Biomedical subjects

W Reichelt

Publications and source records attributed to W Reichelt.

At least 19 recordsLinked to original sources

PubMed2006

Transfer of spectral weight and symmetry across the metal-insulator transition in VO(2).

We present a detailed study of the valence and conduction bands of VO2 across the metal-insulator transition using bulk-sensitive photoelectron and O K x-ray absorption spectroscopies. We observe a giant transfer of spectral weight with distinct features that require an explanation which goes beyond the Peierls transition model as well as the standard single-band Hubbard model. Analysis of the symmetry and energies of the bands reveals the decisive role of the V 3d orbital degrees of freedom. Comparison to recent realistic many body calculations shows that much of the k dependence of the self-energy correction can be cast within a dimer model.

Journal Article↗

PubMed2005

Orbital-assisted metal-insulator transition in VO2.

We found direct experimental evidence for an orbital switching in the V 3d states across the metal-insulator transition in VO2. We have used soft-x-ray absorption spectroscopy at the V L2,3 edges as a sensitive local probe and have determined quantitatively the orbital polarizations. These results strongly suggest that, in going from the metallic to the insulating state, the orbital occupation changes in a manner that charge fluctuations and effective bandwidths are reduced, that the system becomes more one dimensional and more susceptible to a Peierls-like transition, and that the required massive orbital switching can only be made if the system is close to a Mott insulating regime.

Journal Article↗

PubMed2002

Glutamate uptake controls expression of a slow postsynaptic current mediated by mGluRs in cerebellar Purkinje cells.

At the cerebellar parallel fiber-Purkinje cell synapse, isolated presynaptic activity induces fast excitatory postsynaptic currents via ionotropic glutamate receptors while repetitive, high-frequency, presynaptic activity can also induce a slow excitatory postsynaptic current that is mediated by metabotropic glutamate receptors (mGluR1-EPSC). Here we investigated the involvement of glutamate uptake in the expression of the mGluR1-EPSC. Inhibitors of glutamate uptake led to a large increase of the mGluR1-EPSC. D-aspartate (0.4 mM) and L(-)-threo-3-hydroxyaspartate (0.4 mM) increased the mGluR1-EPSC approximately 4.5 and approximately 9-fold, respectively, while dihydrokainic acid (1 mM), had no significant effect on the mGluR1-EPSC. D-aspartate (0.4 mM) shifted the concentration-response curve of the depression of the mGluR1-EPSC by the low-affinity mGluR1 antagonist (S)-a-Methyl-4-carboxyphenylglycine [(S)-MCPG] to higher concentrations and decreased the stimulus intensity and the number of necessary stimuli to evoke an mGluR1-EPSC. Depression of the mGluR1-EPSC by rapid pressure application of (S)-MCPG at varying time intervals after tetanic stimulation of the parallel fibers indicated that the glutamate concentration in the peri- and extrasynaptic space decayed with time constants of 36 and 316 ms under control conditions and with inhibition of glutamate uptake, respectively. These results show that expression of the slow mGluR-mediated excitatory postsynaptic current is controlled by glutamate transporter activity. Thus in contrast to fast glutamatergic synaptic transmission, metabotropic glutamate receptor-mediated transmission is critically dependent on the activity and capacity of glutamate uptake.

Animals↗

PubMed2001

Temperature dependence of the optical properties of CuMoO4.

CuMoO4 crystals reversibly change their color from green to brown upon heating, accompanied by a loss in transmittance. UV/VIS spectroscopic analysis revealed that these changes are due to particular electronic properties of the crystal instead of its chemical decomposition or structural change. Investigations were carried out in the temperature range 23-400 degrees C. The intensive green color of the crystal at room temperature is caused by a small transmission window between two absorption bands, the band gap of the crystal in the blue and the 3d9-->4p absorption of the Cu2+ ions in the red. With increasing temperature the band gap shifts towards longer wavelengths, and the crystal changes both color and transmittance. Spectroscopic features of the crystal are discussed together with the temperature dependence of its electrical resistance. Resistance measurements were performed simultaneously to the optical measurements.

