bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemokine CCL2 facilitates ICAM‐1‐mediated interactions of cancer cells and lymphatic endothelial cells in sentinel lymph nodes
Authors: Kawai Yoshiko , Kaidoh Maki , Yokoyama Yumiko , Sano Kenji , Ohhashi Toshio 
Published: December 2008

We examined the effects of CCL1, CCL2, CCL12 and CCL21 on the expression of adhesion molecules in cultured human lymphatic endothelial cells using immunohistochemical staining or Western blot analysis. In addition, we investigated whether the expressed adhesion molecule was able to facilitate the attachment of carcinoma cells to the lymphatic endothelial cells as an in vitro micrometastatic model. CCL2 caused a selective and significant expression of ICAM‐1 on human lymphatic endothelial cells but CCL1, CCL12 and CCL21 did not. By increasing the stimulation time from 4 to 18 and 48 h, the intensity of immunoreactivity for ICAM‐1 was significantly increased in a time‐dependent manner up to 18 h. The ICAM‐1 mRNA levels were also elevated significantly up to 18 h. The CCL2‐mediated immunohistochemical expression of ICAM‐1 was dose‐dependently increased from 10 pg/mL to 1 ng/mL. The CCL2‐mediated expression of ICAM‐1 was significantly reduced by neutralization of CCL2 using a specific CCL2 antibody. The 18‐h treatment with CCL2 caused a significant facilitation of in vitro attachment of MDA‐MB‐231 and MCF‐7 cells to the lymphatic endothelial cells (LECs). The CCL2‐mediated response in the attachment assay was also significantly reduced either by the neutralization of CCL2 or by additional treatment with anti‐ICAM‐1 antibody. Immunohistochemical expression of ICAM‐1, but not E‐selectin, was strongly observed around and within the metastatic region of sentinel lymph node isolated from breast cancer patients. These findings suggest that CCL2 induces selective and significant expression of ICAM‐1 on cultured human lymphatic endothelial cells and then facilitates the attachment of carcinoma cells to the lymphatic endothelial cells, thus providing an in vitro micrometastatic model via the overexpression of ICAM‐1. (Cancer Sci 2009; 100: 419–428)
The prevalence, clinical features and association of HLA‐B27 in sacroiliitis associated with established Crohn’s disease
Authors: ORCHARD T. R. , HOLT H. , BRADBURY L. , HAMMERSMA J. , MCNALLY E. , JEWELL D. P. , WORDSWORTH B. P. 
Published: December 2008

SummaryBackground Sacroiliitis is a recognized complication of Crohn’s disease and may occur distinct from progressive ankylosing spondylitis (AS).Aim To estimate prospectively the prevalence of sacroiliitis in patients with established Crohn’s disease, to characterize the clinical features and to correlate these with the presence of HLA‐B27.Methods All Crohn's disease patients under active follow‐up of between 5 and 12 years duration were invited to participate. Patients underwent a clinical evaluation including symptom questionnaire, rheumatological examination and underwent HLA genotyping. Patients then underwent magnetic resonance imaging (MRI) of the sacroiliac joints. The clinical and radiological factors were correlated with HLA‐B27 status.Results 56 patients underwent initial assessment and 44 had MRI scans. Seventeen of 44 (39%) patients had MRI evidence of sacroiliitis, of whom 5 fulfilled the criteria for AS. Symptoms of low back pain were elicited in a majority of these patients – 11/17 (65%) compared to 3 of 27 (11%) patients with normal scans (P = 0.003). There were no differences in functional indices with the exception of patients with AS. HLA‐B27 was present in seven patients, and all seven had MRI evidence of sacroiliitis, five had AS.Conclusions Sacroiliitis is common in patients with established Crohn’s disease and in the majority of cases, patients have symptoms of inflammatory low back pain if questioned carefully. HLA‐B27 is not associated with isolated sacroiliitis, but is associated with AS. However, possession of HLA‐B27 appears to convey a very high risk of developing axial inflammation in Crohn’s disease.
The effects of guideline implementation for proton pump inhibitor prescription on two pulmonary medicine wards
Authors: VAN VLIET E. P. M. , STEYERBERG E. W. , OTTEN H. J. A. M. , RUDOLPHUS A. , KNOESTER P. D. , HOOGSTEDEN H. C. , VAN GELDER T. , KUIPERS E. J. , SIERSMA P. D. 
Published: December 2008

