bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptosome-Associated Protein of 25 Kilodaltons Modulates Kv2.1 Voltage-Dependent K+ Channels in Neuroendocrine Islet β-Cells through an Interaction with the Channel N Terminus
Authors: MacDonald Patrick E. , Wang Guotang , Tsuk Sharon , Dodo Chikvashvili , Kang Youhou , Tang Lan , Wheeler Michael B. , Cattral Mark S. , Lakey Jonathan R. T. , Salapatek Anne Marie F. , Lotan Ilana , Gaisano Herbert Y. 
Published: October 2002

AbstractInsulin secretion is initiated by ionic events involving membrane depolarization and Ca2+ entry, whereas exocytic SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins mediate exocytosis itself. In the present study, we characterize the interaction of the SNARE protein SNAP-25 (synaptosome-associated protein of 25 kDa) with the β-cell voltage-dependent K+ channel Kv2.1. Expression of Kv2.1, SNAP-25, and syntaxin 1A was detected in human islet lysates by Western blot, and coimmunoprecipitation studies showed that heterologously expressed SNAP-25 and syntaxin 1A associate with Kv2.1. SNAP-25 reduced currents from recombinant Kv2.1 channels by approximately 70% without affecting channel localization. This inhibitory effect could be partially alleviated by codialysis of a Kv2.1N-terminal peptide that can bind in vitro SNAP-25, but not the Kv2.1C-terminal peptide. Similarly, SNAP-25 blocked voltage-dependent outward K+ currents from rat β-cells by approximately 40%, an effect that was completely reversed by codialysis of the Kv2.1N fragment. Finally, SNAP-25 had no effect on outward K+ currents in β-cells where Kv2.1 channels had been functionally knocked out using a dominant-negative approach, indicating that the interaction is specific to Kv2.1 channels as compared with other β-cell Kv channels. This study demonstrates that SNAP-25 can regulate Kv2.1 through an interaction at the channel N terminus and supports the hypothesis that SNARE proteins modulate secretion through their involvement in regulation of membrane ion channels in addition to exocytic membrane fusion.
A Novel Mutation in Helix 12 of the Vitamin D Receptor Impairs Coactivator Interaction and Causes Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets without Alopecia
Authors: Malloy Peter J. , Xu Rong , Peng Lihong , Clark Pamela A. , Feldman David 
Published: October 2002

Abstract
Hereditary vitamin D-resistant rickets (HVDRR) is a genetic disorder most often caused by mutations in the vitamin D receptor (VDR). The patient in this study exhibited the typical clinical features of HVDRR with early onset rickets, hypocalcemia, secondary hyperparathyroidism, and elevated serum concentrations of alkaline phosphatase and 1,25-dihydroxyvitamin D [1,25-(OH)2D3]. The patient did not have alopecia. Assays of the VDR showed a normal high affinity low capacity binding site for [3H]1,25-(OH)2D3 in extracts from the patient’s fibroblasts. However, the cells were resistant to 1,25-dihydroxyvitamin D action as demonstrated by the failure of the patient’s cultured fibroblasts to induce the 24-hydroxylase gene when treated with either high doses of 1,25-(OH)2D3 or vitamin D analogs. A novel point mutation was identified in helix H12 in the ligand-binding domain of the VDR that changed a highly conserved glutamic acid at amino acid 420 to lysine (E420K). The patient was homozygous for the mutation. The E420K mutant receptor recreated by site-directed mutagenesis exhibited many normal properties including ligand binding, heterodimerization with the retinoid X receptor, and binding to vitamin D response elements. However, the mutant VDR was unable to elicit 1,25-(OH)2D3-dependent transactivation. Subsequent studies demonstrated that the mutant VDR had a marked impairment in binding steroid receptor coactivator 1 (SRC-1) and DRIP205, a subunit of the vitamin D receptor-interacting protein (DRIP) coactivator complex. Taken together, our data indicate that the mutation in helix H12 alters the coactivator binding site preventing coactivator binding and transactivation. In conclusion, we have identified the first case of a naturally occurring mutation in the VDR (E420K) that disrupts coactivator binding to the VDR and causes HVDRR.
Homologous and Heterologous Regulation of Somatostatin Receptor 2
Authors: Elberg Gerard , Hipkin R. William , Schonbrunn Agnes 
Published: October 2002

