip-V relationship of various electrochemical gradients for pumped Na+ and Cs+ was studied at constant deltaGATP (approximately -39kJ/mol in cardioballs from sheep Purkinje fibres. Control of the subsarcolemmal ionic concentrations during whole-cell recording was ensured by activation of Ip below its half maximal activity or by measuring the initial Ip following reactivation of the Na+/K+ pump. With gradients close to physiological conditions Ip was outward over the entire voltage range and the Ip-V relationship showed a maximum near zero potential. Steepening the ionic gradients diminished the Ip amplitude and outward pump current was no longer detectable between -65 mV and -110 mV. Flattened ionic gradients increased the Ip amplitude and shifted apparently the reversal potential Erev to more negative values. These changes are in line with theoretical considerations. The measured Ip-V relationships were fitted by curves computed on the basis of a simplified Post-Albers scheme of Na+/Cs+ pumping. The increased Ip amplitude at flat ionic gradients was due to a decrease of [Cs+]o for half maximal Ip activation. The maximal Ip amplitude remained unaffected

Animals↗
PubMed1996

[Early contributions from Erlangen to the theory and practice of ether and chloroform anesthesia. 1. Heyfelder's clinical trial with ether and chloroform].

The era of modern anaesthesia in Germany began on January 24th, 1847. This day, professor in ordinary Johann Ferdinand Heyfelder anaesthetized a patient with sulphuric ether in the clinic of surgery and ophthalmology of the University of Erlangen. By March 17th, 1847, Heyfelder had performed 121 surgical procedures under ether. The operations in majority were teeth-extractions, and a few more complex operations such as the treatment of a harelip or of lip cancer or the resection of the shoulder joint. Heyfelder described in detail 108 of these inhalations in a little book entitled The experiments with sulphuric ether. This monograph published in March, 1847, represents one of the first complete dissertations on sulphuric ether in the German literature. In a special chapter he analyzed the development of various physiological and psychological parameters during etherization. Heyfelder also examined blood and urine of some etherized patients and reported that he did not find any important or specific alterations. In 1847, Heyfelder was probably the first to apply salt-ether in man. After 4 administrations he concluded that salt ether acted more quickly but shorter than sulphuric ether. Advantageous were its application without problems and ease of induction. Disadvantageous were its high volatility, its price and the difficulty of getting it in a pure form. From December, 1847, on Heyfelder started to use chloroform. He was now able to perform more major operations, for example, the total resection of the hip-joint. In his book The experiments with sulphuric ether, salt ether, and chloroform he describes a great number of anaesthetic administrations using these 3 agents. In his summary Heyfelder concluded, that chloroform was undoubtly superior to sulphuric ether mainly because it was a quicker acting and longer lasting agent and leads to deeper narcosis. Moreover its application was much easier for it needed no special apparatus. However, because of its great anaesthetic potency, Heyfelder particularly demanded great caution in the application of chloroform. Explicitely he expected an assistant for chloroformizations, whose only duty was to supervise the inhalations and the patient--a forerunner of the modern specialized anaesthesiologist.

Anesthesiology↗
PubMed1996

Superparamagnetic iron oxide--enhanced versus gadolinium-enhanced MR imaging for differential diagnosis of focal liver lesions.

PURPOSE: To assess AMI-25- versus gadolinium-enhanced magnetic resonance (MR) imaging in the differential diagnosis of liver tumors. MATERIALS AND METHODS: Twenty-nine patients with liver tumors underwent unenhanced, AMI-25-enhanced (15 micromol/kg), and gadolinium-enhanced(0.1 mmol/kg) imaging within 2 weeks. RESULTS: A significant (P< .05) difference in percentage signal intensity loss (PSIL) was seen in benign tumors on AMI-25-enhanced proton-density-weighted images (nine focal nodular hyperplasia [FNH], 41%; one adenoma, 32.4%) versus malignant tumors. Gadolinium-enhanced T1-weighted gradient-echo images showed strong enhancement in benign lesions (seven FNH, 147.5%; one adenoma, 91.3%) and moderate enhancement in malignant tumors (eight hepatocellular carcinomas, 116.2%, 11 metastases, 39.7%). Receiver operating characteristic analysis revealed a threshold PSIL of 10% on AMI-25-enhanced images as the most essential criteria to distinguish benign from malignant lesions (sensitivity, 88%; specificity. 89%). Interobserver analysis for two observers revealed specificity of 93% for AMI-25-enhanced imaging versus 81.5% for gadolinium-enhanced MR imaging. CONCLUSION: AMI-25 decreased the SI of benign tumors and helped differentiate benign from malignant tumors.

