tbuckley/cabot-search huggingface dataset:
Elastic scattering spectroscopy accurately detects high grade dysplasia and cancer in Barrett's oesophagus
Authors: L B Lovat
Journal: Gut (2005)

<b>Background and aims:</b> Endoscopic surveillance of Barrett's oesophagus currently relies on multiple random biopsies. This approach is time consuming, has a poor diagnostic yield, and significant interobserver variability. Elastic scattering spectroscopy is a real time in vivo optical technique which detects changes in the physical properties of cells. The aim of this study was to assess the potential for elastic scattering to detect high grade dysplasia or cancer within Barrett's oesophagus. <b>Methods:</b> Elastic scattering spectroscopy measurements collected in vivo were matched with histological specimens taken from identical sites within Barrett's oesophagus. All biopsies were reviewed by three gastrointestinal pathologists and defined as either "low risk" (non-dysplastic or low grade dysplasia) or "high risk" (high grade dysplasia or cancer). Two different statistical approaches (leave one out and block validation) were used to validate the model. <b>Results:</b> A total of 181 matched biopsy sites from 81 patients, where histopathological consensus was reached, were analysed. There was good pathologist agreement in differentiating high grade dysplasia and cancer from other pathology (kappa = 0.72). Elastic scattering spectroscopy detected high risk sites with 92% sensitivity and 60% specificity and differentiated high risk sites from inflammation with a sensitivity and specificity of 79%. If used to target biopsies during endoscopy, the number of low risk biopsies taken would decrease by 60% with minimal loss of accuracy. A negative spectroscopy result would exclude high grade dysplasia or cancer with an accuracy of &gt;99.5%. <b>Conclusions:</b> These preliminary results show that elastic scattering spectroscopy has the potential to target conventional biopsies in Barrett's surveillance saving significant endoscopist and pathologist time with consequent financial savings. This technique now requires validation in prospective studies.
Association Between Endothelial Nitric Oxide Synthase Glu298Asp Polymorphism and Postchallenge Insulin Levels in Nondiabetic Japanese Subjects
Authors: Noriko Maruyama, Yutaka Yano, Esteban C. Gabazza, Rika Araki, Akira Katsuki, Yasuko Hori, Kaname Nakatani, Yasuhiro Sumida, Yukihiko Adachi
Journal: Diabetes Care (2003)

Endothelial nitric oxide synthase (eNOS) catalyzes NO production in vascular endothelial cells, and NO regulates local blood flow by inducing vasodilation (1). Enhancement of skeletal muscle glucose uptake occurs during elevation of muscle blood flow, which is induced by increased eNOS expression and activated by insulin stimulation (2–4). It was previously reported that low production of NO in eNOS knockout mice causes reduction of insulin-induced blood flow and glucose uptake in whole body (5). These findings suggest that eNOS plays an important role in the regulation of insulin-induced glucose uptake in whole body.

Polymorphism in eNOS exon 7 with G→T conversion at nucleotide position 894 results in amino acid substitution of glutamic acid for aspartic acid in amino acid residue 298 (Glu298Asp). Structural alteration in this variant affects the susceptibility to cleavage and reduces activity of this enzyme (6,7). Dysfunction of eNOS by this polymorphism may cause reduction of insulin-induced blood flow and glucose uptake. It was recently demonstrated that insulin secretion and sensitivity could be assessed by 75-g oral glucose tolerance test (8,9). Therefore, we examined the association of this polymorphism with fasting and postchallenge glucose and insulin levels …
Jun Dimerization Protein 2 (JDP2), a Member of the AP-1 Family of Transcription Factor, Mediates Osteoclast Differentiation Induced by RANKL
Authors: Reimi Kawaida, Toshiaki Ohtsuka, Junichi Okutsu, Tohru Takahashi, Yuho Kadono, Hiromi Oda, Atsuhiko Hikita, Kozo Nakamura, Sakae Tanaka, Hidehiko Furukawa
Journal: The Journal of Experimental Medicine (2003)

