bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation in neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes blocks ethanol action
Authors: BORGHESE CECILIA , WANG LINGNA , BLECK VIRGINIA , HARRIS R ADRON 
Published: November 2003

AbstractAmino acids (AAs) in the extracellular portion of the transmembrane domain of several inhibitory ligand‐gated ion channels participate in an alcohol binding site. To extend these studies to neuronal nicotinic acetylcholine receptors (nAChRs), we focused on an AA (L262) located in the same region of the second transmembrane domain of the α2 subunit of neuronal nAChRs. Single‐point mutation of α2L262 was carried out, the resulting α2 subunits co‐expressed with wild‐type β4 subunits in Xenopus laevis oocytes, and studied using two‐electrode voltage clamp. Ethanol enhancement of ACh responses was diminished [α2(L262F)β4] or abolished [α2(L262G)β4, α2(L262S)β4 and α2(L262A)β4]. Mutation of the homologous AA in β4 [β4(L258A)] did not modify the ethanol modulation and the mutation in α2 was dominant, because ethanol did not enhance ACh responses in α2(L262A)β4(L258A) nAChRs. n‐Alcohols (ethanol through octanol) were applied to α2(L262A)β4 nAChRs. As described previously for other nAChRs, short‐chain alcohols enhanced, intermediate‐chain alcohols had no effect and long‐chain alcohols inhibited ACh responses in the wild‐type receptor. For α2(L262A)β4 nAChRs the alcohol enhancing effect was absent, and the alcohol inhibitory action was increased. Although this suggests removal of an alcohol enhancing site through mutagenesis, we cannot rule out the enhancement of action at an alcohol inhibitory site.
Changes in G‐protein activity mediated through the stimulation of dopamine and GABA B receptors in the mesolimbic dopaminergic system of morphine‐sensitized mice
Authors: NARITA MINORU , SHIBASAKI MASAHIRO , MIZUO KEISUKE , SUZUKI TSUTOMU 
Published: November 2003

AbstractThe behavioural sensitization has been recognized as the increased behavioural response and the undesirable long‐lasting changes in brain functions after repeated administration of abuse drugs. We examined whether behavioural sensitization to hyperlocomotion induced by intermittent morphine treatment could result from any changes in dopamine and GABA B receptor functions to activate G‐proteins in the brain rewarding system in mice. Intermittent morphine treatment results in the upregulation of dopamine receptor‐regulated G‐protein activation in the mouse limbic forebrain, whereas this treatment causes the downregulation of GABA B receptor function to activate G‐protein in the mouse lower midbrain. In behavioural experiments, intermittent administration of morphine in combination with either a dopamine receptor antagonist haloperidol or a GABA B receptor agonist baclofen abolished the development of sensitization to morphine‐induced hyperlocomotion. The present data provide evidence that these G‐protein activation changes may lead to behavioural sensitization to morphine‐induced hyperlocomotion in mice.
A pilot study to assess the impact of naltrexone implant on accidental opiate overdose in ‘high‐risk’ adolescent heroin users
Authors: HULSE GARY , TAIT ROBERT J. 
Published: November 2003

AbstractMorbidity and mortality rates for regular heroin users are much greater than those observed in the general population. In ‘high‐risk’ heroin users implantable naltrexone has been used under Commonwealth Therapeutic Goods Administration Compassionate guidelines in Western Australia since August 2000. This pilot study compared the frequency of accidental opiate overdose and other morbidity resulting in hospital presentations in eight ‘high‐risk’ dependent heroin using adolescents pre‐ and post‐naltrexone implant treatment. We reviewed the hospital medical records retrospectively for the participants across the four public hospitals in Perth. The review period was September 1999‐October 2002. The eight adolescents (aged 15–19 years) initially underwent naltrexone implant treatment between September 2000 and September 2001. The data indicated a dramatic reduction in opiate overdose post‐implantable naltrexone treatment, with a smaller reduction in opiate overdose during oral naltrexone treatment compared to the pre‐oral/implant period. Implant treatment in the high‐risk heroin user may provide an important prophylaxis against mortality associated with accidental opiate overdose. These encouraging findings now require validation using a larger cohort over an extended period.
Writing with voice: an investigation of the use of a voice recognition system as a writing aid for a man with aphasia
Authors: Bruce Carolyn , Edmundson Anne , Coleman Michael 
Published: November 2003