SummaryBackground  It has been demonstrated that 40% of patients admitted to pulmonary medicine wards use proton pump inhibitors (PPIs) without a registered indication.Aim  To assess whether implementation of a guideline for proton pump inhibitor (PPI) prescription on pulmonary medicine wards could lead to a decrease in use and improved appropriateness of prescription.Methods  This prospective study comprised two periods, i.e. the situation before and after guideline implementation. In each period, 300 consecutive patients were included. We registered patient characteristics, medications and occurrence of upper gastrointestinal‐related disorders.Results  After implementation, fewer patients were started on PPIs [21% vs. 13%; odds ratio (OR): 0.56; 95% confidence interval (CI): 0.33–0.97] and more users discontinued their use; however, the latter was not significant (3% vs. 6%; OR for continuation: 0.56; 95% CI: 0.14–2.23). Multivariable logistic regression analysis confirmed that PPI use during hospitalization decreased after implementation (adjusted pooled OR: 0.54; 95% CI: 0.32–0.90). Implementation did not result in a change in reported reasons for PPI prescription. There was no significant difference in the occurrence of upper GI‐related disorders in the first 3 months after discharge.Conclusions  Guideline implementation for PPI prescription on two pulmonary medicine wards resulted in a reduction in the number of patients starting PPIs during hospitalization, but appropriateness of prescribing PPIs was not affected. Further studies are needed to determine how appropriateness of PPI prescription on pulmonary medicine wards can be further improved.
Administration of adalimumab in the treatment of Crohn’s disease of the ileal pouch
Authors: SHEN B. , REMZI F. H. , LAVERY I. C. , LOPEZ R. , QUEENER E. , SHEN L. , GOLDBLUM J. , FAZIO V. W. 
Published: December 2008

SummaryBackground  Crohn’s disease (CD) of the pouch can develop in patients with ileal pouch‐anal anastomosis (IPAA). Scant data are available on the treatment of this disease entity.Aim  To evaluate efficacy and safety of adalimumab in treating CD of the ileal pouch.Methods  From June 2007 to June 2008, 17 IPAA patients with inflammatory (n = 10), fibrostenotic (n = 2) or fistulizing (n = 5) CD of the pouch treated with adalimumab were evaluated. Inclusion criteria were CD of the pouch who failed medical therapy and were otherwise qualified for permanent pouch diversion or excision. All qualified patients received the standard dosing regimen of subcutaneous injection adalimumab (160 mg at week 0, 80 mg at week 1, and 40 mg every other week thereafter). Complete clinical response was defined as resolution of symptoms. Partial clinical response was defined as improvement in symptoms. Endoscopic inflammation before and after therapy was recorded, using the Pouchitis Disease Activity Index (PDAI) endoscopy subscores.Results  The median age was 36 years with 12 patients (70.6%) being male. At 4 weeks, seven patients (41.2%) had a complete symptom response and 6 (35.3%) had a partial response. There was also a significant improvement in the PDAI endoscopy subscores at week 4 (P < 0.05). At the last follow‐up (median of 8 weeks), eight patients (47.1%) had a complete symptom response and 4 (23.5%) had a partial response. Four patients (23.6%) developed adverse effects. Three patients (17.7%) eventually had pouch failure after failing to respond to adalimumab therapy.Conclusion  Adalimumab appeared to be well‐tolerated and efficacious in treating CD of the pouch in this open‐labelled induction study.
What is the scale of prescribing errors committed by junior doctors? A systematic review
Authors: Ross Sarah , Bond Christine , Rothnie Helen , Thomas Sian , Macleod Mary Joan 
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Prescribing errors account for a substantial proportion of medication errors and cause the most significant problems.• There is a dearth of accurate information on the prevalence of prescribing errors, with estimates from 1 to 100% of all patients admitted to hospital. WHAT THIS STUDY ADDS • This review reports the wide ranges of error rates seen, which cannot be compared due to differences in methodology and error definitions used.• A well‐conducted study of prescribing errors by junior doctors using standard definitions and methodology is urgently needed to allow development and assessment of appropriate interventions.AIMSPrescribing errors are an important cause of patient safety incidents, generally considered to be made more frequently by junior doctors, but prevalence and causality are unclear. In order to inform the design of an educational intervention, a systematic review of the literature on prescribing errors made by junior doctors was undertaken.METHODSSearches were undertaken using the following databases: MEDLINE; EMBASE; Science and Social Sciences Citation Index; CINAHL; Health Management Information Consortium; PsychINFO; ISI Proceedings; The Proceedings of the British Pharmacological Society; Cochrane Library; National Research Register; Current Controlled Trials; and Index to Theses. Studies were selected if they reported prescribing errors committed by junior doctors in primary or secondary care, were in English, published since 1990 and undertaken in Western Europe, North America or Australasia.RESULTSTwenty‐four studies meeting the inclusion criteria were identified. The range of error rates was 2–514 per 1000 items prescribed and 4.2–82% of patients or charts reviewed. Considerable variation was seen in design, methods, error definitions and error rates reported.CONCLUSIONSThe review reveals a widespread problem that does not appear to be associated with different training models, healthcare systems or infrastructure. There was a range of designs, methods, error definitions and error rates, making meaningful conclusions difficult. No definitive study of prescribing errors has yet been conducted, and is urgently needed to provide reliable baseline data for interventions aimed at reducing errors. It is vital that future research is well constructed and generalizable using standard definitions and methods.
Clinical implications of ELA2‐, HAX1‐, and G‐CSF‐receptor (CSF3R) mutations in severe congenital neutropenia
Authors: Zeidler Cornelia , Germeshausen Manuela , Klein Christoph , Welte Karl 
Published: December 2008

