bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and functional characterisation of myofibroblasts, macrophages, and lymphocytes migrating out of the human gastric lamina propria following the loss of epithelial cells
Authors: Wu K C , Jackson L M , Galvin A M , Gray T , Hawkey C J , Mahida Y R 
Published: June 2010

BACKGROUNDThe basement membrane of human colonic mucosa contains numerous discrete pores. We have recently shown that following loss of the surface epithelium, many cells migrate out of the colonic lamina propria via basement membrane pores.AIMSTo characterise cells migrating out via basement membrane pores of the human gastric lamina propria, following loss of the surface epithelium.METHODSFresh human gastric mucosal samples were completely denuded of epithelial cells and placed in culture. Tissue samples were studied by electron microscopy (EM) and cells by EM, FACS analysis, immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR).RESULTSEM showed numerous discrete pores (0.65–8.29 μm in diameter) in the subepithelial basement membrane. During culture of mucosal samples denuded of epithelial cells, lymphocytes, macrophages, and myofibroblasts migrated out of the lamina propria via the basement membrane pores. The lymphocytes were predominantly CD45RO+ and CD69+ T cells. Macrophages were shown to express cyclooxygenase (COX) 1 and 2 enzymes. Myofibroblasts were established in culture and, despite prolonged culture and passage, retained their phenotype. They expressed mRNA and protein for COX 1 and 2 enzymes and their release of prostaglandin E2 was inhibited by selective COX 1 and 2 inhibitors.CONCLUSIONSLamina propria cells migrating out of cultured denuded gastric mucosal samples have been characterised phenotypically and functionally. Such cells would be suitable for studies of their interactions with epithelial cells and also with Helicobacter pylori and its products.
Indirect evidence for cholinergic inhibition of intestinal bicarbonate absorption in humans
Authors: Mellander A , Sjövall H 
Published: June 2010

BACKGROUNDThe aim of the study was to test the hypothesis that in the fasting state, proximal intestinal HCO3− absorption, which depends on villus Na+/H+ exchanger activity, is tonically inhibited by a cholinergic atropine sensitive mechanism.SUBJECTSThe experiments were performed in 34 healthy volunteers and in eight patients with intestinal villus atrophy.METHODSHCO3−absorption was measured with a modified triple lumen perfusion technique in the distal duodenum, the most proximal portion of the small intestine. The study was designed to compensate for the inhibitory effects of atropine on intestinal motor activity.RESULTSAtropine had three effects on HCO3− transport: it reduced HCO3− concentration at the proximal aspiration site, it displaced the relation between HCO3− concentration and HCO3− absorption to the left, and it induced a significant acidification of the perfusate at the distal aspiration site. The magnitude of the stimulatory effect on HCO3− absorption was similar to the difference between patients with intestinal villus atrophy and healthy controls.CONCLUSIONThe data suggest that, in the fasting state, duodenal HCO3− absorption, which depends on villus Na+/H+ exchanger activity, may be tonically inhibited by an atropine sensitive cholinergic mechanism.
Evidence of improving survival of patients with rectal cancer in France: a population based study
Authors: Finn-Faivre C , Maurel J , Benhamiche A M , Herbert C , Mitry E , Launoy G , Faivre J 
Published: June 2010

BACKGROUNDOver the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known.AIMSTo determine trends in management and prognosis of rectal cancer in two French regions.SUBJECTS1978 patients with a rectal carcinoma diagnosed between 1978 and 1993.METHODSTime trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed.RESULTSOver the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes’ type A cancer increased from 17.7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978–1981 period to 57.0% for the 1985–1989 period).CONCLUSIONSSubstantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival.
Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats
Authors: Mariadason J M , Catto-Smith A , Gibson P R 
Published: June 2010