Journal Article↗

PubMed2001

Experimental retinal detachment causes widespread and multilayered degeneration in rabbit retina.

Retinal detachment remains one of the most frequent causes of visual impairment in humans, even after ophthalmoscopically successful retinal reattachment. This study was aimed at monitoring (ultra-) structural alterations of retinae of rabbits after experimental detachment. A surgical procedure was used to produce local retinal detachments in rabbit eyes similar to the typical lesions in human patients. At various periods after detachment, the detached retinal area as well as neighbouring attached regions were studied by light and electron microscopy. In addition to the well-known degeneration of photoreceptor cells in the detached retina, the following progressive alterations were observed, (i) in both the detached and the attached regions, an incomplete but severe loss of ganglion cell axons occurs; (ii) there is considerable ganglion cell death, particularly in the detached area; (iii) even in the attached retina distant from the detachment, small adherent groups of photoreceptor cells degenerate; (iv) these photoreceptor cells degenerate in an atypical sequence, with severely destructed somata and inner segments but well-maintained outer segments; and (v) the severe loss of retinal neurons is not accompanied by any significant loss of Müller (glial) cells. It is noteworthy that the described progressive (and probably irreparable) retinal destructions occur also in the attached retina, and may account for visual impairment in strikingly large areas of the visual field, even after retinal reattachment.

Animals↗

PubMed2001

Electrophysiology of rabbit Müller (glial) cells in experimental retinal detachment and PVR.

PURPOSE: To determine the electrophysiological properties of Müller (glial) cells from experimentally detached rabbit retinas. METHODS: A stable local retinal detachment was induced by subretinal injection of a sodium hyaluronate solution. Müller cells were acutely dissociated and studied by the whole-cell voltage-clamp technique. RESULTS: The cell membranes of Müller cells from normal retinas were dominated by a large inwardly rectifying potassium ion (K+) conductance that caused a low-input resistance (<100 M(Omega)) and a high resting membrane potential (-82 +/- 6 mV). During the first week after detachment, the Müller cells became reactive as shown by glial fibrillary acidic protein (GFAP) immunoreactivity, and their inward currents were markedly reduced, accompanied by an increased input resistance (>200 M(Omega)). After 3 weeks of detachment, the input resistance increased further (>300 M(Omega)), and some cells displayed significantly depolarized membrane potentials (mean -69 +/- 18 mV). When PVR developed (in 20% of the cases) the inward K+ currents were virtually completely eliminated. The input resistance increased dramatically (>1000 MOmega), and almost all cells displayed strongly depolarized membrane potentials (-44 +/- 16 mV). CONCLUSIONS: Reactive Müller cells are characterized by a severe reduction of their K+ inward conductance, accompanied by depolarized membrane potentials. These changes must impair physiological glial functions, such as neurotransmitter recycling and K+ ion clearance. Furthermore, the open probability of certain types of voltage-dependent ion channels (e.g., Ca2+-dependent K+ maxi channels) increases that may be a precondition for Müller cell proliferation, particularly in PVR when a dramatic downregulation of both inward current density and resting membrane potential occurs.

Animals↗

PubMed2000

A function of delayed rectifier potassium channels in glial cells: maintenance of an auxiliary membrane potential under pathological conditions.

Müller glial cells from human and guinea-pig retinae were investigated using the whole-cell patch-clamp technique. Human Müller cells from eyes with different diseases were characterized by diminished inwardly-rectifying K(+) currents. A comparable reduction of these currents was achieved in guinea pig Müller cells by treatment with iodoacetate to generate ischemia-like conditions. Consequently, the membrane potentials were reduced significantly in both diseased human and iodoacetate-treated guinea-pig Müller cells as compared to normal controls. However, the potentials were still clearly negative. Delayed rectifier currents could still be recorded under these conditions. Application of quinine blocked the delayed rectifier K(+) channels, and resulted in a total breakdown of the membrane potentials. Thus, it becomes apparent that the glial delayed rectifier K(+) channels are necessary to maintain an 'auxiliary' membrane potential under certain pathological conditions that are characterized by an almost total loss of inward rectifier conductance. Therefore, the delayed rectifier K(+) channels of glial cells may become crucial for the support of basic glial functions.

