Prostaglandin E2 modulates proximal tubule Na+-ATPase activity: cooperative effect between protein kinase A and protein kinase C.

Previous data showed that prostaglandin E2 (PGE2) mediates the inhibitory effect of bradykinin (BK) on proximal tubule (PT) Na+-ATPase activity. The aim of this work was to investigate the molecular mechanisms involved in the effect of PGE2 on PT Na+-ATPase. We used isolated basolateral membrane (BLM) from pig PT, which expresses several components of different signaling pathways. The inhibitory effect of PGE2 on PT Na+-ATPase activity involves G-protein and the activation of protein kinase A (PKA) because: (1) PGE2 increased [³5S]GTPγS binding; (2) GDPßS abolished the inhibitory effect of PGE2; (3) PGE2 increased PKA activity; (4) the inhibitory effect of PGE2 was abolished by PKA inhibitor peptide. We observed that the PKA-mediated inhibitory effect of PGE2 on PT Na+-ATPase activity requires previous activation of protein kinase C. In addition, we observed that PGE2 stimulates Ca²+-independent phospholipase A2 activity representing an important positive feedback to maintain the inhibition of the enzyme. These results open new perspectives to understanding the mechanism involved in the effect of PGE2 on proximal tubule sodium reabsorption.

Visuo-spatial cognition in schizophrenia: confirmation of a preference for local information processing.

During visuo-spatial cognitive tasks, patients with schizophrenia show a preference for local (detailed) rather than global (holistic) information processing. The efficiency of such information processing is influenced by task difficulty. We tested whether patients' preference for local processing would persist if task demands favored global or local processing. Twenty-four stabilized patients with schizophrenia (SZ) and 25 healthy, matched controls (C) were tested in a mental mirroring task. Task difficulty was manipulated while stimulus surface structures were maintained unchanged. Information processing was assessed by recording eye movements. SZ were slower than C in the easiest condition but they made more errors than C in the more difficult conditions. Further, SZ did not adapt their average fixation duration to task demands resulting in longer fixation duration in the easiest condition and shorter fixation duration in the most difficult condition compared to C. These findings suggest that patients employ local information processing even when it is maladaptive for task demands. That is, patients do not adapt their fixation duration to task demands implicating (i) a preference for scanning local stimuli features and (ii) information processing inflexibility. These features need to be taken into account when evaluating visuo-spatial cognitive performance in schizophrenia.

The Rehm-Weller experiment in view of distant electron transfer.

The driving-force dependence of bimolecular fluorescence quenching by electron transfer in solution, the Rehm-Weller experiment, is revisited. One of the three long-standing unsolved questions about the features of this experiment is carefully analysed here, that is, is there a diffusional plateau? New experimental quenching rates are compiled for a single electron donor, 2,5-bis(dimethylamino)-1,3-benzenedicarbonitrile, and eighteen electron acceptors in acetonitrile. The data are analysed in the framework of differential encounter theory by using an extended version of the Marcus theory to model the intrinsic electron-transfer step. Only by including the hydrodynamic effect and the solvent structure can the experimental findings be well modelled. The diffusional control region, the "plateau", reveals the inherent distance dependence of the reaction, which is shown to be a general feature of electron transfer in solution.

Memory-guided saccade abnormalities in schizophrenic patients and their healthy, full biological siblings.

BACKGROUND: Ocular-motor inhibition errors and saccadic hypometria occur at elevated rates in biological relatives of schizophrenic patients. The memory-guided saccade (MS) paradigm requires a subject to inhibit reflexive saccades (RSs) and to programme a delayed saccade towards a remembered target. METHOD: MS, RS, and central fixation (CF) tasks were administered to 16 patients who met the criteria for DSM-IV schizophrenia, 19 of their psychiatrically healthy siblings, and 18 controls. RESULTS: Patients and siblings showed elevated MS error rates reflecting a failure to inhibit RSs to a visible target, as required by the task. In contrast to controls, prior errors did not improve MS accuracy in patients and siblings. CONCLUSIONS: The specific characteristics of the elevated MS error rate help to clarify the nature of the disinhibition impairment found in schizophrenics and their healthy siblings. Failure to inhibit premature saccades and to improve the accuracy of subsequent volitional saccades implicates a deficit in spatial working-memory integration, mental representation and/or motor learning processes in schizophrenia.