BACKGROUNDDietary fibre influences the turnover and differentiation of the colonic epithelium, but its effects on barrier function are unknown.AIMSTo determine whether altering the type and amount of fibre in the diet affects paracellular permeability of intestinal epithelium, and to identify the mechanisms of action.METHODSRats were fed isoenergetic low fibre diets with or without supplements of wheat bran (10%) or methylcellulose (10%), for four weeks. Paracellular permeability was determined by measurement of conductance and 51Cr-EDTA flux across tissue mounted in Ussing chambers. Faecal short chain fatty acid (SCFA) concentrations were assessed by gas chromatography, epithelial kinetics stathmokinetically, and mucosal brush border hydrolase activities spectrophotometrically.RESULTSBody weight was similar across the dietary groups. Conductance and 51Cr-EDTA flux were approximately 25% higher in animals fed no fibre, compared with those fed wheat bran or methylcellulose in the distal colon, but not in the caecum or jejunum. Histologically, there was no evidence of epithelial injury or erosion associated with any diet. The fibres exerted different spectra of effects on luminal SCFA concentrations and pH, and on mucosal indexes, but both bulked the faeces, were trophic to the epithelium, and stimulated expression of a marker of epithelial differentiation.CONCLUSIONSBoth a fermentable and a non-fermentable fibre reduce paracellular permeability specifically in the distal colon, possibly by promoting epithelial cell differentiation. The mechanisms by which the two fibres exert their effects are likely to be different.
Cholinergic blockade inhibits gastro-oesophageal reflux and transient lower oesophageal sphincter relaxation through a central mechanism
Authors: Fang J C , Sarosiek I , Yamamoto Y , Liu J , Mittal R K 
Published: June 2010

BACKGROUNDAtropine, an anticholinergic agent with central and peripheral actions, reduces gastro-oesophageal reflux (GOR) in normal subjects and patients with gastro-oesophageal reflux disease (GORD) by inhibiting the frequency of transient lower oesophageal sphincter relaxation (TLOSR).AIMSTo compare the effect of methscopolamine bromide (MSB), a peripherally acting anticholinergic agent, with atropine on the rate and mechanism of GOR in patients with GORD.METHODSOesophageal motility and pH were recorded for 120 minutes in 10 patients with GORD who were studied on three separate occasions. For the first two recording periods, either atropine (15 μg/kg bolus, 4 μg/kg/h infusion) or saline were infused intravenously. MSB (5 mg orally, four times daily) was given for three days prior to the third recording period.RESULTSAtropine significantly reduced basal LOS pressure (12.6 (0.17) mm Hg to 7.9 (0.17) mm Hg), and the number of TLOSR (8.1 (0.56) to 2.8 (0.55)) and reflux episodes (7.0 (0.63) to 2.0 (0.43)) (p<0.005 for all comparisons). MSB reduced basal LOS pressure (12.6 (0.17) to 8.7 (0.15) mm Hg, p<0.005), but had no effect on the frequency of TLOSR (8.1 (0.56) to 7.5 (0.59)) and reflux episodes (7.0 (0.63) to 4.9 (0.60)) (p>0.05).CONCLUSIONIn contrast to atropine, MSB has no effect on the rate of TLOSR or GOR in patients with GORD. Atropine induced inhibition of TLOSR and GOR is most likely mediated through a central cholinergic blockade.
Trefoil peptide TFF2 (spasmolytic polypeptide) potently accelerates healing and reduces inflammation in a rat model of colitis
Authors: Tran C P , Cook G A , Yeomans N D , Thim L , Giraud A S 
Published: June 2010

BACKGROUNDThe trefoil peptides are major secretory products of mucus cells of the gastrointestinal tract and show increased expression after inflammatory or ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been shown to be cytoprotective, and enhances repair in models of gastric injury.AIMSTo test the healing effects of recombinant human (h)TFF2 in a rat model of chronic colitis.METHODSColitis was induced by intracolonic administration of dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified macroscopically, microscopically by image analysis of tissue histology, and by measuring myeloperoxidase activity.RESULTSInitial validation studies showed that maximal injury and inflammation occurred at the end of the first week after colitis induction (active phase), and that spontaneous healing was complete by eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg; approximately 0.5 mg/rat) for five days after maximal damage had been sustained, reduced both microscopic and macroscopic injury by 80% and inflammatory index by 50% compared with vehicle controls. In addition, endogenous concentrations of rat TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of colitis and were reduced to basal levels by hTFF2 treatment.CONCLUSIONSThis study has shown that hTFF2 enhances the rate of colonic epithelial repair, and reduces local inflammation in a rat model of colitis, and suggests that luminal application of trefoil peptides may have therapeutic potential in the treatment of inflammatory bowel disease.
Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon
Authors: Freier S , Weiss O , Eran M , Flyvbjerg A , Dahan R , Nephesh I , Safra T , Shiloni E , Raz I 
Published: June 2010

