bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of the expression of connective tissue growth factor (CTGF) by alterations of the cytoskeleton
Authors: Ott Christian , Graness Angela , Giehl Klaudia , Goppelt‐Struebe Margarete 
Published: September 2009

Introduction  In closing wounds or developing fibrotic tissue, fibroblasts are exposed to mechanical stress, which leads to alterations in cell morphology and reorganization of the cytoskeleton. The impact of morphological changes on gene expression was investigated in the present study. As a model system, we used a human renal fibroblast cell line and studied the expression of connective tissue growth factor (CTGF). CTGF is a downstream mediator of TGF‐β mediating many of the pro‐fibrotic actions of this growth factor and has also been shown to be up‐regulated by static or dynamic pressure. The molecular mechanisms regulating CTGF expression related to stress are not yet known.Materials and methods  A human renal fibroblast cell line was kindly provided by Dr Müller, Göttingen, Germany. These cells express CTGF upon treatment with soluble stimuli (Heusinger‐Ribeiro et al. 2001; Eberlein et al. 2001). CTGF expression was detected by northern and Western blot analysis. The actin cytoskeleton was visualized by rhodamine phalloidin staining, and microtubules were detected by immunocytochemistry.Results  Low concentrations of the microtubule disrupting agents nocodazole and colchicine strongly up‐regulated CTGF mRNA and protein expression in the human renal fibroblast cell line TK173. The up‐regulation was prevented by stabilization of the microtubules by paclitaxel (taxol). As a consequence of microtubule disruption, the small GTPase RhoA was activated and the actin stress fibers were stabilized. Both effects were related to CTGF induction: interference with RhoA signalling by simvastatin, toxin B and Y27632 prevented up‐regulation of CTGF. The important role of RhoA was supported by an increased CTGF expression upon overexpression of constitutively active RhoA. Direct disassembly of the actin cytoskeleton by latrunculin B interfered with colchicine‐mediated up‐regulation of CTGF expression. Disassembly of actin fibers by cytochalasin D unexpectedly increased CTGF expression. This indicated that the content of F‐actin per se was not the major determinant for CTGF gene expression. It has been shown, however, that cytochalasin D sequesters G‐actin, whereas latrunculin increases the level of G‐actin. Our data are thus in accordance with an inverse correlation between G‐actin levels and CTGF expression.Discussion  These data link alterations in the microtubule and actin cytoskeleton to the expression of CTGF. Recently, decreased levels of G‐actin were observed in vascular smooth muscle cells in response to increased vascular pressure (Cipolla et al. 2002). Our findings thus provide a molecular basis for the observation that CTGF is up‐regulated in cells exposed to mechanical stress.
Homophilic complex formation is prerequisite for MT1‐MMP to degrade type‐I collagen on the cell surface
Authors: Itoh Yoshifumi , Ito Noriko , Nagase Hideaki , Seiki Motoharu 
Published: September 2009