AbstractBackground: People with aphasia may experience difficulties that prevent them from demonstrating in writing what they know and can produce orally. Voice recognition systems that allow the user to speak into a microphone and see their words appear on a computer screen have the potential to assist written communication.Aim: This study investigated whether a man with fluent aphasia could learn to use Dragon NaturallySpeaking® to write.Methods & Procedures: A single case study of a man with acquired writing difficulties is reported. A detailed account is provided of the stages involved in teaching him to use the software. The therapy tasks carried out to develop his functional use of the system are then described. Outcomes included the percentage of words accurately recognized by the system over time, the quantitative and qualitative changes in written texts produced with and without the use of the speech‐recognition system, and the functional benefits the man described.Outcomes & Results: The treatment programme was successful and resulted in a marked improvement in the subject's written work. It also had effects in the functional life domain as the subject could use writing for communication purposes.Conclusions: The results suggest that the technology might benefit others with acquired writing difficulties.
Functional and Phylogenetic Analyses of a Conserved Regulatory Program in the Phloem of Minor Veins
Authors: Ayre Brian G. , Blair Jaime E. , Turgeon Robert 
Published: November 2003

AbstractThe minor-vein phloem of mature leaves is developmentally and physiologically distinct from the phloem in the rest of the vascular system. Phloem loading of transport sugars occurs in the minor veins, and consistent with this, galactinol synthase is expressed in the minor veins of melon (Cucumis melo) as part of the symplastic-loading mechanism that operates in this species. A galactinol synthase promoter from melon drives gene expression in the minor-vein companion cells of both transgenic tobacco (Nicotiana tabacum) and Arabidopsis. Neither of these plants use galactinol in the phloem-loading process, implying that the promoter responds to a minor-vein-specific regulatory cascade that is highly conserved across a broad range of eudicotyledons. Detailed analysis of this promoter by truncation and mutagenesis identified three closely coupled sequences that unambiguously modulate tissue specificity. These sequences cooperate in a combinatorial fashion: two promote expression throughout the vascular system of the plant, whereas the third functions to repress expression in the larger bundles. In a complementary approach, phylogenetic footprinting was used to obtain single-nucleotide resolution of conserved sites in orthologous promoters from diverse members of the Cucurbitaceae. This comparative analysis confirmed the importance of the closely coupled sites but also revealed other highly conserved sequences that may modulate promoter strength or contribute to expression patterns outside of the phloem. The conservation of this regulatory design among species that phloem load by different mechanisms supports a model for organismal development in which tissues and cell types are controlled by relatively ancient and conserved paradigms but expression of genes influencing final form and function are relatively plastic.
SAGE Analysis of Transcriptome Responses in Arabidopsis Roots Exposed to 2,4,6-Trinitrotoluene
Authors: Ekman Drew R. , Lorenz W. Walter , Przybyla Alan E. , Wolfe N. Lee , Dean Jeffrey F.D. 
Published: November 2003

Abstract
Serial analysis of gene expression was used to profile transcript levels in Arabidopsis roots and assess their responses to 2,4,6-trinitrotoluene (TNT) exposure. SAGE libraries representing control and TNT-exposed seedling root transcripts were constructed, and each was sequenced to a depth of roughly 32,000 tags. More than 19,000 unique tags were identified overall. The second most highly induced tag (27-fold increase) represented a glutathione S-transferase. Cytochrome P450 enzymes, as well as an ABC transporter and a probable nitroreductase, were highly induced by TNT exposure. Analyses also revealed an oxidative stress response upon TNT exposure. Although some increases were anticipated in light of current models for xenobiotic metabolism in plants, evidence for unsuspected conjugation pathways was also noted. Identifying transcriptome-level responses to TNT exposure will better define the metabolic pathways plants use to detoxify this xenobiotic compound, which should help improve phytoremediation strategies directed at TNT and other nitroaromatic compounds.
PRT1 of Arabidopsis Is a Ubiquitin Protein Ligase of the Plant N-End Rule Pathway with Specificity for Aromatic Amino-Terminal Residues
Authors: Stary Susanne , Yin Xiao-jun , Potuschak Thomas , Schlögelhofer Peter , Nizhynska Victoria , Bachmair Andreas 
Published: November 2003

