bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of synaptic proteins in the developing rat cerebellum following ionizing radiation
Authors: Goutan E. , Martı́ E. , Ferrer I. 
Published: February 2003

AbstractVarious proteins regulating neurotransmission release and synaptic vesicle exocytosis have been implicated in axonal elongation and synaptic maturation. In the present study, immunohistochemistry to the presynaptic membrane proteins syntaxin‐I and synaptosomal‐associated protein of 25 kDa (SNAP‐25), synaptic vesicle‐associated proteins synaptophysin and synapsin‐I and the neuronal maturation and axonal growth‐related protein GAP‐43, has been carried out in the normal developing cerebellum and following a single dose of ionizing radiation (2 Gy gamma‐rays) at postnatal day 1. Our aim has been to learn about the morphological and possible functional modalities that occur during the progression of neuronal connectivity in normal and abnormal development. Expression of all these proteins is associated with the arrival of afferents in the subcortical white matter and with the maturation of the internal granule cell layer and molecular layer during normal development. In addition, SNAP‐25 and GAP‐43 are strongly expressed in granule cells of the external granule cell layer, thus suggesting that these proteins are involved in cell elongation of granule cells. Apoptosis appears at 3 h and peaks at 6 h following ionizing radiation. Radiation‐induced apoptosis in the external granule cell layer produces a transient decrease in the expression of SNAP‐25 and GAP‐43 in the external granule cell layer. The external granule cell layer recovers at 48 h and external granule cells of proliferating cells also express SNAP‐25 and GAP‐43, thus indicating that proliferating cells in this layer are equipped with proteins involved in cell elongation. Furthermore, expression of synaptophysin, synapsin‐I, syntaxin‐I and SNAP‐25 is the same in the cerebellum of irradiated and normal rats from this time to adulthood (3 months). These results point to the likelihood that recovery of the cerebellar cortex occurs following a single exposure of ionizing radiation during postnatal development.
The effect of chelerythrine on depolarization‐induced force responses in skinned fast skeletal muscle fibres of the rat
Authors: Han Renzhi , Bakker Anthony J 
Published: February 2003

We examined the effect of the protein kinase C (PKC) inhibitor chelerythrine on depolarization‐induced force responses (DIFRs) and sarcoplasmic reticulum (SR) function in single, mechanically skinned skeletal muscle fibres of the rat.
In this study, the DIFRs in the skinned fibres normally underwent an irreversible loss of excitation‐contraction coupling (ECC) after 10–15 responses. Chelerythrine (12 μM) was shown to restore ECC in these fibres. Restored force responses were similar in peak (control 50.8±6.4%, chelerythrine 56.9±12.4% of maximum force, P=0.42, n=21), but significantly broadened compared to initial control responses (full‐width at half maximum, control; 3.7±0.3 s, chelerythrine; 13.3±1.1 s, P<0.001). Early exposure to chelerythrine prevented run‐down of DIFRs. Chelerythrine also induced spontaneous force responses in some fibres.
The PKC inhibitors calphostin C and staurosporine did not restore ECC, and the PKC activator phorbol 12‐myristate 13‐acetate did not promote loss of ECC in the skinned fibres.
Chelerythrine significantly increased SR Ca2+ loading by 8.4±1.7% (P=0.02, n=9) and SR Ca2+ release by at least 14.1±2.7% (P=0.004, n=11) in the skinned fibres.
Chelerythrine had no significant effect on maximum force production or the [Ca2+] producing half maximal activation of the myofilaments. However, chelerythrine did have a small effect on the slope of the force‐Ca2+ relationship (P=0.02, n=10).
Chelerythrine reverses the use‐dependent loss of excitation‐contraction coupling in skinend skeletal muscle fibres by a PKC independent pathway. Chelerythrine may be an important pharmacological probe for examining the mechanisms of contraction‐induced muscle injury.