Introduction  MT1‐MMP degrades a wide variety of extra‐cellular matrix macromolecules and some cell‐surface proteins such as CD44, transglutaminase and αv‐integrin, and activates zymogen of MMP‐2 and MMP‐13. Among these activities, the collagenolytic activity is one of the most important functions of the enzyme in biology, as the phenotypes of MT1‐MMP gene knockout mice, such as abnormal skeletal development and various connective tissue abnormalities, are thought to be attributed to the lack of cellular collagenase activity. We have previously shown that MT1‐MMP forms homophilic complex through its haemopexin (HPX) domain facilitating the activation of proMMP‐2 (Itoh et al. 2001). In this report, we present data that collagen‐degrading activity of MT1‐MMP also requires homophilic complex formation.Methods  COS7 cells were cultured on type‐I collagen film and transfected with MT1‐MMP and its mutant gene to look at collagen degradation activity of these gene products.Results  Co‐expression of the catalytic domain‐deleted mutant of MT1‐MMP (MT1δCat) with the wild‐type enzyme inhibited its homophilic complex formation as well as its ability to activate proMMP‐2 on the cell surface, and MT1δCat also inhibited cell‐surface collagenolytic activity of the wild‐type MT1‐MMP. A chimeric MT1‐MMP mutant (MT‐MMP13) whose catalytic domain, hinge region and HPX domain were replaced with those derived from collagenase‐3 (MMP‐13) did not degrade collagen though MT‐MMP13 was expressed and maintained its proteolytic activity against gelatin on the cell surface. When an interface for homophilic complex formation, the HPX domain derived from MT1‐MMP, was further added to the chimeric enzyme (MT‐MMP13‐HPXmt1), it degraded collagen. Co‐expression of MT1dCat and MT‐MMP13‐HPXmt1 also inhibited the collagenolytic activity.Discussion  Homphilic complex formation is prerequisite for the expression of collagenase activity on the cell surface. Presumably, each MT1‐MMP in the complex has different roles; one unwinds triple‐helical structure of collagen locally and the other cuts peptide bond.
Withdrawal of corticosteroids in inflammatory bowel disease patients after dependency periods ranging from 2 to 45 years: a proposed method
Authors: MURPHY S. J. , WANG L. , ANDERSON L. A. , STEINLAUF A. , PRESENT D. H. , MECHANICK J. I. 
Published: September 2009

SummaryBackground  Even in the biologic era, corticosteroid dependency in IBD patients is common and causes a lot of morbidity, but methods of withdrawal are not well described.Aim  To assess the effectiveness of a corticosteroid withdrawal method.Methods  Twelve patients (10 men, 2 women; 6 ulcerative colitis, 6 Crohn’s disease), median age 53.5 years (range 29–75) were included. IBD patients with quiescent disease refractory to conventional weaning were transitioned to oral dexamethasone, educated about symptoms of the corticosteroid withdrawal syndrome (CWS) and weaned under the supervision of an endocrinologist. When patients failed to wean despite a slow weaning pace and their IBD remaining quiescent, low dose synthetic ACTH stimulation testing was performed to assess for adrenal insufficiency. Multivariate analysis was performed to assess predictors of a slow wean.Results  Median durations for disease and corticosteroid dependency were 21 (range 3–45) and 14 (range 2–45) years respectively. Ten patients (83%) were successfully weaned after a median follow‐up from final wean of 38 months (range 5–73). Disease flares occurred in two patients, CWS in five and ACTH testing was performed in 10. Multivariate analysis showed that longer duration of corticosteroid use appeared to be associated with a slower wean (P = 0.056).Conclusions  Corticosteroid withdrawal using this protocol had a high success rate and durable effect and was effective in patients with long‐standing (up to 45 years) dependency. As symptoms of CWS mimic symptoms of IBD disease flares, gastroenterologists may have difficulty distinguishing them, which may be a contributory factor to the frequency of corticosteroid dependency in IBD patients.
Trajectory analysis: concepts and applications
Authors: Helland‐Hansen W. , Hampson G. J. 
Published: September 2009