Adenosine Triphosphate↗

PubMed2000

Role of glial K(+) channels in ontogeny and gliosis: a hypothesis based upon studies on Müller cells.

The electrophysiological properties of Müller cells, the principal glial cells of the retina, are determined by several types of K(+) conductances. Both the absolute and the relative activities of the individual types of K(+) channels undergo important changes in the course of ontogenetic development and during gliosis. Although immature Müller cells express inwardly rectifying K(+) (K(IR)) currents at a very low density, the membrane of normal mature Müller cells is predominated by the K(IR) conductance. The K(IR) channels mediate spatial buffering K(+) currents and maintain a stable hyperpolarized membrane potential necessary for various glial-neuronal interactions. During "conservative" (i.e., non-proliferative) reactive gliosis, the K(IR) conductance of Müller cells is moderately reduced and the cell membrane is slightly depolarized; however, when gliotic Müller cells become proliferative, their K(IR) conductances are dramatically down-regulated; this is accompanied by an increased activity of Ca(2+)-activated K(+) channels and by a conspicuous unstability of their membrane potential. The resultant variations of the membrane potential may increase the activity of depolarization-activated K(+), Na(+) and Ca(2+) channels. It is concluded that in respect to their K(+) current pattern, mature Müller cells pass through a process of dedifferentiation before proliferative activity is initiated.

Animals↗

PubMed2000

The glutathione content of retinal Müller (glial) cells: effect of pathological conditions.

Maintenance of isolated retinal Müller (glial) cells in glutamate-free solutions over 7 h causes a significant loss of their initial glutathione content; this loss is largely prevented by the blockade of glutamine synthesis using methionine sulfoximine (5 mM). Anoxia does not reduce the glutathione content of Müller cells when glucose (11 mM), glutamate and cystine (0.1 mM each) are present. In contrast, simulation of total ischemia (i.e., anoxia plus removal of glucose) decreases the glutathione levels dramatically, even in the presence of glutamate and cystine. Less severe effects are caused by high extracellular K+ (40 mM). Reactive oxygen species are generated in the retina under various conditions, such as anoxia, ischemia, and reperfusion. One of the crucial substances protecting the retina against reactive oxygen species is glutathione, a tripeptide constituted of glutamate, cysteine and glycine. It was recently shown that glutathione can be synthesized in retinal Müller glial cells and that glutamate is the rate-limiting substance. In this study, glutathione levels were determined in acutely isolated guinea-pig Müller cells using the glutathione-sensitive fluorescent dye monochlorobimane. The purpose was to find out how the glial glutathione content is affected by anoxia/ischemia and accompanying pathophysiological events such as depolarization of the cell membrane. Our results further strengthen the view that glutamate is rate-limiting for the glutathione synthesis in glial cells. During glutamate deficiency, as caused by e.g., impaired glutamate uptake, this amino acid is preferentially delivered to the glutamate-glutamine pathway, at the expense of glutathione. This mechanism may contribute to the finding that total ischemia (but not anoxia) causes a depletion of glial glutathione. In situ depletion may be accelerated by the ischemia-induced increase of extracellular K+, decreasing the driving force for glutamate uptake. The ischemia-induced lack of glutathione is particularly fatal considering the increased production of reactive oxygen species under this condition. Therefore the therapeutic application of exogenous free radical scavengers is greatly recommended.

Animals↗

PubMed1999

Outwardly rectifying K+ channels display clustering in guinea pig retinal Müller cells.