Osteoclasts are multinucleated cells that resorb bones, and are derived from hematopoietic cells of the monocyte/macrophage lineage. The receptor activator of NF-κB ligand (RANKL, also called ODF/TRANCE/OPGL) stimulates both osteoclast differentiation from osteoclast progenitors and activation of mature osteoclasts. To identify genes responsible for osteoclast differentiation, we used a molecular indexing technique. Here, we report a clone of one of these genes whose transcription is induced by soluble RANKL (sRANKL) in both the RAW264.7 cells of the mouse macrophage cell line and the mouse primary bone marrow cells. The predicted protein was found to be a mouse homologue of Jun dimerization protein 2 (JDP2), a member of the AP-1 family of transcription factors, containing a basic region-leucine zipper motif. Transient transfection experiments revealed that overexpression of JDP2 leads to activation of both tartrate-resistant acid phosphatase (TRAP) and cathepsin K gene promoters in RAW264.7 cells. Infection of mouse primary bone marrow cells with retroviruses expressing JDP2-facilitated sRANKL-mediated formation of TRAP-positive multinuclear osteoclasts. Importantly, antisense oligonucleotide to JDP2 strongly suppressed sRANKL-induced osteoclast formation of RAW264.7 cells. Our findings suggest that JDP2 may play an important role in the RANK-mediated signal transduction system, especially in osteoclast differentiation.
HLA-Gm/kappam interaction in sarcoidosis. Suggestions for a complex genetic structure
Authors: M. Martinetti, J-M. Dugoujon, C. Tinelli, A Cipriani, A Cortelazzo, L. Salvaneschi, L Casali, G Semenzato, M Cuccia, M Luisetti
Journal: European Respiratory Journal (2000)

The aetiology of sarcoidosis is still unknown. Environmental exposures are believed to interact with genetic factors in determining the pattern of sarcoidosis presentation, progression and prognosis. The frequency of serological polymorphism of immunoglobulin G heavy chain (Gm) and kappa light chain (kappam) markers in 107 patients with biopsy-proven sarcoidosis and in 227 controls, and their interactions with histocompatibility leukocyte antigen (HLA) class I, II, and III markers, were studied. A "protective" effect of the Gm(3 5*) phenotype in the sarcoid group versus controls (p-value for number of specificities tested (p(c))=0.05, odds ratio 0.15) and a reduced frequency of Gm(3 23 5*) in patients with advanced chest radiographic stage (Chi-squared (two degrees of freedom)(chi2(2df) 17.61, p(c)=0.0058) were observed. With reference to epistatic interactions, the combination Gm(3 23 5*)/BfS had a "protective" effect towards stage II (chi2(2dt) 13.86, p(c)=0.043). Finally, correspondence analysis defined two clusters: HLA-DR4, C4BQ0, Gm(1, 3, 17 23 5*, 21, 28) and BfF associated with stage II, and HLA-DR3, C4AQ0, kappam(1) and Gm(3 23 5*) associated with stage I. These data further support the hypothesis that sarcoidosis results from an interplay of environmental factors and genes, each contributing to the susceptibility/resistance to and/or the clinical heterogeneity of the disease. In addition, these data provide the first evidence of an interaction between immunoglobulin G heavy chain/kappa light chain markers and histocompatibility leukocyte antigen class III genes in a disease.
Comparison of Oral Prednisone and Topical Fluticasone in the Treatment of Eosinophilic Esophagitis: A Randomized Trial in Children
Authors: Elizabeth T. Schaefer, Joseph F. Fitzgerald, Jean P. Molleston, Joseph M. Croffie, Marian D. Pfefferkorn, Mark R. Corkins, Joel D. Lim, Steven J. Steiner, Sandeep K. Gupta
Journal: Clinical Gastroenterology and Hepatology (2008)
Endothelin-dependent effects limit flow-induced dilation of conductance coronary vessels after blockade of nitric oxide formation in conscious dogs
Authors: R Parent
Journal: Cardiovascular Research (2000)

Objective: To determine whether endothelin (ET)-dependent effects limit shear stress-induced dilation of large epicardial coronary arteries after blockade of nitric oxide (NO) formation. Methods: In conscious dogs instrumented for measuring coronary blood flow (CBF) and external diameter (CD) of the circumflex coronary artery, flow-dependent CD dilation was elicited by intracoronary (ic) adenosine (500 ng kg−1 min−1). Results: Ic adenosine increased CBF by 28±4 from 38±5 ml min−1 and CD by 0.25±0.03 from 3.53±0.07 mm without other hemodynamic effects. After Nω-nitro-l-arginine methyl ester (l-NAME), baseline CD fell (P<0.01) to 3.35±0.08 mm but CBF was not significantly altered (36±5 ml min−1). CBF increases caused by adenosine were smaller (17±2 ml min−1, P<0.05) and CD responses were nearly abolished (0.02±0.01 mm, P<0.01). Ic Ro 61-1790, an ETA receptor blocker, given after l-NAME did not significantly influence baseline CBF (36±5 ml min−1) but increased (P<0.01) CD to 3.45±0.09 mm. CBF responses to adenosine were not significantly altered by Ro 61-1790 but CD responses (0.10±0.01 mm) were partially restored (P<0.01). In contrast, blockade of ETB receptors with Ro 46-8443 after l-NAME had no further effects on CD and CBF responses to adenosine. Conclusion: ETA receptor-mediated effects limit flow-dependent dilation of large epicardial coronary arteries in conscious dogs. Suppression of the l-arginine/NO-dependent pathway with l-NAME reveals significant ET-dependent effects.
PMO-212 Patients with positive faecal occult blood test (FOBt) following previous low risk colonoscopy in the bowel cancer screening programme: should current approach be changed?: Abstract PMO-212 Table 1
Authors: D Nylander, M Ritchie
Journal: Gut (2012)

