bluuebunny/crossref_metadata_2025_split huggingface dataset:
Birth weight and psychological distress at age 45–51 years
Authors: Wiles Nicola J. , Peters Tim J. , Leon David A. , Lewis Glyn 
Published: July 2005

BackgroundIt is unclear whether the effect of low birth weight on common affective disorders in later life is director mediated through childhood factors.AimsTo determine whether birth weight has a direct effect on psychological distress in adulthood not mediated by childhood IQ or behavioural problems.MethodParticipants (n=5572) of the Aberdeen Children of the 1950s study had data on birth weight for gestational age and adult psychological distress. Logistic regression was used to examine the association between these factors, with adjustment for confounders and potential childhood mediators.ResultsChildren born full term but weighing less than 5.5 lb had increased odds of psychological distress in later life after adjustment for potential confounders (OR=1.49, 95% CI 1.01–2.20). Further adjustment for childhood IQ and behaviour did not attenuate the association. A 1 s.d. decrease in birth weight for gestational age was associated with a 4% increased odds of psychological distress in adulthood (OR=1.04, 95% CI 0.97–1.12).ConclusionsLow birth weight for gestational age, particularly atterm, was associated with adult psychological distress. This was not mediated by childhood factors, suggesting a direct effect of early life factors on adult mental health. A neurodevelopmental pathway may therefore be implicated.
The role of proteomics in investigating psychiatric disorders
Authors: Pennington K. , Cotter D. , Dunn M. J. 
Published: July 2005

SummaryProteomics is the study of protein expression and function on a genome-wide scale and its application in psychiatric research is relatively new. As protein expression is the mediator of genetic vulnerabilities, it is critical that this area is explored further to increase our understanding of psychiatric disease and reveal potential new treatments.
Socio-economic inequalities in suicide: A European comparative study
Authors: Lorant Vincent , Kunst Anton E. , Huisman Martijn , Costa Giuseppe , Mackenbach Johan 
Published: July 2005

BackgroundSocial factors have been shown to be predictors of suicide. It is not known whether these factors vary between countries.AimsTo present a first European overview of socio-economic inequalities in suicide mortality among men and women.MethodWe used a prospective follow-up of censuses matched with vital statistics in ten European populations. Directly standardised rates of suicide were computed for each country.ResultsIn men, a low level of educational attainment was a risk factor for suicide in eight out often countries. Suicide inequalities were smaller and less consistent in women. In most countries, the greater the socio-economic disadvantage, the higher is the risk of suicide. The population of Turin evidenced no socio-economic inequalities.ConclusionsSocio-economic inequalities in suicide are a generalised phenomenon in western Europe, but the pattern and magnitude of these inequalities vary between countries. These inequalities call for improved access to psychiatric care for lower socio-economic groups.
Modafinil modulates anterior cingulate function in chronic schizophrenia
Authors: Spence Sean A. , Green Russell D. , Wilkinson Iain D. , Hunter Mike D. 
Published: July 2005

BackgroundSchizophrenia is associated with widespread cognitive deficits that have an impact on social function. Modafinil promotes wakefulness and is reported to enhance cognition.AimsTo study the acute effects of modafinil administration upon brain activity and cognitive performance in people with chronic schizophrenia.MethodIn a randomised double-blind placebo-controlled crossover design, 19 patients received either modafinil (100 mg) or placebo prior to undertaking a working memory task with functional magnetic resonance imaging.ResultsSeventeen patients completed the study and another underwent acute relapse 4 days post-drug. Modafinil administration was associated with significantly greater activation in the anterior cingulate cortex during the working memory task. The anterior cingulate cortex signal correlated with cognitive performance, although only a subset of patients exhibited ‘enhancement’.ConclusionsModafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation.
Outcomes of crises before and after introduction of a crisis resolution team
Authors: Johnson Sonia , Nolan Fiona , Hoult John , White Ian R. , Bebbington Paul , Sandor Andrew , McKenzie Nigel , Patel Sejal N. , Pilling Stephen 
Published: July 2005