SummaryCongenital Neutropenia (CN) is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoiesis at the level of the promyelocyte/myelocyte stage with peripheral blood absolute neutrophil counts below 0·5 × 109/l. There are two major subtypes of CN as judged by inheritance: an autosomal dominant subtype, e.g. defined by neutrophil elastase mutations (approximately 60% of patients) and an autosomal recessive subtype (approximately 30% of patients), both presenting with the same clinical and morphological phenotype. Different mutations have been described (e.g. HAX1, p14 etc) in autosomal recessive CN, with HAX1 mutations in the majority of these patients. CN in common is considered as a preleukemic syndrome, since the cumulative incidence for leukemia is more than 25% after 20 years of observation. Leukemias occur in both, the autosomal dominant and recessive subtypes of CN. The individual risk for each genetic subtype needs to be further evaluated. Numbers of patients tested for the underlying genetic defect are still limited. Acquired G‐CSFR (CSF3R) mutations are detected in approximately 80% of CN patients who developed acute myeloid leukemia independent of the ELA2 or HAX1 genetic subtype, suggesting that these mutations are involved in leukemogenesis. As the majority of patients benefit from G‐CSF administration, HSCT should be restricted to non‐responders and patients with leukaemic transformation.
Expansion of haematopoietic stem cells from normal donors and bone marrow failure patients by recombinant hoxb4
Authors: Tang Yong , Chen Jichun , Young Neal S. 
Published: December 2008

SummaryIn this study six versions of recombinant human hoxb4 proteins were produced and their effectiveness evaluated in expanding human haematopoietic stem and progenitor cells in vitro and in vivo. An N‐terminal‐tat and C‐terminal histidine‐tagged version of hoxb4 (T‐hoxb4‐H) showed the highest activity in expanding colony forming cells (CFCs) and long‐term culture‐initiating cells (LTC‐ICs) when used at 50 nmol/l concentration in cell culture. Human cord blood CD34+ cells cultured with 50 nmol/l T‐hoxb4‐H showed a significant increase in severe‐combined immunodeficient mouse‐repopulating cells (SRCs). In a mouse model of immune‐mediated bone marrow (BM) failure, T‐hoxb4‐H showed an additive effect with cyclosporine in alleviating pancytopenia. In addition, T‐hoxb4‐H expanded CFC and LTC‐IC on BM samples from patients with refractory severe aplastic anaemia and myelodysplastic syndromes: after culturing with 50 nmol/l T‐hoxb4‐H for 4 d, BM cells from 10 of the 11 patients showed increases in CFC and LTC‐IC, and the increase in LTC‐IC was statistically significant in samples from four patients. Recombinant human hoxb4 could be a promising therapeutic agent for BM failure.
Peripheral blood progenitor cell collection adverse events for childhood allogeneic donors: variables related to the collection and safety profile
Authors: Sevilla Julián , González‐Vicent Marta , Lassaletta Alvaro , Ramírez Manuel , Pérez‐Martínez Antonio , Madero Luis , Díaz Miguel Angel 
Published: December 2008

