bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre‐ and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons
Authors: Cheng Gong , Kendig Joan J 
Published: January 2005

A common anaesthetic endpoint, prevention of withdrawal from a noxious stimulus, is determined primarily in spinal cord, where glycine is an important inhibitory transmitter. To define pre‐ and postsynaptic anaesthetic actions at glycinergic snyapses, the effects of volatile anaesthetic agents on spontaneous and evoked glycinergic currents in spinal cord motor neurons from 6 – 14‐day old rats was investigated.
The volatile anaesthetic agents enflurane, isoflurane and halothane significantly increased the frequency of glycinergic mIPSCs, enflurane to 190.4% of control±22.0 (mean±s.e.m., n=7, P<0.01), isoflurane to 199.0%±28.8 (n=7, P<0.05) and halothane to 198.2%±19.5 (n=7, P<0.01). However without TTX, isoflurane and halothane had no significant effect and enflurane decreased sIPSC frequency to 42.5% of control±12.4 (n=6, P<0.01). All the anaesthetics prolonged the decay time constant (τ) of both spontaneous and glycine‐evoked currents without increasing amplitude. With TTX total charge transfer was increased; without TTX charge transfer was unchanged (isoflurane and halothane) or decreased (enflurane).
Enflurane‐induced mIPSC frequency increases were not significantly affected by Cd2+ (50 μM), thapsigargin (1 – 5 μM), or KB‐R7943 (5 μM). KB‐R7943 and thapsigargin together abolished the enflurane‐induced increase in mIPSC frequency.
There are opposing facilitatory and inhibitory actions of volatile anaesthetics on glycine release dependent on calcium homeostatic mechanisms and sodium channels respectively. Under normal conditions (no TTX) the absolute amount of glycinergic inhibition does not increase. The contribution of glycinergic inhibition to anaesthesia may depend on its duration rather than its absolute magnitude.

British Journal of Pharmacology (2002) 136, 673–684; doi:10.1038/sj.bjp.0704760
Comparison of the expression of calcitonin receptor‐like receptor (CRLR) and receptor activity modifying proteins (RAMPs) with CGRP and adrenomedullin binding in cell lines
Authors: Choksi Tejal , Hay Debbie L , Legon Stephen , Poyner David R , Hagner Stefanie , Bloom Stephen R , Smith David M 
Published: January 2005

The calcitonin receptor‐like receptor (CRLR) and specific receptor activity modifying proteins (RAMPs) together form receptors for calcitonin gene‐related peptide (CGRP) and/or adrenomedullin in transfected cells.
There is less evidence that innate CGRP and adrenomedullin receptors are formed by CRLR/RAMP combinations. We therefore examined whether CGRP and/or adrenomedullin binding correlated with CRLR and RAMP mRNA expression in human and rat cell lines known to express these receptors. Specific human or rat CRLR antibodies were used to examine the presence of CRLR in these cells.
We confirmed CGRP subtype 1 receptor (CGRP1) pharmacology in SK‐N‐MC neuroblastoma cells. L6 myoblast cells expressed both CGRP1 and adrenomedullin receptors whereas Rat‐2 fibroblasts expressed only adrenomedullin receptors. In contrast we could not confirm CGRP2 receptor pharmacology for Col‐29 colonic epithelial cells, which, instead were CGRP1‐like in this study.
L6, SK‐N‐MC and Col‐29 cells expressed mRNA for RAMP1 and RAMP2 but Rat‐2 fibroblasts had only RAMP2. No cell line had detectable RAMP3 mRNA.
SK‐N‐MC, Col‐29 and Rat‐2 fibroblast cells expressed CRLR mRNA. By contrast, CRLR mRNA was undetectable by Northern analysis in one source of L6 cells. Conversely, a different source of L6 cells had mRNA for CRLR. All of the cell lines expressed CRLR protein. Thus, circumstances where CRLR mRNA is apparently absent by Northern analysis do not exclude the presence of this receptor.
These data strongly support CRLR, together with appropriate RAMPs as binding sites for CGRP and adrenomedullin in cultured cells.