AbstractWe previously demonstrated that phosphorylation of somatostatin receptor 2A (sst2A) is rapidly increased in transfected cells both by agonist and by the protein kinase C (PKC) activator phorbol myristate acetate (PMA). Here, we investigate whether PKC-mediated receptor phosphorylation is involved in the homologous or heterologous regulation of endogenous sst2 receptors in AR42J pancreatic acinar cells upon stimulation by agonist or by cholecystokinin (CCK) or bombesin (BBS). Somatostatin, PMA, CCK, and BBS all increased sst2A receptor phosphorylation 5- to 10-fold within minutes. Somatostatin binding also caused rapid internalization of the ligand-receptor complex, and PMA, CCK, and BBS all stimulated this internalization further. Additionally, sst2 receptor-mediated inhibition of adenylyl cyclase was desensitized by all treatments. Somatostatin, as well as peptidic (SMS201–995) and nonpeptidic (L-779,976) sst2 receptor agonists increased the EC50 for somatostatin inhibition 20-fold. In contrast, pretreatment with BBS, CCK, or PMA caused a modest 2-fold increase in the EC50 for cyclase inhibition. Whereas the PKC inhibitor GF109203X abolished sst2A receptor phosphorylation by CCK, BBS, and PMA, it did not alter the effect of somatostatin, demonstrating that these reactions were catalyzed by different kinases. Consistent with a functional role for PKC-mediated receptor phosphorylation, GF109203X prevented PMA stimulation of sst2 receptor internalization. Surprisingly, however, GF109203X did not inhibit BBS and CCK stimulation of sst2A receptor endocytosis. These results demonstrate that homologous and heterologous hormones induce sst2A receptor phosphorylation by PKC-independent and -dependent mechanisms, respectively, and produce distinct effects on receptor signaling and internalization. In addition, the heterologous hormones also modulate sst2 receptor internalization by a novel mechanism that is independent of receptor phosphorylation.
Intracellular calcium activity in isolated bovine adrenal chromaffin cells in the presence and absence of 60 Hz magnetic fields
Authors: Craviso Gale L. , Poss James , Lanctot Christine , Lundback Steven S. , Chatterjee Indira , Publicover Nelson G. 
Published: October 2002

AbstractThis study examined whether 60 Hz magnetic field (MF) exposure alters intracellular calcium levels ([Ca2+]i) in isolated bovine adrenal chromaffin cells, a classic model of neural responses. [Ca2+]i was monitored by fluorescence video imaging of cells loaded with the calcium indicator fluo‐4 during exposures to magnetic flux densities of 0.01, 0.1, 1.0, 1.4, or 2.0 mT. MFs generated by Helmholtz coils constructed from bifilar wire allowed both 60 Hz field and sham exposures. Following a 5 min monitoring period to establish baseline patterns, cells were subjected for 10 min to a 60 Hz MF, sham field or no field. Reference calcium responses and assessment of cell excitability were obtained by the sequential addition of the nicotinic cholinergic receptor agonist dimethylphenylpiperazinium (DMPP) and a depolarizing concentration of KCl. Throughout an 8 day culture period, cells exhibited spontaneous fluctuations in [Ca2+]i. Comparisons of the number of cells exhibiting transients, the number and types of calcium transients, as well as the time during monitoring when transients occurred showed no significant differences between MF exposed cells and either sham exposed or nonexposed cells. With respect to the percentage of cells responding to DMPP, differences between 1 and 2 mT exposed cells and both nonexposed and sham exposed cells reached statistical significance during the first day in culture. No statistically significant differences were observed for responses to KCl. In summary, our data indicate that [Ca2+]i in chromaffin cells is unaffected by the specific 60 Hz MF intensities used in this study. On the other hand, plasma membrane nicotinic receptors may be affected in a manner that is important for ligand–receptor interactions. Bioelectromagnetics 23:557–567, 2002. © 2002 Wiley‐Liss, Inc.
Occupational exposures to high frequency electromagnetic fields in the intermediate range ( >300 Hz–10 MHz)
Authors: Floderus Birgitta , Stenlund Carin , Carlgren Frank 
Published: October 2002

