bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of chlormethiazole at human recombinant GABAA and NMDA receptors
Authors: Usala Marcello , Thompson Sally Anne , Whiting Paul J , Wafford Keith A 
Published: November 2003

Investigation into the modulatory effects of chlormethiazole at human recombinant γ‐aminobutyric acid A receptor (GABAA) and N‐methyl‐D‐aspartate (NMDA) receptors was undertaken to gain insight into its mechanism of action and determine if the drug exhibited any subtype‐selective activity.
Despite a structural similarity to the β‐subunit‐selective compound loreclezole, chlormethiazole did not show any difference in maximum efficacy and only a slight difference in EC50 in its potentiating action at α1β1γ2 and α1β2γ2 GABAA receptor subtypes with preference for α1β1γ2.
Similar to the previously reported subtype‐dependent activity of pentobarbital, chlormethiazole elicited a significantly greater degree of maximum potentiation on receptors lacking a γ2 subunit, and also those receptors containing an α4 or α6 subunit. This also demonstrates that chlormethiazole does not act via the benzodiazepine binding site.
Unlike pentobarbital and propofol, chlormethiazole elicited only a slight direct GABAA receptor activation at concentrations up to 1 mM. In addition, the drug did not potentiate anaesthetic‐mediated currents elicited by pentobarbital or propofol, suggesting that chlormethiazole may be acting via an anaesthetic binding site.
Chlormethiazole produced weak nonselective inhibition of human NMDA NR1a+NR2A and NR1a+NR2B receptors. IC50's were approximately 500 μM that likely exceed the therapeutic dose range for chlormethiazole, indicating that the primary mechanism of the compounds in vivo activity is via GABAA receptors.

British Journal of Pharmacology (2003) 140, 1045–1050. doi:10.1038/sj.bjp.0705540
Dental erosion and soft drinks: a qualitative assessment of knowledge, attitude and behaviour using focus groups of schoolchildren. A preliminary study
Authors: May J. , Waterhouse P. J. 
Published: November 2003

Summary.Objectives.  This qualitative study was designed to record the perception by Newcastle children of the influences on their choice of drinks and their knowledge of the dental health problems caused by acidic drinks.Methods.  Four focus groups, each involving 8 Newcastle schoolchildren (4 boys and 4 girls) formed the basis of the study. Two age groups, 13–14‐year‐olds and 8–9‐year‐olds, and two socio‐economic groups were investigated, using state schools in Newcastle upon Tyne. A moderator guided the children to discuss their choice of drink and its dental effects amongst themselves.Results.  In total, 32 children participated in the focus groups and the results suggested that 8–9‐year‐olds preferred still, fruit‐flavoured drinks whilst 13–14‐year‐olds preferred carbonated drinks. Taste was the most important influence on drink choice in all age groups. Parents and friends were more influential in younger children, whilst cost, availability and thirst were more important to older children. Younger children did not believe advertisements whilst older children thought they might work if seen enough times. Dental knowledge was confused in all age groups and only the 13–14‐year‐old‐high socio‐economic groups knew that acidic drinks were bad for the teeth. Different methods for addressing the problem of erosion were suggested by different age groups. There was very little difference between the socio‐economic groups in the areas discussed.Conclusions.  The children's knowledge of dental diseases and the effect of drinks on the teeth were confused. The factors that influence drink choice appear to change with age, rather than socio‐economic status.
Effects of phosphate availability on the root system architecture: large‐scale analysis of the natural variation between Arabidopsis accessions
Authors: CHEVALIER F. , PATA M. , NACRY P. , DOUMAS P. , ROSSIGNOL M. 
Published: November 2003