British Journal of Pharmacology (2002) 136, 784–792; doi:10.1038/sj.bjp.0704761
Elevated mean arterial pressure in the ovariectomized rat was normalized by ETA receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis
Authors: Mercier Isabelle , Pham‐Dang Mylan , Clement Robert , Gosselin Hugues , Colombo Federico , Rouleau Jean‐Lucien , Calderone Angelino 
Published: January 2005

The influence of menopause on ventricular function and remodelling remains undefined. The following study examined the effect of ovariectomy on ventricular contractility, cardiac hypertrophy and extracellular matrix protein expression.
Elevated circulating levels of the vasoconstrictor endothelin‐1 have been reported in post‐menopausal women. Moreover, endothelin‐1 has been shown to influence blood pressure, ventricular function and cardiac remodelling. In this regard, the potential pathophysiological role of endothelin‐1 in the ovariectomized rat was assessed via the administration of the selective endothelinA receptor (ETA) antagonist BMS‐182874.
In 3 and 6 week ovariectomized female Sprague – Dawley rats, uterus atrophy was associated with a significant increase in mean arterial pressure, and left ventricular systolic pressure, as compared to sham. By contrast, right ventricular contractile indices were normal in the ovariectomized rat. Despite increased systolic load, left ventricular hypertrophy was not evident, prepro‐atrial natriuretic peptide (prepro‐ANP) mRNA levels and collagen protein content were similar to sham.
The treatment of ovariectomized rats with BMS‐182874 (60 mg kg−1 per day) did not reverse uterus atrophy. However, BMS‐182874 normalized mean arterial pressure, and left ventricular systolic pressure in the ovariectomized rat.
Thus, despite elevated blood pressure, ovariectomized rats were not associated with either cardiac hypertrophy or fibrosis. Lastly, endothelin‐1, acting via the stimulation of the ETA receptor represents an integral mechanism implicated in the increase of mean arterial pressure following ovariectomy.

British Journal of Pharmacology (2002) 136, 685–692; doi:10.1038/sj.bjp.0704765
The anti‐epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA‐ and glycine‐gated currents
Authors: Rigo J‐M , Hans G , Nguyen L , Rocher V , Belachew S , Malgrange B , Leprince P , Moonen G , Selak I , Matagne A , Klitgaard H 
Published: January 2005

In this studyin vitroandin vivoapproaches were combined in order to investigate if the anti‐epileptic mechanism(s) of action of levetiracetam (LEV; Keppra®) may involve modulation of inhibitory neurotransmission.GABA‐ and glycine‐gated currents were studiedin vitrousing whole‐cell patch‐clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessedin vivoin sound‐susceptible mice. The effect of LEV was compared with reference anti‐epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide.LEV contrasted the reference AEDs by an absence of any direct effect on glycine‐gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA‐gated currents. A similar action on GABA‐elicited currents was observed with the reference AEDs, except ethosuximide.These minor direct effects contrasted with a potent ability of LEV (EC50=1 – 10 μM) to reverse the inhibitory effects of the negative allosteric modulators zinc and β‐carbolines on both GABAAand glycine receptor‐mediated responses.Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of β‐carbolines on GABA‐gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine‐gated currents and only clonazepam and phenobarbital inhibited the action of DMCM.LEV (17 mg kg−1) produced a potent suppression of sound‐induced clonic convulsions in mice. This protective effect was significantly abolished by co‐administration of the β‐carboline FG 7142, from a dose of 5 mg kg−1. In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg−1) was without any effect on the protection afforded by LEV.The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti‐epileptic mechanism(s) of action of LEV.British Journal of Pharmacology(2002)136, 659–672; doi:10.1038/sj.bjp.0704766
Docosahexaenoic acid potentiates interleukin‐1β induction of nitric oxide synthase through mechanism involving p44/42 MAPK activation in rat vascular smooth muscle cells
Authors: Hirafuji Masahiko , Machida Takuji , Tsunoda Marito , Miyamoto Atsushi , Minami Masaru 
Published: January 2005

