bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of regulatory T‐cell suppression – a diverse arsenal for a moving target
Authors: Sojka Dorothy K. , Huang Yu‐Hui , Fowell Deborah J. 
Published: March 2008

SummaryNaturally‐occurring regulatory T cells (Tregs) are emerging as key regulators of immune responses to self‐tissues and infectious agents. Insight has been gained into the cell types and the cellular events that are regulated by Tregs. Indeed, Tregs have been implicated in the control of initial activation events, proliferation, differentiation and effector function. However, the mechanisms by which Tregs disable their cellular targets are not well understood. Here we review recent advances in the identification of distinct mechanisms of Treg action and of signals that enable cellular targets to escape regulation. Roles for inhibitory cytokines, cytotoxic molecules, modulators of cAMP and cytokine competition have all been demonstrated. The growing number of inhibitory mechanisms ascribed to Tregs suggests that Tregs take a multi‐pronged approach to immune regulation. It is likely that the relative importance of each inhibitory mechanism is context dependent and modulated by the inflammatory milieu and the magnitude of the immune response. In addition, the target cell may be differentially susceptible or resistant to distinct Treg mechanisms depending on their activation or functional status at the time of the Treg encounter. Understanding when and where each suppressive tool is most effective will help to fine tune therapeutic strategies to promote or constrain specific arms of Treg suppression.
Apoptosis‐induced inhibition of CD1d‐mediated antigen presentation: different roles for caspases and signal transduction pathways
Authors: Khan Masood A. , Sriram Venkataraman , Renukaradhya Gourapura J. , Du Wenjun , Gervay‐Hague Jacquelyn , Brutkiewicz Randy R. 
Published: March 2008

SummaryThe stimulation of programmed cell death can either enhance or inhibit antigen presentation by classic major histocompatibility complex molecules. In the current study, we report that the induction of apoptosis by topoisomerase I inhibition or elevation of intracellular ceramide levels substantially impairs CD1d‐mediated antigen presentation. In the former case, such a reduction occurred via the regulation of both the p38 mitogen‐activated protein kinases and protein kinase C δ signal transduction pathways as well as the caspase cascade, whereas the latter was p38‐(but not caspase)‐dependent. Confocal microscopic analysis showed an altered intracellular distribution of CD1d following the inhibition topoisomerase I or by an increase in intracellular ceramide levels, that was prevented by p38 and caspase inhibitors. Thus, the induction of apoptosis in antigen presenting cells severely compromises CD1d‐mediated antigen presentation by multiple mechanisms.
The malaria vector mosquito Anopheles gambiae expresses a suite of larval‐specific defensin genes
Authors: Meredith J. M. , Hurd H. , Lehane M. J. , Eggleston P. 
Published: March 2008

AbstractcDNAs of Anopheles gambiae Defensin 2 (AgDef2), Defensin 3 (AgDef3) and Defensin 4 (AgDef4), identified in the genome sequence, have been characterized and their expression profiles investigated. In contrast to both typical defensins and insect antimicrobial peptides generally, the newly identified defensins were not upregulated with acute‐phase kinetics following immune challenge in insects or cell culture. However, mRNA abundance of AgDef2, AgDef3 and AgDef4 increased significantly during the larval stages. Promoter analysis of all three genes failed to identify putative immune response elements previously identified in other mosquito defensin genes. As previous studies failed to identify these larval‐specific defensins, it seems likely that further antimicrobial peptide genes with nontypical expression profiles will be identified as more genome sequences become available.
Identification of aphid salivary proteins: a proteomic investigation of Myzus persicae
Authors: Harmel N. , Létocart E. , Cherqui A. , Giordanengo P. , Mazzucchelli G. , Guillonneau F. , De Pauw E. , Haubruge E. , Francis F. 
Published: March 2008

AbstractThe role of insect saliva in the first contact between an insect and a plant is crucial during feeding. Some elicitors, particularly in insect regurgitants, have been identified as inducing plant defence reactions. Here, we focused on the salivary proteome of the green peach aphid, Myzus persicae. Proteins were either directly in‐solution digested or were separated by 2D SDS‐PAGE before trypsin digestion. Resulting peptides were then identified by mass spectrometry coupled with database investigations. A homemade database was constituted of expressed sequence tags from the pea aphid Acyrtosiphon pisum and M. persicae. The databases were used to identify proteins related to M. persicae with a nonsequenced genome. This procedure enabled us to discover glucose oxidase, glucose dehydrogenase, NADH dehydrogenase, α‐glucosidase and α‐amylase in M. persicae saliva. The presence of these enzymes is discussed in terms of plant–aphid interactions.
The role of Candida albicans FAR1 in regulation of pheromone‐mediated mating, gene expression and cell cycle arrest
Authors: Côte Pierre , Whiteway Malcolm 
Published: March 2008