<h3>Introduction</h3> In the UK FOBt Bowel Cancer Screening Programme (BCSP), patients between 60 and 75 are invited to submit stool specimens 2 yearly. Those who have either two weakly positive (+ve) or one abnormal FOBt are recommended to undergo colonoscopy. This recommendation stands, even if they have had a previous colonoscopy within the BCSP, regardless of the findings or time frame. In theory therefore a patient may be recommended colonoscopy every 2 years if they have any persisting non-neoplastic lesions that cause bleeding. BSG guidance however recommends surveillance colonoscopy in 5 years (or not at all) for patients with low risk adenoma.<sup>1</sup> All endoscopists in BCSP have been assessed and deemed competent colonoscopists. Also all procedures are carefully monitored by specialist practitioners. Thus this is the most quality assured setting for colonoscopy practice in the health service. We aimed (a) To determine if there were patients who returned to for 2nd BCSP colonoscopy in under 5 years, despite previous colonoscopy being classed as low risk or non-neoplastic. (b) To determine if 2nd colonoscopy gave prognostically significant result. <h3>Methods</h3> The BCSP database was used to identify cases with 1st colonoscopy reported as normal, low risk adenomas or “abnormal but no adenoma”. Any of these who had a 2nd colonoscopy within the BCSP for +ve FOBt were noted and their reports obtained to get the findings of both procedures. The study period was April 2007 to October 2011. <h3>Results</h3> 40 patients, deemed low risk at 1st BCSP colonoscopy returned new positive FOBt kits in following screening round. Of these two declined 2nd colonoscopy when contacted (initial colonoscopy findings were one Crohns, one diverticulosis). In three cases, interval between colonoscopies was 4 years, all the rest being 2 years. All colonoscopy findings are in Abstract PMO-212 table 1. All adenomas were 3 mm or less. <h3>Conclusion</h3> A small number of patients will have positive FOBt tests despite a “low risk” colonoscopy in BCSP for neoplasia within previous 2 years. In our patient group, a 2nd colonoscopy in this period showed no new prognostically significant findings. Our data suggests that there is no need to deviate from the BSG recommendation and perform repeat procedures for “low risk” patients in &lt;5 years in the BCSP. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <i>Gut</i> 2010;<b>59</b>:666.
HAEMATOPOIETIC BUT NOT MESENCHYMAL STEM CELLS CONTRIBUTE TO THE STROMAL MICROENVI.RONMENT IN CHOLANGIOCARCINOMA AND DO NOT TRANSDIFFERENTIATE INTO MALIGNANT BILE DUCTS
Authors: Andrew J. Robson, Kay Samuel, Antonella Pellicoro, John P. Iredale, Stuart J. Forbes
Journal: Hepatology (2010)
Epidermal Growth Factor Receptor R497K Polymorphism Is a Favorable Prognostic Factor for Patients with Colorectal Carcinoma
Authors: Wei-Shu Wang, Po-Min Chen, Tzeon-Jye Chiou, Jin-Hwang Liu, Jen-Kou Lin, Tzu-Chen Lin, Huann-Sheng Wang, Yeu Su
Journal: Clinical Cancer Research (2007)