Electrically tunable resistance of a metal.

Electric field-induced tuning of material properties is usually restricted to nonmetals such as semiconductors and piezoelectric ceramics. We show that variations of the electrical resistance of a metal (Pt) in the range of several percent can be reversibly induced at low charging voltages making use of a nanocrystallite-electrolyte composite. The charge-induced resistance variation is analyzed taking into account the modification of the charge carrier density and scattering rate by surface charging. The contribution arising from the charge-induced variation of the lattice constant is found to be small.

Use of ultrabright LEDs for the determination of static and time-resolved florescence information of liquid and solid crude oil samples.

Ultrabright light emitting diodes (LEDs) are an inexpensive alternative to laser diodes (LDs) and other short wavelength emitting light sources. They have a high stability, a long lifetime, and a very low power consumption. A large number of publications are already available for fluorescence applications using this type of LEDs. Most of them are describing fluorescence intensity measurements. Only some of them are dealing with time-resolved methods, like single photon timing. LED modulation fluorometry is a very recent application, which can also be used for environmental investigations, like the detection of polycyclic aromatic hydrocarbons (PAHs). This article demonstrates the possible application of ultrabright LEDs for the time-resolved fluorescence detection of crude oil contaminated samples.

Electron self-exchange kinetics determined by MARY spectroscopy: theory and experiment.

The electron self-exchange between a neutral molecule and its charged radical, which is part of a spin-correlated radical ion pair, gives rise to line width effects in the fluorescence-detected MARY (magnetic field effect on reaction yield) spectrum similar to those observed in EPR spectroscopy. An increasing self-exchange rate (i.e., a higher concentration of the neutral molecule) leads to broadening and subsequent narrowing of the spectrum. Along with a series of MARY spectra recorded for several systems (the fluorophores pyrene, pyrene-d(10) and N-methylcarbazole in combination with 1,2- and 1,4-dicyanobenzene) in various solvents, a theoretical model is developed that describes the spin evolution and the diffusive recombination of the radical pair under the influence of the external magnetic field and electron self-exchange, thereby allowing the simulation of MARY spectra of the systems investigated experimentally. The spin evolution of the radicals in the pair is calculated separately using spin correlation tensors, thereby allowing rigorous quantum mechanical calculations for real spin systems. It is shown that the combination of these simulations with high resolution, low noise experimental spectra makes the MARY technique a novel, quantitative method for the determination of self-exchange rate constants. In comparison to a simple analytical formula which estimates the self-exchange rate constant from the slope of the linear part of a line width vs concentration plot, the simulation method yields more reliable and accurate results. The correctness of the results obtained by the MARY method is proved by a comparison with corresponding data from the well-established EPR line broadening technique. With its less stringent restrictions on radical lifetime and stability, the MARY technique provides an alternative to the classical EPR method, in particular for systems involving short-lived and unstable radicals.

[Active language development in children with severe hearing loss and deafness in relation to technical auditory management]. / Die aktive Sprachentwicklung hochgradig hörgeschädigter und gehörloser Kinder in Abhängigkeit von der hörtechnischen Versorgung.

The extent of vocabulary depends on the success of rehabilitation in hearing, language and speech. In hearing impaired and deaf children, it is important to select the optimum technical device-hearing aid or cochlear implant. This study was performed on 30 children with hearing aids or cochlear implants using the Test of Expressive Vocabulary for Children Aged 3-6 years (Kiese-Himmel and Kozielski). The development of vocabulary was recorded over 12 months. The results were analysed dependent on the degree of hearing loss, age at primary diagnosis, duration of treatment and kind of hearing aid used. These were compared with the reference data from a normally hearing population. Cochlear implant users had better language development than hearing aid users despite a lower grade of hearing loss in the hearing aid group. In general, the extent of the expressive vocabulary was less in hearing impaired children than in the reference population. However, in terms of hearing age, the language development of some cochlear implant users was similar to that of normal children.

