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Biomedical subjects

W Schwarz

Publications and source records attributed to W Schwarz.

At least 19 recordsLinked to original sources
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↗
PubMed1992

cis-trans isomers of lycopene and beta-carotene in human serum and tissues.

Since cis or trans isomers of carotenoids may have different biological reactivities, the isomeric composition of lycopene and beta-carotene was measured in serum and seven human tissues. In addition to all-trans lycopene, at least three cis-isomers (9-, 13-, and 15-cis) were present, accounting for more than 50% of total lycopene. 13- and 15-cis-beta-carotene, however, were present at only 5% of the all-trans isomer. In addition, 9-cis-beta-carotene was present in tissue samples but not in serum. There were interindividual differences in carotenoid levels of the different tissue types, but liver, adrenal gland, and testes always contained significantly higher amounts of the carotenoids than kidney, ovary, and fat; carotenoids in brain stem tissue were below the detection limit. beta-Carotene was the major carotenoid in liver, adrenal gland, kidney, ovary, and fat, whereas lycopene was the predominant carotenoid in testes.

Adipose Tissue↗
PubMed1992

In vitro activation of peripheral mononuclear cells by zinc in HIV-infected patients and healthy controls.

Zinc is a mitogen for peripheral blood mononuclear cells (PBMC). The optimal mitogenic concentration was found to be 0.05 mmol/l (327 micrograms/dl), four times higher than physiological serum levels. Maximal proliferation was observed after 6 days. Limited dilution technique revealed a frequency of zinc reactive cells of 1:3467 (median; range 1:1628-1:6235). Cord blood mononuclear cells from four of six healthy children could be stimulated to proliferate by zinc. A normal zinc-induced proliferative response could be demonstrated in all six HIV-infected patients in the Walter-Reed-stage I, in nine of 11 patients in Walter-Reed II and in only two of five patients in Walter-Reed III. In Walter-Reed IV to VI all eight patients showed a weak response to zinc (less than 50% of the healthy day control). Decreased zinc serum levels were found in 10 of 28 patients and in one of 16 controls. There was a significant correlation of a diminished zinc-induced proliferation with lower serum levels of zinc and a reduced proportion of CD4 helper cells in HIV-1-infected men. Because of a suppression of mitogenesis by high dose of zinc an excessive intake of zinc as used by some HIV-1-infected patients can presently not be recommended. The value of zinc-induced proliferation for monitoring HIV-infected patients has still to be established.

Cells, Cultured↗
PubMed1991

Up-regulation of sodium pump activity in Xenopus laevis oocytes by expression of heterologous beta 1 subunits of the sodium pump.

Recent evidence suggests that the beta subunit of the Na+ pump is essential for the alpha subunit to express catalytic activity and for assembly of the holoenzyme in the plasma membrane. We report here that injection into Xenopus laevis oocytes of cRNAs specific for beta 1 subunit isoforms of the Na+ pump of four species (Torpedo californica, chicken, mouse and rat) causes a time-dependent increase in the number of ouabain-binding sites, both in the plasma membrane and in internal membranes. Expression of the beta 1 subunit of the Na+ pump of mouse and rat in the oocytes could be substantiated by immunoprecipitation using a polyclonal antiserum against the mouse beta 1 subunit. Scatchard analysis in permeabilized cells disclosed that the affinity for ouabain is unchanged after expression of each of the beta 1 subunits. A proportional increase in ouabain-sensitive 86Rb+ uptake indicates that the additionally expressed ouabain-binding sites on the cell surface represent functional Na+ pumps. The findings support the concept of Geering. Theulaz, Verrey, Häuptle & Rossier [(1989) Am. J. Physiol. 257, C851-C858] that beta 1 subunits expressed in oocytes associate with an excess of endogenous alpha subunits of the Na+ pump to form a hybrid enzyme. In addition, all of the beta 1 isoforms investigated in the present study were also capable of combining with the co-expressed alpha 1 subunit of the Torpedo Na+ pump to produce a functional enzyme. Injection of cRNA encoding for the Torpedo alpha 1 subunit alone had no effect on the ouabain-binding capacity of the surface and intracellular membranes of the oocyte.

Animals↗
PubMed1991

Conditions for a backward-running Na+/K+ pump in Xenopus oocytes.

Current generated by the electrogenic Na+/K+ pump protein was determined in oocytes of Xenopus laevis as strophantidine-sensitive current measured under voltage clamp. Under conditions of reduced intracellular [Na+] and [ATP], both to values below 1 mM, and in extracellularly K(+)-free medium, the Na+/K+ pump seems to operate in a reversed mode pumping Na+ into the cell and K+ out of the cell. This is demonstrated by strophantidine-induced hyperpolarization of the membrane and inward-directed current mediated by the pump protein. In addition, strophantidine-sensitive uptake of 22Na+ can be demonstrated under these conditions. The pump current decreases with membrane depolarization as expected for a pump cycle that involves inward movement of positive charges during Na+ translocation.