Abstract
The gene PRT1 of Arabidopsis, encoding a 45-kD protein with two RING finger domains, is essential for the degradation of F-dihydrofolate reductase, a model substrate of the N-end rule pathway of protein degradation. We have determined the function of PRT1 by expression in yeast (Saccharomyces cerevisiae). PRT1 can act as a ubiquitin protein ligase in the heterologous host. The identified substrates of PRT1 have an aromatic residue at their amino-terminus, indicating that PRT1 mediates degradation of N-end rule substrates with aromatic termini but not of those with aliphatic or basic amino-termini. Expression of model substrates in mutant and wild-type plants confirmed this substrate specificity. A ligase activity exclusively devoted to aromatic amino-termini of the N-end rule pathway is apparently unique to plants. The results presented also imply that other known substrates of the plant N-end rule pathway are ubiquitylated by one or more different ubiquitin protein ligases.
Reexamining the Role of the Accessory Plasmid pAtC58 in the Virulence of Agrobacterium tumefaciens Strain C58
Authors: Nair Gauri R. , Liu Zhenying , Binns Andrew N. 
Published: November 2003

Abstract
Isogenic strains of Agrobacterium tumefaciens carrying pTiC58, pAtC58, or both were constructed and assayed semiquantitatively and quantitatively for virulence and vir gene expression to study the effect of the large 542-kb accessory plasmid, pAtC58, on virulence. Earlier studies indicate that the att (attachment) genes of A. tumefaciens are crucial in the ability of this soil phytopathogen to infect susceptible host plants. Mutations in many att genes, notably attR and attD, rendered the strain avirulent. These genes are located on pAtC58. Previous work also has shown that derivatives of the wild-type strain C58 cured of pAtC58 are virulent as determined by qualitative virulence assays and, hence, pAtC58 was described as nonessential for virulence. We show here that the absence of pAtC58 in pTiC58-containing strains results in reduced virulence but that disruption of the attR gene does not result in avirulence or a reduction in virulence. Our studies indicate that pAtC58 has a positive effect on vir gene induction as revealed by immunoblot analysis of Vir proteins and expression of a PvirB::lacZ fusion.
Site-Specific Integration ofAgrobacterium tumefaciensT-DNA via Double-Stranded Intermediates
Authors: Tzfira Tzvi , Frankman Leah Renée , Vaidya Manjusha , Citovsky Vitaly 
Published: November 2003

AbstractAgrobacterium tumefaciens-mediated genetic transformation involves transfer of a single-stranded T-DNA molecule (T strand) into the host cell, followed by its integration into the plant genome. The molecular mechanism of T-DNA integration, the culmination point of the entire transformation process, remains largely obscure. Here, we studied the roles of double-stranded breaks (DSBs) and double-stranded T-DNA intermediates in the integration process. We produced transgenic tobacco (Nicotiana tabacum) plants carrying an I-SceI endonuclease recognition site that, upon cleavage with I-SceI, generates DSB. Then, we retransformed these plants with two A. tumefaciens strains: one that allows transient expression of I-SceI to induce DSB and the other that carries a T-DNA with the I-SceI site and an integration selection marker. Integration of this latter T-DNA as full-length and I-SceI-digested molecules into the DSB site was analyzed in the resulting plants. Of 620 transgenic plants, 16 plants integrated T-DNA into DSB at their I-SceI sites; because DSB induces DNA repair, these results suggest that the invading T-DNA molecules target to the DNA repair sites for integration. Furthermore, of these 16 plants, seven plants incorporated T-DNA digested with I-SceI, which cleaves only double-stranded DNA. Thus, T-strand molecules can be converted into double-stranded intermediates before their integration into the DSB sites within the host cell genome.
Prostate cancer management: (1) an update on localised disease
Authors: Bott S R J , Birtle A J , Taylor C J , Kirby R S 
Published: November 2003

Abstract
Prostate cancer is receiving ever more publicity with the result that more men are having their prostate specific antigen checked and a greater proportion of men are diagnosed with potentially curable localised disease. Advances in the therapeutic modalities including radical surgery, external beam radiotherapy, and brachytherapy have reduced the incidence of side effects and now offer patients a choice of treatments depending on their tumour characteristics, age, and co-morbidity. A significant proportion of men do not need intervention and may be safely kept under a “watch and wait” policy. The use of genetic markers may in the future distinguish between patients most likely to benefit from radical therapy and those in who either palliation or observation is more appropriate. This review examines the potentially curative options, as well as expectant management, outlining the pros and cons of each. The use of adjuvant and neoadjuvant therapy is also discussed.
Inpatient management of diabetes: survey in a tertiary care centre
Authors: Deepak P J , Sunitha K , Nagaraj J , Sanjukta A , Bhattacharyya A 
Published: November 2003