The cell-attached configuration of the patch-clamp technique was used to characterize the outward currents in acutely isolated Müller cells from the guinea pig retina. Sixty-five of 353 patches displayed macroscopic, outwardly rectifying currents due to depolarizing voltage steps. Single channel transitions were found in only two patches. The remaining patches did not reveal any voltage-dependent currents. Tail current analysis revealed a reversal potential close to the resting membrane potential. The currents disappeared if internal K+ was replaced by Cs+ in inside-out patches. From these results we conclude that guinea pig Müller cells possess voltage-dependent K+ channels that are distributed in clusters.

Animals↗

PubMed1999

Neuron-glia signaling via alpha(1) adrenoceptor-mediated Ca(2+) release in Bergmann glial cells in situ.

Adrenoceptors were among the first neurotransmitter receptors identified in glial cells, but it is not known whether these receptors meditate glial responses during neuronal activity. We show that repetitive nerve activity evoked a rise of intracellular calcium in Bergmann glia and neighboring Purkinje neurons of cerebellar slices of mice. The glial but not the neuronal calcium transient persisted during block of ionotropic and metabotropic glutamate receptors. In contrast, the glial calcium response was abolished by cyclopiazonic acid and prazosin; however, prazosin affected neither the inward current nor the resulting depolarization that accompanied the stimulus-induced glial calcium transients. The glial depolarization was attenuated by 38% by the mixture of glutamate receptor blockers, which abolished the evoked neuronal depolarization and afterhyperpolarization. Ba(2+) reduced the glial currents by 66% without affecting the concomitant calcium transients. In the presence of Ba(2+), the mixture of glutamate receptor blockers exerted no effect on the glial inward current or calcium rise. Furthermore, Ba(2+) greatly potentiated both the activity-related Purkinje cell inward current and the accompanying neuronal calcium rises. The results indicate that release of noradrenaline from afferent fibers activates a glial alpha(1) adrenoceptor that promotes calcium release from intracellular stores. Glial calcium rises are known to stimulate a diversity of processes such as transmitter release, energy metabolism, or proliferation. Thus the adrenoceptor-mediated mechanism described here is well suited for feedback modulation of neuronal function that is independent of glutamate.

2-Amino-5-phosphonovalerate↗

PubMed1999

Human Müller glial cells: altered potassium channel activity in proliferative vitreoretinopathy.

PURPOSE: To determine differences of K+ channel activity between Müller glial cells obtained from retinas of healthy human donors and of patients with retinal detachment and proliferative vitreoretinopathy. METHODS: Müller cells were enzymatically isolated from retinas of healthy donors and from excised retinal pieces of patients. The whole-cell and the cell-attached configurations of the patch-clamp technique were used to characterize the current densities of different K+ channel types and the activity of single Ca2+ -activated K+ channels of big conductance (BK). RESULTS: Cells from patients displayed a less negative mean membrane potential (-52.8 mV) than cells from healthy donors (-80.6 mV). However, the membrane potentials in cells from patients scattered largely between -6 and -99 mV. The inwardly rectifying K+ permeability in cells from patients was strongly reduced (0.3 pA/pF) when compared with cells from healthy donors (6.0 pA/pF). At the resting membrane potential, single BK channels displayed a higher mean activity (open probability, Po, and channel current amplitude) in cells from patients (Po, 0.30) than in cells from healthy donors (Po: 0.03). The variations of BK current amplitudes were correlated with the variations of the membrane potential. CONCLUSIONS: The dominant expression of inwardly rectifying channels in cells from healthy donors is thought to support important glial cell functions such as the spatial buffering of extracellular K+. The downregulation of these channels and the less negative mean membrane potential in cells from patients should impair spatial buffering currents and neurotransmitter clearance. The increased activity of BK channels may support the proliferative activity of gliotic cells via feedback regulation of Ca2+ entry and membrane potential.

4-Aminopyridine↗

PubMed1998

Ionic mechanisms in glutamate-induced astrocyte swelling: role of K+ influx.