Adenine Nucleotides↗
PubMed1991

Stimulation of the Na+/K+ pump by external [K+] is regulated by voltage-dependent gating.

Wild-type and mutants with alpha-subunits truncated at the N terminus of Na+/K+ pumps of Torpedo electroplax were expressed in Xenopus oocytes by injection of cRNAs encoding for one of the alpha-subunits and for the beta-subunit. Currents generated by the pump were investigated under voltage clamp in Na(+)-free solution, a condition where stimulation by external [K+] is the only voltage-dependent and rate-determining step in the pump cycle (Rakowski, R. F., Vasilets, L. A., LaTona, J., and Schwarz, W. (1991) J. Membr. Biol. 121, 177-187). Voltage dependence of the apparent Km value for pump stimulation and of maximum transport activity was investigated. Truncation of the intracellular N-terminal end of the alpha-subunit at the trypsin-accessible site (alpha delta K37, leaving Lys37) leads to nearly complete inhibition of pump current at physiological potentials, whereas ouabain binding capacity is retained indicating an essential involvement of the N-terminal end in the process of ion translocation. Truncation at the N-terminal end leaving Lys28 (alpha delta K28) or Thr29 (alpha delta T29) leads to removal of 6 or 7 lysine residues, respectively, and has no effect on maximum transport activity. On the other hand, the mutated pumps with alpha delta K28 or alpha delta T29 exhibit more pronounced voltage dependences for stimulation of pump current by external [K+] compared with the wild-type Torpedo pump. In particular, a pronounced increase in voltage dependence of the apparent affinity of pump stimulation is obtained by the removal of the Lys28. The results support the view that the lysine-rich region in the N-terminal end affects the cation binding to the pump molecule and that Lys28 is important.

Animals↗
PubMed1991

Endogenous L-glutamate transport in oocytes of Xenopus laevis.

The existence of an endogenous Na(+)-glutamate cotransporter in the oocytes of Xenopus laevis is demonstrated. The transporter does not accept D-glutamate as substrate. The dependence on substrate displays two saturating components with low (K1/2 = 9 mM) and high (K1/2 = 0.35 microM) affinities for L-glutamate. The dependence on external Na+ exhibits a saturating component with a K1/2 value of about 5 mM and a component that has not saturated up to 110 mM Na+. In voltage-clamped oocytes, it is possible to demonstrate that Na(+)-dependent L-glutamate transport is directly coupled to countertransport of Rb+. The analysis of the voltage dependence of the Na+,K(+)-dependent L-glutamate uptake suggests that positive charges are moved inwardly during the transport cycle.

Amino Acid Transport System X-AG↗
PubMed1991

Comparison of a Na+/D-glucose cotransporter from rat intestine expressed in oocytes of Xenopus laevis with the endogenous cotransporter.

Epithelial Na+/D-glucose cotransport was incorporated into the plasma membrane of Xenopus oocytes after microinjection of poly(A)(+)-mRNA from rat intestine tissue and was detected by measurements of uptake of [14C]AMG (methyl alpha-D-glucopyranoside). In mRNA-injected oocytes, the rate of AMG uptake exceeds the rate of endogenous Na+/AMG cotransport by a factor of up to 30. It is demonstrated that the additionally expressed transport differs qualitatively from the endogenous transport with respect to several parameters which is a prerequisite for the demonstration of expression of a foreign transporter: (1) The expressed system is more sensitive to external glucose or AMG and to the specific inhibitor phlorizin, (2) it is less sensitive to external Na+ and to changes in membrane potential, and (3) it is susceptible to inhibition by monoclonal antibodies, known to bind specifically to Na+/glucose cotransporters and to modulate the cotransport in kidney and intestine. The use of the antibodies allows one to distinguish between endogenous Na+/AMG cotransport and foreign cotransport expressed by injection of foreign mRNA. The expression of the foreign transport leads to transport rates that are high enough to detect the electrical current generated by the Na+/glucose cotransport. This allows future characterization of the cotransport system under voltage-clamp conditions by analyzing membrane current.

Animals↗
PubMed1991

[Potential antiestrogens of the 1,2-diphenyl-1-pyridyl-but-1-ene type. 2. Biological testing].

Z-1-(4-hydroxyphenyl)-1-(4-resp. 3-pyridyl)-2-phenyl-but-1-enes Z-1 and Z-2 and their acetates Z-1a and Z-2a are weak estrogens (uterine weight test, immature mouse), which cause a marked tumor growth inhibition on the hormone-dependent MXT mammary carcinoma of the mouse. No or just slight estrogenic side effects determined by uterine weight are detectable in this tumor experiment.

