bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Characterization and Expression Analysis of a Gene, OsENT2, Encoding an Equilibrative Nucleoside Transporter in Rice Suggest a Function in Cytokinin Transport
Authors: Hirose Naoya , Makita Nobue , Yamaya Tomoyuki , Sakakibara Hitoshi
Published: April 2005

We identified four genes for potential equilibrative nucleoside transporters (ENTs) from rice (Oryza sativa; designated OsENT1 through OsENT4). Growth analysis of budding yeast (Saccharomyces cerevisiae) cells expressing OsENTs showed that OsENT2 transported adenosine and uridine with high affinity (adenosine, K  m = 3.0 μ  m; uridine, K  m = 0.7 μ  m). Purine or pyrimidine nucleosides and 2′-deoxynucleosides strongly inhibited adenosine transport via OsENT2, suggesting that OsENT2 possesses broad substrate specificity. OsENT2-mediated adenosine transport was resistant to the typical inhibitors of mammalian ENTs, nitrobenzylmercaptopurine ribonucleoside, dilazep, and dipyridamole. The transport activity was maximal at pH 5.0 and decreased slightly at lower as well as higher pH. In competition experiments with various cytokinins, adenosine transport by OsENT2 was inhibited by isopentenyladenine riboside (iPR). Direct measurements with radiolabeled cytokinins demonstrated that OsENT2 mediated uptake of iPR (K  m = 32 μ  m) and trans-zeatin riboside (K  m = 660 μ  m), suggesting that OsENT2 participates in iPR transport in planta. In mature plants, OsENT2 was predominantly expressed in roots. The OsENT2 promoter drove the expression of the β-glucuronidase reporter gene in the scutellum during germination and in vascular tissues in germinated plants, suggesting a participation of OsENT2 in the retrieval of endosperm-derived nucleosides by the germinating embryo and in the long-distance transport of nucleosides in growing plants, respectively.
COBRA, an Arabidopsis Extracellular Glycosyl-Phosphatidyl Inositol-Anchored Protein, Specifically Controls Highly Anisotropic Expansion through Its Involvement in Cellulose Microfibril Orientation
Authors: Roudier François , Fernandez Anita G. , Fujita Miki , Himmelspach Regina , Borner Georg H.H. , Schindelman Gary , Song Shuang , Baskin Tobias I. , Dupree Paul , Wasteneys Geoffrey O. , Benfey Philip N.
Published: April 2005

The orientation of cell expansion is a process at the heart of plant morphogenesis. Cellulose microfibrils are the primary anisotropic material in the cell wall and thus are likely to be the main determinant of the orientation of cell expansion. COBRA (COB) has been identified previously as a potential regulator of cellulose biogenesis. In this study, characterization of a null allele, cob-4, establishes the key role of COB in controlling anisotropic expansion in most developing organs. Quantitative polarized-light and field-emission scanning electron microscopy reveal that loss of anisotropic expansion in cob mutants is accompanied by disorganization of the orientation of cellulose microfibrils and subsequent reduction of crystalline cellulose. Analyses of the conditional cob-1 allele suggested that COB is primarily implicated in microfibril deposition during rapid elongation. Immunodetection analysis in elongating root cells revealed that, in agreement with its substitution by a glycosylphosphatidylinositol anchor, COB was polarly targeted to both the plasma membrane and the longitudinal cell walls and was distributed in a banding pattern perpendicular to the longitudinal axis via a microtubule-dependent mechanism. Our observations suggest that COB, through its involvement in cellulose microfibril orientation, is an essential factor in highly anisotropic expansion during plant morphogenesis.
Antiquity of MicroRNAs and Their Targets in Land Plants
Authors: Axtell Michael J. , Bartel David P.
Published: April 2005

MicroRNAs (miRNAs) affect the morphology of flowering plants by the posttranscriptional regulation of genes involved in critical developmental events. Understanding the spatial and temporal dynamics of miRNA activity during development is therefore central for understanding miRNA functions. We describe a microarray suitable for detection of plant miRNAs. Profiling of Arabidopsis thaliana miRNAs during normal development extends previous expression analyses, highlighting differential expression of miRNA families within specific organs and tissue types. Comparison of our miRNA expression data with existing mRNA microarray data provided a global intersection of plant miRNA and mRNA expression profiles and revealed that tissues in which a given miRNA is highly expressed are unlikely to also show high expression of the corresponding targets. Expression profiling was also used in a phylogenetic survey to test the depth of plant miRNA conservation. Of the 23 families of miRNAs tested, expression of 11 was detected in a gymnosperm and eight in a fern, directly demonstrating that many plant miRNAs have remained essentially unchanged since before the emergence of flowering plants. We also describe an empirical strategy for detecting miRNA target genes from unsequenced transcriptomes and show that targets in nonflowering plants as deeply branching as ferns and mosses are homologous to the targets in Arabidopsis. Therefore, several individual miRNA regulatory circuits have ancient origins and have remained intact throughout the evolution and diversification of plants.
Changing Chinese employment relations since WTO accession
Authors: Zhu Ying , Warner Malcolm
Published: April 2005

Purpose

This paper examines the challenges facing China's employment relations after its WTO accession and consequently, the implications for further reform.

