bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum
Authors: Ajioka Y , Watanabe H , Jass J R , Yokota Y , Kobayashi M , Nishikura K 
Published: June 2010

Background—Serrated adenoma is a new morphological subtype of colorectal adenoma. The lesion provides a distinct morphological route to carcinoma, but the underlying genetic changes have not yet been investigated.Aims—To determine the frequency of K-ras mutation in serrated adenoma.Methods—The frequency of K-ras codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.Results—Although most of the serrated adenomas were large (average size 11.4 mm) and polypoid, K-rascodon 12 point mutation was detected in only one of the 20 (5%), which is a significantly lower frequency than that in sporadic polypoid adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of carcinoma in situ, indicating their malignant potential and the existence of a serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of carcinoma in situ.Conclusions—K-ras mutation is uncommon in serrated adenomas, indicating a different spectrum of genetic alterations in these lesions from those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma represents a new genetic pathway in the histogenesis of colorectal carcinoma.
Ductal dilatation and stenting for residual hepatolithiasis: a promising treatment strategy
Authors: Sheen-Chen S-M , Cheng Y-F , Chen F-C , Chou F-F , Lee T-Y 
Published: June 2010

Background and aims—Hepatolithiasis is prevalent in south-east Asia and presents a difficult management problem. Intrahepatic strictures with or without awkward ductal angulation of the biliary tree are the main reasons for the reported high incidence of postoperative residual stones. Without proper treatment, biliary strictures and residual stones can lead to repeated episodes of cholangitis, liver abscess, secondary biliary cirrhosis, portal hypertension, and death from sepsis or hepatic failure. The purposes of our treatment strategy were to achieve complete clearance of the stones and relief of bile stasis.Methods—From January 1991 to July 1992, 90 patients with residual postoperative hepatolithiasis and intrahepatic strictures were treated. Postoperative ductal dilatation with percutaneous transhepatic cholangioscopy tube stenting through a mature T tube tract was performed. Choledochoscopic electrohydraulic lithotripsy was applied when impacted or large stones were encountered.Results—Complete clearance of stones was achieved in 78 patients (87%). Mild haemobilia occurred in five patients (5.5%) and fever developed in seven patients (7.7%), and these patients recovered after conservative treatment. The rate of stone recurrence after a mean follow up of 43 months was 8%. Intrahepatic cholangiocarcinoma developed in one patient (1.1%).Conclusion—Postoperative ductal dilatation and stenting, combined with endoscopic electrohydraulic lithotripsy when indicated, is an effective and safe treatment with a low recurrence rate for complicated residual hepatolithiasis with biliary stricture.
Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans
Authors: Coulie B , Tack J , Peeters T , Janssens J 
Published: June 2010

Background—During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity.Aims—To study the involvement of a cholinergic pathway in the motor effects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT1receptor agonist sumatriptan.Methods—In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n=10), atropine (15 μg/kg intravenous bolus plus 15 μg/kg/h over 30 minutes; n=10), or sumatriptan (6 mg subcutaneously; n=10) was administered, followed by infusion of erythromycin 40 mg or 200 mg.Results—After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p<0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p<0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not differ significantly after atropine or sumatriptan versus placebo.Conclusions—The antral motor effects of erythromycin in humans are mediated via different pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor.
Pancreatic dysfunction and its association with fat malabsorption in HIV infected children
Authors: Carroccio A , Fontana M , Spagnuolo M I , Zuin G , Montalto G , Canani R B , Verghi F , Di Martino D , Bastoni K , Buffardi F , Guarino A 
Published: June 2010

