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Biomedical subjects

W Eberhardt

Publications and source records attributed to W Eberhardt.

At least 91 records · Page 5Linked to original sources
PubMed1994

Pyrrolidine dithiocarbamate differentially affects interleukin 1 beta- and cAMP-induced nitric oxide synthase expression in rat renal mesangial cells.

Inducible nitric oxide synthase (NOS) is expressed in renal mesangial cells in response to two principal classes of activating signals that interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin 1 (IL-1) or tumour necrosis factor alpha and agents that elevate cellular levels of cAMP. We have used pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of nuclear factor kappa B (NF kappa B), to determine its role in IL-1 beta- and cAMP-triggered NOS expression. Micromolar amounts of PDTC suppress IL-1 beta-, but not cAMP-stimulated nitrite production, the stable end product of NO formation in mesangial cells. Furthermore, PDTC completely inhibited the increase of NOS mRNA in response to IL-1 beta, while only marginally affecting cAMP-induced NOS mRNA levels. Our data suggest that NF kappa B activation is an essential component of the IL-1 beta signalling pathway responsible for NOS gene activation and that cAMP triggers a separate signalling cascade not involving NF kappa B. These observations may provide a basis for the synergistic stimulation of NOS expression by cytokines and cAMP in mesangial cells.

Amino Acid Oxidoreductases↗
PubMed1994

GABA uptake into isolated retinal Müller glial cells of the guinea-pig detected electrophysiologically.

In order to investigate GABA uptake into Müller glial cells electrophysiologically, we used the whole-cell voltage-clamp technique. Since Müller cells were insensitive to application of muscimol and baclofen, the expression of GABAA and GABAB receptors can be excluded. Therefore, the observed GABA current must be due to an electrogenic GABA transporter. This transporter is driven by the transmembrane Na+ gradient, as replacement of the extracellular Na+ by choline inhibits the GABA current. Currents evoked by cis-4-aminocrotonic acid, a GABAC specific agonist, are also inhibited by replacement of extracellular Na+, indicating that this compound is a substrate for the uptake. The competitive GABA uptake blockers beta-alanine and nipecotic acid are substrates of the transporter as well, and produce 42% and 65% of the currents elicited by the same GABA concentration, respectively. Affinity of the transporter for GABA is high, the Km value being 5 microM at -80 mV.

Animals↗
PubMed1994

Na+ channels of Müller (glial) cells isolated from retinae of various mammalian species including man.

Within the last few years, the expression of voltage-dependent, TTX-sensitive Na+ channels has been demonstrated in several types of neuroglial cells such as astrocytes and Schwann cells. Recently, we reported the occurrence of such Na+ currents in retinal Müller (glial) cells from dog and cat. This paper deals with the description of the properties of Na+ currents in Müller cells isolated from retinae of several mammalian species, as well as from human retinae. These Na+ currents were eliminated by TTX (1 microM), and by exposure to sodium-free extracellular solution; typically, they were demonstrable only after blocking most of the K+ conductance by Ba2+ (1 mM). Voltage-dependent activation and inactivation characteristics and time constants of the Na+ currents were similar to those of currents carried by neuronal Na+ channels. The estimated number of sodium channels per cell was low (about 1,500 channels per 7,500 microns 2), and the K+ conductance exceeded the peak Na+ conductance by an average factor of 5. Thus, the cells were incapable of generating action-potential-like responses under current clamp. Modelling estimations show that triggering of glial Na+ currents under physiological conditions, if any, can at best occur by emhaptic transmission at perinodal sites of optic axons. It is speculated that glial Na+ channels might be involved in neuroglial signalling events.

Animals↗
PubMed1994

Three distinct types of voltage-dependent K+ channels are expressed by Müller (glial) cells of the rabbit retina.

There is ample evidence that retinal radial glial (Müller) cells play a crucial role in retinal ion homeostasis. Nevertheless, data on the particular types of ion channels mediating this function are very rare and incomplete; this holds especially for mammalian Müller cells. Thus, the whole-cell variation of the patch-clamp technique was used to study voltage-dependent currents in Müller cells from adult rabbit retinae. The membrane of Müller cells was almost exclusively permeable to K+ ions, as no significant currents could be evoked in K(+)-free internal and external solutions, external Ba2+ (1 mM) reversibly blocked most membrane currents, and external Cs+ ions (5 mM) blocked all inward currents. All cells expressed inwardly rectifying channels that showed inactivation at strong hyperpolarizing voltages (> or = -120 mV), and the conductance of which varied with the square root of extracellular K+ concentration ([K+]e). Most cells responded to depolarizing voltages (> or = -30 mV) with slowly activating outward currents through delayed rectifier channels. These currents were reversibly blocked by external application of 4-aminopyridine (4-AP, 0.5 mM) or tetraethylammonium (TEA, > 20 mM). Additionally, almost all cells showed rapidly inactivating currents in response to depolarizing (> or = -60 mV) voltage steps. The currents were blocked by Ba2+ (1 mM), and their amplitude increased with the [K+]e. Obviously, these currents belonged to the A-type family of K+ channels. Some of the observed types of K+ channels may contribute to retinal K+ clearance but at least some of them may also be involved in regulation of proliferative activity of the cells.

4-Aminopyridine↗
PubMed1994

[Surgery of locally advanced non-small-cell bronchial cancer after intensive preoperative chemo-/radiotherapy].

From March 1991 to June 1993 50 patients with local advanced NSCLC (mediastinoscopy obligatory) have been entered into an ongoing trial with preoperative chemotherapy and simultaneous chemo-/radiotherapy, followed by re-mediastinoscopy and surgery. Clinical response rates after chemotherapy amounted to 66.8% after chemo/radiotherapy 77.5%, no severe toxicity was observed. 36 patients ultimately underwent operation, 29 with a curative, 5 with a palliative resection and 2 with an explorative thoracotomy. Pathological complete remission rates of the primary tumor were found in 11 (32.3%), R0-resection in 18 (52.9%) and R1-resection in 5 (14.7%) cases. Sterilisation rates of mediastinal nodes were found in 86.3% of N2 tumors and 66.6% of N3 tumors. Median survival time ranged between 21 months for stage III a and 16 months for III b disease. This intensive preoperative neoadjuvant treatment is tolerable and effective, the requirements for a randomised comparative trial was met.

Adult↗