Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 541 records · Page 30Linked to original sources

PubMed1989

gamma-Aminobutyric acid-induced ion movements in the guinea pig hippocampal slice.

gamma-Aminobutyric acid (GABA)-induced regional changes of extracellular Cl, K and Na concentration ([Cl]o, [K]o, [Na]o), as well as of the extracellular space were measured with ion-sensitive microelectrodes in guinea pig hippocampal slices. Microdrop application of GABA to the pyramidal cell layer of CA3 or CA1 induced a decrease of [Cl]o, while application to the dendritic layer of CA3 or CA1 induced an increase of [Cl]o in addition. All changes of [Cl]o persisted in the presence of TTX and were blocked by bath-applied bicuculline. The GABA-induced decrease of [Cl]o was reduced by bicuculline application to the pyramidal cell layer. The increase of [Cl]o was blocked by bicuculline application to the dendritic layer. Additionally, GABA induced an increase of [K]o and decreases/increases of [Na]o. Changes of [Cl]o, [K]o and [Na]o together were approximately electroneutral. [Cl]o increases were exaggerated and [Cl]o decreases partly masked by shrinkage of the extracellular space after GABA application. Changing [K] in the superfusate transiently changed GABA-induced [Cl]o movements in a way predicted from a change in driving force due to the effect of [K] on membrane potential. Then a partial recovery followed towards the original [Cl]o change. We conclude that inward and outward Cl transports maintain [Cl]i below equilibrium in CA3 and CA1 pyramidal somata and above equilibrium in CA3 and CA1 dendrites. The significance of this Cl-distribution for hippocampal inhibition is discussed.

Animals↗

PubMed1989

Membrane-bound IgM obstructs B cell development in transgenic mice.

Rearranged immunoglobulin genes encoding either the secreted (microsecond) or membrane (micron) form of IgM were introduced into the mouse germ line. We report here the phenotypic analysis of lymphocyte populations in these mice (T microsecond and T micron). In T microsecond mice the transgenic mu chain is present in serum antibodies. The frequencies of B cells in the various B cell compartments of T microsecond mice are normal or slightly reduced compared to littermates. In T micron mice, however, B cell (but not T cell) development is severely affected. Spleens of 8-week-old T micron mice contain about 3%-8% B cells, increasing to approximately 20% at the age of 8 months. These cells express endogenous IgM. B cells expressing only transgenic micron chains are not detectable. In the bone marrow B cells are almost completely depleted. A B cell population characterized by reduced levels of IgD on the cell surface is enriched in the spleen and present at almost normal levels in the peritoneum of T micron mice.

Animals↗

PubMed1989

Peroxidative damage and nephrotoxicity of dichlorovinylcysteine in mice.

Male NMRI mice were treated i.p. with dichlorovinylcysteine (DCVC) in a dosage of 2.5-500 mg/kg-1 and renal cortical slices from naive mice were incubated with 0-125 micrograms/ml-1 DCVC. The effects of DCVC on blood urea nitrogen (BUN), reduced glutathione (GSH) content, malondialdehyde (MDA) production, p-aminohippuric acid (PAH)- and tetraethylammonium (TEA)-accumulation and glucose synthesis (gluconeogenesis) were measured. DCVC depleted GSH in a time- and dose-dependent manner. Depletion of renal cortical GSH by DCVC was more pronounced in the kidney cortex than in the liver. DCVC caused a dose-dependent increase of ethane exhalation and of MDA production in the renal cortex. When animals were kept in a closed system, decrease in oxygen concentration increased the peroxidative damage. No increase of MDA concentration was observed in the liver. Treatment of mice with DCVC induced a dose-dependent increase in BUN and decreased the accumulation of PAH and TEA in renal cortical slices. Pretreatment of mice with aminooxyacetic acid (AOAA) and (+) cyanidanol-3 (CY) caused a significant reduction in DCVC-induced lipid peroxidation and nephrotoxicity. In vitro incubation of renal cortical slices of naive mice with DCVC resulted in a concentration-dependent increase in MDA and a concentration-dependent decrease in the accumulations of PAH, TEA and of gluconeogenesis. In conclusion, the interaction of DCVC and/or its metabolites with membrane lipids may be responsible for lipid peroxidation and nephrotoxicity. The formation of lipid peroxidation products was greater under hypoxic conditions and appeared to be related to the DCVC-induced nephrotoxicity. This data suggests lipid peroxidation as a possible mechanism of DCVC-induced nephrotoxicity.

