bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2X3 receptor localizes into lipid rafts in neuronal cells
Authors: Vacca Fabrizio , Amadio Susanna , Sancesario Giuseppe , Bernardi Giorgio , Volonté Cinzia 
Published: April 2004

AbstractP2X receptors are a family of seven (P2X1–7) cation channels gated by extracellular ATP, widely expressed in neurons and nonneuronal cells. Lipid rafts are cholesterol/sphingolipid‐rich membrane domains, involved in many cellular processes, including transmembrane receptor signaling, vesicle traffic, and protein sorting. We provide direct biochemical evidence that P2X3 receptor localizes into lipid rafts, in primary cultures of cerebellar granule neurons as well as in brain and dorsal root ganglia extracts. We show that P2X3 exhibits all the characteristics distinctive of a protein associated with lipid rafts. These characteristics include resistance to detergent extraction at 4°C, solubility after extraction of cholesterol from membranes with either saponin or methyl‐β‐cyclodextrin, and partitioning to low buoyant density fractions after sucrose gradient centrifugation in both detergent‐containing and detergent‐free conditions. Furthermore, P2X3 localizes in raft‐containing fractions in transiently transfected SH‐SY5Y neuroblastoma cells. The present finding contributes to the characterization of the functional localization of P2X3 in neurons and provides a novel potential mechanism for correct targeting and dynamic activation of this receptor. © 2004 Wiley‐Liss, Inc.
Assessing the nature of psychological contracts: a validation of six dimensions
Authors: Sels Luc , Janssens Maddy , Van Den Brande Inge 
Published: April 2004

AbstractThe purpose of this study is to develop a feature‐oriented assessment of psychological contracts, an underdeveloped approach to psychological contracts. Relying on theoretical frameworks in psychological contract research, industrial relations studies, and a cross‐national study on psychological contracts, we identify six dimensions that capture the nature of psychological contracts: tangibility, scope, stability, time frame, exchange symmetry, and contract level. We validate this expanded conceptualization of psychological contracts by developing a nomological network and testing it in a large, representative sample of 1106 employees. The results indicate the significance of formal contract characteristics and HR practices as two antecedents shaping the nature of psychological contracts. In addition, the hypothesized relationships between the three dimensions of time frame, exchange symmetry, and contract level with affective commitment are confirmed as well as the relationships between tangibility, scope and flexibility with personal control. The results further indicate the importance of assessing both employer and employee obligations given the differential effect of the contract makers. Copyright © 2004 John Wiley & Sons, Ltd.
Career communities: a preliminary exploration of member‐defined career support structures
Authors: Parker Polly , Arthur Michael B. , Inkson Kerr 
Published: April 2004

AbstractThis paper explores the concept of career communities: social structures that provide career support and frequently transcend the boundaries of any single organization. The theoretical background notes the convergence of a number of different perspectives from both career development and organization studies, pertaining to the social contextualization of careers. The methodology involved eliciting expressions of the (individual) subjective career from the members of three potential career communities, and then exploring (communal) inter‐subjective interpretations in focus groups. Our results suggest that career communities typically involve a hybrid of types rather than any one pure type. Preliminary support is found for the view that career communities facilitate career support, sensemaking and learning. The results invite further research into career communities and have implications for organizational behavior and human resource management, suggesting greater appreciation of the extra‐organizational as well as intra‐organizational communities in which careers develop. Copyright © 2004 John Wiley & Sons, Ltd.
Differential protein profiling in renal‐cell carcinoma
Authors: Shi Ting , Dong Fan , Liou Louis S. , Duan Zhong‐Hui , Novick Andrew C. , DiDonato Joseph A. 
Published: April 2004