Summary Candida albicans cells homozygous for the MTLa locus respond to α‐mating pheromone by activating gene expression and triggering morphological changes, and the cells undergo a pheromone‐mediated cell cycle arrest that can be influenced by nutritional conditions. Disruption of C. albicans ORF19.7105, which is the predicted homologue of the yeast FAR1 gene, blocks pheromone‐mediated morphological changes, prevents pheromone‐mediated cell cycle arrest, greatly compromises mating and also blocks pheromone‐triggered gene induction. C. albicans ORF19.7105 is not pheromone inducible, but overexpression of this gene from the actin promoter greatly enhances pheromone‐mediated cell cycle arrest, leading to clear halos in growth inhibition assays on a variety of solid media. Transcriptional profiling of the ORF19.7105‐overexpressing strain has established an enhanced responsiveness of pheromone‐induced genes. Thus the C. albicans FAR1 gene is a dosage‐dependent regulator of the pheromone response, and is critically required for all aspects of mating process of this pathogenic fungus.
Patterns of non‐fatal farm injury in New England, NSW
Authors: WOLFENDEN KEVIN , SANSON‐FISHER ROB 
Published: March 2008

ABSTRACT: The farm is known to be a dangerous place for those who work it, live there or visit. Little however is known about the patterns of injury of these groups or the influence of different farming types. This study used injury surveillance at hospital accident and emergency departments to identify and compare injury patterns by age, status of person, and farm type.Child and adult injury patterns were similar in most regards except the level of occupational and leisure injuries. Differences existed across the various status groups, most markedly between employees/contractors and visitors. There were also marked differences in injury patterns across farm types, reflecting the predominant farm activity.Implications of the injury patterns in developing preventive action are discussed, as is the value of injury surveillance in identifying such variations.
Development of a pilot course in applied pharmacology for nurses working in rural settings
Authors: ALDERMAN CHRISTOPHER P. , COSH DAVID G. , PETERS PETER G. , THOMPSON CHRISTOPHER J. 
Published: March 2008

ABSTRACT: In 1991, the Society of Hospital Pharmacists of Australia (SHPA) made a successful application for a seeding grant for a project entitled ‘An intensive course in applied pharmacology for nurses working in rural settings’. Funding was provided under the Rural Health Support, Education and Training (RHSET) program, and was used to conduct a pilot course in pharmacology and drug information for nurses at the North West Nurse Education Centre, Whyalla, South Australia, during August/September 1991. A total of 40 nurses attended the course and were provided with course materials which contained background information on the topics to be discussed during a two‐day seminar.In a subsequent mailing to 320 nurses currently practising in the rural south‐east region of South Australia, interest levels in a similar seminar proposed for Mount Gambier were canvassed. Keen interest was expressed by nurses working in a variety of country centres in the region, and a formal offer of complimentary use of teaching facilities in the Mount Gambier Hospital was received. A second course was conducted during July 1992, and attracted over 40 nurses from a variety of practice backgrounds. SHPA was able to conduct both courses using considerably less funding than allocated under the original budget of the RHSET grant for the initial project.A statistically significant improvement in participants' pharmacology and drug information knowledge was demonstrated using a multiple choice assessment prior to, and immediately after the course.
Retrieval Principles for Rural GPs
Authors: CABLE GORDON G. 
Published: March 2008

ABSTRACT: The isolated rural general practitioner will, from time to time, be faced with a critically ill patient or medical emergency which requires a higher level of care than can be provided locally. These patients need to be resuscitated, stabilised and transferred to another centre and therefore may need to be escorted by medical personnel. Retrieval services aim to provide a level of expertise and equipment which can be taken to the patient so that management of the patient is optimised prior to transport and continued during transport.The medical retrieval teams which operate from Sydney are:

• Westpac Surf Life Saving Association, based at Prince Henry Hospital;
• NRMA Careflight, based at Westmead Hospital, and
• neonatal teams from Royal Alexandra Hospital for Children and Prince of Wales Children's Hospital.