Animals↗

PubMed1989

Carbachol and pirenzepine discriminate effects mediated by two muscarinic receptor subtypes on hippocampal neurons in vitro.

Measurement of [Cch] in the bath and in slices demonstrated a considerable concentration discrepancy between the bath and the extracellular space. With fast (bolus) application of Cch this discrepancy is due to the speed of diffusion, while equilibration with continuous application is considerably impaired by cellular uptake of Cch (Creese and Taylor, 1967). Low concentrations (less than or equal to 1 microM) of Cch reduce the afterhyperpolarization following a train of action potentials and depolarize the membrane. Analysis of [Cch]0 (t) and the effects of pirenzepine allowed these effects to be assigned to two different muscarinic receptor subtypes.

Acetylcholine↗

PubMed1989

Effects of (-)baclofen on inhibitory neurons in the guinea pig hippocampal slice.

Intracellular recordings were made from electrophysiologically identified inhibitory neurons in the dentate hilus. (-)Baclofen (0.1-0.5 mumol/l), applied by the bath, strongly hyperpolarized inhibitory neurons, reduced their input resistance and induced outward currents under voltage clamp at holding potentials of -60 mV in cells recorded with KCl-filled electrodes. Increasing the (-)baclofen concentration (up to 1 mumol/l) did not increase the amplitude of the outward current, but increased its duration. (-)Baclofen depressed Cl-dependent IPSPs evoked by perforant path stimulation in inhibitory neurons, granule cells and CA3 neurons. In the case of inhibitory neurons and CA3 neurons, depression of IPSPs, membrane hyperpolarization and increase in membrane conductance concurred. All effects were blocked by BaCl2 (1 mmol/l) in the superfusate. In the case of granule cells, depression of IPSPs by (-)baclofen outlasted an only small membrane hyperpolarization, conductance increase or outward current. High concentrations (up to 10 mumol/l) of (-)baclofen depressed evoked IPSPs of granule cells for an extended period of time, but the other effects remained small and transient. IPSPs elicited in granule cells by microdrop application of glutamate to the dentate hilus were also blocked by (-)baclofen, but spontaneous IPSPs were only reduced in amplitude. We suggest that the blockade of GABAA receptor-mediated IPSPs of hippocampal neurons by the GABAB receptor agonist (-)baclofen can be explained by a K-dependent hyperpolarization of inhibitory neurons.

Animals↗

PubMed1989

The DiGeorge sequence. II. Immunologic findings in partial and complete forms of the disorder.

We present immunological in vitro data on a group of 16 patients with the DiGeorge sequence (DGS). Detailed tests gave evidence that the decrease in number and function of mature T-cells is closely correlated with phenotypic expression and represents a wide immunological spectrum ranging from normal function to severe combined immunodeficiency with B-cells. Careful immunological testing in DGS may help to plan therapeutic procedures (i.e. thymic factor therapy or bone marrow transplantation), may also have prognostic significance and help to gain insight into mechanisms operative in disturbances of T-cell regulation.

Adenosine Deaminase↗

PubMed1989

Threshold tracking provides a rapid indication of ischaemic resistance in motor axons of diabetic subjects.

An early abnormality in the peripheral nerves of patients with diabetes mellitus is that it takes a long period of limb ischaemia to block conduction. As a diagnostic test, however, the procedure is time consuming (30 min of ischaemia). We have now used an electronic feedback system to track threshold changes in human motor axons during and after a short period of ischemia (10 min) induced by a pressure cuff. The strength of stimulus current applied over an appropriate nerve was adjusted to maintain a constant amplitude of muscle action potential. This method reveals an increase in excitability during the first few minutes of ischaemia, and a post-ischaemic depression. Both changes in excitability were consistently much reduced in diabetic subjects compared with normal controls.

Action Potentials↗

PubMed1989

Lipid peroxidation: a possible mechanism of trichloroethylene-induced nephrotoxicity.