Design/methodology/approach

Theoretical questions are considered in relation to the debate on globalization vs the nation‐state over political, economic and social issues. By examining the challenges from both internal and external sources, the paper investigates the impact on the employment relations system at both macro‐ and micro‐levels.

Findings

The major finding of this paper is that the current system of employment relations system in China is in the process of transformation towards a “hybrid” model combining authoritarianism and neo‐corporatism.

Originality/value

This paper provides the most recent analysis on the impact of WTO accession on the changing pattern of employment relations in China. It helps people who are interested in transitional economy in general and in China in particular to have a better understanding about the transformation of employment relations system under the influence of different forces.
The management of voice in non‐union organisations: managers’ perspectives
Authors: Dundon Tony , Wilkinson Adrian , Marchington Mick , Ackers Peter
Published: April 2005

Purpose

Given the emergence of new legal initiatives for union recognition, declining levels of union membership and the growth of alternative forms of employee representation, this paper aims to examine the management of employee voice in non‐union firms.

Design/methodology/approach

The research adopts a case study approach in seven non‐union organisations from different sectors of economic activity in the UK. Several themes guided the design of the research instruments. Interviews were conducted with managerial respondents responsible for the design and implementation of employee voice at each case study, including non‐personnel practitioners.

Findings

Provides information on: the meaning of non‐union voice; the range of practices adopted; the potential outcomes; and apparent barriers to the implementation of non‐union voice arrangements.

Research limitations/implications

The research collected data from managerial respondents only, and this limitation is noted. Further research in this area is suggested, particularly from employee stakeholders involved in the processes of employee involvement.

Originality/value

The paper addresses a gap on employee voice in non‐union settings. It suggests that it is too simple to dismiss voice in non‐union organisations as ineffective and inconsequential.
Change‐oriented leadership, satisfaction and performance in work groups
Authors: Gil Francisco , Rico Ramón , Alcover Carlos M. , Barrasa Ángel
Published: April 2005

Purpose

To analyse the impact of change‐oriented leaders on group outcomes. An explanatory model is proposed, in which the team climate (in particular as it relates to innovation) mediates between change‐oriented leadership and group outcomes, while group potency reinforces this relationship.

Design/methodology/approach

This study is designed as a correlative and cross‐level research. The sample comprises 318 health‐care professionals in 78 health‐care teams at different public hospitals throughout Spain.

Findings

Hierarchical regression analysis was used to evaluate mediating and moderating effects. Results offer considerable empirical support for the proposed model.

Research limitations/implications

It would be of interest to increase the sample, differentiate it by service, and to get samples from other sectors, as well as to carry out experimental and longitudinal research. It would also be interesting to further explore the conditions that implement change‐oriented leadership impact, analysing environment, external relations and so on, to examine the relationships between other variables and to study their effects on new forms of work organisation and on virtual teams.

Practical implications

To make more useful change‐oriented leader actions, it would be advisable to identify, modify or improve team climate, using strategies such as management by objectives, delegation and empowerment and so on. It would also be necessary to boost group potency before going ahead with change, for example, by developing the skills of team members, or by fostering the self‐confidence of the team.

Originality/value

This paper contributes to developing actual research about how change‐oriented leaders influence team outputs.
Fashion and clothing: the construction and communication of gay identities
Authors: Schofield Kate , Schmidt Ruth Ä.
Published: April 2005

Purpose

This paper explores the importance of clothes for gay males as semiotic markers for identity creation and communication in order to highlight the increasing fragmentation of this market and the role of consumption practices as cultural markers.

Design/methodology/approach

The study is grounded in qualitative data from participant observation, diaries interviews and a focus group of Manchester‐based respondents; findings are linked back to literature on postmodernism, image and identity.

Findings

Findings point to communication of individual identity through clothes; firstly, on a community level, as a marker of “gayness”; secondly, on a neo‐tribal level, indicating tribal allegiance and aiding inter‐tribal communication; thirdly, on a situational level, where clothing facilitates acceptance and integration. The proactive use of clothing as a semiotic marker enables the fluid construction and linking of multiple identities. Findings indicate the existence of quite specific codes with (gay) culturally embedded meanings which gay men can choose to identify with and make use of, or not, in different situations. Thus fashion is an important means of differentiation and communication of personal and group identities and affiliations.

Research limitations/implications

This is an in‐depth study of a small sample of subjects located in Manchester only. Despite satisfactory respondent and ecological validity it would therefore be desirable to extend the study to a larger sample size and replicate it in other settings before making wider generalisations.

Practical implications

Implications for marketers include the need to move away from treating this market as homogeneous as well as opportunities for “tribal marketing”.

Originality/value

Through its in‐depth qualitative approach the paper represents a rich picture of the UK gay fashion market which has a good degree of respondent validity and useful insights for marketers.
Examining the effects of service brand communications on brand evaluation
Authors: Grace Debra , O'Cass Aron
Published: April 2005

Purpose

This study seeks to examine the effects of three communication avenues, namely controlled communication (e.g. advertising/promotions), uncontrolled communications (word‐of‐mouth (WOM)/publicity), and brand name, on consumer service brand evaluation.