AbstractCharacterizing the alterations of protein expression in cancer cells can be very useful in providing insight into the changes in the functional pathways and thus the fundamental mechanisms of cancer development at the molecular level. In this study, we profiled protein expressions in eleven pairs of primary cell cultures derived from renal‐cell carcinoma (RCC) tissues and patient‐matched normal kidney tissues utilizing two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE). Together with the immunoblot analysis of proteins from the RCC tissues, the study also demonstrated that the alterations of protein expression observed in RCC primary cell cultures reflected those observed in the original RCC tissues. We analyzed the expression profiles and identified proteins differentially expressed in RCC primary cell cultures by 2‐D PAGE and mass spectrometry (MS). We found sixteen proteins were overexpressed and seven proteins underexpressed in RCC. The deregulated expressions of proteins include those involved in metabolism, cellular morphology, heat shock response, cell growth, etc. Overexpression of three proteins, αβ‐crystallin, manganese superoxide dismutase (MnSOD), and annexin IV, most commonly observed in primary RCC cell cultures, were also observed by immunoblot analysis of proteins from the RCC tissues from which the primary cell cultures were derived. Semi‐quantitative reverse transcription (RT)‐polymerase chain reaction (PCR) analysis revealed the direct correlation between deregulated gene expression and the corresponding protein abundance in two of the three most commonly upregulated proteins we found in RCC. © 2004 Wiley‐Liss, Inc.
Modulation of gene expression by hypoxia in human umbilical cord vein endothelial cells: A transcriptomic and proteomic study
Authors: Scheurer Simone B. , Raybak Jascha N. , Rösli Christoph , Neri Dario , Elia Giuliano 
Published: April 2004

AbstractHypoxia is a characteristic feature of many human pathologies, including cancer. The sustained proliferation rate of tumor cells leads to alterations of the tumor microenvironment, that progressively becomes more acidic, nutrient‐deprived, and hypoxic. The reduced partial pressure of oxygen triggers the onset of an adaptive response, aimed at increasing the local oxygen concentration by several complementary actions. Although directly exposed to the blood stream, endothelial cells lining the vascular lumen in tumors also can be exposed to hypoxia and therefore can contribute to the onset of the adaptive response that leads to tumor angiogenesis. Aiming at getting a detailed insight into the oxygen‐dependent regulation of the transcriptional program of vascular endothelial cells and at identifying new relevant markers that may be used as targets for therapeutic intervention in tumor angiogenesis, we have performed a broad‐range transcriptomic analysis, using the Affymetrix HG‐U133A Gene Chips, of mRNA expression levels in human umbilical cord vein endothelial cells (HUVEC), exposed in vitro to hypoxia for different time periods. The transcriptomic analysis was complemented by a semiquantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis of mRNA levels and alternative splicing for some selected extracellular matrix protein genes, and by a proteomic analysis, using two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE) and tandem mass spectrometry for protein separation and identification, of hypoxic and normoxic HUVEC whole‐cell lysates and subcellular fractions. Our analysis confirmed previous findings on genes whose expression is regulated by oxygen concentration but also identified new genes (e.g., CXCR4, claudin 3, CD24, tetranectin, Del‐1, procollagen lysyl hydroxylase 1 and 2) which are transcriptionally upregulated in hypoxic conditions.
The New Cesium Praseodymium Thiophosphate Cs3Pr5[PS4]6
Authors: Komm Theresa , Schleid Thomas 
Published: April 2004

AbstractTransparent platelet‐shaped green single crystals of the title compound were obtained by the reaction of cesium bromide, praseodymium, sulfur, and red phosphorus in the molar ratio 1:2:8:2 with an excess of CsBr as flux in evacuated silica ampoules at 950 °C for fourteen days. Cs3Pr5[PS4]6 crystallizes monoclinically in the space group C2/c (a = 1627.78(7), b = 1315.09(6), c = 2110.45(9) pm, β = 103.276(5)°; Z = 4). Its crystal structure is different from all the other alkali‐metal containing ortho‐thiophosphates of the lanthanides, since it is not possible to formulate a layer containing the praseodymium centered sulfur polyhedra ([PrS8]13—, d(Pr—S) = 286 — 307 pm) and the isolated [PS4]3— tetrahedra (d(P—S) = 202 — 207 pm, ∢(S—P—S) = 104 — 106°). All these tetrahedra are edge‐sharing with the metal polyhedra to build up a framework instead. The coordination sphere of the half occupied (Cs2)+ cations (CN = 10 + 2) can be described as two six‐membered sulfur rings in chair conformation containing a “cesium‐pair” in the middle. In contrast the (Cs1)+ cations are surrounded in the not unusual configuration of tetracapped trigonal prisms (CN = 10, better 10 + 2 as well).
Neurokinin NK1 and NK3 receptors as targets for drugs to treat gastrointestinal motility disorders and pain
Authors: Sanger Gareth J 
Published: April 2004