The purpose of this study was to investigate whether lipid peroxidation plays a role in (TCE) trichloroethylene-induced nephrotoxicity in mice at different oxygen concentrations. Male NMRI mice (25-30 g) were treated i.p. with TCE in a dosage of 125-1000 mg/kg in sesame oil. To determine the TCE-induced depletion of reduced glutathione (GSH) in the kidney cortex and liver tissue, mice were given 1000 mg/kg TCE i.p., then killed between 0 and 6 h after TCE administration and GSH was measured was non-protein sulfhydryls. In another series of experiments, mice were administered 125 to 1000 mg/kg TCE i.p. with or without a 2 h i.p. pretreatment with 1500 mg/kg L-buthionine-S-R-sulfoximine (BSO). Mice were then exposed to a 10, 15, 20 or 100% oxygen atmosphere for 3 h and lipid peroxidation in vivo was measured as exhalation of ethane. Subsequently, mice were killed and malondialdehyde (MDA) generation was measured in the liver and kidney cortex. Ethane evolution was estimated by gas chromatography and MDA was determined as thiobarbituric acid reactive substances. In a further series of experiments mice were treated in the same manner as for ethane and MDA determination and the changes in blood urea nitrogen (BUN) and accumulation of the organic ion p-aminohippurate (PAH) were determined. PAH accumulation by renal cortical slices were measured as the slice to medium (S/M) ratio. Six hours after administration of 1000 mg/kg TCE to mice, GSH was significantly depleted to about 60% of control in the kidney cortex but not in the liver. Three hours after TCE administration, MDA content in the kidney cortex and ethane exhalation increased in a dose-dependent manner only under a 10% oxygen atmosphere. Under the same experimental conditions, MDA content remained unchanged in the liver. BSO depletion of GSH prior TCE administration induced an increase of the MDA content in the kidney cortex and an increase of the ethane exhalation in vivo. At 10% oxygen concentration, TCE induced a dose-dependent increase in BUN and a dose-dependent decrease of PAH accumulation by the renal cortical slices. Thus, the results of the present study suggest that, under hypoxic conditions, lipid peroxidation plays a role in TCE nephrotoxicity.

Animals↗

PubMed1989

Fast optical monitoring of microscopic excitation patterns in cardiac muscle.

Many vital processes depend on the generation, changes, and conduction of cellular transmembrane potentials. Optical monitoring systems are well suited to detect such cellular electrical activities in networks of excitable cells and also tissues simultaneously at multiple sites. Here, an exceptionally fast array system (16 x 16 photodiodes, up to 4,000,000 samples per second, 12-bit resolution) for imaging voltage-sensitive dye fluorescence, permitted real time measurements of excitation patterns at a microscopic size scale (256 pixels within an area of 1.8-8 mm2), in rat cardiac muscle in vitro. Results emphasize a recent hypothesis for cardiac impulse conduction, based on cardiac structural complexities, that is contradictory to all continuous cable theory models.

Action Potentials↗

PubMed1989

Anti-CD4 antibody treatment of patients with rheumatoid arthritis: I. Effect on clinical course and circulating T cells.

Eight patients with arthritis (seven with rheumatoid, one with psoriatic arthritis) were treated for 7 d with a daily injection of 10 mg of mouse monoclonal anti-CD4 antibodies (three with VIT4, five with MT151). With the exception of a short-lasting low-grade fever in one patient, no side effects were observed. Clinical symptoms (morning stiffness, number of swollen joints, pain assessment and Ritchie articular index) improved in all patients within 7 d of treatment. Improvement lasted from 3 weeks to greater than or equal to 5 months (mean approximately 11 weeks). Rheumatoid factors, immune complexes and other laboratory parameters did not change during or after treatment. Skin reactivity to recall antigens was suppressed in four out of six patients during treatment but returned to pretreatment levels within 6 weeks. Immunofluorescent analysis revealed a short-lasting drop of T cells, mainly of the CD4+ CDw29+ subset, but monocytes were also affected. The injected antibody was detectable on circulating cells for about 10 h. Within 20-24 h, the cell distribution returned to pretreatment levels. In six out of eight patients an anti-mouse-Ig response was seen. We conclude that mouse anti-CD4 monoclonal antibody (MoAb) treatment is well tolerated and that the cellular immunological changes observed are short-lasting. The low incidence of side effects may justify further clinical studies to evaluate the clinical efficacy of such treatment.