AbstractThe aim of this study was to identify work situations with electromagnetic fields of 300 Hz–10 MHz and to characterize the occupational exposure. Work place investigations included descriptions of the work environment and physical measurements. We estimated electric (E) and magnetic (H) fields by spot measurements in air, by logged exposure data, and when possible, we recorded induced currents in limbs. The instruments used were Wandel and Golterman EFA‐3, NARDA 8718, Holaday HI‐3702. The exposure sources comprised five induction furnaces, seven induction heaters, one surface treatment equipment, four units of electronic article surveillance (EAS), and medical devices for surgery and muscle stimulation. The induction furnaces operated at 480 Hz–7 kHz, and the maximum values of logged data varied between 512–2093 V/m (E field) and 10.5–87.3 A/m (H field). The induction heaters (3.8 kHz–1.25 MHz) also showed high maximum exposure values of both E and H fields. Three EAS units, an electromagnetic plate at a library, a luggage control unit, and an antitheft gate, showed E fields reaching 658–1069 V/m. The H fields were comparatively lower, except for the antitheft gate (5 and 7.5 kHz) showing a maximum value of 27.2 A/m (recorded during repair). Induced currents of 5–13 mA were measured for the medical devices. The study improves the basis for an exposure assessment for epidemiological studies of long term effects of exposures to high frequency electromagnetic fields. Bioelectromagnetics 23:568–577, 2002. © 2002 Wiley‐Liss, Inc.
Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumor drug potency in a human adenocarcinoma cell line
Authors: Ruiz‐Gómez M.J. , de la Peña L. , Prieto‐Barcia M.I. , Pastor J.M. , Gil L. , Martínez‐Morillo M. 
Published: October 2002

AbstractThe resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA‐2/1cch. The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P < 0.01), exhibiting 6.1% of survival at 47.5 μg/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 μg/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P < 0.001). Cisplatin showed a significant reduction in the % of survival (44.2–39.1%,P < 0.05) at 25 Hz and 47.5 μg/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA‐2/1cch, with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation. Bioelectromagnetics 23:578–585, 2002. © 2002 Wiley‐Liss, Inc.
Cylindrical waveguide applicator for in vitro exposure of cell culture samples to 1.9‐GHz radiofrequency fields
Authors: Gajda G.B. , McNamee J.P. , Thansandote A. , Boonpanyarak S. , Lemay E. , Bellier P.V. 
Published: October 2002

AbstractAn applicator for in vitro cell culture exposure was developed based on a circularly polarized, cylindrical waveguide for the 1.9‐GHz frequency band used by Personal Communications Services (PCS) in Canada. The applicator consists of two coaxial Petri dishes that sit on the open end of the cylindrical waveguide. The inner 60‐mm Petri dish contains the cell culture while the outer 150‐mm dish contains coolant water, which is circulated from a pump. A dosimetric evaluation was made using thermometric and E‐field probe techniques. The latter allowed the entire inner dish to be scanned to determine the range of specific absorption rates (SARs) pertinent to the expected position of the cells. A representative SAR rate (SAR per unit of input power) of 8.6 ± 2.1 W/kg/W (95th percentile) was determined 1 mm from the bottom, for a 10 ml sample volume of standard medium. Evaluation of the cooling system demonstrated that following an initial 0.3 °C temperature increase, a constant temperature was maintained for 24 h when the waveguide was energized to achieve an average sample SAR of 10 W/kg. These properties enable both acute and sub‐acute in vitro bio‐effect studies to be performed on a variety of cell culture samples. Bioelectromagnetics 23:592–598, 2002. © 2002 Wiley‐Liss, Inc.
Immunomodulating action of low intensity millimeter waves on primed neutrophils
Authors: Safronova Valentina G. , Gabdoulkhakova A.G. , Santalov B.F. 
Published: October 2002

AbstractComparative investigation of the susceptibility of intact and primed neutrophils of the NMRI strain mice to low intensity millimeter wave (mm wave) irradiation (41.95 GHz) was performed. The specific absorption rate was 0.45 W/kg. Isolated neutrophils were primed by a chemotactic peptide N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) at a subthreshold concentration of 10 nM for 20 min, and then the cells were activated by 1 μM fMLP. Production of the reactive oxygen species (ROS) was estimated by the luminol dependent chemiluminescence technique. It was found that the preliminary mm wave irradiation of the resting cells at 20 °C did not act on the ROS production induced by the chemotactic peptide. The exposure of the primed cells results in a subsequent increase in the fMLP response. Therefore, the primed neutrophils are susceptible to the mm waves. Specific inhibitors of the protein kinases abolished the mm wave effect on the primed cells. The data indicate that protein kinases actively participate in transduction of the mm wave signal to effector molecules involved in neutrophil respiratory burst. Bioelectromagnetics 23:599–606, 2002. © 2002 Wiley‐Liss, Inc.
Exposure to power frequency magnetic fields and X‐Rays induces GAP‐43 gene expression in human glioma MO54 cells
Authors: Ding Gui‐Rong , Nakahara Takehisa , Miyakoshi Junji 
Published: October 2002