NK1 and NK3 receptors do not appear to play significant roles in normal GI functions, but both may be involved in defensive or pathological processes. NK1 receptor antagonists are antiemetic, operating via vagal sensory and motor systems, so there is a need to study their effects on other gastro‐vagal functions thought to play roles in functional bowel disorder's. Interactions between NK1 receptors and enteric nonadrenergic, noncholinergic motorneurones suggest a need to explore the role of this receptor in disrupted colonic motility. NK1 receptor antagonism does not exert consistent analgesic activity in humans, but similar studies have not been carried out against pain of GI origin, where NK1 receptors may have additional influences on mucosal inflammatory or ‘irritant’ processes. NK3 receptors mediate certain disruptions of intestinal motility. The activity may be driven by tachykinins released from intrinsic primary afferent neurones (IPANs), which induce slow EPSP activity in connecting IPANs and hence, a degree of hypersensitivity within the enteric nervous system. The same process is also proposed to increase C‐fibre sensitivity, either indirectly or directly. Thus, NK3 receptor antagonists inhibit intestinal nociception via a ‘peripheral’ mechanism that may be intestine‐specific. Studies with talnetant and other selective NK3 receptor antagonists are, therefore, revealing an exciting and novel pathway by which pathological changes in intestinal motility and nociception can be induced, suggesting a role for NK3 receptor antagonism in irritable bowel syndrome.British Journal of Pharmacology (2004) 141, 1303–1312. doi:10.1038/sj.bjp.0705742
CRF1receptor signaling pathways are involved in stress‐related alterations of colonic function and viscerosensitivity: implications for irritable bowel syndrome
Authors: Taché Y , Martinez V , Wang L , Million M 
Published: April 2004

The characterization of corticotropin releasing factor (CRF) and, more recently, the discovery of additional CRF‐related ligands, urocortin 1, urocortin 2 and urocortin 3, the cloning of two distinct CRF receptor subtypes, 1 (CRF1) and 2 (CRF2), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress. Activation of brain CRF1receptor signaling pathways is implicated in stress‐related endocrine response and the development of anxiety‐like behaviors.Compelling evidence in rodents showed also that both central and peripheral injection of CRF and urocortin 1 mimic acute stress‐induced colonic response (stimulation of motility, transit, defecation, mucus and watery secretion, increased ionic permeability and occurrence of diarrhea) in rodents. Central CRF enhances colorectal distention‐induced visceral pain in rats. Peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans.Nonselective CRF1/CRF2antagonists and selective CRF1antagonists inhibit exogenous (central or peripheral) CRF‐ and acute stress‐induced activation of colonic myenteric neurons, stimulation of colonic motor function and visceral hyperalgesia while selective CRF2antagonists have no effect. None of the CRF antagonists influence basal or postprandial colonic function in nonstressed animals.These findings implicate CRF1receptors in stress‐related stimulation of colonic function and hypersensitivity to colorectal distention. Targeting CRF1‐dependent pathways may have potential benefit against stress or anxiety‐/depression‐related functional bowel disorders.British Journal of Pharmacology(2004)141, 1321–1330. doi:10.1038/sj.bjp.0705760
Activation and sensitisation of the vanilloid receptor: role in gastrointestinal inflammation and function
Authors: Geppetti Pierangelo , Trevisani Marcello 
Published: April 2004

The exquisite specific excitatory and desensitising actions of capsaicin on a subpopulation of primary sensory neurons have been instrumental in identifying the roles of these neurons in nociception, reflex responses and neurogenic inflammation.
Structure activity studies with capsaicin‐like molecules have suggested that a ‘receptor’ should mediate the effects of capsaicin on sensory neurons. The cloning of the vanilloid receptor‐1 (VR1) has confirmed this hypothesis.
VR1 (TRPV1) belongs to the transient receptor potential (TRP) family of channels, and its activation by various xenobiotics, noxious temperature, extracellular low pH and high concentration of certain lipid derivatives results in cation influx and sensory nerve terminal excitation.
TRPV1 may dimerise or form tetramers or heteromers with PLC‐γ and TrkA or even with other TRPs. TRPV1 is markedly upregulated and/or ‘sensitised’ under inflammatory conditions via protein kinase C‐ɛ‐, cAMP‐dependent PK‐ and PLC‐γ‐dependent pathways or by exposure to dietary agents as ethanol.
TRPV1 is expressed on sensory neurons distributed in all the regions of the gastrointestinal tract in myenteric ganglia, muscle layer and mucosa. There is evidence of TRPV1 expression also in epithelial cells of the gastrointestinal tract.
High expression of TRPV1 has been detected in several inflammatory diseases of the colon and ileum, whereas neuropeptides released upon sensory nerve stimulation triggered by TRPV1 activation seem to play a role in intestinal motility disorders.
TRPV1 antagonists, which will soon be available for clinical testing, may undergo scrutiny for the treatment of inflammatory diseases of the gut.