ABSTRACTDevelopmental plasticity is one main adaptative response of plants to the availability of nutrients. In the present study, the naturally occurring variation existing in Arabidopsis for the growth responses to phosphate availability was investigated. Initially details of the effects of phosphate starvation for the four currently used accessions Cvi, Col, Ler and Ws were compared. A set of 10 growth parameters, concerning the aerial part and the root system, was measured in both single‐point and time‐course experiments. The length of the primary root and the number of laterals were found to be consistently reduced by phosphate starvation in all four accessions. These two robust parameters were selected to further screen a set of 73 accessions originating from a wide range of habitats. One‐half of the accessions showed also a reduced primary root and less lateral roots when phosphate‐starved, and 25% were not responsive to phosphate availability. For the last quarter of accessions, phosphate starvation was found to affect only one of the two growth parameters, indicating the occurrence of different adaptative strategies. These accessions appear to offer new tools to investigate the molecular basis of the corresponding growth responses to phosphate availability.
Experimental reconstruction of dog's esophagus with biotype artificial esophagus
Authors: ZHI Fa Chao , ZHANG Lan Jun , PENG Xiu Fan , WU Xiang Hui , PAN De Shou , WAN Tian Mo , LIU Si De , ZHANG Zhen Shu , ZHOU Dian Yuan 
Published: November 2003

OBJECTIVE:  At present, there are few materials available for esophagus reconstruction anywhere in the world. The reported survival rate in animals during the perioperative period is comparatively low. The present study assessed the feasibility of using a biotype artificial esophagus in the reconstruction of a dog's esophagus.METHODS:  In 30 mongrel dogs, a portion of the thoracic esophagus was resected and an 8 cm section of artificial esophagus was transplanted to reconstruct the organ. The survival rate, food intake and process of healing were observed.RESULTS:  Of the 30 dogs, 28 survived the peri­operative period (93.3% survival). Two dogs (6.7%) developed an anastomotic fistula; 19 dogs survived for 1 year, a survival rate of 79.2% (19/24) with the remaining six dogs were killed according to the experimental protocol. Detachment of the artificial esophagus occurred on average 28.8 days after operation and the dogs suffered from varying degrees of dysphagia 23−45 days after operation. Gradual remission occurred after 4 months. The histological study revealed that the regenerated esophagus was composed of fibrous and connective tissues and the luminal surface was covered with squamous epithelium in 3−6 months.CONCLUSION:  The transplanted artificial esophagus detached after the surrounding ‘regenerated esophagus’ had formed, and the squamous epithelium gradually covered the luminal surface. Continuous remodeling of the ‘regenerated esophagus’ gradually relieved the stenosis. Whether detachment of the implant and the postoperative stenosis can be solved is the key problem restricting the use of the biotype artificial esophagus in clinical practice.
Markers for dopaminergic neurotransmission in the cerebellum in normal individuals and patients with Parkinson's disease examined by RT‐PCR
Authors: Hurley Michael J. , Mash Deborah C. , Jenner Peter 
Published: November 2003

AbstractThe presence of neuronal elements that are indicative of dopaminergic neurotransmission in cerebellum suggest that this brain region may contribute to the motor symptoms or dyskinesia seen in Parkinson's disease. Reverse transcription polymerase chain reaction (RT‐PCR) was used to examine the expression of markers for dopaminergic neurotransmission in the cerebellum from postmortem brain tissue obtained from normal subjects and patients dying with Parkinson's disease who were receiving treatment with dopaminergic drugs. Dopamine D1−3 receptors, tyrosine hydroxylase and dopamine transporter mRNA was detected in the uvula and nodulus (lobules 9 and 10, respectively) of the vermis of cerebellum from normal individuals. In Parkinson's disease, the level of dopamine D1 and D3 receptor mRNA was significantly reduced in lobule 9 and the level of tyrosine hydroxylase mRNA was significanty reduced in lobule 10. No alteration in the level of dopamine D2 receptor or dopamine transporter mRNA was found in either lobule in patients with Parkinson's disease. These results show that mRNA expression for the functional components of dopaminergic neurotransmission is present in human cerebellum. The discrete changes in the levels of dopamine D1 and D3 receptors and tyrosine hydroxylase mRNA in cerebellum from l‐DOPA treated Parkinson's disease patients suggests that this brain area has a role in the symptoms of Parkinson's disease and/or the beneficial/side‐effects of treatment.
BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs
Authors: Garraway Sandra M. , Petruska Jeffrey C. , Mendell Lorne M. 
Published: November 2003