These teams utilise helicopters provided by NRMA Careflight. SLSA and Childflight and fixed wing aircraft from NSW Air Ambulance. Road ambulance retrievals are also provided within the metropolitan area.Country areas in NSW are serviced by retrieval teams from Base Hospitals such as Orange Base Hospital and Tamworth Base Hospital. These services arc primarily by road, but distance sometimes necessitates the use of fixed or rotary wing aircraft.This paper aims to discuss stabilisation of patients prior to transport. There is nothing more daunting than to have strange medical personnel descend on your local hospital and seemingly ‘take over’. Nursing and medical staff who have been caring for the patient, in many cases for hours, may feel pushed aside and not understand why certain things are done to their patient. This discussion will hopefully shed some light on the mysterious ‘transport environment’ so that personnel at the referring hospital can help prepare the patient appropriately and understand the needs of the retrieval team.
INCREASED CARDIAC SYMPATHETIC DRIVE AND REDUCED VAGAL MODULATION FOLLOWING ENDOTHELIN RECEPTOR ANTAGONISM IN HEALTHY CONSCIOUS RATS
Authors: Souza Hugo CD , Terzini Geisa CSV , Da Silva Valdo JD , Martins‐Pinge Marli C , Salgado Helio C , Salgado Maria‐Cristina O 
Published: March 2008

SUMMARY

The present study evaluated changes in autonomic control of the cardiovascular system in conscious rats following blockade of endothelin (ET) receptors with bosentan.
Rats were treated with bosentan or vehicle (5% gum arabic) for 7 days by gavage.
Baseline heart rate (HR) was higher in the bosentan‐treated group compared with the control group (418 ± 5 vs 357 ± 4 b.p.m., respectively; P < 0.001). This baseline tachycardia was associated with a lower baroreflex sensitivity of the bradycardiac and tachycardiac responses in the bosentan‐treated group compared with the control group. Sequential blockade of the parasympathetic and sympathetic autonomic nervous system with methylatropine and propranolol showed a higher intrinsic HR in the bosentan‐treated group compared with the control group (411 ± 5 vs 381 ± 4 b.p.m., respectively; P < 0.05). This was accompanied by a higher cardiac sympathetic tone (31 ± 1 vs 13 ± 1%, respectively; P < 0.01) and a lower vagal parasympathetic tone (69 ± 2 vs 87 ± 2%, respectively; P < 0.01) in the bosentan‐treated group compared with the control group. Variance and high‐frequency oscillations of pulse interval (PI) variability in absolute and normalized units were lower in the bosentan‐treated group than in the control group. Conversely, low‐frequency (LF) oscillations of PI variability in absolute and normalized units, as well as variance and LF oscillations of systolic arterial pressure variability, were greater in the bosentan‐treated group than the control group.
Overall, the data indicate an increased cardiac sympathetic drive, as well as lower vagal parasympathetic activity and baroreflex sensitivity, in conscious rats after chronic blockade of ET receptors with bosentan.
CARDIOPROTECTION BY l‐GLUTAMATE DURING POSTISCHAEMIC REPERFUSION: REDUCED INFARCT SIZE AND ENHANCED GLYCOGEN RESYNTHESIS IN A RAT INSULIN‐FREE HEART MODEL
Authors: Kristiansen Steen B , Løfgren Bo , Støttrup Nicolaj B , Kimose Hans‐Henrik , Nielsen‐Kudsk Jens E , Bøtker Hans E , Nielsen Torsten T 
Published: March 2008

