bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the interaction of CNP with tubulin and microtubules required for process extension in oligodendrocytes?
Authors: Lee J. , Gravel M. , Braun P. E. 
Published: July 2010

Oligodendrocytes (ODC) differentiate and undergo vast membrane synthesis and process extension to form myelin. What are the molecular mechanisms underlying these events? The myelin protein, CNP, appears to play an important role. Recent work from our lab and others provide strong evidence that CNP is associated with the cytoskeleton and may be involved in process extension. Intriguingly, CNP has an enzymatic activity, whose in vivo relevance is unknown, since substrates with 2′,3′‐cyclic termini have not yet been determined for CNP. To elucidate the function of CNP, a 55‐kDa polypeptide, which copurifies with CNP by immunoprecipitation from rat brain, was identified as tubulin by mass spectrometry. Cultured ODC and CNP‐transfected COS‐7 cells showed extensive microtubule colocalization along the main processes and the cell body. COS‐7 cells expressing high levels of CNP exhibited major morphological changes similar to cultured ODC: rounding of the cell body, process extension, and extensive branching of the processes. Deletion mutant studies reveal that tubulin binding and cell transformation are mediated by the C‐terminal catalytic domain. However, the catalytic activity of CNP is not responsible for these morphological changes, since expression of enzymatic inactive mutants in non‐neuronal cells resembled cells expressing wild‐type CNP. Furthermore, RICH (Regeneration Induced CNPase Homologue), a protein that is expressed in fish retinal ganglion cells and shares extensive homology with CNP in the C‐terminal domain, can bind to tubulin and cause similar cytoskeletal transformations in non‐neuronal cells. Our results suggest that binding of CNP to microtubules facilitates cytoskeletal rearrangements necessary for process extension and myelination in ODC.Acknowledgements:  Supported by the CIHR and FCAR.
Role of melatonin in affecting disturbances of central regulation of reproduction by neurotoxicants
Authors: Arutjunyan A. V. , Stepanov M. G. , Kerkeshko G. O. , Prokopenko V. M. , Korenevsky A. V. 
Published: July 2010

An effect of neurotropic xenobiotic 1,2‐dymethylhydrazine (DMH) on hypothalamic regulation of female rat reproduction has been studied. A disturbance of diurnal rhythms of biogenic amines in brain areas responsible for gonadoliberin synthesis and secretion (preoptic area of the hypothalamus – PA, and median eminence – ME), and in suprachiasmatic nuclei of the hypothalamus as a main circadian rhythms pace‐maker, has been found. DMH has been shown to be able to cause various changes in diurnal rhythms of the biogenic amines (dopamine, norepinephrine, serotonin) contents in these brain areas, and in reactive oxygen species (ROS) formation in PA, which can be due to diurnal variations in neurotransmitter levels in this area of the hypothalamus. Taking into account a role of melatonin produced in the pineal gland in circadian rhythms organization, an effect of exogenous melatonin on the above changes caused by DMH has been investigated. The gonadoliberin contents in PA and ME of rats undergone administration of DMH and melatonin have been studied. DMH has been shown not to cause sensible changes in the gonadoliberin contents in PA and ME, while melatonin itself and on the background of DMH administration significantly decreased gonadoliberin levels. Administration of DMH causes less significant changes in biogenic amines compared to melatonin. Also, melatonin in both absence and presence of DMH aggravates ROS formation in PA as well as in the whole hypothalamus. Our data allow supposition that exogenious melatonin is not capable of recovering processes of regulation of reproduction that were disturbed by neurotoxicant xenobiotics.Acknowledgements:  Supported by RBRF grant #00‐04‐48967.
Inflammatory Bowel Disease Developing in Paediatric and Adult Age
Authors: Guariso Graziella , Gasparetto Marco , Visonà Dalla Pozza Laura , D'Incà Renata , Zancan Lucia , Sturniolo Giancarlo , Brotto Francesca , Facchin Paola 
Published: July 2010