AIMSTo study changes in the expression of insulin-like growth factors (IGFs) and their receptors, as well as production of the IGF-I and IGF-II polypeptides, in adenocarcinoma of the colon.METHODSMalignant tissue obtained at operation was used. Total RNA was extracted and specific IGF-I and IGF-II and their receptor mRNAs were measured by a solution hybridisation RNase protection assay. IGF-I and IGF-II polypeptides were measured by specific immunoassays.RESULTSAll normal tissues expressed IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate (Man-6-P) receptor. IGF-I mRNA could not be detected but the polypeptide was present in small but equal amounts in normal and malignant tissue. IGF-II was expressed 40 times more abundantly in colonic tumours than in adjacent normal tissue and the concentration of the corresponding polypeptide was twice as high in the malignant tissue. IGF-I receptor expression was increased by a factor of 2.5 and IGF-II/Man-6-P receptor by a factor of 4.CONCLUSIONSThis study confirms that in adenocarcinoma of the human colon there is increased expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor message is increased and the increase in IGF-II message is accompanied by a doubling of the IGF-II protein in the tumour tissue compared with the adjacent normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also be involved in development of adenocarcinoma of the colon. There is rapidly accumulating evidence implicating the IGF system in the development of malignancy of the large bowel.
An ambulant porcine model of acid reflux used to evaluate endoscopic gastroplasty
Authors: Kadirkamanathan S S , Yazaki E , Evans D F , Hepworth C C , Gong F , Swain C P 
Published: June 2010

BACKGROUNDThere is a lack of suitable models for testing of therapeutic procedures for gastro-oesophageal reflux disease. Endoscopic sewing methods might allow the development of a new less invasive surgical approach to treatment of gastrointestinal disorders.AIMSTo develop an animal model of gastro-oesophageal reflux for testing the efficacy of a new antireflux procedure, endoscopic gastroplasty, performed at flexible endoscopy without laparotomy or laparoscopy.METHODSAt endoscopy a pH sensitive radiotelemetry capsule was sewn to the oesophageal wall, 5 cm above the lower oesophageal sphincter, in six large white pigs. Ambulant pH recordings (48–96 hours; total 447 hours) were obtained. The median distal oesophageal pH was 6.8 (range 6.4–7.3); pH was less than 4 for 9.3% of the time. After one week, endoscopic gastroplasty was performed by placing sutures below the gastro-oesophageal junction, forming a neo-oesophagus of 1–2 cm in length. Postoperative manometry and pH recordings (24–96 hours; total 344 hours) were carried out.RESULTSFollowing gastroplasty, the median sphincter pressure increased significantly from 3 to 6 mm Hg and in length from 3 to 3.75 cm. The median time pH was less than 4 decreased significantly from 9.3% to 0.2%.CONCLUSIONSThese are the first long term measurements of oesophageal pH in ambulant pigs. The finding of spontaneous reflux suggested a model for studying treatments of reflux. Endoscopic gastroplasty increased sphincter pressure and length and decreased acid reflux.
Mesalazine (5-aminosalicylic acid) induced chronic hepatitis
Authors: Deltenre P , Berson A , Marcellin P , Degott C , Biour M , Pessayre D 
Published: June 2010

