bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular cloning and characterization of avian bombesin‐like peptide receptors: new tools for investigating molecular basis for ligand selectivity
Authors: Iwabuchi Maiko , Ui‐Tei Kumiko , Yamada Kazuhiko , Matsuda Yoichi , Sakai Yasushi , Tanaka Kohichi , Ohki‐Hamazaki Hiroko 
Published: June 2003

Bombesin (BN), originally isolated from amphibians, is structurally related to a family of BN‐like peptides found in mammals, which include gastrin‐releasing peptide (GRP) and neuromedin B (NMB). These peptides have important effects on secretion, smooth muscle contraction, metabolism and behavior. Here we report cloning and characterization of two subtypes of BN‐like peptide receptors in Aves.
The amino‐acid sequence of chick GRP‐R (chGRP‐R) is highly identical with mammalian and amphibian GRP‐R, and this receptor showed high affinity for GRP, BN and synthetic bombesin agonist, [D‐Phe6, β‐Ala11, Phe13, Nle14]bombesin(6–14) ([FAFNl]BN(6–14)). The chGRP‐R gene was localized to chicken chromosome 1q23distal‐q24proximal, where chick homologs of other human X‐linked genes have also been mapped.
ChBRS‐3.5, having sequence similarities to both mammalian bombesin‐like peptide receptor subtype‐3 and amphibian bombesin‐like peptide receptor subtype‐4, showed high affinity for [FAFNl]BN(6–14), moderate affinity for BN, but low affinity for both GRP and NMB.
Expression of both receptors was detected in brain, but only chGRP‐R was expressed in gastrointestinal (GI) tissues.
When expressed in Chinese hamster ovary K1 cells, these receptors mediate intracellular calcium mobilization upon agonist stimulation. These results suggest that a novel BN peptide may occur in Aves as an endogenous ligand for chBRS‐3.5.
The receptor sequences responsible for ligand selectivities were discussed and this knowledge about avian BN‐like peptide receptors will help us to understand the molecular basis for agonist sensitivities of BN‐like peptide receptors.

British Journal of Pharmacology (2003) 139, 555–566. doi:10.1038/sj.bjp.0705282
The antipsychotic drug chlorpromazine inhibits HERG potassium channels
Authors: Thomas Dierk , Wu Kezhong , Kathöfer Sven , Katus Hugo A , Schoels Wolfgang , Kiehn Johann , Karle Christoph A 
Published: June 2003

Acquired long QT syndrome (aLQTS) is caused by prolongation of the cardiac action potential because of blockade of cardiac ion channels and delayed repolarization of the heart. Patients with aLQTS carry an increased risk for torsade de pointes arrhythmias and sudden cardiac death. Several antipsychotic drugs may cause aLQTS. Recently, cases of QTc prolongation and torsade de pointes associated with chlorpromazine treatment have been reported. Blockade of human ether‐a‐go‐go‐related gene (HERG) potassium channels, which plays a central role in arrhythmogenesis, has previously been reported to occur with chlorpromazine, but information on the mechanism of block is currently not available. We investigated the effects of chlorpromazine on cloned HERG potassium channels to determine the biophysical mechanism of block.
HERG channels were heterologously expressed in Xenopus laevis oocytes, and ion currents were measured using the two‐microelectrode voltage‐clamp technique.
Chlorpromazine blocked HERG potassium channels with an IC50 value of 21.6 μM and a Hill coefficient of 1.11.
Analysis of the voltage dependence of block revealed a reduction of inhibition at positive membrane potentials.
Inhibition of HERG channels by chlorpromazine displayed reverse frequency dependence, that is, the amount of block was lower at higher stimulation rates. No marked changes in electrophysiological parameters such as voltage dependence of activation or inactivation, or changes of the inactivation time constant were observed.
In conclusion, HERG channels were blocked in the closed and activated states, and unblocking occurred very slowly.

British Journal of Pharmacology (2003) 139, 567–574. doi:10.1038/sj.bjp.0705283
Homo‐ and heteroexchange of adenine nucleotides and nucleosides in rat hippocampal slices by the nucleoside transport system
Authors: Sperlágh Beáta , Szabó Gábor , Erdélyi Ferenc , Baranyi Mária , Sylvester Vizi E 
Published: June 2003