BackgroundCrisis resolution teams (CRTs) are being introduced throughout England, but their evidence base is limited.AimsTo compare outcomes of crises before and after introduction of a CRT.MethodA new methodology was developed for identification and operational definition of crises. A quasi-experimental design was used to compare cohorts presenting just before and just after a CRT was established.ResultsFollowing introduction of the CRT, the admission rate in the 6 weeks after a crisis fell from 71% to 49% (OR 0.38, 95% CI 0.21–0.70). A difference of 5.6 points (95% CI 2.0–8.3) on mean Client Satisfaction Questionnaire (CSQ–8) score favoured the CRT. These findings remained significant after adjustment for baseline differences. No clear difference emerged in involuntary hospitalisations, symptoms, social functioning or quality of life.ConclusionsCRTs may prevent some admissions and patients prefer them, although other outcomes appear unchanged in the short term.
Triage in mental health – a new model for acute in-patient psychiatry
Authors: Inglis Gary , Baggaley Martin 
Published: July 2005

Aims and MethodIn-patient psychiatric care needs urgent improvement and development. A new model of psychiatric care (triage) has been used for 6 months across an adult psychiatric service covering a London borough.ResultsPreliminary results show that the new model has reduced bed occupancy, leading to more-efficient throughput, with positive feedback from patients and staff. Important factors contributing to these positive changes include a whole-systems approach, senior medical input 6 days a week, creative use of information technology and a highly skilled multidisciplinary team.Clinical ImplicationsThe introduction of the new model has resulted in a more-efficient use of beds. Further evaluation will enable us to assess the impact on other parts of the service. As with all innovations, the improvements must be sustained once the initial enthusiasm has passed.
G Protein-Coupled Receptor Kinase 2 Mediates Endothelin-1-Induced Insulin Resistance via the Inhibition of Both Gαq/11 and Insulin Receptor Substrate-1 Pathways in 3T3-L1 Adipocytes
Authors: Usui Isao , Imamura Takeshi , Babendure Jennie L. , Satoh Hiroaki , Lu Juu-Chin , Hupfeld Christopher J. , Olefsky Jerrold M. 
Published: July 2005

Abstract
G protein-coupled receptor kinases (GRKs) regulate seven-transmembrane receptors (7TMRs) by phosphorylating agonist-activated 7TMRs. Recently, we have reported that GRK2 can function as a negative regulator of insulin action by interfering with G protein-q/11 α-subunit (Gαq/11) signaling, causing decreased glucose transporter 4 (GLUT4) translocation. We have also reported that chronic endothelin-1 (ET-1) treatment leads to heterologous desensitization of insulin signaling with decreased tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and Gαq/11, and decreased insulin-stimulated glucose transport in 3T3-L1 adipocytes. In the current study, we have investigated the role of GRK2 in chronic ET-1-induced insulin resistance. Insulin-induced GLUT4 translocation was inhibited by pretreatment with ET-1 for 24 h, and we found that this inhibitory effect was rescued by microinjection of anti-GRK2 antibody or GRK2 short interfering RNA. We further found that GRK2 mediates the inhibitory effects of ET-1 by two distinct mechanisms. Firstly, adenovirus-mediated overexpression of either wild-type (WT)- or kinase-deficient (KD)-GRK2 inhibited Gαq/11 signaling, including tyrosine phosphorylation of Gαq/11 and cdc42-associated phosphatidylinositol 3-kinase activity. Secondly, ET-1 treatment caused Ser/Thr phosphorylation of IRS-1 and IRS-1 protein degradation. Overexpression of KD-GRK2, but not WT-GRK2, inhibited ET-1-induced serine 612 phosphorylation of IRS-1 and restored activation of this pathway. Taken together, these results suggest that GRK2 mediates ET-1-induced insulin resistance by 1) inhibition of Gαq/11 activation, and this effect is independent of GRK2 kinase activity, and 2) GRK2 kinase activity-mediated IRS-1 serine phosphorylation and degradation.
Regulation of Protein Kinase B Tyrosine Phosphorylation by Thyroid-Specific Oncogenic RET/PTC Kinases
Authors: Jung Hye Sook , Kim Dong Wook , Jo Young Suk , Chung Hyo Kyun , Song Jung Hun , Park Jong Sun , Park Ki Cheol , Park Su Hyeon , Hwang Jung Hwan , Jo Ki-Won , Shong Minho 
Published: July 2005