ABSTRACTShoreline and shelf‐edge trajectories describe the migration through time of sedimentary systems, using geomorphological breaks‐in‐slope that are associated with key changes in depositional processes and products. Analysis of these trajectories provides a simple descriptive tool that complements and extends conventional sequence stratigraphic methods and models. Trajectory analysis offers four advantages over a sequence stratigraphic interpretation based on systems tracts: (1) each genetically related advance or retreat of a shoreline or shelf edge is viewed in the context of a continuously evolving depositional system, rather than as several discrete systems tracts; (2) subtle changes in depositional response (e.g. within systems tracts) can be identified and honoured; (3) trajectory analysis does not anticipate the succession of depositional events implied by systems‐tract models; and (4) the descriptive emphasis of trajectory analysis does not involve any a priori assumptions about the type or nature of the mechanisms that drive sequence development. These four points allow the level of detail in a trajectory‐based interpretation to be directly tailored to the available data, such that the interpretation may be qualitative or quantitative in two or three dimensions. Four classes of shoreline trajectory are recognized: ascending regressive, descending regressive, transgressive and stationary (i.e. nonmigratory). Ascending regressive and high‐angle (accretionary) transgressive trajectories are associated with expanded facies belt thicknesses, the absence of laterally extensive erosional surfaces, and relatively high preservation of the shoreline depositional system. In contrast, descending regressive and low‐angle (nonaccretionary) transgressive trajectories are associated with foreshortened and/or missing facies belts, the presence of laterally extensive erosional surfaces, and relatively low preservation of the shoreline depositional system. Stationary trajectories record shorelines positioned at a steeply sloping shelf edge, with accompanying bypass of sediment to the basin floor. Shelf‐edge trajectories represent larger spatial and temporal scales than shoreline trajectories, and they can be subdivided into ascending, descending and stationary (i.e. nonmigratory) classes. Ascending trajectories are associated with a relatively large number and thickness of shoreline tongues (parasequences), the absence of laterally extensive erosional surfaces on the shelf, and relatively low sediment supply to the basin floor. Descending trajectories are associated with a few, thin shoreline tongues, the presence of laterally extensive erosional surfaces on the shelf, and high sediment supply to basin‐floor fan systems. Stationary trajectories record near‐total bypass of sediment across the shelf and mass transfer to the basin floor.
A short low‐dose imatinib trial allows rapid identification of responsive patients in hypereosinophilic syndromes
Authors: Intermesoli Tamara , Delaini Federica , Acerboni Sara , Salmoiraghi Silvia , Spinelli Orietta , Guerini Vittoria , Vannucchi Alessandro M. , Mappa Silvia , Rossi Giuseppe , Rossi Valentina , Di Bona Eros , Paratore Simona , Carobbio Alessandra , Rambaldi Alessandro , Barbui Tiziano , Bassan Renato 
Published: September 2009

SummaryAlthough imatinib may be effective in hypereosinophilic syndromes, the exact response kinetics are not known. Imatinib was administered at 100–400 mg/d each week in a 12‐week response‐oriented schedule, targeting a complete clinical and haematological remission (CR). CR was achieved in 11/23 patients (6/6 with FIP1L1‐PDGRFA rearrangement and 5/17 without, P = 0·006), most after 2 weeks of 100 mg/d imatinib. The maximum imatinib dose had no effect in early unresponsive patients. Low‐dose, short‐course imatinib may represent a rational choice for identifying responsive cases, both within and outside the pre‐defined FIP1L1 rearrangement subset.
How individuals with phenylketonuria experience their illness: an age‐related qualitative study
Authors: Vegni E. , Fiori L. , Riva E. , Giovannini M. , Moja E. A. 
Published: September 2009

AbstractBackground  The aim of the study was to explore the illness experience of individuals affected by phenylketonuria (PKU) and its differences in different patient age groups.Methods  A qualitative–interpretative methodology was used through in‐depth interviews. Textual data were explored using the principles of grounded theory.Results  Forty‐seven patients participated in the study, aged from 10 to >25 years old. The results suggested the age‐related PKU experience: (1) a paradox, either to feel normal but isolated from the social context, or to be different while participating in the convivial aspects of the social being; and (2) the need for education about the disease tailored to the individual and growing needs. Specific themes seem to characterize each age range.Conclusions  This study constitutes a first attempt at understanding PKU from a non‐medical‐biological perspective.
Perception of vulnerability among mothers of healthy infants in a middle‐income country
Authors: Dogan D. G. , Ertem I. O. , Karaaslan T. , Forsyth B. W. 
Published: September 2009