ABSTRACTBackground and Objective:In recent decades, there has been a significant increase in the incidence of inflammatory bowel disease (IBD). It has yet to be established whether the manifestations of IBD are similar in paediatric and adult ages. The objective of this study was to compare the phenotypic expression of the disease between patients with childhood‐onset IBD and adulthood‐onset cases, all afferent to the same clinical centre.Patients and Methods:Descriptive and multivariate analyses were completed on retrospective and prospective data of paediatric‐onset and adult‐onset consecutive cases who were diagnosed and followed at the same tertiary referral hospital of the University of Padua, Italy, during a period of 14 years (1994–2008). Paediatric‐onset patients were further divided into age brackets (0–5, 6–12, and 13–17 year‐olds). Analyses were conducted using the SAS package, version 9.1 (SAS Institute Inc, Cary, NC).Results:Three hundred twelve patients were analysed. At disease onset, the manifestations which were more frequent among the 133 paediatric patients (50.4% with diagnosis of Crohn disease [CD], 43.6% with ulcerative colitis, and 6% with unclassified IBD) with respect to the adult‐onset patients were perianal disease (12.8%) (P < 0.0001) and extraintestinal manifestations (14.3%) (P = 0.043). Among the 179 adult patients (55.3% with diagnosis of ulcerative colitis, 36.3% with CD, and 8.3% with unclassified IBD) instead, severe abdominal pain (P = 0.008), diarrhoea (P = 0.005), and anorexia (P < 0.0001) were more frequently observed. During the follow‐up, the presence of extraintestinal manifestations (50.4%) (P = 0.005) and perianal disease (44.8% of the patients with childhood‐onset CD) (P = 0.006) was observed more often in the paediatric‐onset group.Conclusions:In our cases, the phenotypic expression of IBD developing in paediatric age differs from that seen in adults.
Pilot study: rapamycin in advanced hepatocellular carcinoma
Authors: Schöniger‐Hekele M. , Müller C. 
Published: July 2010

SummaryBackground  The PI3K/Akt/mTOR signal pathway is involved in hepatocarcinogenesis. Rapamycin (=sirolimus), a specific mTOR inhibitor, leads to G(1) arrest of many malignant cell lines and currently, analogues of rapamycin are being investigated as a cancer chemotherapeutic adjuvant.Aim  To study the toxicity and tolerability of rapamycin therapy in patients with advanced hepatocellular carcinoma (HCC).Methods  Between June 2005 and February 2007, patients with advanced HCC, not eligible for any established therapy, were included in the study.Results  Eighteen patients (F/M: 5/13) with compensated liver cirrhosis (Child A n = 11, Child B n = 5, Child C n = 2) and histologically proven HCC were included in this study. According to the BCLC staging system, most of the patients enrolled had an advanced HCC: BCLC stage B: n = 2, Barcelona Clinic Liver‐Cancer (BCLC) stage C: n = 14, BCLC stage D: n = 2. Overall, therapy with rapamycin was well tolerated. Most common toxicities were thrombocytopaenia and anaemia. We did not observe any partial or complete tumour response. At 3 months, two patients had stable disease and at 6 months, all patients had progressed. The median overall survival was 5.27 months, median time to progression was 3 months.Conclusion  Rapamycin is well tolerated in patients with advanced HCC, but only minimally effective.
short report: Bleeding disorders in Lowe syndrome patients: evidence for a link between OCRL mutations and primary haemostasis disorders
Authors: Lasne Dominique , Baujat Geneviève , Mirault Tristan , Lunardi Joël , Grelac Françoise , Egot Marion , Salomon Rémi , Bachelot‐Loza Christilla 
Published: July 2010

SummaryLowe syndrome (LS) is a rare X‐linked disorder caused by mutations in the oculocerebrorenal gene (OCRL), encoding OCRL, a phosphatidylinositol 5–phosphatase with a RhoGAP domain. An abnormal rate of haemorrhagic events was found in a retrospective clinical survey. Herein, we report the results of exploration of haemostasis in six LS patients. All patients had normal coagulation tests but prolonged closure times (CTs) in the PFA–100 system. Healthy donors’ blood samples incubated with a RhoA kinase inhibitor had prolonged CTs. This suggests that an aberrant RhoA pathway in platelets contributes to CT prolongation and primary haemostasis disorders in LS.
Preventing obesity at weaning: parental views about the EMPOWER programme
Authors: Barlow J. , Whitlock S. , Hanson S. , Davis H. , Hunt C. , Kirkpatrick S. , Rudolf M. 
Published: July 2010