Abstract

Aims
Good glycaemic control in hospitalised patients with diabetes mellitus improves wellbeing and aids recovery. This survey aimed to: (1) assess glycaemic control in patients with diabetes admitted to hospital for reasons other than diabetes, (2) compare the glycaemic control in patients treated in medical and surgical units, and (3) see the impact of specialists’ input on glycaemic control.

Methods
The first 150 patients admitted to hospital were identified; those with acute metabolic complications of diabetes mellitus, acute myocardial infarction, pregestational or gestational diabetes, and patients in different intensive care units were excluded. Case notes were reviewed with particular attention to glycaemic control, frequency of blood monitoring, complications, and the actions taken to improve glycaemic control.

Results
Four of the 150 patients died in hospital. When subcutaneous insulin was used glycaemic control was good in 48%, suboptimal in 15%, and poor in 37% of patients. The results were not significantly different with subcutaneous or intravenous insulin. There was also no difference in glycaemic control among medical and surgical patients. Patients managed by designated specialists had better control than those managed by physicians (p&lt;0.001). Hypoglycaemia was documented in 20% and two patients developed non-ketotic hyperosmolar coma while in hospital. In a few cases treatment at discharge was not changed despite poor control while in hospital.

Conclusion
More attention should be given to improving glycaemic control in patients hospitalised for reasons other than diabetes. Particular care should be taken to modify the dose of insulin needed to get good glycaemic control; control was better with specialists’ input. A follow up survey will be conducted.
Examination of the hands: an insight into the health of a Welsh population
Authors: White H A , Alcolado R , Alcolado J C 
Published: November 2003

Abstract
When asked to examine a patient in a clinical examination, undergraduates and postgraduates characteristically begin with a painstaking observation of the hands. It was of concern that this is done mainly for the benefit of the examiners and that, in routine clinical practice, examination of the hands receives scant attention. The case notes of 70 general medical and surgical inpatients were reviewed and it was found that in only seven was there any mention of physical examination of the hands; in three of these “no clubbing” was the only entry. However, when the authors carefully examined the hands of 197 patients, at least one clinical sign was found in 87 (44%) cases. Heberden’s nodes, cigarette tar staining, and the spectrum of Dupuytren’s contractures were the most common findings. In this population in the South Wales valleys, coal deposits were also commonly seen in men.
Role of frozen section histology in diagnosis of infection during revision arthroplasty
Authors: Musso A D , Mohanty K , Spencer-Jones R 
Published: November 2003

Abstract
The accurate diagnosis of deep infection in total joint arthroplasty is difficult. No single test on its own is entirely reliable. Frozen section histology has been used for the last two decades as an adjunct to diagnose infection with variable results. In this retrospective analysis, experience of the use of frozen section histology as a diagnostic tool in 45 cases of suspected infected total joint arthroplasty is reported.
Taking intraoperative cultures as the “gold standard”, the results showed 50% sensitivity, 95% specificity, positive predictive value of 60%, negative predictive value of 92%, and an accuracy of 89%, which is similar to other existing reports in the literature. Based on these findings, the use of frozen section histology in diagnostic work-up of all suspected cases of total joint infection is recommended.
Multiple brain abscesses in a patient with bilateral pulmonary arteriovenous malformations and immunoglobulin deficiency
Authors: Tse K-C , Ooi G C , Wu A , Ho P L , Ip S K , Jim M H , Lam Y M , Fan Y W , Tso W K , Tsang K W 
Published: November 2003