AbstractBackground  Although four decades have passed since the concept of ‘vulnerable children’ has been introduced into paediatric literature, research on vulnerability is limited to high‐income, Western countries. To adapt and adopt practices that have been advised for paediatricians to prevent ‘the vulnerable child syndrome’, information is needed also on the prevalence and correlates of perceived vulnerability in children in low‐ and middle‐income (LAMI) countries.Objective  To determine the rate and correlates of the perception of vulnerability among healthy young children in a healthy population of children in Ankara, Turkey.Methods  In this cross‐sectional observational study, participants comprised of a ‘prescriptive sample’ of healthy, thriving children with no known health risk for vulnerability. Maternal perception of child vulnerability was assessed using the Child Vulnerability Scale (CVS). Potential risks factors for vulnerability including history of threatened abortion during pregnancy, child gender, birth order, maternal and paternal age and education were collected using a structured questionnaire.Results  A total of 519 children – 264 boys (50.9%) and 255 girls (49.1%) – comprised the sample. The internal consistency of the CVS was 0.71. Item‐total scale corrrelations were 0.30 or above for all of the eight items. The median CVS score of the sample was 2.0 and 30 mothers (5.8%) were found to perceive their children as vulnerable. None of the socio‐demographic variables that were investigated were found to be associated with high vulnerability scores.Conclusion  This study is the first to examine maternal perceived vulnerability of healthy children in a middle‐income country. The findings imply that a high proportion of healthy children are perceived as vulnerable by their mothers and that previously studied socio‐demographic factors do not explain perceived vulnerability. The results of this study may provide a comparison point for studies on childhood vulnerability in LAMI countries.
Disabled children in the UK: a quality assessment of quantitative data sources
Authors: Read J. , Blackburn C. , Spencer N. 
Published: September 2009

AbstractBackground  The limitations of reliable and accessible UK national and local quantitative data on the prevalence of childhood disability and the characteristics and circumstances of disabled children and their households have been recognized for some time. This paper reports the findings from a study that scoped and quality‐assessed existing quantitative UK national and regional data sets on disabled children and their families.Methods  A comprehensive search of relevant data sources with information on disabled children was undertaken. Data sources were evaluated with reference to: disability definitions and questions; potential to generate nationally representative prevalence estimates of disabled children; study design; population coverage; sampling issues; social and demographic data; appropriateness for identifying childhood as opposed to adult disability.Results  Thirty‐seven data sources with information on childhood disability were identified, of which 30 met the inclusion criteria: nine cross‐sectional surveys, nine longitudinal and panel studies, seven administrative data sets, four specific condition databases and one was another type. Definitions and questions varied across data sources. Long‐standing illness and limiting long‐standing illness were the most consistently used definitions. Repeated cross‐sectional surveys were found to be most appropriate for estimating overall prevalence but, with the exception of the Population Census, sample sizes were too small to study prevalence and characteristics by some population sub‐groups such, including age by year, minority ethnic status and socio‐economic position. Few data sources included questions appropriate for identifying childhood as opposed to adult disability or collected information from disabled children themselves.Conclusions  Our findings summarize the currently available quantitative data sources on childhood disability and highlight the limitations. We make recommendations for the future development of more robust childhood disability data and issues requiring further research. To assist policy makers and service providers to make use of current data sources we have produced a brief online guide based on our findings.
Allelic variants of CD40 and CD40L genes interact to promote antibiotic‐induced cutaneous allergic reactions
Authors: Kim Sae‐H , Lee J‐E , Kim Sang‐H , Jee Y‐K , Kim Y‐K , Park H‐S , Min K‐U , Park H‐W ,   The Adverse Drug Reaction Research Group in Korea
Published: September 2009

SummaryBackground
The danger hypothesis provides a new perspective of the mechanisms underlying drug allergy. In this study, we evaluated associations between variations in the genes involved in danger signal pathways and antibiotic‐induced cutaneous allergic reactions (AICARs).Methods
Two hundred cases with urticaria, angio‐oedema, maculopapular rash, and erythema multiforme caused by antibiotics were extracted from the database of the Adverse Drug Reaction Research Group in Korea. All cases were confirmed by an allergy specialist. Causative antibiotics included penicillin, cephalosporin, quinolone, and others (approximately 40 different types). Ten single nucleotide polymorphisms (SNPs) in seven genes (−318C>T, +49A>G, and +6230G>A in CTLA4, IVS+17T>C in CD28, −3479T>G and I170V in CD86, −1C>T in CD40, −3458A>G in CD40LG, −308G>A in TNF, and −31T>C in IL1B) were scored for cases and for healthy subjects without a history of AICARs.Results
Our analysis failed to reveal differences in the distribution of the 10 SNPs between cases and controls. However, we could find a gene–gene interaction between −1C>T in CD40 and −3458A>G in CD40L using multifactor dimensionality reduction analysis. Subjects with minor alleles of both SNPs showed a significant risk for developing AICARs [P=0.017, odds ratio (OR) (95% confidence interval)=2.93 (1.20–7.97)].Conclusion
Our findings suggest that a genetic interaction between CD40 and CD40L favours the development of AICARs.
Cytology of the ‘penile’ neovagina in transsexual women
Authors: Weyers S. , Lambein K. , Sturtewagen Y. , Verstraelen H. , Gerris J. , Praet M. 
Published: September 2009