BACKGROUNDTreatment of ulcerative colitis or Crohn’s disease with sulphasalazine causes several adverse effects, including hepatitis. Sulphasalazine is cleaved by colonic bacteria into 5-aminosalicylic acid and sulphapyridine. Received wisdom was that 5-aminosalicylic acid was topically active, whereas sulphapyridine was absorbed and caused immunoallergic side effects. Mesalazine, a slow release formulation of 5-aminosalicylic acid, was expected to be a safe alternative. However, several cases of acute hepatitis have been reported.CASE REPORTA 65 year old man had increased liver enzymes, anti-nuclear and anti-smooth muscle autoantibodies and IgG levels, and lesions of chronic hepatitis after 21 months of mesalazine treatment. Although liver dysfunction had been identified eight months earlier, simvastatin rather than mesalazine had been withdrawn, without any improvement. In contrast, liver enzyme and IgG levels became normal and autoantibodies disappeared after discontinuation of mesalazine administration.CONCLUSIONContrary to initial expectations, mesalazine can cause most of the sulphasalazine induced adverse effects, and hepatic side effects may be almost as frequent. When liver dysfunction occurs, mesalazine administration should be discontinued to avoid the development of chronic hepatitis and liver fibrosis.
Is fascin really a useful marker in distinguishing between classical Hodgkin's lymphoma and various types of Non-Hodgkin's lymphomas in difficult cases?
Authors: Idrees Romana , Ahmad Zubair , Qureshi Asim , Ahsan Aamir , Pervez Shahid 
Published: June 2010

BackgroundFascin is an actin cross-linking protein, which is part of the cytoskeleton and involved in cell motility in several cell types. The differentiation of epithelial cells is greatly influenced by cell–matrix and cell–cell interactions, which play an important role in the normal organisation and stabilisation of epithelial cells and maintain the cells in a non-migratory state. The malignant conversion of epithelial cells results from a phenotypic switch to a migratory state, which allows tumour invasion beyond the basement membrane, as well as metastasis. Such a switch requires complex rearrangements of the actin cytoskeleton and is governed by multiple actin-binding proteins including fascin. In non-neoplastic lymphoid tissue, fascin expression is highly selective and is predominantly localised in dendritic cells, while lymphocytes, plasma cells, etc are uniformly non-reactive. However, all or nearly all Reed–Sternberg cells and their variants in all types of Hodgkin's lymphoma express fascin and are strongly immunoreactive for fascin.ConclusionLymphomas (Hodgkin's and non-Hodgkin's) are among the commonest malignancies seen in our practice. The Section of Histopathology at the Aga Khan University, Karachi is the largest centre for histopathology in Pakistan, a densely populated country with an estimated population of 170 million. The authors wanted to test the utility of Fascin in distinguishing between Hodgkin's lymphoma and morphologically closely related forms of non-Hodgkin's lymphoma such as diffuse large B cell non-Hodgkin's lymphoma and anaplastic large cell lymphoma in difficult cases. If found useful, this antibody could help us in reaching a correct diagnosis in difficult cases and allow appropriate patient management.
Aberrant upregulation of MUC4 mucin expression in cutaneous condyloma acuminatum and squamous cell carcinoma suggests a potential role in the diagnosis and therapy of skin diseases
Authors: Chakraborty Subhankar , Swanson Benjamin J , Bonthu Neelima , Batra Surinder K 
Published: June 2010

AimMucins comprise a family of high-molecular-weight glycoproteins. MUC4, a large transmembrane mucin, has recently emerged as a novel marker for diagnosis, prognosis and therapy in several malignancies. However, its role in skin pathologies remains unknown. The aim of this study was to analyse the expression of MUC4 in cutaneous pathologies by immunohistochemistry for potential diagnostic, prognostic and therapeutic applications.MethodsA total of 330 tissue spots representing the normal skin, and benign and malignant cutaneous diseases, were analysed after staining with the monoclonal antibody to human MUC4 (clone 8G7).ResultsWhile the normal epidermis showed a negative to weak-positive expression of MUC4, its expression was significantly upregulated in squamous cell carcinomas (SCCs) where the intensity of staining correlated negatively with tumour grade and positively with age. A moderately strong MUC4 expression was also noted in 2/20 cancer adjacent normal skin and 2/21 chronically inflamed skin tissues, while 10/19 cases of vulval condyloma acuminate, 3/12 of vulval hyperplasia and 2 cases of verruca vulgaris also showed strong MUC4 positivity. Malignant melanoma, basal cell carcinoma and cutaneous cysts were negative.ConclusionThe results indicate that MUC4 expression is aberrantly upregulated in cutaneous SCCs, vulval condylomas and verruca vulgaris. Further, it appears that MUC4 expression in the skin may be modulated by chronic inflammation and the presence of an adjacent cutaneous malignancy in certain cases. These observations suggest a novel role for MUC4 mucin in the pathogenesis of cutaneous SCC and a possible application as a diagnostic and/or prognostic marker in cutaneous pathologies.
HuR Regulates β-Tubulin Isotype Expression in Ovarian Cancer
Authors: Raspaglio Giuseppina , De Maria Ilaria , Filippetti Flavia , Martinelli Enrica , Zannoni Gian Franco , Prislei Silvia , Ferrandina Gabriella , Shahabi Shohreh , Scambia Giovanni , Ferlini Cristiano 
Published: June 2010