British Journal of Pharmacology (2003) 138, 417–426. doi:10.1038/sj.bjp.0705035
Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2‐(2‐benzofuranyl)‐2‐imidazoline in rat locus coeruleus neurons
Authors: Ruiz‐Durántez Eduardo , Torrecilla María , Pineda Joseba , Ugedo Luisa 
Published: February 2003

The aim of this study was to determine if 2‐(2‐benzofuranyl)‐2‐imidazoline (2‐BFI) interacts with the opioid system in the rat locus coeruleus, using single‐unit extracellular recordings.
In morphine‐dependent rats, acute administration of the selective imidazoline receptor ligands 2‐BFI (10 and 40 mg kg−1, i.p. and 100 μg, i.c.v.) or valldemossine (10 mg kg−1, i.p.) did not modify the naloxone‐induced hyperactivity of locus coeruleus neurons compared with that observed in the morphine‐dependent control group.
After chronic administration of 2‐BFI (10 mg kg−1, i.p., three times daily, for 5 days) and morphine, naloxone‐induced hyperactivity and tolerance to morphine were attenuated. This effect was not observed when a lower dose of 2‐BFI (1 mg kg−1, i.p.) or valldemossine (10 mg kg−1, i.p.) were used.
Acute administration of 2‐BFI (10 and 40 mg kg−1, i.p. and 100 μg, i.c.v.) but not valldemossine (40 mg kg−1, i.p.) diminished the potency of morphine to inhibit locus coeruleus neuron activity in vivo (ED50 values increased by 2.3, 2.9; and 3.1 fold respectively). Similarly, the potency of Met5‐enkephalin to inhibit locus coeruleus neurons was decreased when 2‐BFI (100 μM) was applied to rat brain slices (EC50 increased by 5.6; P<0.05).
The present data demonstrate that there is an interaction between 2‐BFI and the opioid system in the locus coeruleus. This interaction leads to an attenuation of both the hyperactivity of locus coeruleus neurons during opiate withdrawal and the development of tolerance to morphine when 2‐BFI is chronically administered. These results suggest that imidazoline drugs may prove to be useful agents for the management of opioid dependence and tolerance.

British Journal of Pharmacology (2003) 138, 494–500. doi:10.1038/sj.bjp.0705052
RSD931, a novel anti‐tussive agent acting on airway sensory nerves
Authors: Adcock J J , Douglas G J , Garabette M , Gascoigne M , Beatch G , Walker M , Page C P 
Published: February 2003

The anti‐tussive effects, of the local anaesthetic, lidocaine and carcainium chloride (RSD931) have been investigated in guinea‐pigs and rabbits.
Pre‐treatment of guinea‐pigs with aerosols of lidocaine or RSD931 at 0.1, 1.0 and 10 mg ml−1 reduced the number of citric acid‐induced coughs by 9.3, 32.6 and 40.9% (P>0.05) for lidocaine and by 25.3% (P>0.05), 40.4% (P>0.05) and 97.6% (P<0.01) for RSD931, respectively and increased the latency to onset of cough at 10.0 mg ml−1 only. In addition, RSD931 at 10 mg ml−1 reduced citric acid‐evoked cough responses in rabbits (with prior exposure to ozone at 3 p.p.m. for 1 h) from 22.1±5.1 to 2.7±0.9 coughs (P<0.01).
Acute pre‐treatment of guinea‐pigs with aerosols of lidocaine or RSD931 at 10.0 and 30.0 mg ml−1 reduced the number of capsaicin‐evoked coughs by 42.2 and 10.3% (P>0.05) (lidocaine) and by 25% (P>0.05) and 76.9% (P<0.01) (RSD931), respectively. Lidocaine had little effect on the latency of cough onset at either 10.0 or 30.0 mg ml−1, however, RSD at 30.0 mg ml−1 significantly (P<0.05) prolonged the latency of cough onset.
RSD931 (10.0 mg ml−1) significantly (P<0.05–<0.01) reduced the spontaneous and histamine‐evoked discharges in Aδ‐fibres originating from airway, rapidly adapting stretch receptors (RARs) without affecting histamine‐evoked bronchoconstriction. Lidocaine at 10.0 mg ml−1 also significantly (P<0.05) inhibited the spontaneous and histamine‐induced discharges of RARs without affecting histamine‐evoked bronchoconstriction.
Aerosols of RSD931 (10.0 mg ml−1) caused a transient, but significant (P<0.05), activation of pulmonary C‐fibre endings 2.5 min after administration started. RSD931 had no significant (P>0.05) effects on discharges in bronchial C‐fibres originating from bronchial C‐fibre endings, capsaicin‐evoked discharges of either pulmonary or bronchial C‐fibre endings or on capsaicin‐evoked bronchoconstriction. In contrast, lidocaine (10.0 mg ml−1) significantly (P<0.05) inhibited spontaneous and capsaicin‐induced discharges in both pulmonary and bronchial C‐fibres respectively. Lidocaine also significantly (P<0.05) reduced capsaicin‐evoked bronchoconstriction.
These studies suggest that the anti‐tussive actions of RSD931 are mediated via inhibition of discharges in Aδ‐fibres originating from airway RARs. The mechanism of action of RSD931 is distinct from that of the local anaesthetic lidocaine and RSD931 may represent a novel class of anti‐tussive agent.