Here, we investigated how nucleotides and nucleosides affect the release of tritiated purines and endogenous adenosine 5′‐triphosphate (ATP) from superfused rat hippocampal slices.
ATP elicited concentration‐dependent [3H]purine efflux from slices preloaded with [3H]adenosine. High‐performance liquid chromatography analysis of the effluent showed that the tritium label represented the whole set of adenine nucleotides and nucleosides, and ATP significantly increased the outflow of [3H]ATP.
Adenosine 5′‐diphosphate, adenosine, uridine, uridine 5′‐triphosphate, α,β‐methylene‐ATP and 3′‐O‐(4‐benzoylbenzoyl)‐ATP were also active in eliciting [3H]purine release. Adenosine (300 μM) also evoked endogenous ATP efflux from the hippocampal slices.
Reverse transcription‐coupled‐polymerase chain reaction analysis revealed that mRNAs encoding a variety of P2X and P2Y receptor proteins are expressed in the rat hippocampus. Nevertheless, neither P2 receptor (i.e. pyridoxal‐5‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid, 30 μM, suramin, 300 μM and reactive blue 2, 10 μM), nor adenosine receptor (8‐cyclopentyl‐1,3‐dipropylxanthine, 250 nM and dimethyl‐1‐propargylxanthine, 250 nM) antagonists modified the effect of ATP (300 μM) to evoke [3H]purine release.
The nucleoside transport inhibitors, dipyridamole (10 μM), nitrobenzylthioinosine (10 μM) and adenosine deaminase (2–10 U ml−1), but not the ecto‐adenylate kinase inhibitor diadenosine pentaphosphate (200 μM) significantly reduced ATP‐evoked [3H]purine efflux.
In summary, we found that ATP and other nucleotides and nucleosides promote the release of one another and themselves by the nucleoside transport system. This action could have relevance during physiological and pathological elevation of extracellular purine levels high enough to reverse the nucleoside transporter.

British Journal of Pharmacology (2003) 139, 623–633. doi:10.1038/sj.bjp.0705285
Variability in determination of point of needle insertion in peripheral nerve blocks: A comparison of experienced and inexperienced anaesthetists
Authors: Grant S. A. , Breslin D. S. , MacLeod D. B. , Demeyts D. , Martin G. , D'Ercole F. , Hardman D. 
Published: June 2003

SummaryAccurate identification of surface landmarks is essential for the successful performance of peripheral nerve blocks. The variability between experienced and inexperienced practitioners in identifying anatomical landmarks has not been studied previously. Anaesthetists were asked to identify the point of needle insertion for posterior lumbar plexus and sciatic nerve blocks on a volunteer using a standard textbook description. The chosen point for needle insertion was described in terms of X and Y co‐ordinates, measured in millimetres, from a zero reference point marked on a volunteer's back. Fifteen experienced and 22 inexperienced anaesthetists took part in the study. The lumbar plexus block mean [range] values for the X, Y co‐ordinates were 80 [62–108], 66 [46–86] and 92 [49–150], 62 [0–131] in the experienced and inexperienced groups, respectively. The sciatic nerve block X, Y co‐ordinates were 77 [62–99], 70 [49–89] and 68 [29–116], 62 [26–93] in the experienced and inexperienced groups, respectively. The variance for the point of needle insertion was significantly greater in the inexperienced group (p < 0.01) for both the lumbar plexus and sciatic nerve blocks. We conclude that with increasing experience, there is decreased variability in determining the point of needle insertion using anatomical landmarks.
A comparison of intra‐operative or postoperative exposure to music – a controlled trial of the effects on postoperative pain
Authors: Nilsson U. , Rawal N. , Unosson M. 
Published: June 2003

SummaryThe effect of intra‐operative compared to postoperative music on postoperative pain was evaluated in a controlled trial. In all, 151 patients undergoing day case surgery for inguinal hernia repair or varicose vein surgery under general anaesthesia were randomly allocated to three groups: group 1 listened to music intra‐operatively, group 2 listened to music postoperatively and group 3, the control group, listened to ‘white noise’. The anaesthetic and postoperative analgesic techniques were standardised. Pain was assessed using a numeric rating scale (0–10) and patients requirements for postoperative morphine, paracetamol and ibuprofen was recorded. The effect of music on nausea, fatigue and anxiety was also investigated. The results showed that patients exposed to music intra‐operatively or postoperatively reported significantly lower pain intensity at 1 and 2 h postoperatively and patients in the postoperative music group required less morphine at 1 h compared to the control group. No differences were noted in the other variables. This study demonstrates that there is a short‐term pain‐reducing effect of music therapy however, the beneficial effects do not differ if the patient is exposed to music intra‐operatively or postoperatively.
The information requested by patients prior to giving consent to anaesthesia
Authors: Moores A. , Pace N. A. 
Published: June 2003