Antibodies, Anti-Idiotypic↗

PubMed1989

Anti-CD4 antibody treatment of patients with rheumatoid arthritis: II. Effect of in vivo treatment on in vitro proliferative response of CD4 cells.

In treating rheumatoid arthritis (RA) patients with anti-CD4 antibodies (MT151 10 mg/day, 7 d) we observed diminished skin-test response to recall antigens and reduced proliferative response to antigens and mitogens (in vitro) 2-4 h following the injection. To investigate whether this diminished response is due to functional impairment of CD4+ cells, we analyzed the proliferative response of CD4+ cells to various stimuli, in conditions where the CD4 structure was either cross-linked or not. We found that in vivo anti-CD4-antibody-coated cells could be induced to proliferate if the anti-CD4 antibody was cross-linked with an anti-CD3 antibody [BMA030-F(ab')2] added in vitro and per se non-mitogenic. Also, without cross-linking the cell-bound anti-CD4 antibodies, no impairment of the proliferative capacity of CD4-antibody-coated cells could be detected; double fluorescence analyses of phytohaemagglutinin (PHA)- or CD3-stimulated cells showed that a similar proportion of CD4+ cells proliferated before and after anti-CD4-antibody treatment. The diminished proliferation observed following anti-CD4 treatment correlated to the reduced number of CD3+ and CD4+ cells in culture, which suggests that altered cell distribution might be one factor contributing to the impaired immune response.

Antibodies, Monoclonal↗

PubMed1989

Differentiated reconstruction of the orbicularis oris muscle in unilateral labioplasty.

Repair of the cleft lip aims to restore the normal anatomy. The most important step in treatment of unilateral deformities is the differential re-arrangement of muscle components to correct the insertion and reorientate the direction of their fibres. The three different components of the orbicularis oris muscle must be repaired independently, to permit each to function separately. After insertion of the nasal bundle into the anterior nasal spine, correction of the misdirected nasolabial bundle and end-to-end union of the deep fibres, better cosmetic and functional results were achieved.

Child, Preschool↗

PubMed1989

[Immunoreactive somatostatin in the peripheral olfactory system and nasal mucosa of the human].

Immunohistochemically, the cyclic retradecapeptide somatostatin was demonstrated in periglomerular cells and fibres of the glomerular layer (Fig. 3) of the human olfactory bulb as well as in the superficial granule layer and fibres (Fig. 2) of the olfactory tract. Additionally, somatostatin was found in endothelial cells of subepithelial arterioles and capillaries of the regio olfactoria (Fig. 4a, b) and superior turbinate. We assume that somatostatin has a paracrine transmitter function in the peripheral olfactory system and a regulative function on the blood flow of the superior nasal mucosa.

Adolescent↗

PubMed1989

[Photodynamic laser tumor therapy with a hematoporphyrin derivative in spinocellular carcinoma of the external ear].

Haematoporphyrine-derivative (hpd) selectively photosensitises malignant tumours following intravenous application. 48 hours after injection of hpd an integral laser-light application of the tumour and the surrounding normal tissue was performed. We report on the successful administration of this photodynamic therapy in a patient with a spinocellular carcinoma of the auricle. 16 days after therapy the tumour showed a complete response without damage of the also irradiated surrounding normal tissue. Apart from a temporary sensitivity to light no side effects of the therapy were seen.

Carcinoma, Squamous Cell↗

PubMed1989

Continuous arteriovenous hemofiltration in premature infants.

Five critically ill premature infants with acute renal failure (ARF) and hypervolemia were treated by continuous arteriovenous hemofiltration (CAVH). Prostacyclin was used to prevent hemofilter clotting. Mean treatment duration was 53.6 +/- 14 h. Mean blood flow rates of 1.6 +/- 0.22 ml/min and filtration fractions of 17.2 +/- 3.7% produced mean ultrafiltration rates of 8.3 +/- 3.1 ml/kg.h. Fluid overload was easily corrected by means of CAVH. The mean prehemofiltration serum creatinine and urea levels were 2.3 +/- 0.4 and 77 +/- 29.7 mg/dl; the mean posthemofiltration levels were 2.38 +/- 0.43 and 92 +/- 34.4 mg/dl, respectively. Hemofilter clotting occurred every 14 h. Urinary output was restored in three infants. Three of the five infants died, but none of the deaths was related to ARF or CAVH. CAVH is a safe and simple method to control fluid and metabolic imbalances in critically ill premature infants.