The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and inducible NO synthase (iNOS) expression induced by interleukin (IL)‐1β, and whether the effect of DHA is related to its effect on mitogen‐activated protein kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle cells (VSMCs).
DHA and eicosapentaenoic acid (EPA), although less potent, increased the NO production induced by IL‐1β (3 ng ml−1) in a concentration‐dependent manner (3–30 μM) Arachidonic acid had no significant effect. The stimulatory effect of DHA (30 μM) on the NO production was more obvious at lower concentrations of IL‐1β.
IL‐1β induced iNOS protein and mRNA expressions, which were significantly potentiated by DHA. EPA (30 μM) had a tendency to increase the iNOS protein and mRNA expressions, but arachidonic acid had no effect.
IL‐1β‐induced iNOS protein expression was significantly inhibited by PD 98059 (10 μM), a selective inhibitor of p44/42 MAPK kinase, both in the absence and the presence of DHA. SB 203580 (10 μM), a selective inhibitor of p38 MAPK activity, had no significant effect, although had a tendency to inhibit slightly.
IL‐1β increased the phosphorylation of p44/42 MAPK, while it did not apparently increase the phosphorylation of p38 MAPK. DHA significantly potentiated the IL‐1β‐induced phosphorylation of p44/42 MAPK, while it had no significant effect on the phosphorylation of p38 MAPK.
These results suggest that DHA increases NO production by potentiating iNOS expression induced by IL‐1β through mechanism involving p44/42 MAPK signalling cascade in rat VSMCs. The present study may contribute to the understanding of basic mechanisms underlying the beneficial effects of DHA on various cardiovascular disorders.

British Journal of Pharmacology (2002) 136, 613–619; doi:10.1038/sj.bjp.0704768
Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts
Authors: Scaffidi Amelia K , Mutsaers Steven E , Moodley Yuben P , McAnulty Robin J , Laurent Geoffrey J , Thompson Philip J , Knight Darryl A 
Published: January 2005

Oncostatin M (OSM), a member of the interleukin‐6 (IL‐6) cytokine family, acts on a variety of cells and elicits diversified biological responses, suggesting potential roles in the regulation of cell survival, differentiation and proliferation.
We have examined the effect of OSM on the regulation of human lung fibroblast proliferation, collagen production and spontaneous apoptosis. The proliferative effects of OSM (0.5 – 100 ng ml−1) were assessed using a MTS assay as well as [3H]‐thymidine incorporation and cell counts at 24 and 48 h. Hydroxyproline was measured as an index of procollagen production by high pressure liquid chromotography (HPLC). Apoptosis was determined by annexin staining.
OSM enhanced the mitotic activity of lung fibroblasts in a time and dose dependent manner. Maximum proliferation of 57% above control was observed after incubation for 48 h with 2 ng ml−1 OSM (P<0.05).
Incubation with the mitogen activated protein kinase (MAPK) kinase inhibitor, PD98059 or the tyrosine kinase inhibitor, genestein both significantly reduced the mitogenic effect of OSM (P<0.05).
In contrast, proliferation in response to OSM was not regulated by induction of cyclo‐oxygenase and subsequent prostaglandin E2 (PGE2) release or by IL‐6.
OSM also stimulated fibroblasts to synthesize pro‐collagen by a maximum of 35% above control levels after 48 h (P<0.05).
OSM significantly inhibited the spontaneous apoptosis of fibroblasts at 24 and 48 h.
These results provide evidence that OSM has pro‐fibrotic properties and suggest that it may play a role in normal lung wound repair and fibrosis.

British Journal of Pharmacology (2002) 136, 793–801; doi:10.1038/sj.bjp.0704769
Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal KATP channels
Authors: Lawrence C L , Rainbow R D , Davies N W , Standen N B 
Published: January 2005