SummaryPatients in a teaching hospital in Scotland were given the opportunity to ask for further information relating to their peri‐operative anaesthetic management. One investigator visited all of the patients pre‐operatively and asked a standard list of anaesthetic‐related questions. Our objectives were to determine what additional information patients would request before giving their consent to anaesthesia. The majority of patients (n=469, 67%) had no further questions at a point when so‐called consent could have been obtained. Of the questions asked, 209 (66%) were related to anaesthesia and 93 (30%) to the proposed surgery. Only two patients in the group studied requested a full explanation of their peri‐operative anaesthetic management. The question most commonly asked related to the duration of surgery, with less priority being given to questions relating to complications of anaesthesia.
Effect of milrinone on vecuronium‐induced neuromuscular block
Authors: Nakajima H. , Hattori H. , Aoki K. , Katayama T. , Saitoh Y. , Murakawa M. 
Published: June 2003

SummaryWe examined the effect of milrinone, a phosphodiesterase III inhibitor, on neuromuscular block induced by vecuronium. Thirty adult patients were randomly assigned to one of two equal groups: the milrinone group and the control group. Subjects in the milrinone group received an intravenous loading dose of milrinone 5 μg.kg−1.min−1 for 10 min, followed by an infusion at a rate of 0.5 μg.kg−1.min−1. Subjects in the control group received normal saline at a rate of 0.1 ml.kg−1.h−1. Thirty minutes after the beginning of the infusion of milrinone, anaesthesia was induced with intravenous thiopental 4 mg.kg−1 and fentanyl 2 μg.kg−1, and was maintained with isoflurane in oxygen and nitrous oxide. Neuromuscular blockade was monitored electromyographically at the adductor pollicis muscle. The times from the administration of vecuronium 0.1 mg.kg−1 to the onset of neuromuscular block and the return of the first, second, third, and fourth response of the train‐of‐four were compared between the two groups. Times to the recovery of the ratio of the first twitch to the control twitch to 25%, 50% and 75%, and times to the recovery of train‐of‐four ratio to 25%, 50% and 75% were also compared between the two groups. The onset of neuromuscular block in the milrinone group was significantly slower than in the control group. The times to the returns of the four twitches of the train‐of‐four, times to recovery of the ratio of the first twitch to the control twitch to 25% and 50%, and the times to the recovery of the train‐of‐four ratio to 25% and 50% were significantly shorter in the milrinone group than in the control group. We conclude that milrinone delays the onset of neuromuscular blockade but hastens its recovery in anaesthetised patients receiving vecuronium.
Influence of glucose control, lipoproteins, and haemostasis function on brachial endothelial reactivity and carotid intima‐media area, stiffness and diameter in Type 1 diabetes mellitus patients
Authors: Johansson J. , Reichard P. , Jensen‐Urstad K. , Rosfors Stefan , Jensen‐Urstad M. 
Published: June 2003

AbstractBackgroundThe objectives of this study were to determine the influence of glucose control on lipoprotein and haemostasis variables in Type 1 diabetes mellitus patients and to evaluate the global impact of these metabolic risk factors on brachial artery reactivity and carotid artery atherosclerosis, stiffness and diameter.DesignFollow up of Type 1 diabetes patients randomized to insulin‐intensive conventional treatment (ICT,n = 29) or insulin‐standard treatment (ST,n = 25) in the Stockholm Diabetes Intervention Study (SDIS) more than 14 years ago.ResultsThe intensive conventional treatment patients had lower glycosylated haemoglobin (HbA1c) compared with the ST patients, i.e. 7·01 (SD 0·51) vs. 8·31 (0·97), while concentrations of the lipoprotein and haemostasis variables analyzed were virtually similar. The carotid artery intima‐media area was associated with high HbA1c, high serum (S)‐cholesterol levels, and low high‐density lipoprotein (HDL)‐cholesterol levels. Carotid artery stiffness was associated with high systolic blood pressure, high HbA1c, high fibrinogen, and high HDL‐cholesterol. Brachial artery endothelial reactivity was higher for women and those with low S‐cholesterol.ConclusionIn patients with Type 1 diabetes, glucose control appeared to have no effect on either lipoproteins or haemostasis variable concentrations. Poor glucose control, and high levels of S‐cholesterol, systolic blood pressure and plasma fibrinogen were associated with development of atherosclerosis, thus emphasising the importance of global risk factor control in patients with Type 1 diabetes mellitus.
Exercise induces excessive normetanephrine responses in hypertensive diabetic patients
Authors: Raber W. , Raffesberg W. , Waldhäusl W. , Gasic S. , Roden M. 
Published: June 2003

