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H Wiegand

Publications and source records attributed to H Wiegand.

At least 37 records · Page 2Linked to original sources

Inhibition by lead of the calcium plateau current at mouse motor nerve endings.

The inhibition by lead of motor terminal calcium plateau signals has been studied using extracellular, perineuronal electrodes applied to the M. triangularis sterni preparation of the mouse. The long-lasting calcium pateau signal induced by 3,4-DAP (250 mumol) and TEA (10 mmol) blockade of presynaptic potassium channels was irreversibly blocked by micromolar lead concentrations in a concentration-dependent manner. These results suggest that lead antagonizes neuronal calcium channels involved in transmitter release from motor nerve terminals.

Action Potentials↗

Effects of deltamethrin on catecholamine secretion of bovine chromaffin cells.

The effects of the pyrethroid deltamethrin (D) on catecholamine secretion of cultured bovine chromaffin cells were investigated in vitro using high performance liquid chromatography (HPLC). Spontaneous release of catecholamines was increased by 10 microM and 100 microM D. This increase could partially be prevented by the simultaneous use of 2 microM tetrodotoxin (TTX), which reduced the increase by 10 microM D of catecholamine secretion by 90% and that of 100 microM D by 50%. TTX 2 microM alone did not alter the spontaneous release in comparison to controls. Medullary chromaffin cells consist of two cell groups, one secreting mainly epinephrine (E), the other norepinephrine (NE). The ratio between the spontaneously secreted catecholamines E and NE was increased after treatment with D, indicating a dominant effect on E secreting cells.

Adrenal Medulla↗

Effects of tetrandrine on calcium channel currents of bovine chromaffin cells.

Calcium channel currents of bovine chromaffin cells are blocked by the bis-benzyl-isoquinoline alkaloid tetrandrine, which is isolated from the roots of the chinese medical herb Stephania tetrandra. The half-maximal inhibition (IC50) occurred at a concentration of about 10 microM. Bovine chromaffin cells possess no low-voltage-activated, but different types of high-voltage activated calcium channel currents. Tetrandrine blocks omega-conotoxin-sensitive N-type, dihydropyridine-sensitive L-type and omega-conotoxin- and dihydropyridine-insensitive calcium channel currents of chromaffin cells. The I/V relationship in not shifted by tetrandrine, indicating that the block is not voltage-dependent. After tetrandrine application the currents become transient in a depolarization- and a concentration-dependent manner. Tetrandrine blocks open calcium channels and the block is use-dependent. When the holding potential returns to resting levels, the channels are unblocked in about 1 sec.

Alkaloids↗

CALCIUM CHANNEL CURRENTS IN CULTURED PARS INTERCEREBRALIS NEUROSECRETORY CELLS OF ADULT LOCUSTA MIGRATORIA

The medial neurosecretory cells (MNSCs) of the pars intercerebralis in the brain of insects release various hormonal factors that control essential physiological and developmental functions such as moulting, reproduction and metabolism (Wigglesworth, 1940; Girardie, 1966; Goldsworthy, 1969), and these cells are therefore of considerable biological significance. A culture system for locust embryonic pars intercerebralis neurosecretory cells has recently been developed (Vanhems et al. 1993), and Rossler and Bickmeyer (1993) have established an in vitro system for growing larval and adult medial neurosecretory cells. Calcium plays an important role in neural physiology: neurosecretion depends on calcium influx into the cells and calcium currents carry the rising phase of action potentials in different types of insect neurones (Orchard, 1976; Pitman, 1979); calcium also mediates other ionic currents (Thomas, 1984). It is therefore of considerable interest to characterize the types of calcium channel currents found in locust neurosecretory neurones.

Journal Article↗

Neurophysiological aspects of hippocampal neurotoxicity.