British Journal of Pharmacology (2003) 138, 407–416. doi:10.1038/sj.bjp.0705056
A unique phenotype of 5‐HT2C, agonist‐induced GTPγ35S binding, transferable to 5‐HT2A and 5‐HT2B, upon swapping intracellular regions
Authors: Alberts Glen L , Chio Christopher L , Im Wha Bin , Slightom Jerry L 
Published: February 2003

The human 5‐HT2C receptor, when expressed heterologously in various mammalian cell lines (HEK293, SH‐EP and NIH‐3T3) at various receptor densities (6 to 45 pmol mg−1 protein), mediates robust agonist‐induced GTPγ35S binding from coupling to Gi subtypes of G proteins, in addition to Gq/11. Such a phenotype, however, was not seen with the human 5‐HT2A and 5‐HT2B receptors, indicating their common pathway with 5‐HT2C limited to Gq/11, not including Gi.
Because intracellular regions are largely responsible for signalling pathways, we prepared the chimeras of the 5‐HT2A and 5‐HT2B receptors where the second and third intracellular loops, and the C‐terminal region were replaced with the 5‐HT2C counterparts.
The chimeras showed robust agonist‐induced GTPγ35S binding. Relative intrinsic efficacies of agonists from the GTPγ35S binding were nearly identical to the reported values for their parent receptors as measured with Ca2+ or [3H]‐inositol phosphate accumulation. Also the chimeras displayed the same ligand‐binding properties as the parent receptors.
We conclude that the phenotype of agonist‐induced GTPγ35S binding is unique to 5‐HT2C among the 5‐HT2 receptor family, and is transferable to 5‐HT2A and 5‐HT2B, upon swapping intracellular sequences, without altering their receptor pharmacology.

British Journal of Pharmacology (2003) 138, 427–434. doi:10.1038/sj.bjp.0705058
Contribution of Na+‐Ca2+ exchanger to pinacidil‐induced relaxation in the rat mesenteric artery
Authors: Tsang Suk Ying , Yao Xiaoqiang , Wong Chi Ming , Au Chak Leung , Chen Zhen Yu , Huang Yu 
Published: February 2003

Pinacidil relaxes blood vessels through opening the KATP channels with a resultant membrane hyperpolarization and inhibition of Ca2+ influx. The aim of this study was to examine the mechanisms thereby pinacidil induces K+ channel‐independent relaxation in isolated endothelium‐denuded rat mesenteric artery.
Pinacidil‐induced relaxation was inhibited by glibenclamide (1–10 μM) in phenylephrine‐preconstricted rings, but was unaffected by glibenclamide after inhibition of K+ channels and VGCCs. Pinacidil‐induced K+ channel‐independent relaxation remained unchanged after treatment with cyclopiazonic acid (10 μM), thapsigargin (1 μM), ouabain (100 μM), propranolol (10 μM), Rp‐cAMPS triethylamine (30 μM), L‐NNA (100 μM), or ODQ (10 μM).
Pinacidil induced more relaxant effect in the presence of nifedipine than in the presence of 60 mM K+ plus nifedipine. Pretreatment with Na+‐Ca2+ exchanger inhibitors, nickel (30–300 μM) or benzamil (20 μM) attenuated pinacidil‐induced relaxation in normal or in nifedipine‐containing solution. Pinacidil (1 μM) produced less relaxant effect with decreasing extracellular Na+ concentration. Na+‐free condition abolished the inhibitory effect of benzamil. Both nickel and benzamil inhibited pinacidil‐induced relaxation in the presence of glibenclamide (10 μM). Nickel (300 μM) did not affect the relaxant response to sodium nitroprusside.
Pinacidil relaxed the rings preconstricted by active phorbol and U46619 with similar potency.
The present results indicate that stimulation of the forward mode Na+‐Ca2+ exchange pathway is in part responsible for pinacidil‐induced K+ channel‐independent vasorelaxation. Pinacidil also induces K+ channel‐dependent but VGCCs‐independent relaxation. The PKC‐mediated cellular pathway may be a target site for pinacidil only in higher concentrations.