Adenoma↗
PubMed1996

Liver tumors: comparison of MR imaging with Gd-EOB-DTPA and Gd-DTPA.

PURPOSE: To compare the usefulness of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in the diagnosis of focal liver lesions. MATERIALS AND METHODS: Thirty-one patients with focal liver lesions underwent T2- and T1-weighted spin-echo magnetic resonance (MR) imaging and fast low-angle shot two-dimensional MR imaging before, during, and after intravenous administration of three different doses of Gd-EOB-DTPA (12.5, 25, and 50 mumol per kilogram body weight). Gd-DTPA-enhanced imaging (dose, 0.1 mmol per kilogram body weight) was performed in the same patients within 1 week of Gd-EOB-DTPA imaging. RESULTS: During the perfusion phase (the 3 minutes after injection of contrast material), the dynamic enhancement characteristics seen after injection of 25 and 50 mumol of Gd-EOB-DTPA were similar to those seen with Gd-DTPA. At the lowest dose of Gd-EOB-DTPA (12.5 mumol), the dynamic enhancement characteristics were not comparable to those seen with Gd-DTPA. During the hepatobiliary phase (1.5 minutes to 4 hours after injection), Gd-EOB-DTPA-enhanced images yielded a dose-independent, statistically significant improvement in the detection rate of additional metastases, hepatocellular carcinomas, and hemangiomas compared with unenhanced and Gd-DTPA-enhanced images (P < .05). CONCLUSION: Gd-EOB-DTPA-enhanced MR imaging enables improved detection of hepatic lesions over Gd-DTPA-enhanced MR imaging while providing comparable differential diagnostic information.

Adult↗
PubMed1995

Involvement of the GTP binding protein Rho in constitutive endocytosis in Xenopus laevis oocytes.

To study an endocytotic role of the GTP-binding protein RhoA in Xenopus oocytes, we have monitored changes in the surface expression of sodium pumps, the surface area of the oocyte and the uptake of the fluid-phase marker inulin. Xenopus oocytes possess intracellular sodium pumps that are continuously exchanged for surface sodium pumps by constitutive endo- and exocytosis. Injection of Clostridium botulinum C3 exoenzyme, which inactivates Rho by ADP-ribosylation, induced a redistribution of virtually all intracellular sodium pumps to the plasma membrane and increased the surface area of the oocytes. The identical effects were caused by injection of ADP-ribosylated recombinant RhoA into oocytes. The C3 exoenzyme acts by blocking constitutive endocytosis in oocytes, as determined using a mAb to the beta 1 subunit of the mouse sodium pump as a reporter molecule and oocytes expressing heterologous sodium pumps. In contrast, an increase in endocytosis and a decrease in the surface area was induced by injection of recombinant Val14-RhoA protein or Val14-rhoA cRNA. PMA stimulated sodium pump endocytosis, an effect that was blocked by a specific inhibitor of protein kinase C (Gö 16) or by ADP-ribosylation of Rho by C3. Similarly, the phorbol ester-induced increase in fluid-phase endocytosis in oocytes was inhibited by Gö 16, C3 transferase, or by injection of ADP-ribosylated RhoA. In contrast to C3 transferase, C. botulinum C2 transferase, which ADP-ribosylates actin, had no effect on sodium pump endocytosis or PMA-stimulated fluid-phase endocytosis. The data suggests that RhoA is an essential component of a presumably clathrin-independent endocytic pathway in Xenopus oocytes which can be regulated by protein kinase C.

ADP Ribose Transferases↗
PubMed1995

All-trans beta-carotene preferentially accumulates in human chylomicrons and very low density lipoproteins compared with the 9-cis geometrical isomer.

Following ingestion of a beta-carotene isomer mixture (Betatene) containing nearly equal amounts of all-trans and 9-cis beta-carotene (all-trans/9-cis beta-carotene ratio approximately 1.5), concentrations of all-trans beta-carotene increased for 6 or 8 h in the chylomicron fraction of plasma from four of seven human subjects. A substantially lower increase in the 9-cis beta-carotene concentration was observed, with the accumulation of the all-trans isomer being 10- to 50-fold higher than that of the 9-cis isomer, calculated on the basis of the beta-carotene isomer pattern in the ingested mixture. A similar effect was observed in the VLDL fraction. Three of the seven subjects did not respond to beta-carotene ingestion. In the subjects that did respond, the all-trans/9-cis beta-carotene ratios in chylomicrons and VLDL suggest an efficient isomer-selective mechanism for intestinal uptake across the mucosa or very rapid elimination into tissues.

