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Biomedical subjects

U Zimmermann

Publications and source records attributed to U Zimmermann.

At least 19 recordsLinked to original sources
PubMed1996

Identification of adrenomedullin receptors in cultured rat astrocytes and in neuroblastboma x glioma hybrid cells (NG108-15).

Adrenomedullin (ADM) is a hypotensive peptide with structural homology, including a ring structure linked by a disulfide bridge, to calcitonin gene-related peptide (CGRP), calcitonin and amylin. ADM is predominantly synthesized in the adrenal medulla, but immunoreactive ADM has also been detected in the human brain. Here we have characterized ADM binding sites in cultured rat astrocytes using human [125I]ADM(1-52) as radioligand. Half-maximal inhibition of [125I]ADM(1-52) binding by intact rat ADM(1-50) amounted to 0.27 +/- 0.03 nM (n = 15). The related peptides rat alpha-CGRP, rat amylin and salmon calcitonin displaced [125I]ADM(1-52) at 85-, 148-, and > 4000-fold higher concentrations. Half-maximal stimulation of cAMP accumulation by rat ADM(1-50) was obtained with 1.00 +/- 0.12 nM (n = 16). Rat alpha-CGRP was 214-fold, and rat amylin and salmon calcitonin were > 1000-fold less potent. Concerning cAMP accumulation the results were indistinguishable in mouse neuroblastoma x rat glioma hybrid cells (NG108-15), but here rat alpha-CGRP was > 1000-fold less potent than rat ADM(1-50). Human ADM(22-52) and human CGRP-I(8-37), which lack the ring structure, failed to stimulate cAMP accumulation, but they antagonized rat ADM(1-50) stimulated cAMP accumulation with inhibitory constants of 365 +/- 93 nM and 92 +/- 2 nM In astrocytes, and 45 +/- 3 nM and 1300 +/- 500 nM in NG108-15 cells. Rat ADM(1-50) did not raise cytosolic free calcium concentrations in astrocytes and NG108-15 cells. In conclusion, we have identified novel ADM receptors coupled to cAMP formation in cultured rat astrocytes and NG108-15 cells. Different interactions with the homologous peptide CGRP as well as truncated receptor antagonists ADM(22-52) and CGRP(8-37) in rat astrocytes and neuroblastoma x glioma hybrid cells are consistent with ADM receptor isotypes in the brain.

Animals↗
PubMed1996

Electrorotation of erythrocytes treated with dipicrylamine: mobile charges within the membrane show their "signature" in rotational spectra.

In this study, electrorotation spectra of individual cells (that is, frequency dependence of cell rotation speed) have been proved to yield information not only about the passive electric properties of cell constituents, but also about the presence of mobile charges within the plasma membrane being part of ion carrier transport systems. Experiments on human erythrocytes pretreated with the lipophilic anion dipicrylamine (DPA) gave convincing evidence that these artificial mobile charges adsorbed to the plasma membrane contributed significantly to the rotational spectrum at relatively low conductivity of the external medium (2-5 mS m-1). Theoretical integration of the mobile charge concept into the single-shell model (viewing the cell as a homogenous sphere surrounded by a membrane) led to a set of equations which predicted electrorotational behavior of DPA-treated cells in dependence on medium conductivity. The quantitative data on the partition and the transmembrane translocation rate of the DPA anion extracted from the experimental rotational spectra agreed well with the corresponding literature values.

Electrophysiology↗
PubMed1996

Expression of neurotrophin receptor trkB in rat cochlear hair cells at time of rearrangement of innervation.

The spatio-temporal distribution of the high-affinity neurotrophin receptor trkB was monitored during postnatal development of the rat cochlea. In addition to expression in presumptive afferent type I collaterals, afferent type II fibers, and efferent fibers, trkB immunoreactivity also transiently appeared in the sensory hair cells themselves, from postnatal days 5-9 in the basal turn, and from postnatal days 9-13 in the apical turn. A comparison of trkB with p75(NGFR), which is expressed in afferent and efferent fibers, and GAP-43 and synaptophysin, which are expressed in efferent fibers, revealed a time/space correlation of trkB receptor expression in hair cells with the rearrangement of their innervation. Co-expression of the neurotrophin receptor and its ligand has been proposed to be functionally involved in regulating the survival of neurons independent of target-derived neurotrophin factor. Thus, the presence of trkB in target hair cells, suggests that auto/paracrine mechanisms play a role during this critical period of rearrangement of neural connections.