Design/methodology/approach

This study employed a quantitative methodology and data were gathered from consumers intercepted in a shopping mall via a self‐completed survey.

Findings

The results show that controlled communications and brand name have a significant effect on customer satisfaction, brand attitudes and brand reuse intentions. WOM was shown to have a significant influence only on brand reuse intentions. In addition, comparisons made across different retail service types (e.g. stores and banks) showed differences in relationships between the examined variables.

Research limitations/implications

The brand stimuli used in the survey instrument limit the findings to retail stores and banks and, thus, may not be applicable in all service situations. On this basis, it is recommended that future research should further explore the key constructs of this study in other service settings.

Practical implications

The findings suggest that controlled communications and brand name are pivotal in establishing consumer expectations, thus influencing satisfaction and brand attitudes. Therefore, these types of advertising should be utilised to communicate realistic service experiences, while brand names should reinforce consumer confidence, trust and safety in usage. Positive WOM advocating proven reliability and consistency of the brand should be encouraged and rewarded to encourage new usage and reusage behaviour.

Originality/value

The value of this paper lies in the comparison of different brand communications with different consumer responses to the brand not previously examined. The results therefore suggest ways in which marketers can maximise the benefits of their communications.
How social accounts and participation during change affect organizational learning
Authors: Lines Rune
Published: April 2005

Purpose

The purpose of this paper is to examine how the way change implemented effects organizational learning. More specifically, we study the relationships between the use of social accounts, participation and organizational learning in the context of strategic change. The use of social accounts and participation are often promoted during change, but up to this point, their influences on organizational learning have not been studied.

Design/methodology/approach

A multi‐change and multi‐organization study, using a critical incident technique (i.e. informants provide information from a specific change experience), provides the data for testing a set of theory driven hypotheses that link aspects of the change process to learning outcomes.

Findings

Findings show that social accounting and participation are positively associated with organizational learning, but that the influence of social accounting is negatively moderated by participation. Social accounts framed as threats to system survival were unrelated to organizational learning.

Practical implications

In order to maximize learning during change organizations should attempt to involve members with different values and expertise throughout the process. The use of formalized communication programs would add little to organizational learning if participative change processes are applied. Although threat appeals could be useful for creating readiness for change, their impact on organizational learning seem to be marginal.

Originality/value

For knowledge intensive and learning dependent organizations, the study provides some guidance to change management.
Business process re‐engineering pays after enterprise resource planning
Authors: Martin Ian , Cheung Yen
Published: April 2005

Purpose

The purpose of the paper is to demonstrate that significant improvements through business process re‐engineering can still be achieved after the implementation of enterprise resource planning systems. While the business process re‐engineering benefits of enterprise resource planning systems have been widely published, the opportunities for process improvement after the installation of integrated systems have not been extensively explored.

Design/methodology/approach

This paper results from a case study of the highly successful intervention in the purchasing and accounts payable functions of Mobil Oil Australia Limited undertaken well after the implementation one of the widely used off‐the‐shelf enterprise resource planning systems, SAP (Systems, Applications and Products in Data Processing).

Findings

Significant benefits were achieved in the purchasing and accounts payable functions of Mobil Oil Australia Limited, via a focus on best practice and radical process improvement. Invoices and invoice processing were largely eliminated. Cheque usage was reduced by 87 per cent and the staff paying accounts cut by almost 75 per cent.

Originality/value

The case study demonstrates clearly to companies and practitioners that business process re‐engineering can achieve “dramatic improvements in cost, quality, service and speed” even after an enterprise resource planning solution has been implemented via a focus on best practice benchmarking and using best practice to provide a target for the change team. Companies can leverage existing, often substantial, investments in installed systems to further improve their processes and increase the return on those investments.
Drug Enforcement and Crime: Recent Evidence from New York State*
Authors: Shepard Edward M. , Blackley Paul R.
Published: April 2005

Objective. The objective of this article is to provide evidence about the effectiveness of drug law enforcement as a tool for reducing other types of crime. Considerable resources are devoted to enforcing our nation's drug laws, but existing research suggests that intensifying drug law enforcement may serve to increase, rather than decrease, crime.

Method. Using data for 62 counties in New York State for 1996–2000, we estimate a set of models that evaluate the effects of recent drug arrests on reported rates of assault, robbery, burglary, and larceny. The estimated statistical model includes controls for fixed effects, time effects, autocorrelation, and heteroskedasticity.

Results. The consistency of results is striking—there is no model in which drug arrests are found to have a significant negative relationship with crime. All crimes are positively related to arrests for the manufacture and sale of “hard drugs.” Increases in total per capita drug arrests and arrests for “hard drug” possession are accompanied by higher rates for all crimes except assault. Increased arrests for the manufacture or sale of marijuana are associated with increases in larcenies.