AbstractBackground Exaggerated sympathoadrenal function has been accused of contributing to hypertension in type‐2 diabetes. Recently, plasma unconjugated (free) metanephrines were reported to be stable markers of catecholamine hypersecretion. Thus, we aimed to examine whether unconjugated metanephrines are reliable markers of stress response induced by standardized cycling exercise and to identify differences in such stress responses between hypertensive and/or diabetic patients.Design Type‐2 diabetic patients with (DM/H; n= 8, 50 ± 7 years, HbA1c: 7·7 ± 0·6%) or without hypertension (DM/N; n = 6, 48 ± 10 years, 7·5 ± 1·8%) and nondiabetic hypertensive patients (H; n = 8, 56 ± 4 years) were studied during incremental cycling exercise (15 min) to 75% of individual VO2max and during recovery (60 min). Plasma catecholamines and unconjugated metanephrines were measured by high‐performance liquid chromatography with electrochemical detection. Hormone responses were quantified from the areas under the concentration‐time curves and compared with those of age‐, sex‐ and BMI‐matched healthy volunteers (CON, n= 22).Results Blood pressure responses of DM/H and H, but not DM/N, were greater than those of CON (P < 0·01), whereas heart rates increased similarly in all groups. Unconjugated normetanephrine responses were only increased (P = 0·04) in DM/H (2156 vs. 1133 pg mL−1 min−1) but not in DM/N (1528 vs. 1300 pg mL−1 min−1) and H (1960 vs. 1425 pg mL−1 min−1) when compared with respective CON. Unconjugated metanephrines did not change from baseline, whereas catecholamine responses were comparable in all groups.Conclusions The excessive response of plasma unconjugated normetanephrine to cycling may serve as a marker of exaggerated sympathoadrenal function in hypertensive type‐2 diabetic patients.
Heat‐shock protein 70 favours human liver recovery from ischaemia‐reperfusion
Authors: Boeri D. , Dondero F. , Storace D. , Maiello M. , Pasqualini M. , Pellicci R. 
Published: June 2003

AbstractBackground Pringle's manoeuvre controls excessive bleeding, but results in ischaemia‐reperfusion injury during liver surgery. Activation of the heat‐shock protein system of cell defense has been demonstrated after ischaemia‐reperfusion injury in animal tissues. The aim of the present study was to determine whether the ischaemia‐reperfusion accompanying hepatic surgery induces heat‐shock protein 70 (HSP70) in human liver and whether the induction of HSP70 is related to the recovery of liver function.Methods Heat‐shock protein 70 and γ‐actin mRNAs were assayed in the liver biopsies of 10 subjects undergoing partial hepatectomy for localized lesions. Measurements were performed before the Pringle's manoeuvre and at the end of the surgery. Transaminases and fibrinogen were measured before and at 12, 24 and 36 h following hepatectomy.Results After an average 40 ± 8‐min period of warm ischaemia, a significant increase of HSP70 mRNA (187 ± 67%, 2P < 0·05) was observed. The acute increase of HSP70 mRNA correlates with the decrease of transaminases (AST: rs −0·964, ALT: rs –0·891, P < 0·002) and the increase of fibrinogen (rs −0·7, P < 0·02) observed between 12 and 24 h following surgery.Conclusions Heat‐shock protein 70 is induced by ischaemia‐reperfusion injury in human liver. Its induction seems to have beneficial effects, including a prompt reduction of transaminases and a rapid recovery of fibrinogen synthesis.
Low HDL cholesterol concentration is associated with increased intima‐media thickness independent of arterial stiffness in healthy subjects from families with low HDL cholesterol
Authors: Alagona C. , Soro A. , Westerbacka J. , Ylitalo K. , Salonen J.T. , Salonen R. , Yki‐Järvinen H. , Taskinen M.‐R. 
Published: June 2003