British Journal of Pharmacology (2003) 138, 453–460. doi:10.1038/sj.bjp.0705062
The preferential β3‐adrenoceptor agonist BRL 37344 increases force viaβ1‐/β2‐adrenoceptors and induces endothelial nitric oxide synthase viaβ3‐adrenoceptors in human atrial myocardium
Authors: Pott C , Brixius K , Bundkirchen A , Bölck B , Bloch W , Steinritz D , Mehlhorn U , Schwinger R H G 
Published: February 2003

The present study investigated the effects of the preferential β3‐AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca2+‐transient and eNOS‐activity in human right atrial myocardium.
BRL concentration‐dependently caused an increase in FOC that was paralleled by an increase in Ca2+‐transient and a shortening of time to half peak relaxation (T0.5T). These effects were abolished in the presence of propranolol (0.3 μM).
BRL acted as a competitive antagonist towards isoprenaline and in binding experiments it was shown to have a distinct affinity towards β1/2‐AR.
In immunohistochemical experiments BRL (10 μM) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 μM).
BRL increased directly detected NO in DAF‐staining experiments. This increase was significantly smaller in the presence of the NO‐inhibitor L‐NAME.
The inotropic effects of BRL were not changed in the presence of L‐NMA.
These results suggest that the inotropic effects of BRL in human atrium are mediated via β1/2‐AR, whereas the increase of atrial eNOS‐activity is due to β3‐ adrenergic stimulation. This increase in eNOS‐activity did not influence atrial myocardial contractility. In conclusion, this study shows that β3‐adrenergic stimulation is present in human atrium, but may not be functionally as significant as in the left ventricle.

British Journal of Pharmacology (2003) 138, 521–529. doi:10.1038/sj.bjp.0705065
Knowledge Partitioning in the Interfirm Division of Labor: The Case of Automotive Product Development
Authors: Takeishi Akira 
Published: February 2003

Drawing on an empirical study on automakers' management of supplier involvement in product development in Japan, this paper shows that when the design of a component is outsourced to a supplier, how much automakers know about the component matters for them to gain a better outcome. While the actual tasks of designing and manufacturing components could be out-sourced, automakers should retain the relevant knowledge to obtain better component design quality. The paper argues that knowledge partitioning should be distinguished from task partitioning, and provides some implications for the knowledge-based theory of the firm.The results indicate that effective pattern of knowledge partitioning differs by the nature of component development project in terms of technological newness. For regular projects, it is more important for the automaker to have a higher level of architectural knowledge (how to coordinate various components for a vehicle) than of component-specific knowledge, which is supposed to be provided by the supplier. However, when the project involves new technology for the supplier, it is important for the automaker to have a higher level of component-specific knowledge to solve unexplored engineering problems together with the supplier. In innovative projects, effective knowledge partitioning seems to demand some overlap between an automaker and a supplier, rather than efficient and clear-cut boundaries that are optimal for regular projects. Such “fluid” nature of knowledge boundaries contingent on the project types poses a challenge for firms seeking both technological leadership and efficiency in established products.Developing and maintaining knowledge about an outsourced component is by no means easy. When the actual design tasks are outsourced, automakers miss substantial opportunities to gain relevant knowledge through learning by doing. Also, obtained knowledge may be diffused among competitors through shared suppliers. Another problem for automakers is that component-specific knowledge is important for only limited cases (innovative projects). Even worse, component-specific knowledge has a trade off relationship with architectural knowledge.Such an inherent dilemma of managing knowledge, however, may provide some automakers with the opportunity to achieve sustainable competitive advantage. Additional analysis shows that one automaker managed both types of knowledge better than others in a manner that deals effectively with the dilemma. Its organizational mechanisms include career development policies, extensive documentation of technological information, internal training programs, and incentive schemes. The difficulty in implementing those mechanisms in a consistent and complementary manner seems to explain why there was a significant variance among automakers in knowledge level, even when the actual tasks were carried out by a shared supplier.
Intercalation of 8-Hydroxyquinoline into Al-Smectites by Solid-Solid Reactions
Authors: Khaorapapong Nithima , Kuroda Kazuyuki , Ogawa Makoto 
Published: February 2003