AbstractBackground  Infant growth and lifestyle are now recognized as being critical determinants of later obesity. EMPOWER (Empowering Parents to Prevent Obesity at Weaning: Exploratory Research) was developed as an intervention for parents whose babies are at high risk. Delivered by specially trained health visitors, it is underpinned by the Family Partnership Model and uses a strengths‐based, solution‐focused way of working with families.Methods  Mothers of babies participating in the pilot of EMPOWER in Leeds were recruited to take part in a study to examine perceptions about the programme's acceptability and usefulness. Interviews were taped and transcribed, and thematic analysis undertaken.Results  Families talked positively about the approach of the EMPOWER health visitor with her emphasis on listening, partnership working and shared problem‐solving. Parents particularly valued the use of a non‐judgemental approach, which they felt had helped them to discuss openly, sensitive issues such as weight and diet. They identified a number of important benefits ranging from increased knowledge about the most appropriate types and amount of food to feed their toddler, to more far‐reaching changes within the family as a whole, including modifications to their own diet and lifestyle. Programmes of this nature were perceived as more valuable than the standard help that is currently available.Conclusion  The EMPOWER programme appears to be both acceptable and valued by targeted parents and a potentially effective means of supporting high‐risk families to prevent their children from developing obesity. An exploratory randomized controlled trial is now underway to ascertain the feasibility of conducting a definitive phase 3 trial.
An epidemiologic study of irritable bowel syndrome in adolescents and children in South China: a school‐based study
Authors: Zhou H. , Li D. , Cheng G. , Fan J. , Lu H. 
Published: July 2010

AbstractBackground  To explore the prevalence of irritable bowel syndrome (IBS) among school‐aged children in South China, and identify distribution characteristics and contributing factors.Methods  Primary, middle and high school students (n= 2013) were recruited from schools in Shanghai. Students completed two questionnaires, one for IBS in adolescents and children and the Screen for Child Anxiety Related Emotional Disorders (SCARED).Results  (1) The prevalence of IBS among students was 20.72% and the incidence increased with age. (2) Several physical factors and overuse of analgesics were significantly associated with IBS. (3) The prevalence of anxiety disorder was higher in older students, and in females vs. males. Students with IBS tended towards anxiety‐related emotional disorders (38.14% vs. 18.96%). (4) IBS students scored higher in all SCARED categories. Within IBS students, those who frequently sought medical care reported higher scores in the somatization/panic category.Conclusion  (1) Irritable bowel syndrome is a common disorder among adolescents in South China and prevalence increases with age. (2) Gastrointestinal infection, abuse of analgesics and psychological factors might be related to the incidence of IBS. (3) The tendency towards anxiety‐related emotional disorders also increases with age, suggesting a possible correlation with IBS and underlining the importance of positive family and school environments. Although the prevalence of anxiety‐related emotional disorders was higher in females than males, this trend was not correlated with the occurrence of IBS.
Intestinal parasites, nutritional status and physchomotor development delay in migratory farm worker's children
Authors: Koruk I. , Simsek Z. , Tekin Koruk S. , Doni N. , Gürses G. 
Published: July 2010

AbstractObjective  The aim of this study was to investigate the prevalence of intestinal parasites, nutritional status and physchomotor developmental delay and anaemia in children of migratory seasonal farm worker families.Material and methods  In this cross‐sectional study, 168 children aged between 6 and 59 months selected through probability sampling method were contacted in the Sanliurfa district of south‐eastern Anatolia of Turkey. The data were collected using a structured questionnaire, anthropometry and Ankara Developmental Screening Inventory to measure physchomotor development. In order to evaluate the anaemia, finger‐prick blood samples were used and laboratory analyses of faecal samples were conducted.Results  55.4% of children were infected by intestinal parasites. The most common infections involved the protozoan parasite Giardia intestinalis (37.2%). Of the children 17.8% had general psychomotor development delay. Regarding the nutritional status of the 168 children who participated, 38.1% were stunted, 20.8% were underweight, and 5.4% were wasted. Of these children, 16.6% were anaemic.Conclusion  The findings demonstrated that the children of migratory seasonal farm workers were defined as a high‐risk group in terms of nutritional status, intestinal parasites and physchomotor development delay. Therefore, the effective delivery of mobile environmental and individual primary healthcare services to the farm workers' children must be ensured both while residing in the agricultural zone and in their permanent addresses.
Depletion of CD4+CD25+ T cells switches the whey‐allergic response from immunoglobulin E‐ to immunoglobulin free light chain‐dependent
Authors: Van Esch B. C. A. M. , Schouten B. , Blokhuis B. R. J. , Hofman G. A. , Boon L. , Garssen J. , Knippels L. M. J. , Willemsen L. E. M. , Redegeld F. A. 
Published: July 2010