Identification and analysis of chemical neurotoxicity in the central nervous system deals with synaptic transmission and plasticity. The hippocampus slice technique rendered a powerful tool for electrophysiological analysis of these events as modulated by neurotoxic chemicals. It does not only allow the detection of potentially harmful compounds, but also the elucidation of their mechanism of action. This might render it possible to analyze the risk of neurotoxic chemicals on the basis of quantitative data.

Animals↗

Effects of chronic low level lead exposure on the expression of GFAP and vimentin mRNA in the rat brain hippocampus analysed by in situ hybridization.

In this study we used in situ hybridization to examine the effects of chronic low level lead toxicity during different periods of brain development. Low level lead is known to affect astroglia. GFAP and Vimentin were chosen as glialtypic markers for neurotoxicity. The effects of lead were investigated on male Wistar rats. Animals were divided into four groups: a control group, a permanent group exposed during gestation, lactation and post-weaning (E0-P100), a perinatal group exposed during gestation and postnatally until weaning (E0-P16), and a post-weaning exposed group (P16-P100). All experimental animals were fed a diet containing 750 ppm lead acetate. With respect to Vimentin mRNA no major differences could be detected among the treatment groups. Significant differences in GFAP mRNA levels were detected in the post-weaning group relative to controls. In this group we observed a strong increase of GFAP mRNA in the polymorphic zone of the dentate gyrus and in the CA1 region of the hippocampus. Permanent and perinatal groups showed no overt changes compared to controls. Our findings suggest that an irritation of the mature astrocyte results in a change from the quiescent to the reactive state. The majority of astrocytes that have been exposed during their development and differentiation fail to react even if the exposure is continued to adulthood. This suggests an irreversible insult by low level lead exposure during this period of time.

Animals↗

Chronic prenatal and postnatal Pb2+ exposure increases [3H]MK801 binding sites in adult rat forebrain.

We have measured the binding of [3H]MK801 to the N-methyl-D-aspartate (NMDA) receptor-ion channel in membrane preparations from adult rat forebrain exposed to lead (Pb2+) during gestation, lactation, and postweaning. Our results indicate a 30.9% increase in the number of [3H]MK801 binding sites in Pb2+ exposed animals relative to controls. No significant changes in the affinity constant were observed. The level of blood Pb2+ for which such changes were measured was 13.9 +/- 2.8 micrograms/dl. These results indicate that alterations in the NMDA receptor-ion channel complex are present at blood Pb2+ levels which are environmentally relevant and suggest that chronic Pb2+ exposure during development can influence the NMDA receptor complex in the adult rat brain.

Animals↗

Impairment of long-term potentiation and learning following chronic lead exposure.

Chronic lead exposure during brain development is known to affect functions of the central nervous system. We exposed rats chronically to low levels of lead at different developmental stages in order to determine the most sensitive periods of exposure. Active avoidance learning and hippocampal long-term potentiation were tested in the same animals. If the exposure period comprised the prenatal and the early postnatal phase and was continued into adulthood, learning as well as long-term potentiation were impaired. Starting the exposure not before 16 days postnatally, however, neither affected learning nor hippocampal potentiation. These results reflect the higher vulnerability of the immature as compared to the mature hippocampus to lead-induced functional deficits.

Animals↗

Development of calcium currents in cultures of mouse spinal cord and dorsal root ganglion neurones.

Cultured spinal cord (SC) and dorsal root ganglion (DRG) neurones of 11-13 day old foetal mice were investigated electro-physiologically during differentiation in vitro using the whole-cell patch-clamp technique. High-voltage-activated calcium currents (HVA) and low-voltage-activated (LVA) calcium currents were measured using barium ions as charge carrier. During differentiation in vitro the soma diameter of SC-neurones increased with age (0-42 days in vitro) from 10.3 +/- 2.7 microns to 25.1 +/- 5.9 microns. The capacitance of the soma increased from 7.4 +/- 2.3 pF to 34 +/- 6 pF. The inward calcium current amplitudes increased from 200 pA to 3 nA, while the LVA current amplitude increased only from 50 pA to 100-150 pA. The currents per membrane area through HVA calcium channels increased in the investigated time while the currents through LVA channels decreased.