Acute Kidney Injury↗

PubMed1989

Transient hypogammaglobulinemia of infancy: Five new cases, review of the literature and redefinition.

The clinical and immunological data of 5 patients with transient h hypogammaglobulinemia of infancy (THI) are presented and compared to published data. In THI, there is distinction between patients who can mount a specific immune response, by producing specific antibodies to bovine serum albumin, diphtheria toxin, and isohemagglutinins, and patients with more severe forms of immunodeficiency. With only 5 reported cases of THI in 11 years and analysis of more than 8000 sera-, our data support the notion that THI is a relatively rare disorder. THI can only be diagnosed with certainty in retrospect, although the ability to mount an active, specific immune response is a strong indicator for the diagnosis. We propose a more accurate definition of THI to help avoid clinical misjudgement.

Agammaglobulinemia↗

PubMed1989

Potentiation and suppression by eserine of muscarinic synaptic transmission in the guinea-pig hippocampal slice.

1. The effects of the anticholinesterase eserine on CA3 pyramidal cells and dentate gyrus granule cells in guinea-pig hippocampal slices were investigated with single-electrode current-clamp and voltage-clamp recording. 2. In the majority of cells superfused with eserine (0.5-10 microM) for 3-10 min, tetanic stimulation near the cell layers elicited a delayed depolarization (slow EPSP; duration up to 60 s) at a pre-stimulation membrane potential of -60 mV. The slow EPSP was blocked by atropine (1 microM). 3. Under voltage clamp at -60 mV holding potential, an apparent inward current (slow EPSC) with a similar time course to the slow EPSP was observed. 4. The amplitude of the delayed inward current was about 50 pA. The amplitude increased at holding potentials more positive than -60 mV. At holding potentials negative to -60 mV, the delayed inward current was too small to allow reliable analysis. In the absence of eserine, there was a delayed inward current, which was rather small, however, due to a superimposed outward current. 5. Eserine reduced the after-hyperpolarization following a train of action potentials. This effect was antagonized by atropine, but not to pirenzepine. In voltage-clamp recording, eserine reduced a current termed IAHP. 6. CA3 neurones treated with eserine exhibited a region of negative slope conductance (in tetrodotoxin). The slow inward current which developed at clamp potentials between -50 and -40 mV was reduced by Ni2+ (50 microM). The effect of eserine on slope conductance increased with time of exposure. In all neurones superfused with eserine for more than 60 min, burst discharges were observed. Burst discharges were blocked by atropine and Ni2+, but not by pirenzepine. 7. In cells superfused with eserine for more than 1 h, tetanic stimulation failed to elicit a slow EPSP or EPSC. Currents induced by focal acetylcholine (ACh) application were first enhanced by eserine, but blocked after exposure to eserine for more than 1 h. Blockade of ACh-induced currents was also observed after bath application of carbachol (CCh) in a concentration (0.2 microM) in which it did not induce an inward current at -60 mV holding potential. Further, the slow EPSP faded when elicited by repeated tetanic stimulation. 8. While the observed effects of eserine on hippocampal neurones can be explained by eserine's well-known ability to block acetylcholinesterase activity, our data indicate that the effects of eserine involve more than one muscarinic receptor site, i.e. desensitizing and non-desensitizing postsynaptic receptor sites.

Action Potentials↗

PubMed1989

Relations between visual acuity, refraction and the pattern reversal visual-evoked cortical potential in aphakia.

The investigations included 20 aphakic patients. Relations were established between visual acuity, refraction and the pattern reversal visual-evoked cortical potentials (PRVECP). Close correlations were found between the three values. The optimum correction for obtaining best visual acuity, the skiascopic value, and the correction value for obtaining the largest PRVECP amplitude at minimum peak time differ by an average of 0.5 dptr.

Aged↗