Conclusions. The empirical findings raise serious questions about the effectiveness of drug enforcement as a crime‐control measure and suggest that significant social costs may arise from existing approaches to drug control.
Induction of myocardial connective tissue growth factor in pacing‐induced heart failure in pigs
Authors: Ahmed M. S. , von Lueder T. G. , Øie E. , Kjekshus H. , Attramadal H.
Published: April 2005

Aims:  Connective tissue growth factor (CTGF) is a secreted, heparin‐binding, and extracellular matrix associated protein shown to stimulate many of the cellular events underlying fibrosis. Previous investigations have revealed that myocardial CTGF is substantially induced in ischaemic heart failure, particularly in the ischaemic and peri‐ischaemic region. The purpose of the present study was to investigate to what extent myocardial induction of CTGF is a general response to congestive heart failure (CHF) and to what extent CTGF is a decisive effector of fibrosis.

Methods:  Experimental heart failure in pigs was induced by rapid pacing at 220–240 beats min−1 for 3 weeks (CHF pigs; n = 12).

Results:  The CHF pigs exhibited significant left ventricular (LV) dilatation, reduced contractility, and increased cardiac filling pressures. Northern blot analysis demonstrated that myocardial CTGF mRNA levels in CHF pigs were fivefold higher (P < 0.05) than those in control pigs (n = 10). Similar elevations of immunoreactive CTGF (sixfold; P < 0.05) were observed in myocardial tissue samples prepared for Western blot analysis. Immunohistochemical analysis of myocardial tissue sections revealed predominant expression in interstitial and perivascular fibroblasts and endothelial cells. Myocardial procollagen α1(I) mRNA levels were also significantly elevated (sixfold; P < 0.05) in CHF pigs compared with controls, whereas myocardial tissue contents of collagen were not statistically different between the groups.

Conclusion:  Induction of myocardial CTGF in heart failure is not just a response to ischaemia, but rather a general response to evolving heart failure. Yet, induction of myocardial CTGF was clearly not a sufficient effector of fibrosis.
The mitotic clock in skeletal muscle regeneration, disease and cell mediated gene therapy
Authors: Mouly V. , Aamiri A. , Bigot A. , Cooper R. N. , Di Donna S. , Furling D. , Gidaro T. , Jacquemin V. , Mamchaoui K. , Negroni E. , Périé S. , Renault V. , Silva‐Barbosa S. D. , Butler‐Browne G. S.
Published: April 2005

The regenerative capacity of skeletal muscle will depend on the number of available satellite cells and their proliferative capacity. We have measured both parameters in ageing, and have shown that although the proliferative capacity of satellite cells is decreasing during muscle growth, it then stabilizes in the adult, whereas the number of satellite cells decreases during ageing. We have also developed a model to evaluate the regenerative capacity of human satellite cells by implantation into regenerating muscles of immunodeficient mice. Using telomere measurements, we have shown that the proliferative capacity of satellite cells is dramatically decreased in muscle dystrophies, thus hampering the possibilities of autologous cell therapy. Immortalization by telomerase was unsuccessful, and we currently investigate the factors involved in cell cycle exits in human myoblasts. We have also observed that insulin‐like growth factor‐1 (IGF‐1), a factor known to provoke hypertrophy, does not increase the proliferative potential of satellite cells, which suggests that hypertrophy is provoked by increasing the number of satellite cells engaged in differentiation, thus possibly decreasing the compartment of reserve cells. We conclude that autologous cell therapy can be applied to specific targets when there is a source of satellite cells which is not yet exhausted. This is the case of Oculo–Pharyngeal Muscular Dystrophy (OPMD), a late onset muscular dystrophy, and we participate to a clinical trial using autologous satellite cells isolated from muscles spared by the disease.
Abnormal renal structural alterations during the development of diabetes mellitus in Otsuka Long‐Evans Tokushima Fatty rats*
Authors: Koike T. , Tomoda F. , Kinuno H. , Inoue H. , Takata M.
Published: April 2005

Aim:  The aim of this study was to investigate the renal structural properties in diabetic nephropathy.

Methods:  Flow‐pressure and pressure‐glomerular filtration rate (GFR) relationships were determined for maximally vasodilated kidneys at 10 (pre‐diabetic stage) and 42 weeks of age (diabetic stage) in Otsuka Long‐Evans Tokushima Fatty rats (OLETF), an animal model of type 2 diabetes mellitus, using age‐matched Long‐Evans Tokushima Otsuka rats (LETO) as non‐diabetic controls (n = 9 of each age for each strain). Kidneys were then perfusion‐fixed for histological analysis.

Results:  At 10 weeks of age, the slope of flow–pressure relationship (minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature) was steeper in OLETF than in LETO. In contrast, the threshold pressure for beginning filtration (preglomerular‐to‐postglomerular vascular resistance ratio) at pressure–GFR relationship did not differ between the two strains; however, the slope of the relationship (glomerular filtration capacity) was lower in OLETF than in LETO. Thus, in the kidneys of 10‐week‐old OLETF rats, vascular narrowing and impaired glomerular filtration capacity already existed with no abnormalities in preglomerular‐to‐postglomerular vascular resistance ratio. From the age of 10–42 weeks, the following results were obtained: (1) Minimal renal vascular resistance decreased in both strains, but it diminished markedly in OLETF. (2) The pressure for beginning filtration increased in LETO, but remained unchanged in OLETF. (3) Glomerular filtration capacity decreased to the similar extent in both strains. (4) Histologically, the vascular lumen and wall thickness increased in the interlobular arteries of both strains. However, vascular luminal widening was more pronounced in OLETF, resulting in the reduction in wall to lumen ratio. (5) Glomerular injuries and increased blood pressure occurred only in OLETF.