Background—Nutrient malabsorption frequently occurs in HIV infected children, but very few studies have investigated exocrine pancreatic digestive capacity in these cases.Aims—To investigate pancreatic function in HIV infected children and to determine whether faecal fat loss, a prominent feature of intestinal dysfunction, is associated with pancreatic dysfunction.Patients—Forty seven children with HIV infection without apparent pancreatic disease and 45 sex and age matched healthy controls.Methods—Pancreatic function was evaluated by measuring elastase 1 concentration and chymotrypsin activity in stools by ELISA and colorimetric methods, respectively. Intestinal function was evaluated by measuring fat and protein loss by the steatocrit method and by faecal α1 antitrypsin concentration.Results—14 (30%) had abnormal pancreatic function tests: seven had isolated elastase activity deficiency, three isolated chymotrypsin deficiency, and four pancreatic deficiencies in both enzymes. Patient enzyme values were significantly lower than those of controls. Low faecal pancreatic enzymes were not associated with symptoms. Twelve children had steatorrhoea and four had increased α1 antitrypsin. Steatorrhoea was significantly associated with reduced faecal pancreatic enzymes. There was a significant negative correlation between elastase 1 concentration and steatocrit. Children with pathological faecal elastase 1 or chymotrypsin values did not differ from the other HIV infected children with respect to nutritional and immunological status, stage of HIV disease, presence of opportunistic infections, or drug administration.Conclusions—Abnormal pancreatic function tests are a frequent feature of paediatric HIV infection; this condition is associated with steatorrhoea, which probably contributes to the disease.
Management of fibrosing pancreatitis in children presenting with obstructive jaundice
Authors: Sylvester F A , Shuckett B , Cutz E , Durie P R , Marcon M A 
Published: June 2010

Background—Children with fibrosing pancreatitis are conventionally treated surgically to relieve common bile duct (CBD) obstruction caused by pancreatic compression. Residual pancreatic function has not been formally tested in these patients.Aims—To evaluate the usefulness of non-surgical temporary drainage in children with fibrosing pancreatitis and to assess pancreatic function after resolution of their CBD obstruction.Patients—Four children (1.5–13 years; three girls).Methods and results—Abdominal sonography and computed tomography revealed diffuse enlargement of the pancreas, predominantly the head. The CBD was dilated due to compression by the head of the pancreas. Pancreatic biopsy specimens obtained in three patients showed notable acinar cell atrophy and extensive fibrosis. Cystic fibrosis was excluded. No other cause of pancreatitis was identified. Pancreatic tissue from one patient contained viral DNA sequences for parvovirus B19 detected by polymerase chain reaction; serum IgM to parvovirus was positive. Three patients had temporary drainage of the CBD and one patient underwent a choledochojejunostomy. Serial imaging studies revealed resolution of the CBD obstruction with reduction in pancreatic size. Exocrine pancreatic function deteriorated. Three patients developed pancreatic insufficiency within two to four months of presentation. The fourth patient has notably diminished pancreatic function, but remains pancreatic sufficient. None has diabetes mellitus.Conclusions—Temporary drainage of the CBD obstruction is recommended in fibrosing pancreatitis in children along with close monitoring of the clinical course, before considering surgery.
Identification of common epitopes on gliadin, enterocytes, and calreticulin recognised by antigliadin antibodies of patients with coeliac disease
Authors: Krupičková S , Tučková L , Flegelová Z , Michalak M , Walters J R F , Whelan A , Harries J , Vencovský J , Tlaskalová-Hogenová H 
Published: June 2010