Dimerization of organic free radicals in solution. 1. Temperature dependent measurements.

Dimerization enthalpies and equilibrium constants have been determined for the radical anion of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), the radical cations of N,N,N',N'-tetramethyl-p-phenylenediamine, N,N-dimethyl-p-phenylenediamine, 2,3,5,6-tetramethyl-p-phenylenediamine, N,N,N',N'-tetraethyl-p-phenylenediamine, N,N-diethyl-p-phenylenediamine and N,N,N'-trimethyl-p-phenylenediamine. Neutral radicals investigated are 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and galvinoxyl. Solvent used was acetone, EtOH/Et2O-mixture (2:1 volume), propionitrile/butyronitrile-mixture (1:1 M) and dichloromethane. Measured dimerization enthalpies deltaHdim vary from -72.1 to -16.6 k/mol.

Quantum mechanical investigation of the inner-sphere reorganization energy of cyclooctatetraene/cyclooctatetraene radical anion. Part I.

The inner-sphere reorganization energy of the electron self-exchange of the couple cyclooctatetraene/cyclooctatetraene radical anion has been investigated by quantum mechanical calculations. The more stable Jahn Teller distorted B2g conformation of the radical anion has been used in this study. Two different theories have been applied in this first part. The harmonic approximation in the classical Marcus scheme has been modified by using projected force constants, which are obtained from the complete force constant matrix and the geometry changes of the molecule during the ET (introduced by Mikkelsen). A different approach (introduced by Nelsen) combines the different energies of the neutral and radical anion with and without relaxation corresponding to the vertical ionization potential and the vertical electron affinity. The electronic energies of the neutral molecule and the radical anion differ dramatically applying three different levels of quantum mechanical calculations (UAM1, UB3LYP, PMP2 with three different basis sets with and without diffuse functions). Nevertheless the Nelsen method gives almost consistent results for the inner-sphere reorganization energies: 120.1 kJ/mol for semiempirical UAM1 method, 159.3 kJ/mol, 156.4 kJ/mol and 158.3 kJ/mol for density functional UB3LYP/6-31G*, UB3LYP/6-31++G* and UB3LYP/AUG-cc-pVDZ calculations and 192.5 kJ/mol for ab-initio PMP2/6-31G* investigations, respectively. These values are in agreement with earlier experimental work supposing the total reorganization energy to be larger than 38 kcal/mol assuming an electron self-exchange rate of 10(4) M(-1) s(-1). The simple harmonic approximation of Marcus relation has not yet been applied for a molecule like cyclooctatetraene with large torsional geometry changes. Using the projected force constants after scaling, considerably different results for the inner-sphere reorganization energy have been calculated: 738.1 kJ/mol for the UB3LYP/6-31G*, 743.3 kJ/mol for UB3LYP/6-31++G* and 759.1 kJ/mol for UB3LYP/AUG-cc-pVDZ level of theory. Comparison with our concentration dependent EPR experiments are controversial to the earlier experimental results, but the latter supports the assumption that the electron self-exchange occurs in a time scale so that the molecules cannot complete their vibrational motions. Therefore the projected Marcus relation is not valid for cyclooctatetraene/cyclooctatetraene radical anion including a large torsional change during the electron transfer.

Application of semiconductor light sources for investigations of photochemical reactions.

Semiconductor light sources, like laser diodes or ultrabright light emitting diodes, are widely used in optical spectroscopy. In this presentation an overview of applications in photochemistry is given. Since the beginning of the 1990s an increasing number of publications with the application of semiconductor light sources appeared. Three different techniques were used: single photon counting with short pulses, phase-modulation fluorometry using a conventional modulation spectrometer, or a lock-in amplifier. Using continuous wave laser diodes in the visible region, which are available from 690 to 630 nm (and, recently, down to 400 nm), a new compact fluorescence spectrometer was developed in our laboratory. Using the phase fluorometric method, measurements down to 100 ps are now possible. Values can be measured in steps of 10 ps with good reproducibility using a high-frequency signal generator and a GHz digital storage oscilloscope. Several investigations have been carried out applying this technique including time-resolved detection of crude oil as an example for possible practical applications.