Abstract Purpose: It has been shown that the R497K polymorphism of the epidermal growth factor receptor (EGFR) has attenuated functions in ligand binding, tyrosine kinase activation, and growth stimulation. Because the activation of EGFR results in an unfavorable prognosis of patients with colorectal carcinoma, a pilot study was conducted to assess the influence of this polymorphism on colorectal carcinoma patients. Experimental Design: We retrospectively analyzed the effect of the R497K polymorphism of EGFR on clinicopathologic features in 209 colorectal carcinoma patients, including 100 with stage II/III colorectal carcinoma receiving curative surgery and the other 109 with metastatic diseases. Results: An excellent correlation in codon 497 statuses examined by patients' WBCs and tumor tissues was found but no significant between-group difference in patients with or without colorectal carcinoma (P = 0.97). A marked decrease on EGFR phosphorylation (P &amp;lt; 0.01) and c-Myc activation (P = 0.02) was observed in patients with R497K polymorphism, which is associated with decreased invasion (P = 0.01), lower nodal involvement (P = 0.02), reduced subsequent metastasis (P &amp;lt; 0.01), and longer disease-free (P &amp;lt; 0.01) as well as overall (P &amp;lt; 0.01) survival in stage II/III colorectal carcinoma patients who had received curative surgery. For patients with metastatic colorectal carcinoma, this polymorphism was associated with a higher response to 5-fluorouracil/oxaliplatin treatment (P = 0.02) and a longer survival (P &amp;lt; 0.01). By multivariate analysis, this polymorphism was also identified as an independent prognostic factor (P = 0.03). Conclusions: These data suggest that the R497K polymorphism of the EGFR, by reducing its activation and a consequential down-regulation of its target genes, could be a key determinant for reduced tumor recurrence of stage II/III colorectal carcinoma patients receiving curative surgery and a longer survival of patients with stage II/III as well as metastatic colorectal carcinoma.
Helicobacter pylori treatment in the era of increasing antibiotic resistance
Authors: D. Y. Graham, L. Fischbach
Journal: Gut (2010)

With few exceptions, the most commonly recommended triple <i>Helicobacter pylori</i> regimen (proton pump inhibitor (PPI), amoxicillin and clarithromycin) now provides unacceptably low treatment success. A review of worldwide results suggests that successful eradication using a triple regimen is not consistently observed in any population. Clinicians should use 'only use what works locally' and ignore consensus statements and society guidelines if they are not consistent with local results. Clinical trials should be result based, with the goal of identifying regimens with &gt;90–95% success. New treatments should be only be compared with the currently locally effective treatment (&gt;90%) or a historical untreated control (which has been shown to reliably yield 0% eradication); trials using placebos or treatments known to be inferior are with rare exceptions unethical. If a highly effective regimen is not available locally, we recommend trying a 14 day concomitant quadruple treatment regimen containing a PPI, amoxicillin, clarithromycin and a nitroimidazole; 10 day sequential treatment (PPI plus amoxicillin for 5 days followed by a PPI, clarithromycin and a nitroimidazole for 5 days); or 14 day bismuth-containing quadruple treatments. Treatments needing further evaluation include those containing furazolidone or nitazoxanide, hybrids of sequential–concomitant therapies and amoxicillin–PPI dual therapy with PPI doses such that they maintain intragastric pH &gt;6.
Ursodeoxycholic acid inhibits eosinophil degranulation in patients with primary biliary cirrhosis
Authors: Kiyoshi Yamazaki, Kazuyuki Suzuki, Atsushi Nakamura, Shunichi Sato, Keith D. Lindor, Kenneth P. Batts, James E. Tarara, Gail M. Kephart, Hirohito Kita, Gerald J. Gleich
Journal: Hepatology (1999)

Eosinophilia is a distinctive feature of primary biliary cirrhosis (PBC), especially in its early stages. Intriguingly, treatment with ursodeoxycholic acid (UDCA) ameliorates eosinophilia as well as liver tests in patients with PBC. It remains unknown, however, whether eosinophils in PBC patients are functionally activated and whether UDCA inhibits eosinophil activation. In the present study, we systematically examined eosinophil dynamics in the blood and liver in patients with stage I to II PBC before and after UDCA treatment. We determined serum concentrations of eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]) by radioimmunoassay and quantitated eosinophil degranulation using computer-assisted morphometry after MBP immunohistochemistry. Before UDCA treatment, patients with PBC (n = 25) showed significantly higher circulating eosinophil counts ( P &lt; .05) and serum concentrations of MBP ( P &lt; .0005) and EDN ( P &lt; .02) compared with patients with chronic viral hepatitis (n = 22), autoimmune hepatitis (n = 10), and obstructive jaundice (n = 12). Four-week UDCA treatment significantly reduced blood eosinophil counts ( P &lt; .0001) and serum MBP ( P &lt; .0001) and EDN ( P &lt; .0001) levels in PBC patients. MBP immunohistochemistry and computer-assisted quantitative morphometry showed infiltration and degranulation of eosinophils in the portal tract in patients with PBC and significant reductions in the number of sites and the area occupied by extracellular MBP deposits after UDCA treatment for 2 years ( P &lt; .02) but not in placebo-treated patients. Our results suggest that eosinophils in patients with PBC are not only increased in number, but also release granule proteins, and that UDCA treatment inhibits this eosinophil activation/degranulation
Nasal and paranasal disease in adult cystic fibrosis patients
Authors: JD Kerrebijn, RM Poublon, SE Overbeek
Journal: European Respiratory Journal (1992)