BackgroundSera of patients with coeliac disease, containing IgA and IgG antigliadin antibodies (AGA) and various IgA autoantibodies, react with isolated enterocytes. AGA cross react with enterocyte antigens, one of which has been identified as calreticulin.AimsTo characterise the antigenic structures of gliadin, enterocytes, and calreticulin recognised by AGA from patients with active coeliac disease.MethodsAGA were isolated from sera of nine patients by affinity chromatography and tested by competitive ELISA using 40 α-gliadin synthetic dodecapeptides (A1–F6).ResultsReactivity of gliadin with all purified AGA tested was inhibited by peptide A4 at the N-terminal region; by C2, C3, and D4 at the central region; and by F3 and F4 at the C-terminal region of the gliadin molecule. AGA cross reactivity with enterocytes was inhibited by peptides A4, D1–D4, and F6 and with calreticulin by peptides A4, D3, and D4. As dominant epitopes AGA of coeliac patients recognise similar structures corresponding to peptides A4, D3, D4, and F6 present on gliadin, enterocytes, and calreticulin. Substitution of glutamine in the A4 peptide by glutamic acid caused loss of inhibitory capacity. Shortening of peptide A4 on the N-terminal by three amino acids increased its inhibitory effect.ConclusionsAGA of patients with coeliac disease react with similar structures on gliadin and potential autoantigens on enterocytes.
Risk of primary biliary liver cirrhosis in patients with coeliac disease: Danish and Swedish cohort data
Authors: Sørensen H T , Thulstrup A M , Blomqvist P , Nørgaard B , Fonager K , Ekbom A 
Published: June 2010

BACKGROUNDSeveral case reports, but only a few studies, have examined the coexistence of coeliac disease and primary biliary cirrhosis.AIMTo estimate the risk of primary biliary cirrhosis in two national cohorts of patients with coeliac disease in Denmark and Sweden.METHODSThrough record linkage all Danish patients hospitalised with coeliac disease were followed for possible occurrence of primary biliary cirrhosis from 1 January 1977 until 31 December 1992. All patients hospitalised with coeliac disease in Sweden from 1987 to 1996 were also followed in a separate analysis.RESULTSA total of 896 patients with coeliac disease were identified in Denmark with a median follow up period of 9.1 years for a total of 8040 person-years at risk. Two cases of primary biliary cirrhosis were observed where 0.07 were expected, giving a standardised incidence ratio of 27.6 (95% confidence interval 2.9 to 133.5). A total of 7735 patients with coeliac disease were identified in Sweden with a median follow up period of 5.1 years for a total of 39 284 person-years at risk. Twenty two people with primary biliary cirrhosis were identified compared with 0.88 expected, giving a standardised incidence ratio of 25.1 (95% confidence interval 15.7 to 37.9).CONCLUSIONPatients with coeliac disease are at increased risk of having primary biliary cirrhosis.
HLA-DR and -DQ phenotypes in inflammatory bowel disease: a meta-analysis
Authors: Stokkers P C F , Reitsma P H , Tytgat G N J , van Deventer S J H 
Published: June 2010

BACKGROUNDSusceptibility to inflammatory bowel disease (IBD) is partially genetically determined and the HLA class II genes are candidates for a role in genetic susceptibility to IBD, because their products play a central role in the immune response. Multiple studies have reported associations between HLA-DR or -DQ phenotypes and either ulcerative colitis or Crohn’s disease, but much of the data are still controversial.AIMSTo estimate overall associations between HLA class II phenotypes and IBD, and to establish the relative risk conferred by HLA-DR and -DQ phenotypes by meta-analysis.METHODSMedline was searched for publications reporting on the relation between IBD and HLA class II phenotypes. Raw data were extracted by recalculating the number of phenotypes or the number of alleles of the main antigens. Odds ratios and confidence intervals were calculated according to the Mantel-Haenszel method.RESULTSDR2, DR9, and DRB1*0103 were positively associated with ulcerative colitis, and a negative association was found for DR4 and ulcerative colitis. For Crohn’s disease a positive association was found with DR7, DRB3*0301, and DQ4 and a negative association with DR2 and DR3.CONCLUSIONSBoth ulcerative colitis and Crohn’s disease are associated with specific HLA class II phenotypes. Further analysis of these phenotypes and subgroup analysis may elucidate how these alleles contribute to susceptibility to IBD.
STATISTICAL MODELS OF CRIMINAL BEHAVIOR: THE EFFECTS OF LAW ENFORCEMENT ACTIONS
Authors: JONES PAUL A. , BRANTINGHAM P. JEFFREY , CHAYES LINCOLN R. 
Published: June 2010