Activation of monocytes by three OspA vaccine candidates: lipoprotein OspA is a potent stimulator of monokines.

The outer surface protein (Osp) A of Borrelia burgdorferi is the first Lyme antigen to be tested in a vaccine for humans. Three forms of OspA vaccine candidates were investigated by the induction of the cytokines interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, IL-10 and interferon (IFN)-gamma as markers of monocyte activation and immune stimulation: lipidated OspA (L-OspA), non-lipidated OspA (NL-OspA), and a fusion protein of 81 amino acids of the nonstructural protein 1 of influenza virus with OspA (NS1-OspA). All OspA preparations induced IL-1 beta, IL-6 and TNF-alpha in a concentration-dependent manner with peak levels at 12-24 h. These cytokines were entirely derived from the monocyte fraction. In peripheral blood mononuclear cells from 10 healthy donors, L-OspA at 10 micrograms ml-1 induced up to 4-fold more IL-1 beta, IL-6, and TNF-alpha than the other OspA preparations (P < or = 0.0068), followed by NS1-OspA, which was still superior to NL-OspA. L-OspA. L-OspA also induced high levels of IL-10 within 24 h but no significant amounts of IFN-gamma. This superior stimulating activity of L-OspA on unstimulated monocytes predominantly depended on N-terminal lipidation of OspA. Similarities to other lipoproteins and synthetic lipopeptides suggest that lipidation confers adjuvant properties on OspA. High induction of IL-10 by L-OspA further suggested a negative feedback on monocyte activation by the lipidated form. The in vitro results are in line with in vivo results in mice, monkeys and humans and indicates that lipoprotein OspA has the best potential for induction of a protective effect in humans, compared to non-lipidated antigens.

Cytogenetic, oncogenetic, and histopathologic characteristics of colorectal carcinomas with 17p abnormalities.

From a total of 65 colorectal adenocarcinomas studied by cytogenetic methods, 33 were selected for the present study; in addition to other karyotypic anomalies, these 33 showed a loss of the short arm of chromosome 17. This loss was either the result of a deletion or rearrangement, or caused by the loss of a whole chromosome 17. The 17p- tumors were characterized by a high grade of karyotypic abnormality including a high incidence of cases with double minutes. A gain of chromosomes 2, 7, 19, and 20, and the loss of chromosome 18 and the Y-chromosome were the most frequent numerical anomalies associated with 17p-, as were structural changes of chromosomes 1 and 5. The most impressive difference in the pattern of proto-oncogene over-expression between the 17p- tumors and those without this anomaly was the significantly increased frequency of cases with c-erbB over-expression. Some significant, but also loose, associations were found between cytogenetic/oncogenetic and histopathologic or clinical features of these tumors. The patterns of genetic changes in cells of colorectal carcinomas may thus reflect the potential of the future development, rather than the present clinical features, of the respective tumor. Therefore, the character of the change seems to be more prognostic than diagnostic.

Serum prolactin concentrations and epilepsy. A study which compares healthy subjects with a group of patients in presurgical evaluation and circadian variations with those related to seizures.

In 20 healthy subjects (10 female and 10 male) and 17 patients undergoing presurgical epilepsy evaluation with intracranial EEG electrodes, circadian variations of serum prolactin (PRL) were measured. A comparison between the peak values found in normals with the postictal rises in patients, led us to consider 700 microU/ml to be the threshold of diagnostic value and the observed rises above this level to be all induced by seizures. In order to assess the clinical value of this threshold, PRL was measured postictally in a further 30 patients with epilepsy and in 11 patients with psychogenic seizures. In none of the latter group did PRL rises exceed 700 microU/ml, while they did so in 39% of the complex partial seizures and in 80% of the tonic-clonic seizures. There was no significant difference with respect to sex (a rise over 700 microU/ml in 42% in male and in 55% in female patients). Based on the findings in 17 patients investigated by means of intracranial electrodes, we were not able to establish different criteria for different focus localisations: in 66% of both temporal as well as frontal lobe seizures the 700 microU/ml level was exceeded. As a trend, in the period preceding an epileptic seizure we found a slightly decreasing PRL level, whereas in healthy persons the PRL concentrations gradually increased in the 40 minutes before the maximum spontaneous peak was reached.