Conclusion:  In conclusion, during progression from the prediabetic to diabetic stage of OLETF, the pre‐existing vascular narrowing was markedly attenuated without the concomitant increase in preglomerular‐to‐postglomerular vascular resistance ratio. Combined with increased blood pressure, these renal structural alterations could lead to the elevation of intraglomerular pressure in OLETF.
Effects of high‐intensity intermittent swimming on PGC‐1α protein expression in rat skeletal muscle
Authors: Terada S. , Kawanaka K. , Goto M. , Shimokawa T. , Tabata I.
Published: April 2005

Aim:  The aim of the present investigation was to elucidate the effects of exercise intensity on exercise‐induced expression of peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) protein in rat skeletal muscle.

Methods:  We measured PGC‐1α content in the skeletal muscles of male Sprague–Dawley rats (age: 5–6 weeks old; body weight: 150–170 g) after a single session of high‐intensity intermittent exercise (HIE) or low‐intensity prolonged swimming exercise (LIE). During HIE, the rats swam for fourteen 20‐s periods carrying a weight (14% of body weight), and the periods of swimming were separated by a 10‐s pause. LIE rats swam with no load for 6 h in two 3‐h sessions, separated by 45 min of rest.

Results:  After HIE, the PGC‐1α protein content in rat epitrochlearis muscle had increased by 126, 140 and 126% at 2, 6 and 18 h, respectively, compared with that of the age‐matched sedentary control rats’ muscle. Immediately, 6 and 18‐h after LIE, the PGC‐1α protein content in the muscle was significantly elevated by 84, 95 and 67% respectively. The PGC‐1α protein content observed 6 h after HIE tended to be higher than that observed after LIE. However, there was no statistically significant difference between the two values (P = 0.12).

Conclusion:  The present investigation suggests that irrespective of the intensity of the exercise, PGC‐1α protein content in rat skeletal muscle increases to a comparable level when stimuli induced by different protocols are saturated. Further, HIE is a potent stimulus for enhancing the expression of PGC‐1αprotein, which may induce mitochondrial biogenesis in exercise‐activated skeletal muscle.
HSP20 phosphorylation and interstitial metabolites in hypoxia‐induced dilation of swine coronary arteries
Authors: Frøbert O. , Buus C. L. , Rembold C. M.
Published: April 2005

Objective:  Hypoxia induces coronary artery dilation, but the responsible mechanism is largely unknown. Many stimuli induce arterial smooth muscle relaxation by reducing ser19‐myosin regulatory light chain (MLC) phosphorylation. Other stimuli can induce smooth muscle relaxation without reductions in ser19‐MLC phosphorylation. This form of relaxation has been termed force suppression and appears to be associated with heat shock protein 20 (HSP20) phosphorylation on ser16. We investigated whether hypoxia‐induced sustained dilation in swine coronary arteries was promoted without ser19‐MLC dephosphorylation and associated with ser16‐HSP20 phosphorylation. Nitroglycerin vasodilation served as control.

Methods:  In a pressure myograph, the tunica media of intact pre‐contracted (PGF2α; 10−5 m) porcine coronary artery segments were cannulated using a microdialysis catheter. Diameter responses and interstitial lactate/pyruvate ratios were studied during 90 min hypoxia, hypoxia + reoxygenation (60 min), nitroglycerin (100 μm, 90 min), and nitroglycerin + wash‐out (60 min). The arterial segments were snap‐frozen and analysed for ser16‐HSP20 phosphorylation and ser19‐MLC phosphorylation.

Results:  The normalized diameter responses to hypoxia (6.1 ± 4.3%) and nitroglycerin (12.6 ± 1.6%) were both significantly greater than normoxic control arteries (−10.5 ± 1.8%, anova, P < 0.05). Ser16‐HSP20 phosphorylation was increased with hypoxia and nitroglycerin treatment and ser16‐HSP20 phosphorylation correlated with changes in diameters (n = 29, r2 = 0.64, P < 0.001). Ser19‐MLC phosphorylation was not significantly altered by hypoxia. The lactate/pyruvate ratio was significantly increased in hypoxic arteries but did not correlate with diameters or ser16‐HSP20 phosphorylation.

Conclusion:  Ser16‐HSP20 phosphorylation is a potential regulator of hypoxia‐induced dilation in coronary arteries.
Defective excitation‐contraction coupling in hearts of rats with congestive heart failure
Authors: Sjaastad I. , Birkeland J. A. , Ferrier G. , Howlett S. , Skomedal T. , Bjørnerheim R. , Wasserstrom J. A. , Sejersted O. M.
Published: April 2005

Aim:  We examined the cellular basis for depressed cardiac contractility in rats with congestive heart failure (CHF) secondary to myocardial infarction.