SummaryThe use of children as haematopoietic stem cell donors represents an ethical dilemma. For some investigators, this is even more questionable if the children underwent peripheral blood progenitor cell (PBPC) collection. Due to these controversies, information related to adverse events (AE) in paediatric donors and variables related to the collection is scanty. We analysed 152 PBPC collections, and compared the complications and results between young children, older children and adults. The pattern of AE was shown to vary according to the age of the donor. Older paediatric donors and adults had a higher incidence of complaints related to PBPC priming (54·3% vs. 79·7%, respectively) than the youngest children (12%). On the other hand, these donors had a lower incidence of AE during PBPC collection (19·6% older children, 37·3% adults) mainly related to hypocalcaemia, than the youngest donors, who suffered mainly cardiovascular complications due to hypovolaemia (51·7%). The only variables related to collected cell dose were total blood volume processed per donor body weight, and CD34+ cell count before apheresis. The donor/recipient body weight ratio predicted the outcome of collection in a single large volume leukapheresis. Donors with body weight ratio ≥0·75 had 4·69 times higher likelihood to reach the minimum target cell dose.
Identification, characterization and rescue of a novel vasopressin‐2 receptor mutation causing nephrogenic diabetes insipidus
Authors: Ranadive Sayali A. , Ersoy Baran , Favre Helene , Cheung Clement C. , Rosenthal Stephen M. , Miller Walter L. , Vaisse Christian 
Published: December 2008

SummaryObjective  X‐linked nephrogenic diabetes insipidus (XNDI), caused by mutations in the V2 vasopressin receptor (V2R), is clinically distinguished from central diabetes insipidus (CDI) by elevated serum vasopressin (AVP) levels and unresponsiveness to 1‐desamino‐8‐d‐arginine vasopressin (DDAVP). We report two infants with XNDI, and present the characterization and functional rescue of a novel V2R mutation.Patients  Two male infants presented with poor growth and hypernatraemia. Both patients had measurable pretreatment serum AVP and polyuria that did not respond to DDAVP, suggesting NDI. However, both also had absent posterior pituitary bright spot on MRI, which is a finding more typical of CDI.Methods  The AVPR2 gene encoding V2R was sequenced. The identified novel missense mutation was re‐created by site‐directed mutagenesis and expressed in HEK293 cells. V2R activity was assessed by the ability of transfected cells to produce cAMP in response to stimulation with DDAVP. Membrane localization of V2R was assessed by fluorescence microscopy.Results  Patient 1 had a deletion of AVPR2; patient 2 had the novel mutation L57R. In transiently transfected HEK293 cells, DDAVP induced detectable but severely impaired L57R V2R activity compared to cells expressing wild‐type V2R. Fluorescence microscopy showed that myc‐tagged wild‐type V2R localized to the cell membrane while L57R V2R remained intracellular. A nonpeptide V2R chaperone, SR121463, partially rescued L57R V2R function by allowing it to reach the cell membrane.Conclusions  L57R V2R has impaired in vitro activity that can be partially improved by treatment with a V2R chaperone. The posterior pituitary hyperintensity may be absent in infants with XNDI.
Functional analysis of two rare CYP21A2 mutations detected in Italian patients with a mildest form of congenital adrenal hyperplasia
Authors: Concolino Paola , Vendittelli Francesca , Mello Enrica , Minucci Angelo , Carrozza Cinzia , Rossodivita Aurora , Giardina Bruno , Zuppi Cecilia , Capoluongo Ettore 
Published: December 2008

SummaryBackground  More than 90% of all cases of congenital adrenal hyperplasia (CAH) result from steroid 21‐hydroxylase gene (CYP21A2) mutations. Most of these mutations result from intergenic recombinations between CYP21A2 and closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for 5–10% of 21‐hydroxylase deficiency alleles.Objective  Functional analysis of two novel CYP21A2 missense mutations (p.R224W and p.D407N) was performed.Design  Our study was composed of two Italian patients suffering from a very mild form of nonclassic CAH (NC‐CAH). To assay the enzymatic activity of mutants, the in vitro analysis was performed in transiently transfected COS‐1 cells.Results  The residual activities obtained for p.R224W and p.D407N mutants allow their classification as NC‐CAH mutations. These results correlate with the rate of severity of the patients’ disease.Conclusions  In this paper, we report two novel CYP21A2 mutations in two Italian individuals affected by 21‐hydroxylase deficiency. Based on the functional in vitro analysis we can classify these mutations as NC‐CAH variants.
1α,25‐dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection
Authors: Coussens Anna , Timms Peter M. , Boucher Barbara J. , Venton Timothy R. , Ashcroft Anthony T. , Skolimowska Keira H. , Newton Sandra M. , Wilkinson Katalin A. , Davidson Robert N. , Griffiths Christopher J. , Wilkinson Robert J. , Martineau Adrian R. 
Published: December 2008