AbstractWe investigated the distribution and expression of growth associated protein‐43 (GAP‐43) in human glioma cells (MO54) after exposure to a magnetic field (60 Hz, 5 mT), with or without initial X‐ionizing radiation (2 Gy), by using immunocytochemistry and the reverse transcription polymerase chain reaction (RT‐PCR). GAP‐43 was present in the cytoplasm, accumulating in the perinuclear area. An increase in GAP‐43 expression was observed with a peak at 10 h at the mRNA level and at 12 h at the protein level, after exposure to the magnetic field. The increased level of GAP‐43 protein returned to a normal level within 24 h of exposure to a 5 mT magnetic field. The kinetic pattern of GAP‐43 expression induced by X‐ionizing radiation was very similar to that induced by the magnetic field. These results suggest that the stimulation of GAP‐43 expression could occur by a similar mechanism following exposure to X‐rays or magnetic fields. We have provided the first evidence that exposure to a 5 mT magnetic field can induce GAP‐43 gene expression in human glioma MO54 cells. Bioelectromagnetics 23:586–591, 2002. © 2002 Wiley‐Liss, Inc.
Effect of millimeter waves on cyclophosphamide induced suppression of the immune system
Authors: Logani Mahendra K. , Anga Altaf , Szabo Imre , Agelan Alexis , Irizarry Armando R. , Ziskin Marvin C. 
Published: October 2002

AbstractThe effect of millimeter electromagnetic waves (MWs) on cyclophosphamide (CPA) induced toxicity to leukocytes, bone marrow cells, and T‐cell‐mediated immunity was examined. For studying the effect of MWs on CPA induced leukopenia and myelosuppression, BALB/C mice were irradiated for 3 days, 30 min each day, prior to administration of CPA (200 mg/kg). MWs were produced with a Russian made YAV‐1 generator. The device produced 42.2 ± 0.2 GHz modulated wave radiation through a 10 mm × 20 mm rectangular output horn. The animals were irradiated on the nose area. Peak SAR and incident power density were measured as 622 ± 100 W/kg and 31 ± 5 mW/cm2, respectively. For studying the effect of MWs on CPA induced suppression of T‐cell mediated immunity, a delayed type hypersensitivity (DTH) assay in mouse skin was used. The DTH reaction in mouse skin was induced by topical application of dinitrochlorobenzene (DNCB) and quantified by measuring the increase in ear thickness and by histological examination. Treatment of animals with CPA significantly (P < 0.05) reduced leukocyte and bone marrow cell population, but MW irradiation did not show any significant protection from the immunosuppressive effects of CPA. Furthermore, MW irradiation did not protect the animals from CPA induced suppression of T‐cell mediated immunity. Bioelectromagnetics 23:614–621, 2002. © 2002 Wiley‐Liss, Inc.
Orientation of Paramecium swimming in a DC magnetic field
Authors: Nakaoka Yasuo , Takeda Ryutaro , Shimizu Kikuo 
Published: October 2002

AbstractWe found that a ciliated protozoan, Paramecium, swam perpendicular to a static (DC) magnetic field (0.68 T). The swimming orientation was similar even when the ionic current through the cell membrane disappeared after saponin treatment. To determine the diamagnetic anisotropy of intracellular organs, macronuclei, cilia, and secretory vesicles, trichocysts, were selectively isolated. Both cilia and trichocysts tended to align their long axis parallel to the magnetic field (0.78 T). Paramecium mutants that lack trichocysts also swam perpendicular to the magnetic field, although the proportion fraction was smaller than the normal population. Since large numbers of cilia and trichocysts are arranged at right angles to the long axis of the cell, the diamagnetic anisotropies of cilia and trichocysts cause the long axis of the cell to align perpendicular to the magnetic field. In contrast to the DC magnetic field, an alternative (AC) magnetic field (60 Hz, 0.65 T) had almost no effect on the swimming orientation of Paramecium. Bioelectromagnetics 23:607–613, 2002. © 2002 Wiley‐Liss, Inc.
Thermal noise limit on the sensitivity of cellular membranes to power frequency electric and magnetic fields
Authors: Kaune W.T. 
Published: October 2002