Methods:  Six weeks after ligation of the left coronary artery, CHF was confirmed by haemodynamic measures and echocardiographic demonstration of reduced myocardial contractility in vivo. Papillary muscles from CHF animals developed less force than those from sham operated (SHAM) animals. Cell shortening was measured in isolated ventricular myocytes voltage‐clamped with high resistance electrodes. Ca2+ transients were measured in fluo‐4 loaded myocytes.

Results:  Contractions triggered by depolarizing test steps from a post conditioning potential of −70 mV were significantly smaller and had significantly reduced velocity of shortening in CHF compared with SHAM myocytes. However, contractions initiated from −40 mV, were similar in amplitude and velocity of shortening in CHF and SHAM cells. L‐type Ca2+ current was not significantly different between CHF and SHAM cells, whether activated from −70 or −40 mV. Therefore, in SHAM cells, excitation‐contraction coupling exhibited higher gain when contractions were initiated from negative (−70 mV), as compared with depolarized potentials (−40 mV). However, in CHF myocytes, excitation‐contraction coupling gain was selectively depressed with steps from −70 mV. This depression of gain in CHF was not accompanied by a significant reduction in sarcoplasmic reticulum Ca2+ content. Isoproterenol increased Ca2+ transients less in CHF than SHAM myocytes.

Conclusion:  In this post‐infarction model of CHF, the contractile deficit was voltage dependent and the gain of excitation‐contraction coupling was selectively depressed for contractions initiated negative to −40 mV.
Why do complications of gastrointestinal disease and procedures come as serial rather than singular events?
Authors: Sonnenberg A.
Published: April 2005

Background : It often appears as if complications arising from gastrointestinal disease and interventional procedures come in ‘series’ and ‘cluster’ in individual patients.

Aim : The aim of this study was to analyse the clustering of complications in terms of stochastic modelling and Markov chains.

Methods : A patient with gastrointestinal disease is simulated to move along either a ‘bad track’ associated with multiple consecutive complications or a ‘good track’ free of complications, the transitions within each track and between the two tracks being governed by probability values.

Results : Because the occurrence of a single complication increases the risk of further complications, subjects who encounter their first complication are more likely to experience a second, third or even more complications, before they leave the ‘bad track’ and their personal chain of cascading complications becomes discontinued. The model of a Markov chain explains why the overall number of complications in the total population of patients with digestive disease remains low even if individual patients are expected to encounter more than a single complication.

Conclusions : Published complication rates for gastrointestinal procedures underestimate the true risk to the patient, because they do not consider the added vulnerability to cascading complications after the first event.
Effect of different organic acids (citric, malic and ascorbic) on intragastric urease activity
Authors: Agha A. , Opekun A. R. , Abudayyeh S. , Graham D. Y.
Published: April 2005

Background: The mechanism of citric acid‐enhancedHelicobacter pyloriurease activity remains unclear.

Aim: To compare ascorbic, citric and malic acid given at the same concentration and pH on intragastric urease activity.

Methods: Volunteers received 40 mg of famotidine the evening prior to breath testing. After an overnight fast volunteers were randomized to receive 100 mL of water or 100 mmcitric, malic, or ascorbic acid, pH 2.3 containing 75 mg of13C‐urea. At 15 min a second 100 mL solution of one of the test solutions was taken without added urea.

Results: Twelve volunteers were studied (eight men, four women, age 19–57, median 50.7) in a randomized‐crossover study. The mean breath test result at 30 min with ascorbic (17.5 ± 5), malic (25.8 ± 5) and citric acid (29.5 ± 5) were all significantly greater than with water (9.5 ± 3). Citric and malic acid were similar (P = 0.699) and significantly greater than ascorbic acid (P < 0.02). When the ascorbic acid was followed by citric acid, the result was similar to that with citrate alone (25.8 ± 4) and greater than with ascorbic then ascorbic (P = 0.026).

Conclusions: Enhancement ofH. pyloriurease activity is not strictly a function of the pH. We propose the effect is related to differential effects of the availability of nickel, which is required for urease activity. Citric acid and malic acid were essentially equivalent such that malic acid could substitute for citric acid in the UBT; ascorbic acid would be a poor choice.
Multicentre randomized‐controlled clinical trial of Ipocol, a new enteric‐coated form of mesalazine, in comparison with Asacol in the treatment of ulcerative colitis
Authors: Forbes A. , Al‐Damluji A. , Ashworth S. , Bramble M. , Herbert K. , Ho J. , Kang J.‐Y. , Przemioslo R. , Shetty A.
Published: April 2005

Background : 5‐Aminosalicylates remain important in the treatment of ulcerative colitis, but it is uncertain if the various preparations currently available are equivalent given the different delivery systems that exist. Generic prescription of mesalazine (mesalamine) is therefore inappropriate. Ipocol has recently become available as an alternative to Asacol‐MR.

Aim : To compare the two agents in a controlled trial using a non‐inferiority design.

Methods : Eighty‐eight ulcerative colitis patients with a mild to moderate clinical relapse were randomized to one of the two drugs at a daily dose of 2.4 g for 8 weeks. Safety was the key concern; the primary measured end‐point was efficacy as judged from a colitis activity index.