Animals↗

Tetrandrine effects on calcium currents in cultured neurones of foetal mice.

Tetrandrine, a bis-benzyl-isoquinoline alkaloid from the roots of Stefania Tetranda blocks calcium currents in cultured neurones of the spinal cord of foetal mice. The concentration of half-maximal effect (Kd) measured 100 ms after the beginning of a depolarizing pulse (-80 mV-0 mV) is 8 microM. While high- and low-voltage activated (HVA, LVA) currents are both blocked by Tetrandrine, the slowly inactivating HVA currents appear to be a primary target.

Alkaloids↗

Scintimetric evaluation of remodeling after bone fractures in man.

In a review of bone scans of 2000 post-trauma patients, the following rules of bone remodeling after fracture were found: different bones behave differently; lesions in the vicinity of joints show an early and high accumulation of the tracer within the first days after the trauma, whereas fractures of the axial skeleton and shafts of long bones sometimes need up to 12 days to appear on scan; all except skull fractures demonstrate a steady rise of accumulation intensity compared to normal bone for 2-5 wk; the steepness of increase and time of maximum differ significantly for different fracture sites. Calculating a ratio 24:4 hours after injection helps differentiate fractures from soft tissue lesions since fresh fractures show a ratio > 1:1. We found no clinically relevant dependence on sex and age. The scintigraphic/scintimetric behavior of fractures is reproducible and predictable, adding specificity to the well-known high sensitivity of bone scans.

Adult↗

Long-term potentiation in rat hippocampal slices is impaired following acute lead perfusion.

Orthodromically evoked field potentials were recorded in the CA1 region of hippocampal slices while perfusing the slices with media containing lead acetate. High-frequency stimulation (HFS) was applied to the stratum radiatum during lead perfusion. In half of the slices investigated, HFS resulted in an initial increase of the evoked responses which decayed again after about 10 min. In the other half the evoked responses increased only after the washout of lead and this potentiation was comparable to untreated controls. The lead-induced depression of the long-term potentiation might be related to the behavioral deficits observed in chronically lead-exposed mammals.

Animals↗

Colonization of adrenal glands and ovaries of mice by variants of HSV 1 and 2. II. Histopathological, immunohistochemical and in situ hybridization studies.

The herpes simplex virus (HSV)-infected mouse model was used to correlate histopathological lesions in adrenal glands and ovaries with the localisation of viral nucleic acids and viral antigens, employing in situ hybridization and immunohistochemistry. In the adrenals, the lesions were mainly restricted to the zona fasciculata and the zona reticularis, sometimes extending to the medulla. In the ovaries, lesions were detected in follicles and in the stroma. During the course of infection, HSV nucleic acids could be detected earlier than HSV proteins. Next to the center of necrotic foci mainly HSV proteins were detected, whereas peripheral cells were found to contain viral nucleic acids. In situ hybridization revealed no proof of HSV latency in either organ. Among HSV-1 and HSV-2 strains of different neurovirulence, only HSV-2 variant ER- failed to replicate in adrenal glands and ovaries, whereas the neuroinvasive variant ER+ showed the same patterns as the HSV-1 strains used.

Adrenal Glands↗

The intron enhancer of the immunoglobulin kappa gene activates c-myc but does not induce the Burkitt-specific promoter shift.