Children with cystic fibrosis frequently have nasal polyps and sinusitis. This study addresses (para-) nasal disease in 39 adult cystic fibrosis patients. Fifteen patients (39%) had recently had serious nasal symptoms and 26% sinusitis. Seventeen (44%) had nasal polyposis. Almost all sinus radiographs taken showed opacification, which was unrelated to symptoms. Polypectomies and antral irrigations were usually ineffective, whilst more extensive surgery generally gave better results. It is concluded that a substantial number of adult cystic fibrosis patients frequently have upper airway symptoms. Sinus radiographs have little or no diagnostic value. Treatment of (para-) nasal disease in cystic fibrosis patients can be difficult; a guideline for treatment is suggested, calling for simple interventions coupled with intranasal steroids and nasal irrigation in early disease and for endoscopic to radical sinus surgery in recurrent advanced disease.
Aptamer Identification of Brain Tumor–Initiating Cells
Authors: Youngmi Kim, Qiulian Wu, Petra Hamerlik, Masahiro Hitomi, Andrew E. Sloan, Gene H. Barnett, Robert J. Weil, Patrick Leahy, Anita B. Hjelmeland, Jeremy N. Rich
Journal: Cancer Research (2013)

Abstract Glioblastomas display cellular hierarchies with self-renewing tumor-initiating cells (TIC), also known as cancer stem cells, at the apex. Although the TIC hypothesis remains controversial and the functional assays to define the TIC phenotype are evolving, we and others have shown that TICs may contribute to therapeutic resistance, tumor spread, and angiogenesis. The identification of TICs has been informed by the use of markers characterized in normal stem cells, but this approach has an inherent limitation to selectively identify TICs. To develop reagents that enrich TICs but not matched non-TICs or tissue-specific stem cells, we adopted Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX) to identify glioblastoma TIC-specific nucleic acid probes—aptamers—that specifically bind TICs. In this study, using Cell-SELEX with positive selection for TICs and negative selection for non-TICs and human neural progenitor cells, we identified TIC aptamers that specifically bind to TICs with excellent dissociation constants (Kd). These aptamers select and internalize into glioblastoma cells that self-renew, proliferate, and initiate tumors. As aptamers can be modified to deliver payloads, aptamers may represent novel agents that could selectively target or facilitate imaging of TICs. Cancer Res; 73(15); 4923–36. ©2013 AACR.
Ethanol acutely and reversibly suppresses excitation-contraction coupling in cardiac myocytes.
Authors: R S Danziger, M Sakai, M C Capogrossi, H A Spurgeon, R G Hansford, E G Lakatta
Journal: Circulation Research (1991)

We used adult rat cardiac myocytes to examine the acute effects of 0.1-5.0% (vol/vol) ethanol (ETOH) on 1) the cytosolic [Ca2+] (Cai) transient measured as the change in indo 1 fluorescence at 410/490 nm and contraction elicited by electrical stimulation of single cells and 2) the sarcoplasmic reticulum (SR) Ca2+ content in cell suspensions. During stimulation at 1 Hz, clinically relevant ETOH correlations (0.1-0.15% [vol/vol]) caused a 10-15% decrease in the contraction amplitude, measured by myocyte edge tracking, without decreasing the Cai transient that initiates contraction. At higher ETOH concentrations (1-5% [vol/vol]), ETOH caused profound contractile depression and also reduced the magnitude of the Cai transient. These effects were reversed within minutes of ETOH washout. Addition of norepinephrine (10 microM) to the bathing solution or an increase in bathing [Ca2+] in the continued presence of ETOH could also reverse its effects. The relation of the amplitude of the Cai transient to the contraction amplitude measured across a range of bathing [Ca2+] was shifted by ETOH, such that for a given Cai transient a marked reduction in contraction amplitude occurred. In unstimulated myocyte suspensions, ETOH (1-5% [vol/vol]) caused a concentration-dependent depletion of SR Ca2+ content, manifested as a diminution in the Cai increase elicited by caffeine in the presence of extracellular EGTA and no added Ca2+. Thus, in rat cardiac myocytes a reduction in the myofilament Ca2+ response, possibly due to a decrease in myofilament Ca2+ sensitivity, is a mechanism for contractile depression due to clinically relevant ETOH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)