We have investigated the effects of the sulphonylurea, glimepiride, currently used to treat type 2 diabetes, on ATP‐sensitive K+ (KATP) currents of rat cardiac myocytes and on their cloned constituents Kir6.2 and SUR2A expressed in HEK 293 cells.
Glimepiride blocked pinacidil‐activated whole‐cell KATP currents of cardiac myocytes with an IC50 of 6.8 nM, comparable to the potency of glibenclamide in these cells. Glimepiride blocked KATP channels formed by co‐expression of Kir6.2/SUR2A subunits in HEK 293 cells in outside‐out excised patches with a similar IC50 of 6.2 nM.
Glimepiride was much less effective at blocking KATP currents activated by either metabolic inhibition (MI) with CN− and iodoacetate or by the KATP channel opener diazoxide in the presence of inhibitors of F0/F1‐ATPase (oligomycin) and creatine kinase (DNFB). Thus 10 μM glimepiride blocked pinacidil‐activated currents by >99%, MI‐activated currents by 70% and diazoxide‐activated currents by 82%.
In inside‐out patches from HEK 293 cells expressing the cloned KATP channel subunits Kir6.2/SUR2A, increasing the concentration of ADP (1 – 100 μM), in the presence of 100 nM glimepiride, lead to significant increases in Kir6.2/SUR2A channel activity. However, over the range tested, ADP did not affect cloned KATP channel activity in the presence of 100 nM glibenclamide. These results are consistent with the suggestion that ADP reduces glimepiride block of KATP channels.
Our results show that glimepiride is a potent blocker of native cardiac KATP channels activated by pinacidil and blocks cloned Kir6.2/SUR2A channels activated by ATP depletion with similar potency. However, glimepiride is much less effective when KATP channels are activated by MI and this may reflect a reduction in glimepiride block by increased intracellular ADP.

British Journal of Pharmacology (2002) 136, 746–752; doi:10.1038/sj.bjp.0704770
Phylogenetic trends in the abundance and distribution of pit organs of elasmobranchs
Authors: Peach M. B. , Rouse G. W. 
Published: January 2005

AbstractPit organs (free neuromasts of the mechanosensory lateral line system) are distributed over the skin of elasmobranchs. To investigate phylogenetic trends in the distribution and abundance of pit organs, 12 relevant morphological characters were added to an existing matrix of morphological data (plus two additional end terminals), which was then re‐analysed using cladistic parsimony methods (paup* 4.0b10). Character transformations were traced onto the most parsimonious phylogenetic trees. The results suggest the following interpretations. First, the distinctive overlapping denticles covering the pit organs in many sharks are a derived feature; plesiomorphic elasmobranchs have pit organs in open slits, with widely spaced accessory denticles. Second, the number of pit organs on the ventral surface of rays has been reduced during evolution, and third, spiracular pit organs have changed position or have been lost on several occasions in elasmobranch evolution. The concentrated‐changes test inmacclade(version 4.05) was used to investigate the association between a pelagic lifestyle and loss of spiracular pit organs (the only character transformation that occurred more than once within pelagic taxa). Depending on the choice of tree, the association was either nonsignificant atP = 0.06 or significant atP < 0.05. Future studies, using species within more restricted elasmobranch clades, are needed to resolve this issue.
An immunohistochemical study of the extracellular matrix of the tarsal plate in the upper eyelid in human beings
Authors: Milz Stefan , Neufang Joerg , Higashiyama Ichiro , Putz Reinhard , Benjamin Michael 
Published: January 2005

AbstractThe superior tarsus is a plate of tissue that stiffens the upper eyelid, gives it support and determines its form. The purpose of the present study was to relate the composition of its extracellular matrix to its function and to report regional differences that may influence the activity of its Meibomian glands. Fourteen methanol‐fixed specimens were cryosectioned for immunohistochemistry and labelled with a panel of monoclonal antibodies against a wide range of collagens, glycosaminoglycans and proteoglycans. Labelling was detected with avidin–biotin–peroxidase. A further six specimens were formalin‐fixed for routine histology. The tarsal plate immunolabelled strongly for types I, III and VI collagen and for aggrecan, versican, tenascin, cartilage oligomeric matrix protein (COMP) together with a variety of glycosaminoglycans (notably chondroitin 6 sulphate). A region of strong labelling for aggrecan, dermatan sulphate and chondroitin 6 sulphate immediately surrounded the Meibomian glands. The site of labelling corresponded to a layer of acellular and amorphous matrix seen histologically that we have termed the ‘territorial matrix’. The results suggested that the tarsal plate is a specialized connective tissue that is neither purely fibrous nor cartilaginous, yet has an aggrecan content that probably contributes to its stiffness. Its unique character highlights the challenge in choosing an ideal mechanical substitute. As patients with rheumatoid arthritis often have problems relating to tear film deficiency, the ability of aggrecan or COMP to act as autoantigens may be significant. An immune reaction directed against these molecules could alter tarsal gland function by interfering with the interaction between the glands and their territorial matrix.
Quantification of N‐CAM and N‐cadherin expression in axotomized and crushed rat sciatic nerve
Authors: Thornton M. R. , Mantovani C. , Birchall M. A. , Terenghi G. 
Published: January 2005