In Burkitt's lymphoma cells the c-myc gene locus is consistently fused to the constant region of one of the immunoglobulin genes by chromosomal translocation. The translocated c-myc gene is transcriptionally activated and preferentially transcribed from the P1 promoter whenever the exon-intron structure of c-myc remains intact. In order to define elements involved in this promoter shift we have cloned the translocated c-myc allele from Burkitt's lymphoma cell line BL60, which is characterized by several point mutations. The mutated c-myc allele of BL60 was stably introduced into baby hamster kidney and Burkitt's lymphoma cells. S1 nuclease and RNAase protection mapping experiments demonstrated that the mutated c-myc allele was expressed at a low level and with a normal promoter usage (P2 greater than P1) in Burkitt's lymphoma and baby hamster kidney cells. Furthermore, we have studied the expression of a construct consisting of the mutated c-myc allele, part of the bvr1 (Burkitt's variant rearranging region 1) locus, the human immunoglobulin kappa constant region, and the kappa intron enhancer after stable transfection into Burkitt's lymphoma cells. Although c-myc expression was about fivefold increased, the transcripts still initiated predominantly at promoter P2. This indicates that 5 kb of the constant kappa light-chain locus including the kappa intron enhancer is not sufficient to induce the Burkitt's lymphoma-specific promoter shift.

Animals↗

Inhibition by tetrandrine of calcium currents at mouse motor nerve endings.

The inhibition by the bis-benzyl-isoquinoline alkaloid tetrandrine of motor terminal calcium currents has been studied using extracellular, perineuronal electrodes in the M. triangularis preparation of the mouse. The calcium plateau current was irreversibly blocked, whereas the fast calcium current remained unaffected. From these results a calcium antagonism on neuronal calcium channels involved in transmitter release at motor nerve terminals is suggested.

4-Aminopyridine↗

Neurophysiological and psychophysical measurements reveal effects of acute low-level organic solvent exposure in humans.

The organic solvent tetrachloroethylene (Per) is proposed to be a human neurotoxicant. In order to evaluate whether the sensory system is affected by Per at low concentrations, two groups of male volunteers were exposed in an inhalation chamber to 10 and 50 ppm Per, respectively. During the inhalation exposure, which lasted for 4 h per day on four consecutive days, visually evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs) were measured. In addition, in some of these volunteers, the visual contrast sensitivity was determined psychophysically. In the group exposed to 50 ppm Per, the VEP peak latencies N75, P100 and N150 increased in the course of the inhalation period. A comparison of the two groups revealed statistically significant differences of these latency changes during Per exposure. In contrast, the BAEPs of the two groups did not differ significantly during the whole exposure period. The contrast sensitivity functions showed a tendency of increased threshold contrasts at low and intermediate spatial frequencies during exposure to 50 ppm Per. The results indicate visual system dysfunctions in terms of delayed neuronal processing time and altered contrast perception due to acute Per exposure.

Adult↗

Epstein-Barr virus infection rapidly progressing to monoclonal lymphoproliferative disease in a child with selective immunodeficiency.

We report on a 30-month-old previously healthy Turkish boy who presented with fever, hepatosplenomegaly and generalized lymphadenopathy. He died 4 months after admission in spite of treatment with steroids, acycloguanosine and cyclophosphamide. Epstein-Barr virus (EBV) DNA was detected in the patient's bone marrow and in a lymph node biopsy. Cells from the lymph node biopsy showed monoclonal rearrangements of immunoglobulin heavy chain genes but no rearrangements of T-cell receptor beta-chain genes or immunoglobulin kappa chain genes. Serological data indicated chronic active EBV infection. There was a slight increase of CD8 positive cells in peripheral blood and a normal response to T-cell mitogens. However, T-cell lines established with interleukin 2 from lymph node biopsy completely failed to kill autologous EBV-transformed B-cells and K 562 target cells. Moreover, in regression tests the patient's peripheral blood mononuclear cells completely failed to limit outgrowth of autologous EBV infected B-cells. We conclude that the patient's selective immuno-deficiency had led to the rapid development of EBV-associated monoclonal lymphoproliferation.

Antibodies, Viral↗

[The deafferentation concept].

Old and new findings on development and regression of the nervous system in relation to brain plasticity are presented as deafferentiation phenomena in the sensory, nociceptive, visual and auditory systems. Other applications of the deafferentiation concept are discussed.

Afferent Pathways↗