AbstractBrain‐derived neurotrophic factor (BDNF) is up‐regulated and released in the dorsal horn following peripheral inflammation and has therefore been implicated in spinal mechanisms of sensitization. Despite these observations, the mechanisms associated with such a role for BDNF are not yet fully determined. Here, we investigate the effect of BDNF on dorsal root‐evoked synaptic transmission in lamina II neurons. In a transverse spinal cord slice preparation from neonatal rats (P1–15), the whole cell patch‐clamp technique was used to record from these neurons. Brief application of BDNF (50–200 ng/mL) facilitated the evoked synaptic currents; they remained enhanced even after BDNF was washed out. A significant minority of cells was minimally affected by BDNF and consistent with this, not all neurons in lamina II were immunoreactive for the tyrosine kinase (trk) B receptor. No facilitation was elicited when N‐methyl‐d‐aspartate (NMDA) receptors were blocked with D‐APV, when the postsynaptic NMDA receptors were selectively blocked with intracellular MK‐801, or when postsynaptic neurons were loaded with BAPTA. Additionally, inhibiting phospholipase C (PLC) or protein kinase C (PKC) prior to BDNF application completely blocked facilitation. However, once synaptic current underwent BDNF‐induced facilitation, the PKC inhibitors failed to reverse the effect, suggesting that PKC is needed for initiation, but not maintenance of BDNF‐induced facilitation. These results demonstrate that BDNF functions at the spinal level to enhance synaptic efficacy in an NMDA receptor‐dependent manner and requires the action of the PLC/PKC pathway. This action of BDNF may contribute to central sensitization and exaggerated pain states.
Changes in methylation during progressive transcriptional silencing in transgenic subterranean clover
Authors: Hagan Nicholas D. , Spencer Donald , Moore Andrew E. , Higgins Thomas J. V. 
Published: November 2003

SummaryA transgenic line of subterranean clover (Trifolium subterraneum) containing a gene for a sulphur‐rich sunflower seed albumin (ssa gene) and a gene conferring tolerance to the herbicide phosphinothricin (bar gene) was previously shown to stably express these genes as far as the T3 generation. In subsequent generations there was a progressive decline in the level of expression of both of these genes such that, by the T7 generation, the plants were almost completely susceptible to the herbicide and the mean level of sunflower seed albumin was reduced to 10–30% of the level in the T2 and T3 generations. The decline in SSA protein correlated closely with a decline in the level of ssa RNA. In vitro transcription experiments with nuclei isolated from plants of the early and late generations showed that the reduced mRNA level was associated with a reduced level of transcription of the ssa transgene. Transcription of the bar transgene was also reduced in the late generations. Bisulphite sequencing analysis showed that the decline in expression of the ssa gene between T3 and subsequent generations correlated closely with increased CpG methylation in the promoter, but not in the coding region. Analysis of the bar gene promoter showed that high levels of CpG methylation preceded the first detectable decline in expression of the bar gene by one generation, suggesting that methylation was not the direct cause of transgene silencing in these plants.
Mergers and Acquisitions in the Private Sector: What Are the Lessons for Health and Social Services?
Authors: Field Janet , Peck Edward 
Published: November 2003

Abstract In seeking a more seamless provision of health and social care, the government is promoting the merger of the functions of primary and community health services and social services. In the private sector, mergers have been commonplace. The primary aim of this paper is to identify the key concepts and explanatory frameworks in the literature on mergers and acquisitions in the private sector that are relevant to the development of new organizational structures in health and social care. The evidence suggests that it is difficult to merge two organizations successfully. Reasons for this are explored and the implications for health and social care mergers drawn out.
Residence and Migration in Post‐War Soviet Estonia: The Case of Russian‐Born Estonians
Authors: Kulu Hill 
Published: November 2003