AbstractAdhesion molecules are important in supporting axonal regeneration. Qualitative studies have described increased expression of neural cell adhesion molecule (NCAM) and N‐cadherin in models of nerve injury allowing active regeneration. In this study we have used quantitative immunohistochemistry to compare expression of NCAM and N‐cadherin after nerve injury either with active regeneration (crush) into the distal stump or without (axotomy and capping). Quantification was performed 15 days after axotomy in proximal and distal stumps. Quantification after crush either proximal, distal or within the crushed area was performed at 2, 7, 15 and 30 days after injury. Axotomy induced increases in expression in proximal stumps between two and three times those in uninjured nerves for both molecules. In distal stumps, N‐cadherin levels increased seven‐fold, yet NCAM levels did not exceed control values. After crush, NCAM immunoreactivity increased in the crushed area and distal stump in contrast to axotomy and NCAM‐positive axons co‐localized with PGP9.5. N‐cadherin levels in the distal stump increased above control levels, but the magnitude of the increase seen after crush was different to those seen after axotomy. In conclusion, increased expression of adhesion molecules, particularly NCAM, in the distal stump of injured nerves is dependent upon the presence of regenerating axons.
Evaluation of the mouse TgTP6.3 tauGFP transgene as a lineage marker in chimeras
Authors: MacKay Gillian E. , Keighren Margaret A. , Wilson Linda , Pratt Thomas , Flockhart Jean H. , Mason John O. , Price David J. , West John D. 
Published: January 2005

AbstractThe mouse TgTP6.3 transgene, encoding a tauGFP fusion protein, is becoming widely used but has yet to be fully characterized and evaluated as suitable lineage marker. The aim of the present study was to investigate the phenotype of TgTP6.3+/+ homozygotes and TgTP6.3+/– hemizygotes, characterize the expression of the TgTP6.3 transgene in different tissues and critically evaluate its use as a lineage marker. TgTP6.3+/+ homozygotes died between embryonic day 14.5 and weaning, whereas TgTP6.3+/– hemizygotes were mostly viable and fertile but smaller than non‐transgenic siblings. TgTP6.3 expression began in the late two‐cell stage, persisted in most fetal and adult tissues and was uniformly expressed in many (but not all) tissues. TgTP6.3+/– cells were readily identified in many chimeric tissues and their contribution appeared to be quantitatively and spatially normal. Overall, tauGFP expression in hemizygous TgTP6.3+/– cells fulfils the main criteria of a good lineage marker for many tissues. It provides a useful lineage marker, which should be particularly suitable for axons, blood vessels and pre‐implantation embryos.
Anatomics: the intersection of anatomy and bioinformatics
Authors: Bard Jonathan B. L. 
Published: January 2005

AbstractComputational resources are now using the tissue names of the major model organisms so that tissue‐associated data can be archived in and retrieved from databases on the basis of developing and adult anatomy. For this to be done, the set of tissues in that organism (its anatome) has to be organized in a way that is computer‐comprehensible. Indeed, such formalization is a necessary part of what is becoming known as systems biology, in which explanations of high‐level biological phenomena are not only sought in terms of lower‐level events, but are articulated within a computational framework. Lists of tissue names alone, however, turn out to be inadequate for this formalization because tissue organization is essentially hierarchical and thus cannot easily be put into tables, the natural format of relational databases. The solution now adopted is to organize the anatomy of each organism as a hierarchy of tissue names and linking relationships (e.g. the tibia is PART OF the leg, the tibia IS‐A bone) within what are known as ontologies. In these, a unique ID is assigned to each tissue and this can be used within, for example, gene‐expression databases to link data to tissue organization, and also used to query other data sources (interoperability), while inferences about the anatomy can be made within the ontology on the basis of the relationships. There are now about 15 such anatomical ontologies, many of which are linked to organism databases; these ontologies are now publicly available at the Open Biological Ontologies website (http://obo.sourceforge.net) from where they can be freely downloaded and viewed using standard tools. This review considers how anatomy is formalized within ontologies, together with the problems that have had to be solved for this to be done. It is suggested that the appropriate term for the analysis, computer formulation and use of the anatome is anatomics.