AbstractSeveral authors have concluded that thermal electromagnetic noise will be of sufficient magnitude to overwhelm electric and/or magnetic fields induced by environmentally generated, power frequency electric and magnetic fields in the membranes of living cells located in the bodies of humans. Yet, there are research reports that indicate that living cells may respond to power frequency electric and/or magnetic field levels well below the limits set by these thermal noise arguments. The purpose of this study is to suggest that published thermal arguments may not make a full accounting of all membrane force fields of thermal origin, and that when such an accounting is made, the net thermal noise fields may be smaller in the power frequency range than previously thought. If this analysis is correct, there may be no thermal noise barrier that precludes the possibility of cellular membranes of human cells responding to environmental levels of power frequency electric or magnetic fields. Bioelectromagnetics 23:622–628, 2002. © 2002 Wiley‐Liss, Inc.
Ab initio calculations for the optical rotations of conformationally flexible molecules: A case study on six‐, seven‐, and eight‐membered fluorinated cycloalkanol esters
Authors: Grimme Stefan , Bahlmann Arnold , Haufe Günter 
Published: October 2002

AbstractBased on the time‐dependent density functional response theory, an approach for the prediction of optical rotations of enantiomers of conformationally flexible molecules was developed. The method was applied successfully for the determination of the absolute configuration oftrans‐2‐fluorocycloalkanol acetates with different ring rizes. The largest deviations between experimental and theoretical [α]Dvalues are10 deg. · [dm · (g/cc)]−1(about 20% error). These theoretical results suggest that the optical rotation in these molecules is dominated by the local (1R;2R) configuration of the two substituents and that different ring and even axial/equatorial orientations play a less important role. Chirality 14:793–797, 2002. © 2002 Wiley‐Liss, Inc.
Liquid chromatographic retention behavior and enantiomeric separation of three chiral center β‐blocker drug (nadolol) using heptakis (6‐azido‐6‐deoxy‐2, 3‐di‐O‐phenylcarbamolyted) β‐cyclodextrin bonded chiral stationary phase
Authors: Wang Xin , Ching Chi Bun 
Published: October 2002

AbstractNadolol, a β‐blocker used in the management of hypertension and angina pectoris, has three chiral centers and is currently marketed as an equal mixture of its four stereoisomers. Enantiomeric separation of nadolol by high‐performance liquid chromatography was studied on a column packed with novel heptakis (6‐azido‐6‐deoxy‐2, 3‐di‐O‐phenylcarbamolyted) β‐cyclodextrin bonded chiral stationary phase. The retention behavior and resolution of nadolol enantiomers were investigated and discussed with respect to the mobile phase composition and flow rate, pH, ionic strength, and temperature. The optimal separation condition was found; the mobile phase contained 80% buffer solution (1% triethylamine acetate, pH 5.5) and 20% methanol with 0.3 ml/min mobile phase flow rate at a temperature of 20°C. At the optimal conditions, resolution of three stereoisomers of nadolol was obtained with a complete separation of the most active enantiomer, (RSR)‐nadolol. Thermodynamic properties including enthalpy and entropy change of binding to the CSP for the enantiomeric separation were also determined. Chirality 14:798–805, 2002. © 2002 Wiley‐Liss, Inc.
Recent development of asymmetric syntheses based on the Meerwein‐Ponndorf‐Verley reduction
Authors: Nishide Kiyoharu , Node Manabu 
Published: October 2002

AbstractStereoselective Meerwein‐Ponndorf‐Verley (MVP) reductions, including intermolecular MPV reductions, intramolecular MPV reductions (asymmetric 1,5‐ and 1,7‐hydride shifts), catalytic MPV reduction, and reactions related to the MPV reduction are reviewed from the standpoint of asymmetric synthesis. Chirality 14:759–767, 2002. © 2002 Wiley‐Liss, Inc.