SummaryBackground
Symptoms of allergy are largely attributed to an IgE‐mediated hypersensitivity response. However, a considerable number of patients also exhibit clinical features of allergy without detectable systemic IgE. Previous work showed that Ig‐free light chains (IgLC) may act as an alternate mechanism to induce allergic responses. CD4+CD25+ T cells are crucial in the initiation and regulation of allergic responses and compromised function might affect the response to allergens.Objective
To examine the contribution of CD4+CD25+ T cells and IgLC towards the whey‐allergic response.Methods
Mice were sensitized orally with whey using cholera toxin as an adjuvant. CD25+ T cells were depleted in vivo using a CD25 mAb. The acute allergic skin response to whey and ex vivo colon reactivity was measured in the presence or absence of F991, a specific inhibitor of IgLC. Serum whey‐specific antibodies and IgLC in serum and mesenteric lymph node (MLN) supernatants were measured. Depletion of CD4+CD25+ T cells was confirmed in the spleen.Results
Anti‐CD25 treatment strongly reduced whey‐specific antibody levels and resulted in a partial depletion of effector T cells and a major depletion of Foxp3+ regulatory T cells. Surprisingly, despite the abolished specific IgE response, the acute allergic skin response to whey was not affected. IgLC levels were enhanced in the serum and MLN supernatants of CD25‐depleted sensitized mice. F991 inhibited the acute skin response and colon hyperreactivity in anti‐CD25‐treated mice, indicating that these responses were mainly IgLC dependent.Conclusions
Depletion of CD4+CD25+ T cells resulted in a switch from an IgE‐ to an IgLC‐dependent acute skin response and functional hyperresponsiveness of the colon. Our data suggest that CD25+ T cells play a crucial role in balancing cow's milk allergy between IgE and IgE‐independent responses and both mechanisms might play a role in allergic responses to the same allergen. Cite this as: B. C. A. M. van Esch, B. Schouten, B. R. J. Blokhuis, G. A. Hofman, L. Boon, J. Garssen L. M. J. Knippels, L. E. M. Willemsen and F. A. Redegeld, Clinical & Experimental Allergy, 2010 (40) 1414–1421.
Performance of a component‐based allergen‐microarray in the diagnosis of cow's milk and hen's egg allergy
Authors: D'Urbano L. E. , Pellegrino K. , Artesani M. C. , Donnanno S. , Luciano R. , Riccardi C. , Tozzi A. E. , Ravà L. , De Benedetti F. , Cavagni G. 
Published: July 2010

SummaryBackground
The food challenge test (FCT) is the gold standard for the diagnosis of food allergy. This procedure is time consuming, costly and can induce potentially severe symptoms. An ideal in vitro test should allow to avoid the FCT.Objective
To assess the clinical performance of microarray for specific IgE (sIgE) detection in children with challenge‐proven/excluded cow's milk (CM) or hen's egg (HE) allergy.Methods
One‐hundred and four children with suspected IgE‐mediated hypersensitivity to CM or HE were studied. In all patients, skin prick test, ImmunoCAP, microarray and FCT were performed.Results
The microarray components Bos d 8 for CM (27/58 patients) and Gal d 1 (20/46 patients) and Gal d 2 (24/46) for HE were the most frequently recognized allergens. Using the FCT results as the reference parameter, sIgE to Bos d 8 and Gal d 1 had the highest area under the curves. These were not significantly different from those obtained using the ImmunoCAP. Use of 95% clinical decision points (CDP) for sIgE to Bos d 8 and Gal d 1 resulted in higher negative predictive values (78% and 79%, respectively) than those obtained with the ImmunoCAP (57% and 59%).Conclusions
Our results show that in children with suspected CM or HE allergy, the microarray has a good ability to predict the FCT results. In a clinical application perspective, the microarray could be used as a second‐level assay, if the ImmunoCAP sIgE is <95% CDP. This approach would lead to a decrease in the number of the FCT to be performed, as well as of positive FCTs with a subsequent decrease in severe reaction risk. Cite this as: L. E. D'Urbano, K. Pellegrino, M. C. Artesani, S. Donnanno, R. Luciano, C. Riccardi, A. E. Tozzi, L. Ravà, F. De Benedetti and G. Cavagni, Clinical & Experimental Allergy, 2010 (40) 1561–1570.
Expression of CD203c and CD63 in human basophils: relationship to differential regulation of piecemeal and anaphylactic degranulation processes
Authors: MacGlashan D. 
Published: July 2010