AbstractBackground Low high‐density lipoprotein cholesterol (HDL‐C) is associated with increased risk for developing coronary artery disease. Cardiovascular disease is characterized by increased intima‐media thickness (IMT) and arterial stiffness, but the effect of low HDL on these measurements has not been reported.Materials and methods We studied 18 apparently healthy subjects from families with low HDL‐C and 18 control subjects, which were pair‐matched to maximize statistical power. Intima‐media thickness was assessed using ultrasound examination of the carotid arteries. Arterial stiffness was measured using applanation tonometry on the radial artery and pulse‐wave analysis to obtain central aortic pulse‐pressure waveform, from which the augmentation index, a measure of global large artery stiffness, was calculated.Results Low HDL subjects (age 41 ± 3 years, BMI 26·6 ± 1·0 kg m−2) had significantly lower HDL‐C than the control subjects (age 41 ± 3 years, BMI 26·5 ± 1·0 kg m−2; 1·00 ± 0·05 vs. 1·49 ± 0·09 mmol L−1, low HDL vs. control subjects, P < 0·0001). Subjects with low HDL‐C had significantly thicker mean IMTs than the control subjects (0·77 ± 0·03 vs. 0·70 ± 0·02 mm, low HDL vs. control subjects, P < 0·01). The maximal (0·99 ± 0·04 vs. 0·89 ± 0·03 mm, P < 0·01), far wall (0·76 ± 0·04 vs. 0·69 ± 0·02 mm, P < 0·05) and carotid bulb (1·11 ± 0·06 vs. 0·97 ± 0·04 mm) IMTs were also significantly increased, whereas the mean common carotid and the internal artery IMT were not. The age‐related increase in mean IMT was more pronounced in the low HDL subjects than the control subjects (P < 0·01 for difference between elevations of age vs. IMT slopes). There were no differences in central pressure augmentation, the augmentation index, peripheral or central blood pressures between the groups.Conclusions A low HDL‐C concentration is associated with thickening of carotid IMT independent of other risk factors in healthy affected members of low HDL families.
Enhancement of allergic skin wheal responses in patients with atopic eczema/dermatitis syndrome by playing video games or by a frequently ringing mobile phone
Authors: Kimata H. 
Published: June 2003

AbstractBackground Playing video games causes physical and psychological stress, including increased heart rate and blood pressure and aggression‐related feelings. Use of mobile phones is very popular in Japan, and frequent ringing is a common and intrusive part of Japanese life. Atopic eczema/dermatitis syndrome is often exacerbated by stress. Stress increases serum IgE levels, skews cytokine pattern towards Th2 type, enhances allergen‐induced skin wheal responses, and triggers mast cell degranulation via substance P, vasoactive intestinal peptide and nerve growth factor.Materials and methods (1) In the video game study, normal subjects (n = 25), patients with allergic rhinitis (n = 25) or atopic eczema/dermatitis syndrome (n = 25) played a video game (STREET FIGHTER II) for 2 h. Before and after the study, allergen‐induced wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor, and in vitro production of total IgE, antihouse dust mite IgE and cytokines were measured. (2) In the mobile phone study, normal subjects (n = 27), patients with allergic rhinitis (n = 27) or atopic eczema/dermatitis syndrome (n = 27) were exposed to 30 incidences of ringing mobile phones during 30 min. Before and after the study, allergen‐induced wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor were measured.Results Playing video games had no effect on the normal subjects or the patients with allergic rhinitis. In contrast, playing video games significantly enhanced allergen‐induced skin wheal responses and increased plasma levels of substance P, vasoactive intestinal peptide and nerve growth factors in the patients with atopic eczema/dermatitis syndrome. Moreover, playing video games enhanced in vitro production of total IgE and anti‐house dust mite IgE with concomitant increased production of IL‐4, IL‐10 and IL‐13 and decreased production of IFN‐γ and IL‐12 in the patients with atopic eczema/dermatitis syndrome. However, exposure to frequently ringing mobile phones significantly enhanced allergen‐induced skin wheal responses, plasma levels of substance P, vasoactive intestinal peptide and nerve growth factors in the patients with atopic eczema/dermatitis syndrome, but not in the normal subjects or the patients with allergic rhinitis.Conclusion Playing video games enhanced allergic responses with a concomitant increased release of substance P, vasoactive intestinal peptide and nerve growth factor, and skewing of the cytokine pattern toward Th2 type in the patients with atopic eczema/dermatitis syndrome. In addition, exposure to frequently ringing mobile phones also enhanced allergic responses with a concomitant increased release of substance P, vasoactive intestinal peptide and nerve growth factor Collectively, high technology causes stress, which in turn may aggravate symptoms of atopic eczema/dermatitis syndrome.
International clinical placements for undergraduate students
Authors: Grant Elizabeth , Mckenna Lisa 
Published: June 2003

Summary• This paper reports the findings of a study that sought to gain insight into the experiences of third year nursing students who participated in a 4‐week clinical placement in an international setting.• This study is different from many studies describing international placements for undergraduate nursing students as it concentrates on clinical experiences on placement.• Students' reflective journals and face‐to‐face discussions were used to collect data, which were analysed by thematic content analysis.• Categories were identified describing a focus on micro clinical‐based issues that expanded over time to a focus on broader issues reflecting the ‘nursing culture’ of the placement. Students described both positive and negative aspects of being placed in an international clinical setting, with the concept of ‘being different’ emerging.• Whilst the findings cannot be generalized beyond the sample, the study highlights the importance of adequate preparation and support for students on international clinical placements, with emphasis on attention to clinical detail.