We extend an agent-based model of crime-pattern formation initiated in Short et al. by incorporating the effects of law enforcement agents. We investigate the effect that these agents have on the spatial distribution and overall level of criminal activity in a simulated urban setting. Our focus is on a two-dimensional lattice model of residential burglaries, where each site (target) is characterized by a dynamic attractiveness to burglary and where criminal and law enforcement agents are represented by random walkers. The dynamics of the criminal agents and the target-attractiveness field are, with certain modifications, as described in Short et al. Here the dynamics of enforcement agents are affected by the attractiveness field via a biasing of the walk, the detailed rules of which define a deployment strategy. We observe that law enforcement agents, if properly deployed, will in fact reduce the total amount of crime, but their relative effectiveness depends on the number of agents deployed, the deployment strategy used, and spatial distribution of criminal activity. For certain policing strategies, continuum PDE models can be derived from the discrete systems. The continuum models are qualitatively similar to the discrete systems at large system sizes.
Indications and Early Outcomes for Total Pancreatectomy at a High-Volume Pancreas Center
Authors: Janot Monika S. , Belyaev Orlin , Kersting Sabine , Chromik Ansgar M. , Seelig Matthias H. , Sülberg Dominique , Mittelkötter Ulrich , Uhl Waldemar H. 
Published: June 2010

Background. This study aimed to analyse the most common current indications for total pancreatectomy (TP) at a high-volume pancreas center. Method. Prospectively collected data on indications and short-term outcome of all TP's performed from January 2004 until June 2008 were analysed. Results. The total pancreatectomies (TP) were 63, i.e., 6.7% of all pancreatic procedures (). Indications for TP were classified into 4 groups: tumors of advanced stage, (36.5%), technical problems due to soft pancreatic tissue, (28.6%), troubles due to perioperative surgical complications, (23.8%), and therapy-resistant pain due to chronic pancreatitis, (11.1%). Surgical complications occurred in 23 patients (36.5%). The mortality in elective TP was 6.25%. Median postoperative stay was 21 days. Mortality, morbidity and the other perioperative parameters differed substantially according to the indication for pancreatectomy.	Conclusion. Total pancreatectomy is definitely indicated for a limited range of elective and emergency situations. Indications can be: size or localisation of pancreatic tumor, trouble, technical diffuculties and therapy-refractory pain in chronic pancreatitis. A TP due to perioperative complications (troubles) after pancreatic resections is doomed by extremely high morbidity and mortality and should be avoided.
Metastatic Growth from Dormant Cells Induced by a Col-I–Enriched Fibrotic Environment
Authors: Barkan Dalit , El Touny Lara H. , Michalowski Aleksandra M. , Smith Jane Ann , Chu Isabel , Davis Anne Sally , Webster Joshua D. , Hoover Shelley , Simpson R. Mark , Gauldie Jack , Green Jeffrey E. 
Published: June 2010

Abstract
Breast cancer that recurs as metastatic disease many years after primary tumor resection and adjuvant therapy seems to arise from tumor cells that disseminated early in the course of disease but did not develop into clinically apparent lesions. These long-term surviving, disseminated tumor cells maintain a state of dormancy, but may be triggered to proliferate through largely unknown factors. We now show that the induction of fibrosis, associated with deposition of type I collagen (Col-I) in the in vivo metastatic microenvironment, induces dormant D2.0R cells to form proliferative metastatic lesions through β1-integrin signaling. In vitro studies using a three-dimensional culture system modeling dormancy showed that Col-I induces quiescent D2.0R cells to proliferate through β1-integrin activation of SRC and focal adhesion kinase, leading to extracellular signal-regulated kinase (ERK)–dependent myosin light chain phosphorylation by myosin light chain kinase and actin stress fiber formation. Blocking β1-integrin, Src, ERK, or myosin light chain kinase by short hairpin RNA or pharmacologic approaches inhibited Col-I–induced activation of this signaling cascade, cytoskeletal reorganization, and proliferation. These findings show that fibrosis with Col-I enrichment at the metastatic site may be a critical determinant of cytoskeletal reorganization in dormant tumor cells, leading to their transition from dormancy to metastatic growth. Thus, inhibiting Col-I production, its interaction with β1-integrin, and downstream signaling of β1-integrin may be important strategies for preventing or treating recurrent metastatic disease. Cancer Res; 70(14); 5706–16. ©2010 AACR.
Identification of a Metalloprotease-Chemokine Signaling System in the Ovarian Cancer Microenvironment: Implications for Antiangiogenic Therapy
Authors: Agarwal Anika , Tressel Sarah L. , Kaimal Rajani , Balla Marianthi , Lam Francis H. , Covic Lidija , Kuliopulos Athan 
Published: June 2010