Abstract
A 34 year old Chinese man presented with grand mal seizures complicating multiple brain abscesses caused by mixed oral flora. Because of persistent hypoxaemia contrast spiral thoracic computed tomography was done, which revealed bilateral pulmonary arteriovenous malformations (PAVMs). Concomitant IgA and IgG subclass deficiency was also found. The combination of these two conditions appears to have predisposed this patient to presumably paradoxical septic embolism. The patient’s cerebral condition responded to postoperative antibiotic treatment and he eventually received selective coil embolisation of right lower lobe PAVMs, which relieved his hypoxaemia and dyspnoea.
Both Insulin Resistance and Diabetes inPsammomys obesusUpregulate the Hepatic Machinery Involved in Intracellular VLDL Assembly
Authors: Zoltowska M. , Ziv E. , Delvin E. , Lambert M. , Seidman E. , Levy E. 
Published: November 2003

Objective—In the current study, we examined the mechanisms that regulate hepatic apolipoprotein B (apoB)–containing lipoprotein secretion inPsammomys obesus, a good animal model for the investigation of insulin resistance and diabetes.Methods and Results—When fed chow ad libitum, 22% maintained normoglycemia and normoinsulinemia (group A), 33% exhibited normoglycemia and appreciable hyperinsulinemia (group B), and 45% developed overt diabetes (group C). Body weight gain, plasma free fatty acid elevation, hypertriglyceridemia, and hypercholesterolemia characterized groups B and C. Triton WR-1339 injection, at fasting, resulted in higher plasma VLDL-triglyceride and VLDL-apoB accumulation in groups B and C, suggesting increased VLDL production by the liver. Pulse-chase labeling experiments in cultured hepatocytes with [35S]methionine revealed reduced intracellular degradation and enhanced secretion of newly synthesized apoB in groups B and C. Concomitant with the raised triglyceride and cholesterol contents in the livers of groups B and C, there was an increase in lipogenesis and in the activity of microsomal triglyceride transfer protein, monoacylglycerol acyltransferase, and diacylglycerol transferase. Pretreatment of hepatocytes with proteasomal inhibitors eliminated the differences in apoB secretion among groups A, B, and C.Conclusions—Our data indicate that both insulin resistance and diabetes triggered the intracellular machinery involved in VLDL assembly and secretion.
Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization
Authors: Papayannopoulou Thalia 
Published: November 2003

Abstract
Uncovering the molecular mechanisms governing the exit of stem/progenitor cells from bone marrow to peripheral blood at steady state or after their enforced migration has been an ongoing challenge. Recently, however, several new avenues or paradigms in mobilization have emerged from ever-expanding work in humans subjected to granulocyte colony-stimulating factor (G-CSF) mobilization, as well as from studies in normal and gene-deficient mouse models. Although these developments represent notable advances that met with considerable excitement, they have been quenched by surprising vacillations in subsequent research. This perspective highlights recent developments in mobilization along with their controversies. A full understanding of the directional cues that control the migratory behavior and the fate of stem/progenitor cells once they migrate out of bone marrow will await further experimentation, aiming to bridge our current gaps in knowledge.
Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells
Authors: Clark Fiona J. , Gregg Richard , Piper Karen , Dunnion Debbie , Freeman Lisa , Griffiths Mike , Begum Gulnaz , Mahendra Premini , Craddock Charles , Moss Paul , Chakraverty Ronjon 
Published: November 2003

AbstractChronic graft-versus-host disease (cGVHD) is characterized by a state of profound immunodeficiency in association with alloreactive and autoimmune phenomena. These observations indicate an impairment of immunologic tolerance that could involve both central and peripheral mechanisms. Defective thymic function may contribute to dysregulation of central tolerance, but few studies have addressed peripheral tolerance. Recently a population of CD4+CD25+ T cells (Treg cells) has been characterized, which controls immunologic reactivity in vivo and which on transfer can prevent experimental acute GVHD. We investigated the number and function of peripheral blood CD4+CD25high T cells in patients more than 100 days after allogeneic hematopoietic stem cell transplantation. Patients with cGVHD had markedly elevated numbers of CD4+CD25high T cells as compared to patients without GVHD. CD4+CD25high T cells derived from patients in both groups were of donor origin, lacked markers of recent activation, and expressed intracellular CD152. In contrast to controls, CD4+CD25high T cells derived from patients with cGVHD were characterized by lower surface CD62L expression. In vitro, CD4+CD25high T cells were hyporesponsive to polyclonal stimulation and suppressed the proliferation and cytokine synthesis of CD4+CD25- cells, an effect that was independent of interleukin 10. These results indicate that chronic graft-versus-host injury does not occur as a result of Treg cell deficiency.