L-Glutamate (L-GLU) induced astrocyte swelling in a time- and concentration-dependent, as well as Na+- and Ca2+-dependent, and Cl(-)-independent manner. Swelling was prevented by MK-801, cystine, and ouabain. Since L-GLU swelling is ionically dependent, we determined the role of various ions in such swelling. Our results indicate that K+ uptake plays a major role in the mechanism of L-GLU-induced astrocyte swelling. Like swelling, K+ uptake is dependent on Ca2+ and Na+, but not on Cl-. Likewise, K+ uptake was inhibited by MK-801, cystine, and ouabain. The K+ channel blockers, Ba2+ and tetraethylammonium, partially prevented L-GLU-induced swelling. In addition to K+ channels, K+ influx may also be mediated through Na+/K+-ATPase, as its activity is increased by L-GLU uptake along with the required Na+. Taken together, the data suggest that K+ influx plays a key role in the mechanism of L-GLU-mediated astrocyte swelling.

Animals↗

PubMed1998

Subcellular compartmentation of glutathione and glutathione precursors. A high resolution immunogold analysis of the outer retina of guinea pig.

Selective antibodies were used to assess the cellular and subcellular localization of glutathione, and the glutathione precursors gamma-glutamylcysteine, glutamate, and cysteine, in neuronal (photoreceptors) and non-neuronal (pigment epithelial cells and Müller cells) cell types in the outer retina of the guinea pig. In each cell type the highest level of glutathione immunoreactivity occurred in the mitochondria. The labeling density in the cytoplasmic matrix was higher (and the mitochondrial-cytoplasmic gold particle ratio lower) in pigment epithelial cells than in Müller cells and photoreceptors. The latter two cell types showed a mitochondrial-cytoplasmic gold particle ratio of 15.5 and 21.7, respectively. In contrast to glutathione, gamma-glutamylcysteine seemed to be enriched in the cytoplasmic matrix relative to the mitochondria. The immunogold labeling for this dipeptide was stronger in the pigment epithelial cells than in Müller cells and photoreceptors. Glutamate immunoreactivity was high in photoreceptors, intermediate in pigment epithelial cells, and low in Müller cells, while the cysteine immunogold signal was low in each cell type and cell compartment. The present results suggest that glutathione is concentrated in mitochondria but to different degrees in different cells. The low mitochondrial content of gamma-glutamylcysteine (the direct precursor of glutathione) is consistent with biochemical data indicating that glutathione is synthesized extramitochondrially and transported into the mitochondrial matrix. Judged from the immunocytochemical data, cysteine may be a rate-limiting factor in glutathione synthesis in each cell type while glutamate can be rate limiting only in Müller cells.

Animals↗

PubMed1998

Cardiopulmonary resuscitation after cardiac surgery: a two-year study.

OBJECTIVE: The aim of this study was to investigate the incidence of cardiopulmonary resuscitation (CPR) after cardiac surgery and to find predictors of survival. DESIGN: A retrospective study with data obtained by chart review. SETTING: A university hospital 24-bed cardiac surgical intensive care unit (ICU). PARTICIPANTS: Between 1993 and 1994, 4,968 consecutive adult patients who underwent cardiac surgery at the authors' hospital were studied. INTERVENTIONS: None. MAIN RESULTS: One hundred thirteen of these patients (2.3%) were resuscitated. Seventy-nine patients (70%) survived to be discharged from the hospital. Significant predictors of survival were the time between admission to the ICU and initiation of CPR, CPR time, and creatine kinase (CK) and CK-MB values. CONCLUSIONS: The incidence of CPR after cardiac surgery was 2.3% with no difference between valve surgery and CABG. Best results were achieved when arrhythmias or bleeding were the predisposing causes. Further studies have to be undertaken concerning long-term results and quality of life of the discharged patients.

Adult↗

PubMed1998

Distribution of mitochondria within Müller cells--I. Correlation with retinal vascularization in different mammalian species.