SummaryMatrix metalloproteinases (MMP) can degrade all components of pulmonary extracellular matrix. Mycobacterium tuberculosis induces production of a number of these enzymes by human macrophages, and these are implicated in the pathogenesis of pulmonary cavitation in tuberculosis. The active metabolite of vitamin D, 1α,25‐dihydroxyvitamin D3 [1α,25(OH)2D3], has previously been reported to inhibit secretion of MMP‐9 in human monocytes (MN), but its influence on the secretion and gene expression of MMP and tissue inhibitors of MMP (TIMP) in M. tuberculosis‐infected cells has not previously been investigated. We therefore determined the effects of 1α,25(OH)2D3 on expression, secretion and activity of a number of MMP and TIMP in M. tuberculosis‐infected human leucocytes; we also investigated the effect of 1α,25(OH)2D3 on the secretion of interleukin‐10 (IL‐10) and prostaglandin E2 (PGE2), both transcriptional regulators of MMP expression. We found that M. tuberculosis induced expression of MMP‐1, MMP‐7 and MMP‐10 in MN and MMP‐1 and MMP‐10 in peripheral blood mononuclear cells (PBMC). 1α,25(OH)2D3 significantly attenuated M. tuberculosis‐induced increases in expression of MMP‐7 and MMP‐10, and suppressed secretion of MMP‐7 by M. tuberculosis‐infected PBMC. MMP‐9 gene expression, secretion and activity were significantly inhibited by 1α,25(OH)2D3 irrespective of infection. In contrast, the effects of 1α,25(OH)2D3 on the expression of TIMP‐1, TIMP‐2 and TIMP‐3 and secretion of TIMP‐1 and TIMP‐2 were small and variable. 1α,25(OH)2D3 also induced secretion of IL‐10 and PGE2 from M. tuberculosis‐infected PBMC. These findings represent a novel immunomodulatory role for 1α,25(OH)2D3 in M. tuberculosis infection.
CD56bright natural killer (NK) cells: an important NK cell subset
Authors: Poli Aurélie , Michel Tatiana , Thérésine Maud , Andrès Emmanuel , Hentges François , Zimmer Jacques 
Published: December 2008

SummaryHuman natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56bright CD16dim/− and CD56dim CD16+, respectively. In this review, we will focus on the CD56bright NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56dim NK cells. CD56bright NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear.
Oil extractability from enzymatically treated goldenberry (Physalis peruviana L.) pomace: range of operational variables
Authors: Ramadan Mohamed Fawzy , Moersel Joerg‐Thomas 
Published: December 2008

SummaryGoldenberry pomace (seeds and skins) represents a large portion of the waste generated during juice processing (ca. 27.4% of fruit weight). The potential of goldenberry agro‐industrial wastes for use as raw material for production of edible oil was evaluated. Fruit pomace, contained 6.6% moisture, 17.8% protein, 3.10% ash, 28.7% crude fibre and 24.5% carbohydrates. The n‐hexane‐extractable oil content of the raw by‐products was estimated to be 19.3%. Aqueous enzymatic extraction was investigated for recovery of oil from the fruit pomace. The most significant factors affecting extraction were enzyme concentration, the time of digestion with enzymes, substrate concentration in water and the particle size of substrate. A broad variation in oil recovery was obtained depending on the operational conditions during the enzyme‐aided aqueous extraction. The optimum and economical values were those obtained for 4:0.02:1 water:enzyme:substrate ratio. Generally, enzymatic treatment increased the extraction yield. The more than 42% yield by enzymation compared with the nearly 3% yield in the control process (without enzyme) implies a significant increase in yield by about 92.8%. In single‐enzyme trials, cellulase EC gave the best yield. Although proteases slightly improve yield, the enhancement values are much lower than those obtained with Cellulase EC and Pektinace L40. Rapid increase in oil yield occurred as the enzyme concentration increased from 1 to 2 g/100 g substrate. Yield increased with dilution, but it began to fall when the substrate became more diluted. Moreover, extractability increased significantly when particle size reduced. Concerning the oil composition, there were no great changes in the fatty acid pattern of the oils extracted with different hydrolytic enzymes when compared with each other or to the solvent extracted oil. The main purpose of this study was to maximise the efficiency of the enzymatic treatment for oil recovery from goldenberry pomace. As a first step toward developing goldenberry as a commercial crop, the results provide important information for the industrial application of the fruit.