Over-expression of cellular oncogenes in cystadenocarcinomas of the ovary.

A complex analysis of oncogene over-expression in ovarian cystadenocarcinomas of 20 patients was performed. Radioactively labelled cDNAs were synthesized from total cellular RNA from tumor cells and hybridized to dot blot filters. On each filter more than 20 different plasmids containing cloned oncogene fragments were immobilized. In concordance with published data fms was found over-expressed in 40% of the tumors. Elevated expression levels of the EGF receptor was also frequently detected. 35% of the tumors showed elevated N-ras mRNA levels. All those tumors' showed a highly dedifferentiated phenotype and were classified as G3-tumors. More over, simultaneous over-expression of different oncogenes correlated surprisingly strongly with tumor grading.

[Rise in serum prolactin concentration after frontal lobe seizures. Possibilities in differential diagnosis of psychogenic seizures]. / Anstieg der Serum-Prolactinkonzentration nach Frontallappenanfällen. Möglichkeit zur Differentialdiagnose psychogener Anfälle.

The prolactin concentration profile over 24 hours was determined in three men, aged 19, 27 and 43 years, who suffered from treatment-resistant complex-partial and (or) grand mal seizures of frontal lobe origin. All three patients were examined in the course of preoperative epilepsy diagnosis, the seizures being classified by video-EEG recordings, including subdural and sphenoidal foramen ovale electrodes. Seizures were recorded in all three patients (4 grand mal; 2 complex-partial), each of them followed by a rise in serum prolactin concentration (over 700 microU/ml). These findings contradict the theory that prolactin concentration rises only after temporal, not after frontal seizures. Knowing the postseizure serum prolactin concentration may help to distinguish frontal epileptic from psychogenic seizures.

Chromosome and oncogene studies in human rectal and colon carcinomas.

Cytogenetic examinations of 48 rectal and 17 colon carcinomas and analyses of proto-oncogene activation on 67 of the former and 8 of the latter tumors were performed. Besides a general considerable heterogeneity of chromosome counts, some chromosomes were found to contribute non-randomly to hypersomies (# 2, 3, 7, 9, 19, 20 and 6) and to hyposomies (# 14, 15, Y, 21, and 18) in this material. Chromosomal markers non-randomly involved breakpoint clusters on 17p11, 13q11, 7p, 1p11, and 1p36 and on the centromeric regions of chromosomes 1, 8, 14, 15 and 21. Cytogenetic equivalents of gene amplification ("double minutes") were present in only rather small cell fractions (less than 20%) of 50% of the studied tumors. Using a cDNA technique and a battery of respective probes, proto-oncogene overexpression was screened for in the tumor samples, but also in 24 samples of inconspicuous mucosae of tumor patients and in two mucosae of healthy individuals. Simultaneous overexpression of several proto-oncogenes was the most characteristic finding in the tumor cells. However several of the mucosa samples obtained from tumor patients also just exhibited clear signals of proto-oncogene overexpression, which were not found in epithelial cells from non-tumor patients.

Expression of oncogenes in human breast cancer specimens.

More than 60 breast cancer specimens were screened for their expression status of 25 different proto-oncogenes. The screening method is based on in vitro synthesis of a radioactive cDNA copied from the total cellular RNA of tumor tissue. This cDNA is hybridized to cloned oncogene probes which are immobilized to a GeneScreen membrane. Frequently multiple oncogenes were found expressed although expression levels were rather moderate. 25-30% of the analyzed tumors showed significant expression of either erbB, src, raf1, lck or H-ras. Although neu expression--an oncogene believed to be particular relevant as prognostic parameter for mamma carcinoma--was screened for most of the tumors with a heterologous gene probe, expression signals could be detected in about 20% cases. The only notable correlation with classical clinical parameters such as tumor size and proliferation stage, hormone receptor status and different DNA indices was the observation that tumors lacking the progesterone receptor frequently express multiple oncogenes. Advantages and limitations of the cDNA/dot-blot screening for oncogene expression are discussed.