ABSTRACTConventional research has used aggregate statistics and bivariate methods in studying migration in Soviet society and has stressed the critical role of a single (usually structural) determinant in an individual's migration. This research tests the dominant view, using individual level data and multivariate methods. The objective is to clarify the extent to which structural‐environmental factors and the extent to which personal characteristics determined the first residence and migration of Russian‐born Estonians in post‐war Estonia. The data of the retrospective survey on 265 ethnic Estonians born in Russia between 1915 and 1969 and settled in Estonia between 1940 and 1988 are used. It appears that the first residence and migration of the ethnic Estonians was shaped by an immigration cohort – the variable reflecting structural‐environmental conditions. However, several personal characteristics – age, earlier life‐environment, language usage and education – also turned out to be important determinants of residence and migration of the ethnic Estonians. The results provide evidence to the view that migration in the Soviet Union was a complex outcome of interaction of structural forces and people's preferences, and therefore differed less from other parts of the world than often presumed.
Residential Segregation in a Medium‐Sized Post‐Soviet City: Ust’‐Kamenogorsk, Kazakhstan
Authors: Gentile Michael 
Published: November 2003

ABSTRACTThis paper focuses on the occurrence of ethnic and socio‐economic residential segregation in Ust’‐Kamenogorsk, a medium‐sized city in Kazakhstan, using data collected by the author in collaboration with the Eastern Kazakhstan oblast’ statistical authority in an extensive questionnaire survey carried out during January 2001. Together with the marketisation of the city's housing resources, a number of Soviet legacies, including the major industrial enterprises’ housing strategies for their workers and the city's previous status as ‘closed’, are identified. Finally, the paper maps and analyses existing segregation patterns.
Sun protection factor determination in vivo using a single exposure on sunscreen‐protected skin
Authors: Diffey Brian L. 
Published: November 2003

Background: Determining sunscreen sun protection factors (SPFs) in a cohort of volunteers, particularly on products designed to provide high levels of protection, can be time‐consuming. The conventional approach is to administer to each subject a series of exposures (normally between five and seven) on their sunscreen‐protected skin.Method: A method, based on Gaussian statistics, is proposed that requires just a single exposure on the sunscreen‐protected skin in volunteers to arrive at a reliable estimate of the mean SPF of a test product.Results/Conclusion: The method is shown to yield an estimate of a product's mean SPF that is comparable, or better, in accuracy to estimates obtained by conventional multi‐exposure testing.
II. Veterans Affairs Cooperative Study of Polyenylphosphatidylcholine in Alcoholic Liver Disease
Authors: Lieber Charles S. , Weiss David G. , Groszmann Roberto , Paronetto Fiorenzo , Schenker Steven ,   for the Veterans Affairs Cooperative Study 391 Group
Published: November 2003

Background: Polyenylphosphatidylcholine (PPC) has been shown to prevent alcoholic cirrhosis in animals. Our aims were to determine the effectiveness of PPC in preventing or reversing liver fibrosis in heavy drinkers and to assess the extent of liver injury associated with the reduced drinking achieved in these patients.Methods: This randomized, prospective, double‐blind, placebo‐controlled clinical trial was conducted in 20 Veterans Affairs Medical Centers with 789 patients (97% male; mean age, 48.8 years) averaging 16 drinks per day (1 drink = 14 g of alcohol) for 19 years. A baseline liver biopsy confirmed the presence of perivenular or septal fibrosis or incomplete cirrhosis. They were randomly assigned either PPC or placebo. Liver biopsy was repeated at 24 months, and the main outcome measure was the stage of fibrosis compared with baseline. Progression was defined as advancing to a more severe stage.Results: The 2‐year biopsy was completed in 412 patients. PPC did not differ significantly from placebo in its effect on the main outcome. Alcohol intake was unexpectedly reduced in both groups to approximately 2.5 drinks per day. With this intake, 21.4% advanced at least one stage (22.8% of PPC patients and 20.0% of placebo patients). The hepatitis C virus–positive subgroup exhibited accelerated progression. Improvement in transaminases and bilirubin favoring PPC was seen at some time points in other subgroups (hepatitis C virus–positive drinkers or heavy drinkers).Conclusions: PPC treatment for 2 years did not affect progression of liver fibrosis. A trend in favor of PPC was seen for transaminases and bilirubin (in subgroups). One of five patients progressed even at moderate levels of drinking, and thus health benefits commonly associated with moderate drinking do not necessarily extend to individuals in the early stages of alcoholic liver disease.
Legal Aid in South-East Asia and China: Seven Lessons of Bangkok
Authors:   Kirby
Published: November 2003