Administration, Oral↗
PubMed1995

Relationship between flanker identifiability and compatibility effect.

What is the relation between the identifiability of masked flankers and their ability to induce compatibility effects in a letter classification task? Using a within-subjects design (n = 8), we first determined identification performance for two flankers (H or N) around an irrelevant target letter as a function of the time (stimulus onset asynchrony, or SOA) after which the flankers were masked. In a second condition, subjects classified the central letter of the same stimulus patterns irrespectively of the identity of the flankers. The compatibility effects increased with increasing identification performance as a function of SOA, and we found a significant compatibility effect even at an SOA at which the identifiability of the flankers did not differ significantly from zero. We discuss the statistical power of our design and an interpretation of our results in terms of a dissociation between perceptual processes and processes directly activating the motor system (direct parameter specification; cf. Neumann, 1990).

Adult↗
PubMed1994

Coactivation and statistical facilitation in the detection of lines.

The redundant-signals effect describes the general phenomenon that simple reaction times to two simultaneously presented signals are typically faster than the corresponding reaction times to each of the signals presented alone. Recent studies (eg Miller 1982, 1986) indicate that models of probability summation in which an independent detection of both signals is assumed cannot completely account for the observed shortening of the reaction times. Therefore, models in which some kind of coactivation is assumed are often considered as an alternative explanation. In the present study simple reaction times to parallel lines are compared with those to orthogonal lines and single lines. Our first hypothesis is that because of the redundant-signals effect, the reaction time to configurations consisting of two lines (either parallel or orthogonal) will generally be faster than the reaction time to a single line. Furthermore, line detection can be related to orientation-specific line detectors. Therefore, parallel lines may be thought to activate similar line detectors and, by coactivation, facilitate detection. As our second hypothesis we thus expect that the reaction time to parallel lines will be shorter than the reaction time to orthogonal lines. To test these hypotheses, we conducted a simple reaction-time experiment in which signal onset asynchronies ranging from 0 to +/- 56 ms for the orthogonal lines were used. In addition, reaction times to parallel lines and single lines were measured. Both hypotheses are supported by our data. We formulate a stochastic model which is able to explain both statistical facilitation and coactivation in a physiologically plausible way.

Adult↗
PubMed1993

Inward-directed current generated by the Na+,K+ pump in Na(+)- and K(+)-free medium.

In Na(+)- and K(+)-free solution, an inward-directed current can be detected in Xenopus oocytes, which is inhibited by cardiac glycosides and activated by ATP. Therefore, it is assumed to be generated by the Na+,K+ pump. At negative membrane potentials, the pump current increases with more negative potentials and with increasing [H+] in the external medium. This current is not observed when Mg2+ instead of Ba2+ is the only divalent cation present in the bath medium, and it does not depend on whether Na+ or K+ is present internally. At 5 to 10 mM Na+ externally, maximum pump-generated current is obtained while no current can be detected in presence of physiological [Na+]. It is suggested that in low-Na+ and K(+)-free medium the Na+,K+ pump molecule can either form a conductive pathway that is permeable to Ba2+ or protons or operate in its conventional transport mode accepting Ba2+ as a K+ congener. A reversed pump mode or an electrogenic uncoupled Na(+)-efflux mode is excluded.

Animals↗
PubMed1993

Voltage-dependent inhibition of the sodium pump by external sodium: species differences and possible role of the N-terminus of the alpha-subunit.