SUMMARY

Previously, we found that administration of high‐dose l‐glutamate during postischaemic reperfusion improves haemodynamic recovery and enhances glycogen resynthesis. In the present study, we investigated whether the same effect occurs in an insulin‐free model and whether glutamate administration reduces infarct size. Further, we studied whether the cardioprotective effect of glutamate depends on preserved glutamate transamination and KATP channel activity.
In a rat isolated, insulin‐free, perfused heart model, we compared the effects of administration of l‐glutamate (10 mmol/L) during either 45 min no‐flow regional ischaemia plus 120 min reperfusion or reperfusion alone on infarct size and left ventricular (LV) recovery. The effect of glutamate on glycogen metabolism was studied in a model of 30 min global no‐flow ischaemia and 60 min reperfusion. In both models, the effects of inhibition of glutamate transamination and KATP channel activity were examined by adding amino‐oxyacetate (an aminotransferase inhibitor; 0.1 mmol/L) and glibenclamide (a KATP blocker; 10 mmol/L), respectively.
Administration of l‐glutamate reduced infarct size by 60% (P < 0.01) and improved postischaemic LV function (developed pressure and rate pressure product; P < 0.05). l‐Glutamate increased glycogen content after 60 min reperfusion by 65% (P < 0.01). Amino‐oxyacetate, as well as glibenclamide, abolished the glutamate‐mediated reduction in infarct size, haemodynamic improvement and glycogen resynthesis during reperfusion.
In conclusion, l‐glutamate administration from the start of postischaemic reperfusion exerts cardioprotective effects, including reduced infarct size, improved haemodynamic recovery and enhanced glycogen resynthesis. These effects depend on preserved transamination of glutamate and KATP channel activity, but not on insulin administration.
INHIBITION OF ADP‐INDUCED PLATELET AGGREGATION BY CLOPIDOGREL IS RELATED TOCYP2C19GENETIC POLYMORPHISMS
Authors: Chen Bi‐Lian , Zhang Wei , Li Qing , Li Ya‐Lin , He Yi‐Jing , Fan Lan , Wang Lian‐Sheng , Liu Zhao‐Qian , Zhou Hong‐Hao 
Published: March 2008

SUMMARYClopidogrel is one of the most important antithrombotic drugs but has different efficacies in different populations. The aim of the present study was to evaluate the contribution ofCYP2C19genetic polymorphisms to the inhibition of ADP‐induced platelet aggregation by clopidogrel in healthy Chinese volunteers.Eighteen healthy male volunteers (sixCYP2C19*1/CYP2C19*1, sixCYP2C19*1/CYP2C19*2and*3and sixCYP2C19*2/CYP2C19*2and*3) were enrolled in the study. Each subject took 300 mg clopidogrel on the first day and then 75 mg once daily for 2 consecutive days. Blood samples were taken to measure ADP‐induced platelet aggregation at baseline and 4, 24 and 72 h after administration of the first dose of clopidogrel.There were significant decrease in 2 and 5 mmol/L ADP‐induced platelet aggregation at 4, 24 and 72 h after clopidogrel among the three CYP2C19 genotypes compared with baseline (P < 0.001). The change in 5 mmol/L ADP‐induced platelet aggregation in subjects with theCYP2C19*1/CYP2C19*1genotype was greater than that in subjects with theCYP2C19*2/CYP2C19*2and*3genotype at 4 h (49.0 ± 15.5vs29.7 ± 17.4%, respectively;P = 0.029), 24 h (48.7 ± 20.5vs25.0 ± 17.6%, respectively;P = 0.035) and 72 h (45.5 ± 15.2vs26.5 ± 15.8%, respectively;P = 0.030) after clopidogrel administration.In conclusion,CYP2C19*2andCYP2C19*3genetic polymorphisms reduced clopidogrel inhibition of ADP‐induced platelet aggregation, with the degree of inhition dependent on the genetic polymorphism present.
CHRONIC OUABAIN TREATMENT ENHANCES CARDIAC MYOSIN ATPase ACTIVITY IN RATS
Authors: Padilha Alessandra S , Moreira Cleci M , Meira Eduardo F , Siman Fabiana DM , Stefanon Ivanita , Vassallo Dalton V 
Published: March 2008

SUMMARY

Chronic ouabain administration increases blood pressure and produces a positive inotropic effect. However, the temporal changes capable of affecting both arterial and ventricular pressures and myosin ATPase activity during the induced hypertension have not been determined.
The aim of the present study was to investigate the time‐course of the induction of hypertension to define when changes occur in Wistar rats treated with 25 mg/kg per day, s.c., ouabain for 3, 7, 15 or 30 days.
In anaesthetized rats, diastolic blood pressure increased after 7 days treatment with ouabain and after 15 and 30 days treatment, increases were observed in systolic blood pressure, left ventricular systolic pressure and myosin ATPase activity. After 15 days treatment, heart rate (HR) also increased, but after 30 days treatment HR returned to control levels. However, only after 30 days treatment did the left ventricular positive and negative first derivatives of intraventricular pressure (dP/dtmax and dP/dtmin, respectively) increase. Increased arterial and left ventricular systolic pressures and myosin ATPase activity observed after 15 days treatment maintained similar levels as those after 30 days treatment.
The results suggest that changes in arterial and left ventricular pressures, HR and myosin ATPase activity induced by chronic ouabain treatment are time dependent, increasing after 15 days treatment. After 30 days treatment, the increase in systolic and diastolic arterial and ventricular pressures remained stable, as did inotropism. Normalization of HR after 30 days treatment suggests that during the period from Day 16 to Day 30 ouabain‐induced hypertension is dependent, at least in part, on increased sympathetic activity.
CYP2D6*3, *4, *5 AND *6 POLYMORPHISMS AND ANTIPSYCHOTIC‐INDUCED EXTRAPYRAMIDAL SIDE‐EFFECTS IN PATIENTS RECEIVING ANTIPSYCHOTIC THERAPY
Authors: Crescenti Anna , Mas Sergi , Gassó Patricia , Parellada Eduard , Bernardo Miquel , Lafuente Amalia 
Published: March 2008