Abstract
The supply of oxygen and nutrients to solid tumors is inefficient because cancer tissues have an inadequate number of microvessels, thus inducing the selective growth of the most aggressive cancer cells. This explains why many of the factors underlying a poor prognosis are induced in hypoxic/hypoglycemic conditions. Among these factors, a prominent role in several solid tumors is played by the class III β-tubulin gene (TUBB3). The study described here reveals that glucose deprivation enhances TUBB3 expression at both the gene and protein levels in A2780 ovarian cancer cells. In silico analysis of TUBB3 mRNA sequence predicted a putative binding site for the RNA-binding protein Hu antigen (HuR) in the 3′ flanking untranslated region. A hypoglycemic-dependent engagement of this site was shown using RNA pull-down and ribonucleoimmunoprecipitation techniques. Thereafter, HuR gene silencing revealed that TUBB3 translation is HuR dependent in hypoglycemia because HuR silencing inhibited the entry of TUBB3 mRNA into cytoskeletal and free polysomes. Finally, the clinical value of this finding was assessed in a clinical cohort of 46 ovarian cancer patients in whom it was found that HuR cytoplasmic staining was associated with high levels of TUBB3 and poor survival. Cancer Res; 70(14); 5891–900. ©2010 AACR.
STAMP1 Is Both a Proliferative and an Antiapoptotic Factor in Prostate Cancer
Authors: Wang Ling , Jin Yang , Arnoldussen Yke Jildouw , Jonson Ida , Qu Su , Mælandsmo Gunhild M. , Kristian Alexandr , Risberg Bjørn , Wæhre Håkon , Danielsen Håvard E. , Saatcioglu Fahri 
Published: June 2010

Abstract
STAMP1 is predicted to encode a six-transmembrane protein whose expression is highly prostate enriched and is deregulated in prostate cancer. However, the biological role of STAMP1 in prostate cancer cells, or its expression profile at the protein level, is unknown. Here, we find that ectopic expression of STAMP1 significantly increased proliferation of DU145 prostate cancer cells as well as COS-7 cells in vitro; conversely, small interfering RNA–mediated knockdown of STAMP1 expression in LNCaP cells inhibited cell growth and, at least partially, induced cell cycle arrest. In parallel, there were alterations in cell cycle–regulatory gene expression. Knockdown of STAMP1 expression in LNCaP cells also induced significant apoptosis under basal conditions as well as in response to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) alone, or TRAIL + AKT inhibitor LY294002, previously established apoptotic agents in LNCaP cells. Consistently, LNCaP cells with short hairpin RNA–mediated knockdown of STAMP1 were dramatically retarded in their ability to grow as xenografts in nude mice. Interestingly, activation of extracellular signal-regulated kinase, which has previously been implicated in prostate cancer progression, was significantly increased on ectopic expression of STAMP1 in DU145 cells and, conversely, was strongly downregulated on STAMP1 knockdown in LNCaP cells. In the normal prostate, STAMP1 protein is localized to the cytosol and the cell membrane of the prostate epithelial cells; furthermore, its expression is increased in prostate cancer compared with normal prostate. Taken together, these data suggest that STAMP1 is required for prostate cancer growth, which may be a useful target in prostate cancer treatment. Cancer Res; 70(14); 5818–28. ©2010 AACR.