AbstractBetween 10–14 June 1999, Justice Michael Kirby of the High Court of Australia took part in, and summed up a forum on legal aid in Asia held in Bangkok, Thailand. Participants were drawn from centres throughout the region. The forum was organised by the Washington-based International Human Rights Law Group and the Hong Kong based Asian Human Rights Commission - two human rights non-governmental organisations. In his summary Justice Kirby drew on the interventions made during the forum by legal practitioners from the participating states. He suggests a number of lessons and themes for future exploration. His chief point is simple. It applies as much in Australia as in its region. Without affordable and effective access to independent, neutral and professional courts, talk of the rule of law is hollow and liable to be deceptive.
Election Violence in Sri Lanka: Implementing the Right to a Free and Fair Election
Authors:   Saul
Published: November 2003

AbstractThis article assesses the freedom and fairness of the 2001 parliamentary election in Sri Lanka according to a variety of criteria, judging the effects of violence and procedural irregularity on the election outcome. Despite its ambiguity, the international right to a free and fair election, expressed through the principles of the UDHR and the ICCPR, is substantially incorporated in the domestic law of Sri Lanka. The Constitution and elections legislation recognise essential democratic and electoral rights and establish administrative procedures and judicial remedies for enforcing them. Specific controversies over electoral laws have typically been resolved within the framework of the rule of law, through either the political process or the courts, including debates about the method of voting, the powers of the Election Commissioner and the registration of parties. Referendum and emergency powers have, however, been abused to interfere with free elections in some situations. Further, recent elections have degenerated into widespread violence, intimidation and procedural irregularity, culminating in the December 2001 parliamentary election. The violent events of the 2001 election suggest that despite the formal maturity of Sri Lankan election law, the law is not being adequately enforced and deterrence, through criminal sanctions, is failing. While most police and election officials are committed to ensuring the integrity of elections, many politicians and candidates have undermined elections, in a society militarised by a protracted ethnic separatist conflict.
Second language learnability and the acquisition of the argument structure of English locative verbs by Korean speakers
Authors: Joo Hye-Ri 
Published: November 2003

The present research focuses on Korean English as a foreign language (EFL) learners’ knowledge of the locative alternation (e.g., John loaded hay onto the wagon/John loaded the wagon with hay) and its relationship to theories of language-particular and language-universal properties. Korean, the native language of the participants, has a locative alternation resembling that of English. However, although Korean and English are similar in terms of broad-range constraints, they are dissimilar in terms of narrow-range constraints for locative alternations. This study investigates whether the acquisition of such constraints in English locatives by Korean speakers, and whether the first language (L1) influences the second language (L2) acquisition of locative alternations. Two instruments are used in the experiment: a forced-choice picture-description task and a forced-choice sentence selection task. The study investigates an experimental group of Korean learners of English and a control group of native speakers of English. The results are discussed with reference to universality of linking, to the transfer of argument structure and to Pinker’s learnability theory. The primary results are: • The Korean learners of English had acquired the constructional meaning of the locative construction (which is related to Pinker’s (1989) concept of broad-range rules and broad conflation classes), a property claimed to be universal. • They had not achieved native-speaker knowledge of language-particular properties - which narrow conflation class verbs belong to - so that they did not reject ungrammatical sentences; and • Significant L1 transfer effects were not found.