SUMMARY

The aim of the present study was to examine the relationship between CYP2D6 polymorphisms and the risk of antipsychotic (AP)‐induced extrapyramidal symptoms (EPS) in patients receiving AP treatment. The allele status for CYP2D6*3, CYP2D6*4, CYP2D6*5 and CYP2D6*6 was determined in 267 patients receiving AP therapy. Seventy‐nine cases presenting with EPS (Simpson–Angus > 3) and 188 controls without EPS (Simpson‐Angus £ 3) took part in the study.
We found a non‐significant over‐representation of poor metaboliser genotypes among cases, but a significant association between the mutant homozygous genotype for CYP2D6*4 (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.01–16, permutated P value 0.01) and the heterozygous genotype for CYP2D6*6 (OR 5.4, 95% CI 1.13–18, permutated P value 0.003) and the risk of suffering EPS.
These results suggest that the CYP2D6 genotype may be a contributory factor in the development of EPS in patients undergoing AP therapy.
A NEW ELECTROPHYSIOLOGICAL TOOL TO INVESTIGATE THE SPATIAL NEURONAL PROJECTIONS WITHIN THE MYENTERIC ASCENDING REFLEX OF THE MOUSE COLON
Authors: Sibaev Andrei , Yüce Birol , Allescher Hans‐Dieter , Göke Burkhard , Storr Martin 
Published: March 2008

SUMMARY

The intestinal peristaltic reflex is regulated by local microcircuits that, upon activation, result in an oral contraction and anal relaxation of the circular muscle. This contractile response is associated with typical electrophysiological changes in membrane potential resulting from excitatory and inhibitory myenteric pathways.
The aim of the present study was to investigate the influence of local electrical stimulation (ES; single pulses, 15 V, 0.3 msec duration) on the ascending gastrointestinal electrophysiological potentials of the mouse colon using a novel 12‐channel stimulation electrode in a newly designed model of the ascending myenteric pathways with simultaneous intracellular recording.
Local myenteric reflex responses in the proximal colon were initiated by ES (12 bipolar stimulation electrodes (SE) 0.7 mm apart from each other) and excitatory and inhibitory junction potentials (EJP and IJP, respectively) were recorded from circular smooth muscle cells with intracellular recording techniques. In vivo colonic propulsion was determined by measuring the time to expulsion of a 3 mm glass bead inserted 2.5 cm into the distal colon of mouse.
Under basal conditions, circular smooth muscle cells displayed a stable membrane potential (–56.7 ± 6.9 mV; n = 13). Electrical stimulation elicited a tetrodotoxin (3 µmol/L)‐sensitive, neuronal‐induced EJP (cholinergic; atropine (1 µmol/L) sensitive) and a biphasic IJP. Both the EJP and IJP showed characteristic responses dependent on the distance between stimulation and recording sites. The EJP could be recorded over long distances, resulting in a maximal EJP amplitude at a distance of 10 mm distance (represented by stimulation electrodes (SE) number 6/7) and a maximal projection distance of 18–20 mm. Both components of IJP were maximal during direct stimulation (at SE1; stimulation at the recording site) and gradually decreased to SE6/7 (10 mm). At distances greater than 10 mm apart, ES did not produce IJP. The ganglionic blocker hexamethonium (10–100 µmol/L) concentration dependently abolished all inhibitory junction potentials at distances greater than 10 mm and significantly reduced the amplitude of EJP for the first 10 mm. Colonic propulsion was decreased by hexamethonium (40 mg/kg) and atropine (0.7 mg/kg).
Neuronal circuits of the ascending myenteric reflex functionally project distances ranging up to 18–20 mm. Our newly designed setup allows simultaneous electrophysiological investigations of neuronal microcircuitry within the myenteric plexus over short and long distances and enables conclusions to be drawn regarding neuroneuronal and neuromuscular transmission.