Results : There were no unexpected adverse events of clinical consequence. The colitis score improved similarly in both patient groups (by 2.3 with Ipocol and by 1.5 with Asacol: not significant), and a similar proportion was in clinical remission at the end of the study (26.1% for Ipocol and 28.6% for Asacol: not significant). Systemic steroids were needed in 11.9% of the Asacol‐treated patients compared with 6.5% with Ipocol (not significant).

Conclusion : It appears appropriate to conclude that, while not identical to Asacol‐MR, Ipocol offers a safe and similarly effective alternative.
Inflammatory gene signature in ulcerative colitis with cDNA macroarray analysis
Authors: Okahara S. , Arimura Y. , Yabana T. , Kobayashi K. , Gotoh A. , Motoya S. , Imamura A. , Endo T. , Imai K.
Published: April 2005

Background : Most array analyses of ulcerative colitis have focused on identifying susceptibility genes for ulcerative colitis.

Aim : To clarify the changes in gene expression during inflammation in ulcerative colitis colon mucosa using cDNA macroarray.

Methods : From 23 ulcerative colitis patients, 16 each of inflamed and non‐inflamed specimens (total 32 samples for individual analysis) were obtained by colonoscopic biopsy. Eighteen of the 32 samples, used for pairwise analysis, consisted of nine sample pairs, each pair being from the same patient. We examined expression profiles of approximately 1300 genes with cDNA macroarray. Comparisons were made using two kinds of statistics, t‐test and significance analysis of microarray in both analyses. The reproducibility of significant genes from the macroarray analysis was confirmed by real‐time ploymerase chain reaction.

Results : We detected five upregulated genes, categorized into proinflammatory genes (MRP14, GROγ and SAA1) and anti‐inflammatory genes (TIMP1 and Elafin) in inflamed mucosa, and one upregulated gene (L‐FABP) in non‐inflamed mucosa.

Conclusions : As the cDNA macroarray analysis in this study exactly reflects the total profile of gene expression in the clinical setting of ulcerative colitis, the genes identified will be directly applicable to diagnostics or as novel therapeutic targets in active ulcerative colitis.
Managing dyspepsia without alarm signs in primary care: new national guidance for England and Wales
Authors: Mason J. M. , Delaney B. , Moayyedi P. , Thomas M. , Walt R. ,   The North of England Dyspepsia Guideline Development Group
Published: April 2005

Aim : To report new recommendations for the primary care management of dyspepsia without alarm signs in England and Wales.

Method : An independent, representative group of health care professionals, patient representatives and researchers developed the guideline using evidence‐based and small group‐working principles, and incorporated extensive peer‐reviewing and feedback from stakeholder organizations.

Results : Referral to investigate dyspepsia should be made for alarm signs and not on the basis of age alone, reflecting the balance of benefit and harm from endoscopy. Empirical management without formal diagnosis is appropriate for most patients: reviewing patient history, lifestyle, over‐the‐counter medicines, and providing a course of proton‐pump inhibitors and/or Helicobacter pylori test and treatment. Patients with ongoing symptoms require at least annual review to discuss symptoms and lifestyle, and as appropriate, encourage stepping down prescribed medication and returning to self‐care. A new strategy included in the step down process is the use of therapies ‘on‐demand’.

Conclusion : The guideline provides structured and supported recommendations for both undiagnosed and endoscopically investigated dyspepsia. Some favour increased investigation to detect Barrett's oesophagus and carcinoma. However, there is inconclusive evidence that patients without alarm signs will benefit subsequently from endoscopy, while investigation involves a small but real risk of harm.
Symptoms of gastro‐oesophageal reflux disease and the severity of obstructive sleep apnoea syndrome are not related in sleep disorders center patients
Authors: Kim H.‐N. , Vorona R. D. , Winn M. P. , Doviak M. , Johnson D. A. , Catesby Ware J.
Published: April 2005

Background : Studies suggest obstructive sleep apnea syndrome (OSAS) frequently manifests in patients with gastroesophageal reflux disease (GERD) and that there may be a causal relationship.

Aim : To determine the relationship between OSAS and symptoms of GERD.

Methods : Consecutive patients referred to the Sleep Disorders Center (SDC) 18 years and older with polysomnographically defined OSAS were evaluated prospectively for GERD using a validated symptoms questionnaire. The GERD and OSAS relationship was assessed by 1) determining frequency of GERD in patients with and without OSAS; 2) ascertaining the relationship between OSAS severity categories and presence of GERD; 3) examining GERD score in relation to those factors that might affect both GERD and OSAS, e.g. obesity.

Results : One thousand and twenty‐three SDC patients met entry citeria. Amongst participants, GERD was common (29% of women and 17% of males) and OSAS extremely common (58% of women and 80% of males). GERD score did not correlate with OSAS variables. The severity of OSAS did not influence the prevalence of GERD.