SummaryBackgroundActivation of human basophils results in the release of many different mediators and the expression of new cell surface proteins. The markers CD63 and CD203c have been used in recent years to assess basophil activation but there have been many studies that demonstrate that expression of these markers can be dissociated from histamine release.ObjectiveTo determine the signal transduction requirements for CD203c and CD63 expression.MethodsThe current study began by exploring the dependency of CD203c and CD63 expression on protein kinase C (PKC) using known selective inhibitors of PKC.ResultsBetween 30 and 300 nm, Ro‐31‐8220 and bisindoylmaleimide II (Bis II) had no effect on formyl–met–leu–phe‐ or anti‐IgE‐induced CD63 or CD203c but enhanced IgE‐mediated expression of CD63 by an average of 15‐fold at concentrations >1 μm. These results led to the suggestion that these inhibitors altered the normal pathways of degranulation (by a non‐PKC dependent mechanism), shifting the normal presence of piecemeal degranulation to the process termed anaphylactic degranulation (AND). Morphological studies demonstrated that concentrations of Ro‐31‐8220 and Bis II>1 μmdramatically increased the presence of degranulation sacs, a morphological feature of AND.ConclusionIt is proposed that CD63 expression results from only the AND form of histamine release.Cite this as: D. MacGlashan Jr,Clinical & Experimental Allergy, 2010 (40) 1365–1377.
Anti-endothelial cell antibodies in rheumatic heart disease
Authors: Scalzi V , Hadi H Abu , Alessandri C , Croia C , Conti V , Agati L , Angelici A , Riccieri V , Meschini C , Al-Motarreb A , Al-Ansi A , Valesini G 
Published: July 2010

SummaryTo evaluate the anti-endothelial cell antibodies (AECA), anti-cardiolipin antibodies (aCL) and serum mannose-binding lectin (MBL) profiles of a large cohort of Yemeni patients with rheumatic heart disease (RHD) and to correlate these findings with clinical features of the disease. Patients (n = 140) were recruited from Al-Thawra Hospital in Sana'a, Yemen. All had RHD diagnosed according to modified Jones' criteria. We also studied 140 sex- and age-matched healthy blood donors from the same area. Echocardiography was performed according to the recommendations of the American Society of Echocardiography. Solid phase enzyme-linked immunosorbent assays (ELISAs) were used to measure AECA and aCL titres and serum MBL levels. Forty per cent of the patients were AECA-positive, but only 7·8% were positive for aCL antibodies. Serum MBL levels were significantly lower in the RHD group (median 4221 ng/ml versus 5166 ng/ml in healthy controls). AECA titres were correlated positively with patient age, duration of RHD and the severity of aortic stenosis, as determined by echocardiographic findings. In several autoimmune rheumatic diseases, such as systemic lupus erythematosus, vasculitis and scleroderma, AECA have been shown to play pathogenic roles by producing proinflammatory and procoagulant effects (increased expression of adhesion molecules and tissue factors, increased cytokine release) in endothelial cells. In RHD, these autoantibodies might represent a pathological link between activation of the valvular endothelium and valvular damage.
Immune receptor expressed on myeloid cells 1 (IREM-1) inhibits B cell activation factor (BAFF)-mediated inflammatory regulation of THP-1 cells through modulation of the activities of extracellular regulated kinase (ERK)
Authors: Lee S-M , Nam Y-P , Suk K , Lee W-H 
Published: July 2010

Summary
The immune receptor expressed on myeloid cells 1 (IREM-1) has been known to regulate the activities of myeloid cells through its immunoreceptor tyrosine-based inhibition motifs (ITIMs) in its intracellular region. In order to investigate its effect on macrophage activation, a human macrophage cell line (THP-1) was tested after stimulation of its membrane-bound form of B cell activation factor (BAFF), which has been shown to modulate inflammatory activities through induction of proinflammatory mediator expression and suppression of phagocytosis. IREM-1-specific monoclonal antibodies detected the expression of high levels of IREM-1 in THP-1 cells. Cross-linking of IREM-1 with these antibodies resulted in the blockage of the BAFF-mediated expression of interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 through inhibition of the activation of extracellular regulated kinase (ERK) and phosphorylation/degradation of IκB. Furthermore, cross-linking of IREM-1 also reversed the BAFF-mediated inhibition of phagocytosis. In order to demonstrate the role of ITIM in the IREM-1-mediated suppression of BAFF signalling, a decapeptide containing YADL (an ITIM in IREM-1) was fused with HIV–TAT48–57 which was required for the internalization of the synthetic polypeptide (TAT–YADL). TAT–YADL, but not control peptides, recapitulated the effect of the anti-IREM-1 monoclonal antibody. These observations indicate that IREM-1 exerted its inhibitory effect on BAFF-medicated signalling through ITIM-mediated regulation of ERK activities in THP-1 cells.