Animals↗
PubMed1996

Stress hormones in accident patients studied before admission to hospital.

OBJECTIVE: To assess stress hormone response in traumatised patients studied at the site of injury and on their way to hospital. METHODS: The study was prospective. Blood samples were taken from 77 patients immediately after the arrival of the emergency physician at the site of the accident (t1) and shortly before patients' admission to hospital (t2). Plasma concentrations of beta endorphin, cortisol, adrenocorticotrophic hormone (ACTH), prolactin, and growth hormone were measured. RESULTS: Trauma in out-of-hospital patients resulted in remarkably increased concentration of growth hormone within minutes. ACTH, cortisol, and prolactin were only moderately increased. No significant correlations were found between hormone levels and blood pressure or heart rate. The plasma ACTH concentration was significantly lower before admission to hospital than immediately after the accident. Plasma cortisol, prolactin, and growth hormone concentrations were not significantly different between the two points of observation. In samples taken immediately after the accident (t1), there was a positive correlation between both beta endorphin and prolactin and the injury severity score, whereas cortisol levels were negatively correlated with injury severity score, suggesting impaired cortisol release from the adrenal cortex after severe injury. At t1 ACTH was correlated with cortisol and beta endorphin. Patients with head injuries had hormone concentrations similar to those without head injuries but with a similar injury severity score from injuries in other parts of the body. CONCLUSIONS: Lower cortisol concentrations in the very severely injured might be due to failure of the adrenal cortex to respond normally to ACTH stimulation. Growth hormone seems to play a major role in the response to trauma, reflecting an immediate stress response.

Accidents↗
PubMed1996

Shape deformation of the organ of Corti associated with length changes of outer hair cell.

Cochlear outer hair cells (OHC) are commonly assumed to function as mechanical effectors as well as sensory receptors in the organ of Corti (OC) of the inner ear. OHC in vitro and in organ explants exhibit mechanical responses to electrical, chemical or mechanical stimulation which may represent an aspect of their effector process that is expected in vivo. A detailed description, however, of an OHC effector operation in situ is still missing. Specifically, little is known as to how OHC movements influence the geometry of the OC in situ. Previous work has demonstrated that the motility of isolated OHCs in response to electrical stimulation and to K(+)-gluconate is probably under voltage control and causes depolarisation (shortening) and hyperpolarization (elongation). This work was undertaken to investigate if the movements that were observed in isolated OHC, and which are induced by ionic stimulation, could change the geometry of the OC. A synchronized depolarization of OHC was induced in guinea pig cochleae by exposing the entire OC to artificial endolymph (K+). Subsequent morphometry of mid-modiolar sections from these cochleae revealed that the distance between the basilar membrane (BM) and the reticular lamina (RL) had decreased considerably. Furthermore, in the three upper turns OHC had significantly shortened in all rows. The results suggest that OHC can change their length in the organ of Corti (OC) thus deforming the geometry of the OC. The experiments reveal a tonic force generation within the OC that may change the position of RL and/or BM, contribute to damping, modulate the BM-RL-distance and control the operating points of RL and sensory hair bundles. Thus, the results suggest active self-adjustments of cochlear mechanics by slow OHC length changes. Such mechanical adjustments have recently been postulated to correspond to timing elements of animal communication, speech or music.

Animals↗
PubMed1995

Electropermeabilization and fluorescent tracer exchange: the role of whole-cell capacitance.