Abstract
Papillary thyroid carcinoma (PTC) is a heterogenous disorder characterized by unique gene rearrangements and gene mutations that activate signaling pathways responsible for cellular transformation, survival, and antiapoptosis. Activation of protein kinase B (PKB) and its downstream signaling pathways appears to be an important event in thyroid tumorigenesis. In this study, we found that the thyroid-specific oncogenic RET/PTC tyrosine kinase is able to phosphorylate PKB in vitro and in vivo. RET/PTC-transfected cells showed tyrosine phosphorylation of endogenous and exogenous PKB, which was independent of phosphorylation of T308 and S473 regulated by the upstream kinases phosphoinositide-dependent kinase-1 and -2, respectively. The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity. The activation of PKB by RET/PTC blocked the activity of the forkhead transcription factor, FKHRL1, but a Y315F mutant of PKB failed to inhibit FKHRL1 activity. In summary, these observations suggest that RET/PTC is able to phosphorylate the Y315 residue of PKB, an event that results in maximal activation of PKB for RET/PTC-induced thyroid tumorigenesis.
The N-Terminal Juxtamembrane Segment of the V1a Vasopressin Receptor Provides Two Independent Epitopes Required for High-Affinity Agonist Binding and Signaling
Authors: Hawtin Stuart R. , Wesley Victoria J. , Simms John , Argent Cymone C. H. , Latif Khalid , Wheatley Mark 
Published: July 2005

AbstractIt is fundamentally important to define how agonist-receptor interaction differs from antagonist-receptor interaction. The V1a vasopressin receptor (V1aR) is a member of the neurohypophysial hormone subfamily of G protein-coupled receptors. Using alanine-scanning mutagenesis of the N-terminal juxtamembrane segment of the V1aR, we now establish that Glu54 (1.35) is critical for arginine vasopressin binding. The mutant [E54A]V1aR exhibited decreased arginine vasopressin affinity (1700-fold) and disrupted signaling, but antagonist binding was unaffected. Mutation of Glu54 had an almost identical pharmacological effect as mutation of Arg46, raising the possibility that agonist binding required a mutual interaction between Glu54 and Arg46. The role of these two charged residues was investigated by 1) substituting Glu54; 2) inserting additional Glu/Arg in transmembrane helix (TM) 1; 3) repositioning the Glu/Arg in TM1; and 4) characterizing the reciprocal mutant [R46E/E54R]V1aR. We conclude that 1) the positive/negative charges need to be precisely positioned in this N terminus/TM1 segment; and 2) Glu54 and Arg46 function independently, providing two discrete epitopes required for high-affinity agonist binding and signaling. This study explains why Glu and Arg, part of an -R(X3)L/V(X3)E(X3)L- motif, are conserved at these loci throughout this G protein-coupled receptor subfamily and provides molecular insight into key differences between agonist and antagonist binding requirements.
Self-Associative Properties of Quinoline Derivatives in Solution
Authors: Latypov Shamil , Fakhfakh Mohammed A , Jullian Jean-Christophe , Franck Xavier , Hocquemiller Reynald , Figadère Bruno 
Published: July 2005

Abstract
Experimental data from proton NMR studies combined with ab initio calculations (energy and GIAO chemical shifts) indicated that quinoline(s), in solution, exist in equilibrium as a series of stacks (dimers or n-mers) that are slightly different in mutual orientation. The self-association constant depends dramatically on the concentration of the substrate: at low concentration, recognition occurs and dimerization, with association constants that are approximately 200 times larger than for higher n-mers at higher concentration, was observed.
Anion Recognition by 1,3-Benzenedisulfonamide Derivatives Bearing Phenolic Hydroxy Groups in MeCN-d3
Authors: Kondo Shin-ichi , Suzuki Takashi , Toyama Takuya , Yano Yumihiko 
Published: July 2005