British Journal of Pharmacology (2004) 141, 1313–1320. doi:10.1038/sj.bjp.0705768
Involvement of cannabinoid receptors in gut motility and visceral perception
Authors: Hornby Pamela J , Prouty Stephen M 
Published: April 2004

From a historical perspective to the present day, all the evidence suggests that activation of cannabinoid receptors (CBRs) is beneficial for gut discomfort and pain, which are symptoms related to dysmotility and visceral perception. CBRs comprise G‐protein coupled receptors that are predominantly in enteric and central neurones (CB1R) and immune cells (CB2R). In the last decade, evidence obtained from the use of selective agonists and inverse agonists/antagonists indicates that manipulation of CB1R can alter (1) sensory processing from the gut, (2) brain integration of brain‐gut axis, (3) extrinsic control of the gut and (4) intrinsic control by the enteric nervous system. The extent to which activation of CB1R is most critical at these different levels is related to the region of the GI tract. The upper GI tract is strongly influenced by CB1R activation on central vagal pathways, whereas intestinal peristalsis can be modified by CB1R activation in the absence of extrinsic input. Actions at multiple levels make the CB1R a target for the treatment of functional bowel disorders, such as IBS. Since low‐grade inflammation may act as a trigger for occurrence of IBS, CB2R modulation could be beneficial, but there is little supporting evidence for this yet. The challenge is to accomplish CBR activation while minimizing adverse effects and abuse liabilities. Potential therapeutic strategies involve increasing signaling by endocannabinoids (EC). The pathways involved in the biosynthesis, uptake and degradation of EC provide opportunities for modulation of CB1R and some recent evidence with inhibitors of EC uptake and metabolism suggest that these could be exploited for therapeutic gain.British Journal of Pharmacology (2004) 141, 1335–1345. doi:10.1038/sj.bjp.0705783
Explicit formulation of different receptor–G-protein interactions and effector regulation
Authors: Kukkonen Jyrki P. 
Published: April 2004

Abstract
Motivation: G-protein-coupled receptors (GPCRs) can create different intracellular signals depending on which G-proteins they couple to and which intracellular signal-integrators, such as adenylyl cyclases, are expressed in the cell. One and the same GPCR can activate multiple G-protein species, generating signals, which either inhibit or amplify each other. Because of this complexity, extraction of mechanistic information from concentration–response curves is not straightforward.
Results: To tackle this problem, I describe in this paper explicit equations for GPCR-interaction with two G-protein species by different possible mechanisms, and also an equation for the regulation of an effector enzyme by the activated G-proteins or their effectors. Arithmetic solutions to these equations are presented, which resulted in the equations being applicable in a spreadsheet program environment. These equations are useful in simulations to analyze results, to design experiments and to test hypotheses. Some examples of this are presented in this study.
Molecular Genetic Testing for Malignant Hyperthermia Susceptibility
Authors: Girard Thierry , Treves Susan , Voronkov Evgueni , Siegemund Martin , Urwyler Albert 
Published: April 2004

Background
For more than 30 yr, the in vitro contracture test (IVCT) was the only appropriate diagnostic tool for malignant hyperthermia (MH). After the introduction of molecular genetics into MH research, guidelines for molecular genetic diagnosis of MH susceptibility were published. The aim of this study was to establish applicability of the guidelines, sensitivity, and specificity of genetic testing in MH and advantages for studied patients.

Methods
The IVCT was performed following the guidelines of the European MH Group. Mutation analyses were performed by amplification of genomic DNA by polymerase chain reaction and restriction enzyme digestion.

Results
Two hundred eight individuals underwent MH testing between January 2001 and April 2003. In 32 of 67 initially genetic-tested patients, the familial mutation was identified, and they were diagnosed as MH susceptible. The IVCT followed negative genetic test results in 20 patients, and all but one had negative IVCT results. Three patients were scheduled to undergo elective surgery, and IVCT and genetic testing were performed simultaneously. All three had positive IVCT results and were carriers of their familial mutation.