Transmembrane crossing of charged fluorescent tracers such as propidium iodide (PI) and carboxyfluorescein+ (CF) can be used to quantitate membrane permeabilization. Murine myeloma Sp2/0-Ag14 cells were loaded with CF (0.1 fmol/cell) before electropulsation (0.5-3.0 kV/cm, 40 microseconds) in medium containing 25-50 micrograms/ml PI at 21-23 degrees C. Cytograms of PI vs. CF fluorescence showed three readily distinguishable subpopulations: 1) intact living cells with CF but without PI (these form > 95% of the prepulsed population), 2) transiently electropermeabilized but resealed cells showing both CF and low-level PI fluorescence, and 3) permanently permeabilized cells without CF but with very high PI fluorescence. Despite the ready influx of PI, the efflux of CF from transiently permeabilized cells was negligible and was insensitive to pulse parameters; however, electrically killed cells (subpopulation 3) lost all CF fluorescence and probably lost their cytoplasm. This difference in transmembrane passage of the dyes is best explained by binding of intracellular CF to macromolecules (and/or organelles). In isotonic "pulse medium," the membranes resealed after electropulsing with a time constant (tau R) of about 2 min. In 150 mOsm medium, resealing was faster (typically tau R approximately 0.5 min). The population distribution of PI uptake [coefficient of variation (CV) > 40%] was very broad and could not be accounted for by the radius dependence of pulse-induced voltage (CVradius approximately 10%). The variability in PI uptake could be explained if the electrical energy of the charged membrane, which depends on the whole-cell capacitance (Cc), was taken into account. Evaluation of the Cc values with single-cell resolution was based on measurement of the electrical charging time constant of the plasma membrane by electrorotation.

Animals↗
PubMed1995

Synaptophysin and GAP-43 proteins in efferent fibers of the inner ear during postnatal development.

A rearrangement of afferent and efferent fibers occurs in the postnatal development of the inner ear. Growth and synaptogenesis was explored during this critical period by immunohistochemically monitoring the expression of GAP-43 and synaptophysin. Both proteins were colocalized in efferent fibers beyond postnatal day 3 (pn3). Two distinct synaptophysin- and GAP-43-positive fibers innervated different parts of inner hair cells in the first and second postnatal weeks, respectively. GAP-43-positive efferents projecting to outer hair cells upregulated synaptophysin with base to apex gradient between postnatal day 5 and postnatal day 14. In efferents projecting to outer hair cells GAP-43 was downregulated about 6 days beyond synaptogenesis. In efferents projecting to inner hair cells, however, GAP-43 remained upregulated even beyond pn18, indicating continuous synapse replacement of this fiber type. Both proteins thus improved as excellent markers for growth and synaptogenesis of distinct postnatal efferent fibers.

Animals↗
PubMed1995

Does bright-light therapy influence autonomic heart-rate parameters?

30 inpatients suffering from major depression (DSM-III-R), who did not fulfill the criteria of seasonal affective disorder (SAD), were treated with either doxepin or amitripytyline as monotherapy and supportively with bright light for 14 days. From days 15 to 19, bright light was replaced by dim light. 18 drug-free control subjects underwent an analogous sequence of bright- and dim-light applications. Phototherapy was applied between 06:00 and 07:30. Heart-rate (HR) analysis was performed in the patients and control subjects before and after the 5th session of bright and dim lights, respectively. 12 patients (40%) experienced improvement of mood during bright-light therapy (group I) while 18 (60%) did not (group II). Patients of group I, who reached significantly higher scores in the seasonal pattern assessment questionnaire than patients of group II, showed an increase of the coefficient of HR variation (HRV) during deep breathing as well as an increment of the high-frequency (HF) peak of spectral analysis exclusively after the bright-light sessions. Patients of group II did not show a significant alteration of these parameters, neither under the conditions of bright-light treatment nor under dim light. The control subjects experienced an increment of the HF power exclusively after bright light. The results suggest that a distinct subgroup of patients with non-SAD major depression shows a more pronounced light-associated increment of parasympathetically controlled cardiac functions than the other depressed patients and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effects of light and inhibitors of ATP-synthesis on the chloride carrier of the alga Valonia utricularis: is the carrier a chloride pump?