Abstract
The halide anion recognition by 1,3-benzenedisulfonamides derived from 2-aminophenols was studied by 1H NMR titrations in MeCN-d3. The results demonstrated that the receptors achieved high recognition ability with chloride anion.
Rotational Isomerism Involving an Acetylenic Carbon VII. Restricted Rotation about Acetylenic Axis in a Diphenylethyne Derivative with Sterically Crowded m-Terphenyl Moieties
Authors: Toyota Shinji , Yanagihara Takashi , Yoshida Yukihiro , Goichi Michio 
Published: July 2005

Abstract
Bis(2,4,4″,6-tetramethyl-1,1′:3′,1″-terphenyl-2′-yl)ethyne was prepared by the Hart reaction and the Stille coupling as a sterically crowded diphenylethyne derivative. The barrier to rotation about the acetylenic axis was determined by the dynamic NMR method to be 51 kJ mol−1. The restricted rotation is attributed to the steric hindrance of the two mesityl groups in the m-terphenyl moieties.
Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic–pituitary–adrenal axis
Authors: Johnson Elizabeth O , Kamilaris Themis C , Calogero Aldo E , Gold Philip W , Chrousos George P 
Published: July 2005

Objective: Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary–adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic–pituitary–adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex.
Methods: The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 μg of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1α stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined.
Results: Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1α administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated with a significant reduction in adrenocortical reserve. A significant increase in adrenal weights and a decrease in thymus weights were observed in both short- and long-term hyperthyroidism.
Conclusions: The available data confirms that hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally affected still remains unclear. Despite the sustained hyperactivity of the HPA axis, long-term experimentally-induced hyperthyroidism is associated with diminished adrenal functional reserve. The alterations in HPA function in states of disturbed thyroid function were found to be somewhat more pronounced as the duration of thyroid dysfunction increased.
An individualized GH dose regimen for long-term GH treatment in Japanese patients with adult GH deficiency
Authors: Chihara Kazuo , Koledova Ekaterina , Shimatsu Akira , Kato Yuzuru , Kohno Hitoshi , Tanaka Toshiaki , Teramoto Akira , Bates Peter C , Attanasio Andrea F 
Published: July 2005

Objectives: To investigate the effects of growth hormone (GH) treatment, using a dose-adjustment regimen based on serum insulin-like growth factor (IGF)-I concentrations, in adult Japanese hypopituitary patients with GH deficiency.
Study design: Japanese patients who had initially been administered GH (n = 31) or placebo (n = 28) in a 24-week double-blind study received individualized GH treatment in an open-label study for 48 weeks. Body composition from dual-energy X-ray absorptiometry (DXA) and serum IGF-I, IGF-binding protein 3 (IGFBP-3) and lipid levels were determined centrally.
Results: Significant increases in lean body mass (4.5%) and decreases in fat mass (−10.5%) were observed in the group that received individualized GH doses in the present open-label study following placebo in the double-blind study. This was comparable with the changes observed in these parameters (4.7 and −9.2%, respectively) with fixed-dose GH treatment in the double-blind study; this latter group maintained these improvements throughout the open-label study. Individualized dose adjustment allowed for more moderate dose increases than the fixed-dose titration method. Individualized dosing also resulted in a lower mean dose for adult-onset compared with childhood-onset GH-deficient patients (0.032±0.019 versus 0.061±0.023 mg/kg per week for patients treated with GH for 48 weeks in the open-label study following placebo in the double-blind study). Dosing patterns in the two groups were paralleled by the changes in IGF-I and IGFBP-3. The incidence of oedema and cases with high IGF-I level were less frequent under the IGF-I controlled regimen compared with those during the fixed-dose titration method.
Conclusion: Individualized GH administration based on IGF-I levels was safe and effective. This regimen demonstrated differences in dose requirements between adult- and childhood-onset patients. An individualized dose regimen is recommended in adult Japanese GH-deficient patients.
Development and clinical impact of thyroglobulin antibodies in patients with differentiated thyroid carcinoma during the first 3 years after thyroidectomy
Authors: Görges R , Maniecki M , Jentzen W , Sheu Sie n-Yi , Mann K , Bockisch A , Janssen O E 
Published: July 2005