Currents generated by the Na+/K+ ATPase were measured under voltage clamp in oocytes of Xenopus laevis. The dependence of pump current on external [Na+] was investigated for the endogenous Xenopus pump as well as for wild-type and mutated pumps of electroplax of Torpedo californica expressed in the oocytes. The mutants had alpha-subunits truncated before position Lys28 (alpha delta K28) or Thr29 (alpha delta T29) of the N-terminus. The currents generated by all variants of pump molecules in the presence of 5 mM K+ show voltage-dependent inhibition by external [Na+]. The apparent KI values increase with membrane depolarisation, and the potential dependence can be described by the movement of effective charges in the electrical potential gradient across the membrane. Taking into account Na(+)-K+ competition for external binding to the E2P form, apparent KI values and effective charges for the interaction of the Na+ ions with the E2P form can be estimated. For the Xenopus pump the effective charge amounts to 1.1 of an elementary charge and the KI value at 0 mV to 44 mM. For the wild-type Torpedo pump, the analysis yields values of 0.73 of an elementary charge and 133 mM, respectively. Truncation at the N-terminus removing a lysine-rich cluster of the alpha-subunit of the Torpedo pump leads to an increase of the effective charge and decrease of the KI value. For alpha delta K28, values of 0.83 of an elementary charge and 117 mM are obtained, respectively. If Lys28 is included in the truncation (alpha delta T29), the effective charge increases to 1.5 of an elementary charge and the apparent KI value is reduced to 107 mM. The KI values for pump inhibition by external Na+, calculated by taking into account Na(+)-K+ competition, are smaller than the K1/2 values determined in the presence of 5 mM [K+]. The difference is more pronounced for those pump variants that have higher Km values. The variations of the parameters describing inhibition by external [Na+] are qualitatively similar to those described for the stimulation of the pumps by external [K+] in the absence of extracellular [Na+]. The observations may be explained by an access channel within the membrane dielectric that has to be passed by the external Na+ and K+ ions to reach or leave their binding sites. The potential-dependent access and/or the interaction with the binding sites shows species differences and is affected by cytoplasmic lysine residues in the N-terminus.

Animals↗
PubMed1993

Coincidence detectors and two-pulse visual temporal integration: new theoretical results and comparison with data.

Exact predictions for two-pulse visual temporal integration data are derived from the Bouman-van der Velden quantum coincidence model for threshold vision. The predictions of the model start with complete summation for superposed pulses, then pass to a transition zone of partial integration, and finally reach the level of probability summation for pulses presented with large interstimulus intervals. From our results we can clearly reject the assumption of constant integration times with the basic model. We thus generalize the coincidence model to allow for variable integration times, derive the corresponding predictions for two-pulse integration data, and compare these predictions to published data currently available. It is shown that detectors of low order of coincidence generally underestimate the actual reduction of threshold intensity (or equivalently the corresponding increase of the detection probability) for two pulses as compared to the simple-pulse performance.

Cybernetics↗
PubMed1993

A diffusion model of early visual search: theoretical analysis and experimental results.

Meinecke (1989, Exp. 1, cond. HO) showed that the detectability of a visual target embedded in a linear noise array decreases with increasing retinal eccentricity, while the reaction time (RT) of the hits increases. One of the most interesting features of her results was that the RT of the correct rejections is consistently larger than the RT for signals presented near the fovea. This finding suggests that initially visual attention is concentrated near the fixation point and then diffuses across the stimulus array to perform a serial, exhaustive search. We present a diffusion model of early visual-search processes that quantitatively describes this evolution of attention in time and space; in contrast to most previous conceptions, it is based on a genuine relation between the spatial and temporal dimensions of the search processes performed. The model predicts quantitatively both detection performance and RT. We conducted an experiment similar to that of Meinecke (1989), but with an additional variation of the presentation time. All the main features of the 189 predictions could be explained by the model. The interpretation of the four model's parameters is discussed in some detail and compared with previous estimates of the microscopic search speed derived from alternative models. Finally, we consider some possible modifications related to results of Kehrer (1987, 1989), and some generalizations to multi target detection and two-dimensional stimulus arrays.

Adult↗
PubMed1993

Human serum concentrations of all-trans beta- and alpha-carotene but not 9-cis beta-carotene increase upon ingestion of a natural isomer mixture obtained from Dunaliella salina (Betatene).

The uptake of all-trans and 9-cis beta-carotene and of alpha-carotene from a natural carotene preparation from Dunaliella salina, Betatene, was studied in humans. All-trans beta-carotene and alpha-carotene were absorbed well and showed the expected biokinetics with serum peak concentrations between 24 and 48 h. The mean increase in serum concentrations of alpha-carotene was 5.6% of the increase of all-trans beta-carotene, reflecting the composition of these carotenoids in Betatene. 9-cis beta-Carotene, however, was not detected in human serum, even after repeated doses. This could be due to preferential absorption of all-trans beta-carotene, rapid distribution of 9-cis beta-carotene into the tissue, or the presence of isomerase activity processing 9-cis to all-trans beta-carotene.

Adult↗
PubMed1993

Separation of beta-carotene and lycopene geometrical isomers in biological samples.