The effect of metabolic inhibitors, such as cyanide, antimycin A and azide was studied on the chloride transport system of the giant marine alga Valonia utricularis by using the charge pulse relaxation method. Two clearly defined voltage relaxations were resolved. The addition of 10-30 microM cyanide to the artificial sea water (ASW) bathing the algal cells increased the time constants of the slow voltage relaxation, tau 2, significantly when the algal cells were kept in the dark. The cyanide-effect reached a plateau value at 100-300 microM and was fully reversible when cyanide was removed from the ASW. Analysis of the charge pulse data in terms of the Läuger-model demonstrated that the translocation rates of the free, kS, and the charged carrier, kAS, decreased. The decrease of kS was more pronounced than that of kAS. 10 microM antimycin A and 3 mM azide had similar effects on the rate constants when the light was switched off. Upon illumination the cyanide- and antimycin A-, but not the azide-mediated effects disappeared. At concentrations higher than 1 mM cyanide caused a further, dramatic decrease of kS and kAS, while the surface concentration of the carrier molecules, N0, was not affected. This cyanide-effect was also reversible, but not light-dependent. Measurements of the ATP level showed that 3 mM cyanide reduced the ATP level by about 70% both under light and dark conditions. In the presence of 30 microM cyanide (or 10 microM antimycin A) the ATP level decreased by about 50%, but only in the dark. These results suggest two different effects of cyanide on the Cl(-)-carrier system: in the micromolar concentration range cyanide (and antimycin A) reduced predominantly the translocation of the free carrier by inhibition of ATP synthesis by oxidative phosphorylation, whereas in the millimolar concentration range cyanide apparently inhibits the translocation rates of both the free and charged carriers by its binding to the carrier. The results provide some evidence that the chloride transport of V. utricularis could be coupled to metabolic energy but it is an open question whether it is a pump or not.

Adenosine Triphosphate↗
PubMed1995

Adrenomedullin and calcitonin gene-related peptide interact with the same receptor in cultured human neuroblastoma SK-N-MC cells.

Inhibition of human [125I]calcitonin gene-related peptide-I ([125I]hCGRP-I) binding by human adrenomedullin (hADM), its N-terminal truncated fragments, CGRP and amylin, and cyclic AMP accumulation were examined in the human neuroblastoma cell line SK-N-MC. Binding of [125I]hCGRP-I (125 pM) was inhibited by hCGRP-I, hADM(1-52), hADM(13-52), and human amylin with IC50 of 0.32 +/- 0.06, 2.11 +/- 0.26, 3.45 +/- 0.54, and 68.8 +/- 6.6 nM, respectively. hCGRP-I(8-37) and hADM(22-52), which lack the N-terminal ring structure, inhibited [125I]hCGRP-I binding with IC50 of 2.35 +/- 0.45 and > 1000 nM. hCGRP-I, hADM(1-52), hADM(13-52) and human amylin stimulated cAMP accumulation with EC50 of 0.40 +/- 0.05, 18.1 +/- 2.6, 51.3 +/- 9.0 and 925 +/- 159 nM, respectively. hCGRP-I(8-37) (100 nM) antagonized hCGRP-I and hADM(1-52) stimulated cAMP production with the same Ki of 16.6 +/- 1.2 and 16.8 +/- 1.1 nM. In conclusion, human ADM, which is more distantly related to CGRP than amylin, interacts more potently with the CGRP receptor in SK-N-MC cells than amylin. The N-terminal ring structure of hADM, unlike that of hCGRP, is essential for binding to the CGRP receptor. Coupling of hADM binding to cAMP stimulation is less efficient than for hCGRP-I and is reduced by deletion of the unique 12 amino acid sequence of hADM N-terminal to the ring structure.

Adrenomedullin↗
PubMed1995

Immunological identification of candidate proteins involved in regulating active shape changes of outer hair cells.