Objective and design: Cross-sectional studies have reported an increased prevalence of circulating thyroglobulin autoantibodies (TgAbs) in patients with differentiated thyroid carcinoma (DTC). With the advent of more sensitive assays, a longitudinal study monitoring the development of TgAb levels after ablative therapy was warranted.
Methods: One hundred and twelve consecutive patients with follicular cell-derived thyroid cancer were followed for 3 years. All patients had been thyroidectomized and received, on average, two radioiodine therapies. Residual tissue was quantified scintigraphically by 131I 24-h uptake. TgAb and thyroglobulin (Tg) serum levels were determined with a sensitive direct radioligand assay and an IRMA respectively.
Results: The prevalence of TgAbs at the initial examination was 29% (median 130 U/ml). During follow-up, TgAb levels rose transiently in one-tenth of the patients, but the prevalence of demonstrable TgAbs decreased to <10% after 3 years. The median serum half-life of TgAbs in treated DTC patients was 10 weeks. At initial examination (when all patients still had residual thyroid tissue and 17 had metastases), rising TgAb levels were correlated with the inability to detect Tg in 4, 30 and 73% of the patients, when initial TgAbs were <6, 6–50 or >50 U/ml respectively. While the Tg recovery test was valid for all patients, an in vitro dilution assay with TgAb serum reduced Tg values by up to 32%.
Conclusions: The development and course of TgAbs in DTC patients cannot be predicted by initial or residual tumour volume, TgAb or Tg levels. The presence of TgAbs, even in low concentrations, may cause Tg underestimation despite valid recovery tests in DTC patients.
p38 mitogen-activated protein kinase contributes to cell cycle regulation by cAMP in FRTL-5 thyroid cells
Authors: Corrèze C , Blondeau J-P , Pomérance M 
Published: July 2005

Objective: Thyrotropin activates the cAMP pathway in thyroid cells, and stimulates cell cycle progression in cooperation with insulin or insulin-like growth factor-I. Because p38 mitogen-activated protein kinases (p38 MAPKs) were stimulated by cAMP in the FRTL-5 rat thyroid cell line, we investigated (i) the effect of the specific inhibition of p38 MAPKs on FRTL-5 cell proliferation and (ii) the mechanism of action of p38 MAPKs on cell cycle control, by studying the expression and/or the activity of several cell cycle regulatory proteins in FRTL-5 cells.Methods: DNA synthesis was monitored by incorporation of [3H]thymidine into DNA and the cell cycle distribution was assessed by fluorescence-activated cell sorter analysis. Expression of cell cycle regulatory proteins was determined by Western blot analysis. Cyclin-dependent kinase 2 (Cdk2) activity associated to cyclin E was immunoprecipitated and was measured by anin vitrokinase assay.Results: SB203580, an inhibitor of α and β isoforms of p38 MAPKs, but not its inactive analog SB202474, inhibited DNA synthesis and the G1-S transition induced by forskolin plus insulin. SB203580 inhibited specifically p38 MAPK activity but not other kinase activities such as Akt and p70-S6 kinase. Treatment of FRTL-5 cells with SB203580 decreased total and cyclin E-associated Cdk2 kinase activity stimulated with forskolin and insulin. However, inhibition of p38 MAPKs by SB203580 was without effect on total cyclin E and Cdk2 levels. The decrease in Cdk2 kinase activity caused by SB203580 treatment was not due to an increased expression of p21Cip1or p27Kip1inhibitory proteins. In addition, SB203580 affected neither Cdc25A phosphatase expression nor Cdk2 Tyr-15 phosphorylation. Inhibition of p38 MAPKs decreased Cdk2-cyclin E activation by regulating the subcellular localization of Cdk2 and its phosphorylation on Thr-160.Conclusions: These results indicate that p38 MAPK activity is involved in the regulation of cell cycle progression in FRTL-5 thyroid cells, at least in part by increasing nuclear Cdk2 activity.