Animals↗
PubMed1991

Spine deformity index (SDI) versus other objective procedures of vertebral fracture identification in patients with osteoporosis: a comparative study.

Radiologic identification of vertebral fractures is most important in the diagnosis and monitoring of patients with spinal osteoporosis. Different methods, using vertebral height measurements for fracture identification, have therefore been developed. We compared four methods for fracture identification in spinal x-rays of 62 female patients with primary osteoporosis. The methods of Hedlund and Gallagher, Melton et al., and Davies et al. are based on the ratio of heights within one vertebra or of the height ratios of adjacent vertebrae; all three methods result in counting the number of vertebral fractures. The fourth method of Minne et al. relates anterior, middle and posterior heights of the vertebrae between T5 and L5 to the respective heights of T4. The relative vertebral heights of patients with osteoporosis are compared to the respective relative heights (anterior, middle, and posterior) of normal subjects (T5-L5). This allows the identification of fractured vertebrae, as well as a quantification of the extent of deformation due to these fractures (spine deformity index, SDI). The same measurement data of 62 spinal x-rays of anterior, middle, and posterior heights between T4 and L5 were used to detect vertebral fractures by the four different methods. Correlation between the number of identified fractures by the different methods ranged between r = 0.56 and 0.83. On the other hand, we found a remarkable difference in the mean number of identified fractures and a discrepancy in the identification of single vertebrae as fractured or not. All four methods revealed an accumulation of fractures in the midthoracic area and in the region of transition from thoracic to lumbar spine. Vertebral fractures as identified by SDI were not detected by the other three methods in 12-29% of the cases, even if vertebral height reduction was more than 6 mm. The reliability of each method was examined by the determination of "decreasing" number of fractures during follow-up. A decrease in the number of fractures was found in about 25% patients, if using the three methods that count only the number of fractures. We obtained a 3.6% decrease in the number of fractures using the fourth method. Furthermore, the decrease in SDI values in follow-up was within the range of variance. We therefore believe that SDI and related procedures are reliable in quantifying spinal osteoporosis and monitoring during follow-up.

Adult↗
PubMed1991

A negative slope in the current-voltage relationship of the Na+/K+ pump in Xenopus oocytes produced by reduction of external [K+].

To investigate the voltage dependence of the Na+/K+ pump, current-voltage relations were determined in prophase-arrested oocytes of Xenopus laevis. All solutions contained 5 mM Ba2+ and 20 mM tetraethylammonium (TEA) to block K+ channels. If, in addition, the Na+/K+ pump is blocked by ouabain, K(+)-sensitive currents no larger than 50 nA/cm2 remain. Reductions in steady-state current (on the order of 700 nA/cm2) produced by 50 microM ouabain or dihydro-ouabain or by K+ removal, therefore, primarily represent current generated by the Na+/K+ pump. In Na(+)-free solution containing 5 mM K+, Na+/K+ pump current is relatively voltage independent over the potential range from -160 to +40 mV. If external [K+] is reduced below 0.5 mM, negative slopes are observed over this entire voltage range. Similar results are seen in Na(+)- and Ca(2+)-free solutions in the presence of 2 mM Ni2+, an experimental condition designed to prevent Na+/Ca2+ exchange. The occurrence of a negative slope can be explained by the voltage dependence of the apparent affinity for activation of the Na+/K+ pump by external K+, consistent with the existence of an external ion well for K+ binding. In 90 mM Na+, 5 mM K+ solution, Na+/K+ pump current-voltage curves at negative membrane potentials have a positive slope and can be described by a monotonically increasing sigmoidal function. At an extracellular [K+] of 1.3 mM, a negative slope was observed at positive potentials. These findings suggest that in addition to a voltage-dependent step associated with Na+ translocation, a second voltage-dependent step that is dependent on external [K+], possibly external K+ binding, participates in the overall reaction mechanism of the Na+/K+ pump.

Animals↗
PubMed1991

A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine.

H.M. van Praag has been suggesting a reappraisal of syndromes in psychiatry for over 20 years. He has tried to define syndromes originating from the same biochemical disorder. He has denoted this concept as 'functional psychopathology'. As an example of such a functional syndrome, he has cited the serotonin-shortage syndrome which unifies various psychiatric symptoms under a new point of view. The treatment of the serotonin-shortage syndrome is best served by psychopharmaca which raise the metabolism of serotonin in the synaptic cleft, e.g. the selective serotonin re-uptake inhibitors. Borrowing F. Freyhan's concept of 'target symptoms', one can now speak of 'functional target syndromes', within the frame of functional psychopathology.

5-Hydroxytryptophan↗
PubMed1991

[The development of anesthesia in german-speaking regions in the 19th century].