By employing immunological methods, it has been demonstrated that myosin, myosin light chain (MLC) and myosin light chain kinase (MLCK) proteins in outer hair cells (OHC) are immunologically different from isoforms in platelets, smooth muscle and heart muscle, and are probably more related to isoforms found in red blood cells (RBC). Moreover, proteins related to band 3 protein (b3p) and protein 4.1 (p 4.1), ankyrin as well as fodrin and spectrin, but not glycophorin, have been identified in isolated OHCs. Both OHCs and RBC differ from other motile non-muscle cells in their lack of smooth muscle isoforms of actin, their common high levels of spectrin-, ankyrin- and band 3-like proteins, as well as the expression of the 80 kDa protein 4.1 isoform. The data support the notion that motility of OHC may be based upon regulation of the b3p/p 4.1/ankyrin complex, and thus may be reminiscent to the active shape changes in RBC.

Actins↗
PubMed1995

Quantitative NMR microscopy on intact plants.

Quantitative high resolution images on intact young maize plants were acquired by using magnetization-prepared NMR microscopy. Although the spatial resolution is low compared with that of light microscopy, the calculated spin density and T1 maps exhibit contrasts that are in excellent agreement with photomicrographic images. The T2 map gives image contrasts that are not visible in a usual light microscopic image. The diffusion images show an anisotropic behavior of the water self-diffusion coefficient in the vascular bundles, which can be understood by the cell morphology in this plant section. This work demonstrates that quantitative imaging on intact plant systems is possible and that long total acquisition times are no obstacle. Furthermore, the different single parameter maps give a better insight into the morphology of plants under in vivo conditions.

Magnetic Resonance Spectroscopy↗
PubMed1995

A simple device for serial blood collection in human subjects and animals.

A simple system for the continuos withdrawal of blood and the serial collection of blood samples in human subjects and experimental animals is described. It consists of heparin-coated tubing, a connector attached to an indwelling cannula that allows flushing of the i.v. catheter, a peristaltic pump and a fraction collector and an alarm system which is activated when blood flow through the system is interrupted. It can be assembled from parts available in every laboratory or hospital.

Animals↗
PubMed1995

Caloric evoked motile responses of mammalian vestibular sensory cells.

Evokation of caloric nystagmus in microgravity argues against thermal convection as a sufficient explanation for a caloric nystagmic response. By contrast, caloric nystagmus observed in weightlessness suggests a gravity independent mechanism. Here we demonstrate that direct caloric stimulation of isolated living vestibular hair cells from the guinea pig evoked mechanical responses of the sensory cells. Heating of the mechanoreceptor cells from 37 degrees C to 42 degrees C resulted in elongation cooling of the cells from 37 degrees C to 30 degrees C induced shortening of vestibular hair cells. The observed mechanism might contribute to the caloric evokation of a nystagmus both on earth and in orbit.

Animals↗
PubMed1995

Efficient immortalization of rheumatoid synovial tissue B-lymphocytes. A comparison between the techniques of electric field-induced and PEG fusion.

In this study, B-cells isolated from rheumatoid synovial tissue were immortalized, without prior in vitro stimulation, by means of electric-field induced fusion and conventional PEG fusion in order to compare the efficiency of these methods. Two myeloma cell lines were used as fusion partners, the murine myeloma Ag8 and the murine-human heteromyeloma HAB-1. The results of seven fusion experiments performed simultaneously with identical cell populations showed that fusion frequencies obtained by electrofusion were 4 to 35 times higher than by the PEG fusion technique. The morphological and immunohistochemical evaluation of synovial tissues used for fusion showed that only tissues exhibiting a follicular distribution of B-cells with a high percentage of CD 22-positive lymphocytes gave rise to high fusion yields and produced B-cell clones, whereas synovial tissues with the same percentage of plasma cells but lower percentages of CD 22 lymphocytes yielded very low fusion rates. In conclusion, electrofusion is more efficient for immortalizing small amounts of synovial tissue B-lymphocytes than PEG fusion, since high fusion frequencies could be obtained by this technique without the need for prior in vitro stimulation. Synovial tissue exhibiting a follicular distribution of B-lymphocytes with high percentages of CD 22-positive lymphocytes gave rise to high hybridoma yields and therefore an ideal source of human rheumatoid B-cell clones.

Animals↗