The distribution of mitochondria within retinal glial (Müller) cells and neurons was studied by electron microscopy, by confocal microscopy of a mitochondrial dye and by immunocytochemical demonstration of the mitochondrial enzyme GABA transaminase (GABA-T). We studied sections and enzymatically dissociated cells from adult vascularized (human, pig and rat) and avascular or pseudangiotic (guinea-pig and rabbit) mammalian retinae. The following main observations were made. (1) Müller cells in adult euangiotic (totally vascularized) retinae contain mitochondria throughout their length. (2) Müller cells from the periphery of avascular retinae display mitochondria only within the sclerad-most end of Müller cell processes. (3) Müller cells from the vascularized retinal rim around the optic nerve head in guinea-pigs contain mitochondria throughout their length. (4) Müller cells from the peripapillar myelinated region ('medullary rays') of the pseudangiotic rabbit retina contain mitochondria up to their soma. In living dissociated Müller cells from guinea-pig retina, there was no indication of low intracellular pH where the mitochondria were clustered. These data support the hypothesis that Müller cells display mitochondria only at locations of their cytoplasm where the local O2 pressure (pO2) exceeds a certain threshold. In contrast, retinal ganglion cells of guinea-pig and rabbit retinae display many mitochondria although the local pO2 in the inner (vitread) retinal layers has been reported to be extremely low. It is probable that the alignment of mitochondria and the expression of mitochondrial enzymes are regulated by different mechanisms in various types of retinal neurons and glial cells.

Animals↗

PubMed1998

Incidence and risk factors of perioperative cerebral complications. Heart transplantation compared to coronary artery bypass grafting and valve surgery.

OBJECTIVE: The aim of this study was to define the neurologic risk of heart transplantation compared to coronary artery bypass grafting (CABG) and valve surgery. DESIGN: A retrospective study. SETTING: A university hospital. PATIENTS: 8001 patients undergoing heart transplantation, CABG and valve surgery. MEASURES: The incidences of perioperative central nervous system (CNS) complications were compared between different procedures. Risk factors were analysed using univariate and multivariate methods. RESULTS: The overall incidence of CNS complications was 19.8% (78/393) in heart transplantation, 3.1% (176/5734) in elective CABG, 9.5% (161/1689) in elective valve surgery, 10.3% (15/146) in emergency CABG and 51.3% (20/39) in emergency valve surgery. Most powerful predictors of CNS complications were preoperative intra-aortic counterpulsation (IABP) in the heart transplantation group, age >65 years in the CABG group and preoperative use of catecholamine in the valve group. CONCLUSIONS: CNS complications occur much more frequently after heart transplantation than elective CABG and valve surgery. The high incidence of CNS complications after emergency operations as well as preoperative catecholamine and IABP as powerful contributing factors suggest that preoperative cerebral hypoperfusion due to a compromised hemodynamic state facilitates postoperative CNS complications and this may partly explain the high incidence of CNS complications after heart transplantation.

Adolescent↗

PubMed1997

Voltage- and GABA-evoked currents from Müller glial cells of the baboon retina.

The electrophysiological features of isolated baboon Müller cells was investigated using the whole-cell voltage-clamp technique. Application of depolarizing voltage steps evoked transient inward and delayed outward currents. The transient currents disappeared when extracellular Na+ was replaced by choline+ and were substantially decreased by application of tetrodotoxin (1 microM). The outward currents were strongly diminished by extracellular Ba2+ (1 mM), and the hyperpolarization-generated inward currents disappeared following application of Ba2+. The recently described gamma-aminobutyric acid A (GABAA) receptor currents were increased by flunitrazepam, nordiazepam, pentobarbital and Zn2+, as well as by the inverse agonist DMCM. These results suggest that the baboon Müller cells possess the same voltage-dependent current pattern as those from other species, e.g. humans, whereas their GABAA receptors react in an uncharacteristic manner to DMCM and Zn2+, when compared with neuronal GABAA receptors.

Animals↗