S. Weyers, K. Lambein, Y. Sturtewagen, H. Verstraelen, J. Gerris and M. Praet Cytology of the ‘penile’ neovagina in transsexual womenObjective:  The primary objective was to describe the neovaginal cytology in transsexual patients (n = 50) treated with the inverted penile skin technique. Secondary objectives were to compare our cytological findings with patient characteristics including use of oestrogens, sexual orientation and penetrative intercourse.Methods:  The medical and surgical history, sexual orientation and whether there was a current relationship were ascertained. A speculum examination was followed by microscopy of a Pap smear of the neovaginal vault.Results:  Well‐preserved nucleated squamous cells were found in 72%. The correlation between their presence and sexual orientation was highly significant (P = 0.016), with those not sexually interested and homosexually oriented all having nucleated cells on the Pap smear. However, the correlation between these cells and penetrative intercourse failed to reach significance. Four samples showed atypical squamous cells of undetermined significance, all were negative for high‐risk human papillomavirus (HR‐HPV) types. One patient showed a low‐grade squamous intraepithelial lesion that was HR‐HPV positive. There was a significant correlation between the presence of cytological lesions and sexual orientation (P = 0.006). Four percentage of the specimens showed Döderlein bacilli. Inflammation was found in 30.6% of samples with squamous cells.Conclusions:  The penile skin‐lined neovagina of transsexual women can reflect the cytological findings present in biological women. However ‘normal’ cervical cytology, with superficial, intermediate and parabasal cells as well as Döderlein bacilli, was found in only 4% of transsexual women. Although one patient’s Pap test showed koilocytes and was HR‐HPV positive, no high‐grade squamous intraepithelial lesions were identified.
Review paper: more than ringing in the ears: a review of tinnitus and its psychosocial impact
Authors: Holmes Susan , Padgham Nigel D 
Published: September 2009

Aim and objectives.  To provide an overview of tinnitus, current management and its psychosocial impact offering strategies for managing acute and chronic tinnitus in practice.Background.  Tinnitus, characterised by the perception of sound in the absence of external stimuli, is experienced by about 10% of the population at some time in their lives. It may be temporary/longstanding; approximately 5% adults experience severe, persistent tinnitus affecting their lifestyle. Although many adjust successfully, others are disabled by the condition. Though often unrecognised, tinnitus affects many patients regardless of their presenting illness.Design.  A literature review including descriptive, theoretical and empirical material. Databases were searched using the keyword ‘tinnitus’ providing diverse information which was used to address the research questions.Results.  Tinnitus represents more than ‘simple’ ringing in the ears and may be accompanied by many distressing changes. It may be acute or chronic. It is difficult to treat, care may be directed towards management rather than cure. Many patients are, however, told that ‘nothing can be done’.Relevance to clinical practice.  Despite the high prevalence of tinnitus, there is a paucity of relevant nursing literature suggesting that there is an information deficit amongst nurses. The information provided shows that understanding the full impact of the condition and identification of patients’ needs are essential to effective care. Strategies to help affected patients are given.Conclusions.  Tinnitus, a widespread, often intractable condition, affects millions of people; there is considerable debate about its causes. Tinnitus is distressing and may be severe enough to affect lifestyle and quality of life. Affected patients need considerable support and advice on healthcare options, encouragement to try different treatments and recognition that help and hope are available. Though patients may have to learn to live with tinnitus, the most important thing is that they recognise that help is available.