Conclusions
In families with known MH mutations, there is a 50% chance of reliably confirming MH susceptibility by noninvasive testing. The authors found the negative predictive value of genetic testing to be 0.95 (95% confidence interval, 0.75-0.99), but for patient safety, they still recommend following the guidelines for genetic testing in MH and therefore performing an IVCT in case of negative genetic results.
Altered Cell-mediated Immunity and Increased Postoperative Infection Rate in Long-term Alcoholic Patients
Authors: Spies Claudia D. , von Dossow Vera , Eggers Verena , Jetschmann Gesine , El-Hilali Ratiba , Egert Julia , Fischer Marc , Schröder Torsten , Höflich Conny , Sinha Pranav , Paschen Christian , Mirsalim Parwis , Brunsch Ralf , Hopf Jürgen , Marks Christian , Wernecke Klaus-D. , Pragst Fritz , Ehrenreich Hannelore , Müller Christian , Tonnesen Hanne , Oelkers Wolfgang , Rohde Wolfgang , Stein Christoph , Kox Wolfgang J. 
Published: April 2004

Background
Preoperative alteration of T cell-mediated immunity as well as an altered immune response to surgical stress were found in long-term alcoholic patients. The aim of this study was to evaluate perioperative T cell-mediated immune parameters as well as cytokine release from whole blood cells after lipopolysaccharide stimulation and its association with postoperative infections.

Methods
Fifty-four patients undergoing elective surgery of the aerodigestive tract were included in this prospective observational study. Long-term alcoholic patients (n = 31) were defined as having a daily ethanol consumption of at least 60 g and fulfilling the Diagnostic and Statistical Manual of Mental Disorders for either alcohol abuse or alcohol dependence. The nonalcoholic patients (n = 23) were defined as drinking less than 60 g ethanol/day. Blood samples to analyze the immune status were obtained on morning before surgery and on the morning of days 1, 3, and 5 after surgery.

Results
Basic patient characteristics did not differ between groups. Before surgery, the T helper 1:T helper 2 ratio (Th1: Th2) was significantly lower (P < 0.01), whereas plasma interleukin 1beta and lipopolysaccharide-stimulated interleukin 1ra from whole blood cells were increased in long-term alcoholic patients. After surgery, a significant suppression of the cytotoxic lymphocyte ratio (Tc1:Tc2), the interferon gamma:interleukin 10 ratio from lipopolysaccharide-stimulated whole blood cells, and a significant increase of plasma interleukin 10 was observed. Long-term alcoholics had more frequent postoperative infections compared with nonalcoholic patients (54%vs. 26%; P = 0.03).

Conclusions
T helper cell-mediated immunity was significantly suppressed before surgery and possibly led to inadequate cytotoxic lymphocyte and whole blood cell response in long-term alcoholic patients after surgery. This altered cell-mediated immunity might have accounted for the increased infection rate in long-term alcoholic patients after surgery.
Effect of Hypertonic Saline Infusion on Postoperative Cellular Immune Function
Authors: Kølsen-Petersen Jens A. , Nielsen Jens-Ole D. , Tonnesen Else M. 
Published: April 2004

Background
Previous studies found hypertonicity to affect immune responses in intact laboratory animals and in human blood cell cultures. In this study, the authors investigated the cellular immune response to surgery after preoperative infusion of hypertonic saline in humans.

Methods
Sixty-two women scheduled to undergo abdominal hysterectomy were randomly assigned to single-blinded infusion of 4 ml/kg NaCl, 7.5%; 4 ml/kg NaCl, 0.9%; or 32 ml/kg NaCl, 0.9%, over 20 min. Blood was collected at baseline, during surgery, and 1, 24, and 48 h after surgery for the determination of leukocyte and differential counts, flow cytometric phenotyping of mononuclear cells, and natural killer cell activity against K 562 tumor cells. Phytohemagglutinin-induced lymphocyte proliferation, plasma elastase, and neutrophil chemotaxis were measured at the same time points except during surgery. The authors tested cell-mediated immune function in vivo by delayed-type hypersensitivity reaction in the skin.

Results
Surgery induced well-known changes in the cellular immune response, which were unrelated to the tonicity or volume of the infused fluids.

Conclusion
Infusion of a clinically relevant dose of hypertonic saline did not seem to modify the postoperative cellular immune response after elective abdominal hysterectomy.