Conclusion : In a large group of patients referred to a sleep disorders center, there was no relationship between OSAS and GERD symptoms. Also, there was no relationship between the severity of OSAS and the likelihood of GERD symptoms.
Infliximab reverses growth hormone resistance associated with inflammatory bowel disease
Authors: Gentilucci U. Vespasiani , Caviglia R. , Picardi A. , Carotti S. , Ribolsi M. , Galati G. , Petitti T. , Afeltra A. , Cicala M.
Published: April 2005

Background : Increasing evidence shows that inflammation plays a major role in the aetiology of catabolism and wasting observed in inflammatory bowel disease via growth hormone resistance.

Aim : To evaluate the effect of infliximab treatment on the growth hormone/insulin‐like growth factor‐1 axis.

Methods : Fourteen adults with active Crohn's disease or ulcerative colitis underwent three infliximab infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance infusions 8 weeks apart. Blood samples were collected for the analysis of serum growth hormone, insulin‐like growth factor‐1, insulin‐like growth factor‐binding protein‐3 and acid labile subunit.

Results : Serum insulin‐like growth factor‐1 and insulin‐like growth factor‐binding protein‐3 concentrations, which were significantly lower in inflammatory bowel disease patients before treatment compared with controls (P < 0.01), significantly increased during the induction phase (+58% and +29%, respectively, after the second infusion, P < 0.01), and dropped to baseline levels during maintenance therapy. Both insulin‐like growth factor‐1 and insulin‐like growth factor‐binding protein‐3 showed significant negative correlations with C‐reactive protein (ρ = −0.37, P = 0.002; ρ = −0.35, P = 0.01, respectively). Growth hormone and acid labile subunit levels were not statistically different between controls and inflammatory bowel disease patients either at baseline or during treatment.

Conclusions : Infliximab induction treatment reverses growth hormone resistance observed in active inflammatory bowel disease through the suppression of systemic inflammation. The restored growth hormone/insulin‐like growth factor‐1 axis is impaired again following the prolonged interval between maintenance infusions, possibly because of the subclinical reactivation of the inflammatory process.
Impact of liver steatosis on virological response in elderly Italian patients with chronic hepatitis C treated with peg‐interferon alpha‐2b plus ribavarin
Authors: Fabris P. , Floreani A. , Carlotto A. , Baldo V. , Bozzola L. , Giordani M. T. , Negro F. , Rassu M. , Tramarin A. , de Lalla F.
Published: April 2005

Background : Whether liver steatosis affects sustained virological response in patients with chronic hepatitis C is still under discussion.

Aim : To evaluate the impact of liver steatosis in patients treated (for chronic hepatitis C) with combination therapy.

Methods : We evaluated 97 (male/female 82/15, mean age 41.1 years) consecutive naïve patients treated with pegylated interferon alpha‐2b plus ribavirin.

Results : Prevalence and severity of liver steatosis were significantly associated with genotype 3a [grade 3–4 in 14 of 32 patients (44%) vs. 8 of 65 patients (12%) with other genotypes; P = 0.001], while steatosis grade 1 (<10% of hepatocytes affected) was more frequently associated with genotype 1a/1b [9/39 (23%) vs. 4/57 (7%); P = 0.02]. Overall, sustained virological response was 62.8%, and was statistically uninfluenced by the presence/absence of liver steatosis. On the contrary, the following variables were independently associated with sustained virological response at logistic regression analysis: genotype other than 1a/1b, positive association, (odds ratio 3.4, P < 0.04), and low‐grade liver steatosis, negative association, (odds ratio 9.0, P =0.009), whereas sustained virological response was unaffected by severe liver steatosis, which was mainly associated with genotypes 2 and 3 [steatosis grade 2, 18/29 (62%); grade 3, 10/12 (83%); grade 4, 7/10 (70%)].

Conclusions : Only low‐grade liver steatosis negatively affects the outcome of combination therapy, with peginterferon alpha‐2b plus ribavirin, while severe steatosis (which is virus‐related in most cases) has no impact on virological response.
The safety of pegylated interferon alpha‐2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation
Authors: van Zonneveld M. , Flink H. J. , Verhey E. , Senturk H. , Zeuzem S. , Akarca U. S. , Cakaloglu Y. , Simon C. , So T. M. K. , Gerken G. , de Man R. A. , Hansen B. E. , Schalm S. W. , Janssen H. L. A. ,   The HBV 99‐01 Study Group
Published: April 2005

Background: Treatment with interferon‐alpha has been shown to be effective in one‐third of hepatitis B e antigen‐positive chronic hepatitis B patients, but is clinically associated with relevant adverse events.

Aim: To investigate the safety of pegylated interferon alpha‐2b in 300 hepatitis B e antigen‐positive patients with compensated liver disease.

Methods: Patients were treated with pegylated interferon alpha‐2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha‐2b was administered for 100 μg once a week for 32 weeks; thereafter, the dose was reduced to 50 μg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way.

Results: The most frequently reported side‐effects were flu‐like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha‐2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side‐effects was not different between patients treated with pegylated interferon alpha‐2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha‐2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side‐effects (depression, psychosis) and flu‐like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation.

Conclusion: We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha‐2b therapy is safe, and that pre‐existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.