Following the first public demonstration of ether anaesthesia by W.T.G. Morton on October 16, 1846, the pioneers to perform ether anaesthesia in German speaking countries were H. A. Demme, surgeon at the University Hospital Bern, Switzerland, on January 23, 1847, the German surgeon J. F. Heyfelder at Erlangen on January 24, and the Austrian surgeon F. Schuh in Vienna on January 27, 1847. The first books in German language referring to clinical experience with and experimental research on sulphuric ether were published in March/April 1847. After the introduction of chloroform the use of ether anaesthesia rapidly decreased. Chloroform administration was smoother and much more easier not requiring any special apparatus. Chloroform remained the preferred anaesthetic till the end of the century although there happened significantly more deaths due to this agent than to ether. Since 1863 nitrous oxide again was propagated for pain relief in dental practice. German investigators provided pioneering contributions to the development of local and regional anaesthesia. C. Koller, Vienna, was the first to operate on a patient in local anaesthesia with cocaine. The next steps were the introduction of infiltration anaesthesia by C. L. Schleich in 1892/1894 and of spinal anaesthesia by A. Bier in 1899. The ultimate success of local and regional anaesthesia was made possible by using adrenaline with the local anaesthetic (1901) and by the introduction of novocaine in 1905.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1991

[Experiments and models in sequential integration of information].

Using the example of bimodal temporal order judgments, we investigate and explain the transition from static designs mapping single stimulus presentations to single responses to designs which require some kind of integration of the processed information. First, we estimate the parameters of several well-known channel-oriented models (Baron, 1969; Gibbon & Rutschmann, 1969) for temporal order judgments. Subsequently, we generalize these models to explain the results of two more complex experimental designs and derive and test their predictions. Special concern is given to the question whether or not the models parameters remain invariant across the experiments. The basic assumptions of the channel-oriented models are confirmed by our data, they represent a well-suited platform to explain more complex integrative processes. Within a sequential decision design, where subjects are allowed to observe a stimulus arbitrarily often before their terminal decision, the individual representations of the stimuli are additively integrated. Hence, even information, which did not yet lead to a terminal decision, will generally influence the later outcome. This representation of the stimuli is accompanied by a dynamic decision rule, which is clearly time-dependent. Several too simplizistic alternative models can be rejected if (and only if) one derives their predictions in some detail and tests them with sufficient statistical power.

Attention↗
PubMed1990

[Long-term experiences with moxonidine, a new antihypertensive agent].

Monoxidine is a new antihypertensive agent that, as pharmacological studies show, reduces blood pressure by stimulating central presynaptic alpha-2-receptors. In this open multicenter trial, 141 ambulatory hypertensives were treated for 12 months with monoxidine. After a run-in placebo period the mean supine blood pressure was 172.7 +/- 15.0/103.2 +/- 6.0 mmHg. After an individual dose-adjustment phase of 3 weeks starting from a daily dose of 0.2 mg monoxidine, the mean blood pressure decreased to 150.7 +/- 13.4/87.5 +/- 5.5 mmHg. In 96 patients, the blood pressure reduction was achieved within 3 weeks at a dose of 0.2 mg, while 52 patients required a dose of 0.4 mg. Over the 12-month treatment period, no tolerance to the drug developed. In 137/141 cases (97%), the drug was well or very well tolerated. At the state of treatment dryness of mouth was observed in 12.9% and lassitude in 4.8%. On discontinuation of monoxidine, blood pressure gradually increased. All in all, monoxidine proved to be well tolerated, reliable and safe in the long-term treatment of hypertension.

Adolescent↗
PubMed1990

[HIV-1 antigenemia and T-cell activation in HIV-1 infected patients].

In order to study a supposed association between T-cell activation in vivo and HIV-1-antigenemia in HIV-1-infected patients, the detection of p24-antigen in sera was correlated to serum levels of beta-2-microglobulin and C1q-binding immune complexes. Anti-p24-antibodies and the urinary excretion of neopterin were also analysed. In 24 of 80 patients (30%) p24-antigen could be detected, and in 15 of 59 (25.4%) there was a loss of anti-p24-antibodies. Tests revealed elevated serum levels of beta-2-microglobulin in 58 of 80 patients (72.5%), elevated levels of C1q-binding immune complexes in 15 of 66 (22.7%), and increased excretion of neopterin in 52 of 60 (86.7%). Detection of p24-antigen, loss of anti-p24-antibodies, serum levels of beta-2-microglobulin, and urinary excretion of neopterin were significantly correlated to advanced stages of HIV-1 infection. Patients with p24-antigen in the serum showed significantly more frequently elevated serum levels of beta-2-microglobulin and no significant association with increased urinary excretion of neopterin. Because of the high proportion of patients with elevated serum levels of beta-2-microglobulin and increased excretion of urinary neopterin in the absence of detectable p24-antigen in serum, we could not correlate HIV-1-antigenemia to T-cell activation in vivo.

Acquired Immunodeficiency Syndrome↗