The analysis of beta-carotene and lycopene, the two predominant carotenoids in human serum and tissues, was extended to the level of geometrical (cis-trans) isomers by using an improved reversed-phase HPLC methodology. We separated five geometrical isomers of beta-carotene and seven of lycopene in human serum and tissues. 13-cis-beta-Carotene was identified as the predominant cisisomer in human serum, contributing about 5% to total beta-carotene. In tissue, however, considerable amounts of 9-cis- and traces of 15-cis-beta-carotene were also detected. In contrast to beta-carotene, the lycopene isomer patterns in human serum and tissues are quite similar.

Adrenal Glands↗
PubMed1992

Voltage-dependent stimulation of Na+/K(+)-pump current by external cations: selectivity of different K+ congeners.

Currents generated by the endogenous Na+/K+ pump in the oocytes of Xenopus laevis were determined under voltage-clamp as currents activated by different K+ congeners. The voltage dependence of the pump current reflects voltage-dependent steps in the reaction cycle. The decrease of K(+)-activated pump current at positive potentials has been attributed to voltage-dependent stimulation by the external K+ (Rakowski, Vasilets, LaTona and Schwarz (1991) J. Membr. Biol. 121, 177-187). In Na(+)-free solution, activation of the pump by external cations seems to be the dominating voltage-dependent and rate-determining step in the reaction cycle. Under these conditions, the voltage dependence of apparent Km values for pump activation can be analyzed. The dependence suggests voltage-dependent binding of extracellular cations assuming that an effective charge of about 0.4 of an elementary charge is moved in the electrical field during a step associated with the cation binding. The apparent Km values at 0 mV differ for various cations that stimulate pump activity. The values are in mM: 0.10 for Tl+, 0.63 for K+, 0.71 for Rb+, 9.3 for NH4+, and 12.9 for Cs+. The corresponding apparent affinities follow the same sequence as the cation permeability of the K(+)-selective delayed rectifier channel of nerve cells. The results are compatible with the interpretation that the cations have to pass an ion-selective access channel to reach their binding sites in the pump molecule.

Animals↗
PubMed1992

Regulation of endogenous and expressed Na+/K+ pumps in Xenopus oocytes by membrane potential and stimulation of protein kinases.

Modulation of the current generated by the Na+/K+ pump by membrane potential and protein kinases was investigated in oocytes of Xenopus laevis. In addition to a positive slope region in the current-voltage (I-V) relationship of the Na+/K+ pump, a negative slope region has been described in these cells (Lafaire & Schwarz, 1986) and has been attributed to a voltage-dependent apparent Km value for pump stimulation by external [K+] (Rakowski et al., 1991). To study this feature in more detail, Xenopus oocytes were used for comparative analysis of the negative slope of the I-V relationship of the endogenous Na+/K+ pump and of the Na+/K+ pump of the electric organ of Torpedo californica expressed in the oocytes. The effects of stimulation of protein kinases A and C on the negative slope were also analyzed. To investigate the negative slope over a wide potential range, experiments were performed in Na(+)-free solution and in the presence of high concentrations of Ba2+ and tetraethylammonium, to block all nonpump related K(+)-sensitive currents. Pump currents and pump-mediated fluxes were determined as differences of currents or fluxes in solutions with and without extracellular K+. The voltage dependence of the Km value for stimulation of the Na+/K+ pump by external [K+] shows significant species differences. Over the entire voltage range from -140 to +20 mV, the Km value for the Na+/K+ pump of Torpedo electroplax is substantially higher than for the endogenous pump and exhibits more pronounced voltage dependence. For the Xenopus pump, the voltage dependence can be described by voltage-dependent stimulation by external [K+] and can be interpreted by voltage-dependent K+ binding, assuming that an effective charge between 0.37 and 0.56 of an elementary charge is moved in the electrical field. An analogous evaluation of the voltage dependence of the Torpedo pump requires the assumption of movement of two effective charges of 0.16 and 1.0 of an elementary charge. Application of 1,2-dioctanoyl-sn-glycerol (diC8, 10-50 microM), which is known to stimulate protein kinase C, reduces the maximum activity of the Xenopus pumps in the oocyte membrane by 40% and modulates the voltage dependence of K+ stimulation. For the endogenous Xenopus pump, the apparent effective charge increased from 0.37 to 0.51 of elementary charge and the apparent Km at 0 mV increased from 0.46 to 0.83 mM. For the Torpedo pump, one of the apparent effective charges increased from 1.0 to 2.5 of elementary charge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