AbstractOvarian cancer is a lethal gynecologic malignancy that may benefit from new therapies that block key paracrine pathways involved in tumor-stromal interactions and tumor vascularity. It was recently shown that matrix metalloprotease-1 (MMP1) activation of the G protein–coupled receptor protease-activated receptor-1 (PAR1) is an important stimulator of angiogenesis and metastasis in peritoneal mouse models of ovarian cancer. In the present study, we tested the hypothesis that MMP1-PAR1 promotes angiogenesis through its paracrine control of angiogenic chemokine receptors. We found that MMP1-PAR1 activation induces the secretion of several angiogenic factors from ovarian carcinoma cells, most prominently interleukin (IL)-8, growth-regulated oncogene-α (GRO-α), and monocyte chemoattractant protein-1. The secreted IL-8 and GRO-α acts on endothelial CXCR1/2 receptors in a paracrine manner to cause robust endothelial cell proliferation, tube formation, and migration. A cell-penetrating pepducin, X1/2pal-i3, which targets the conserved third intracellular loop of both CXCR1 and CXCR2 receptors, significantly inhibited endothelial cell proliferation, tube formation, angiogenesis, and ovarian tumor growth in mice. Matrigel plugs mixed with MMP1-stimulated, OVCAR-4–conditioned media showed a dramatic 33-fold increase in blood vessel formation in mice. The X1/2pal-i3 pepducin completely inhibited MMP1-dependent angiogenesis compared with a negative control pepducin or vehicle. Conversely, a vascular endothelial growth factor–directed antibody, Avastin, suppressed angiogenesis in mice but, as expected, was unable to inhibit IL-8 and GRO-α–dependent endothelial tube formation in vitro. These studies identify a critical MMP1-PAR1-CXCR1/2 paracrine pathway that might be therapeutically targeted for ovarian cancer treatment. Cancer Res; 70(14); 5880–90. ©2010 AACR.
Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase 1act/Tubulin Interaction Is an Important Determinant of Mitotic Stability in Cultured HT1080 Human Fibrosarcoma Cells
Authors: Cao Jia-ning , Shafee Norazizah , Vickery Larry , Kaluz Stefan , Ru Ning , Stanbridge Eric J. 
Published: June 2010

Abstract
Activation of the mitogen-activated protein kinase (MAPK) pathway plays a major role in neoplastic cell transformation. Using a proteomics approach, we identified α tubulin and β tubulin as proteins that interact with activated MAP/extracellular signal-regulated kinase kinase 1 (MEK1), a central MAPK regulatory kinase. Confocal analysis revealed spatiotemporal control of MEK1-tubulin colocalization that was most prominent in the mitotic spindle apparatus in variant HT1080 human fibrosarcoma cells. Peptide arrays identified the critical role of positively charged amino acids R108, R113, R160, and K157 on the surface of MEK1 for tubulin interaction. Overexpression of activated MEK1 caused defects in spindle arrangement, chromosome segregation, and ploidy. In contrast, chromosome polyploidy was reduced in the presence of an activated MEK1 mutant (R108A, R113A) that disrupted interactions with tubulin. Our findings indicate the importance of signaling by activated MEK1-tubulin in spindle organization and chromosomal instability. Cancer Res; 70(14); 6004–14. ©2010 AACR.