AbstractTris(8-hydroxyquinoline)aluminum (III) complexes (Alq3), one of the molecules studied most widely for organic light-emitting devices, were formed in the interlayer spaces of smectites by solid-solid reactions between Al-smectites (Al-montmorillonite and Al-synthetic saponite (Sumecton)) and 8-hydroxyquinoline (8Hq) at room temperature. The intercalation of 8-hydroxyquinoline molecules into Al-smectites was demonstrated by powder XRD, FTIR, DTA, TG, TG-MS, and chemical analysis. The coordination of the ligand to the interlayer Al cations was proved by FTIR, UV-Vis, and photoluminescence spectroscopies. The luminescence intensity of Alq3-Sumecton was much greater than that of Alq3-montmorillonite, and this was ascribed to the very small amount of quenching impurities in Sumecton.
Expansion of Smectite by Hexadecyltrimethylammonium
Authors: Lee Seung Yeop , Kim Soo Jin 
Published: February 2003

AbstractThe adsorption of hexadecyltrimethylammonium (HDTMA) in smectite was studied by adsorption isotherms, X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM). Smectites that had reacted for 48 h with HDTMA cations equivalent to 0.2–3.0 times the cation exchange capacity (CEC) were converted to HDTMA-exchanged smectites with various d-spacings. Study of HDTMA-smectites by HRTEM suggests that the HDTMA adsorption results in interlayer expansion with various d-spacings and irregular wavy layer structures. We believe that HDTMA loading beyond the CEC of smectite affects the structure of clay by the additional adsorption of HDTMA-Br− via hydrophobic bonding. Surfactant orientation probably depends on the quantity of surfactant in the interlayer. Our TEM study shows that the structure of the adsorbed HDTMA layer in the interlayers of smectite depends on the charge distribution and chemical composition of smectite.
Visible Spectroscopy of Cationic Dyes in Dispersions with Reduced-Charge Montmorillonites
Authors: Bujdák Juraj , Iyi Nobuo 
Published: February 2003

AbstractThe aggregation behavior of one azine and three triphenylmethane cationic dyes in dispersions of reduced-charge montmorillonites (RCMs) was investigated. The extent and types of dye aggregation were monitored using visible spectroscopy. Similar relationships between dye aggregation and layer charge were observed, independent of the structure of the dye cations. High charge-density surfaces induced the formation of H-aggregates, with a face-to-face association between the dye cations that then absorb light at relatively lower wavelengths. Moderate reductions in layer charge were reflected in the lowering of the H-aggregation in favor of monomers, dimers and less densely-packed J-aggregates, absorbing light at higher wavelengths. Dye spectra in the presence of the lowest-charge RCMs resembled those of dilute dye solutions, indicating the absence of dye aggregation of any type in this case. The relationship between dye spectral changes and layer-charge densities of smectites is a general phenomenon which can potentially be used to estimate the layer charge of smectites. However, applying this method to triphenylmethane dyes, which have structurally more complicated cations, may reduce the sensitivity of the probe.
Infrared Study of Reduced and Reduced-Reoxidized Ferruginous Smectite
Authors: Fialips Claire-Isabelle , Huo Dongfang , Yan Laibin , Wu Jun , Stucki Joseph W. 
Published: February 2003

AbstractOxidation-reduction processes within natural systems greatly influence the properties of sediments, soils and clays. The objective of this experimental study was to gather new evidence for the effects of changes in redox conditions (reduction and reoxidation) on structural properties of ferruginous smectite and to understand better the mechanisms involved. The <2 µm fraction of a ferruginous smectite (sample SWa-1), which contains 17.3 wt.% of total structural Fe, was studied by infrared (IR) spectroscopy. The pure Na-saturated clay was reduced by Na dithionite for 10 to 240 min to obtain various Fe(II):(total Fe) ratios ranging from 0 to 1.0. Selected reduced samples were then reoxidized completely by bubbling O2 gas through the suspensions for up to 12 h. Infrared spectra of the initially unaltered, reduced and reduced-reoxidized samples were collected. Reduction generated changes in the three studied spectral regions (O-H stretching, M-O-H deformation, and Si-O stretching), indicating that major modifications occurred within the clay crystal beyond merely a change in Fe oxidation state. partial dehydroxylation and redistribution of Fe, and perhaps Al, cations occurred upon reduction of SWa-1, changing the structural properties of its tetrahedral and octahedral sheets. Water molecules, probably generated by dehydroxylation within the octahedral sheet upon reduction, were tightly bound to the clay surface and were possibly trapped within the clay structure. Except for dehydroxylation and the Fe oxidation state, all these modifications were largely irreversible. The tightly bound water was not completely removed upon reoxidation and the cationic rearrangements generated during reduction were not reversed: either they were preserved as in the reduced state or cations were redistributed into a different configuration from the unreduced clay.