tbuckley/cabot-search huggingface dataset:
Looking beyond histological healing in ulcerative colitis: towards the establishment of a molecular signature for quiescent but progressive disease
Authors: Mathias Chamaillard, Jean-Baptiste Chevaux, Laurent Peyrin-Biroulet
Journal: Gut (2012)

Ulcerative colitis (UC) is a chronic, disabling, progressive inflammatory bowel disease (IBD).1 The condition is associated with an increased risk of colorectal cancer and other serious structural and functional consequences in the long term,1 which include the development of colonic strictures, dysmotility, anorectal dysfunction and impaired permeability.1 In this context, mucosal healing has emerged as a new therapeutic goal in the prevention of the long-term complications of IBD.2 ,3 Indeed, a growing body of evidence indicates that mucosal healing improves the natural course of the disease by lowering the need for colectomy and thus reducing hospitalisation rates in these patients.3 Histological healing is considered as the ultimate marker of quiescent disease activity in UC4 and thus an improvement in the patient's quality of life. However, it is not yet known whether persistent gene expression changes in intestinal tissues are related to incomplete histological healing in asymptomatic UC.

Planell et al 5 have attempted to identify a transcriptional signature associated with the involved mucosa in active/remitting UC patients (when …
THE EFFECT OF BETA-BLOCKERS ON MORTALITY IN SYSTOLIC HEART FAILURE VARIES BY BASELINE RIGHT VENTRICULAR EJECTION FRACTION: A POST HOC ANALYSIS OF THE BEST TRIAL
Authors: Ali Ahmed, Gilbert Perry, Gerasimos Filippatos, Marjan Mujib, Margaret Feller, Yan Zhang, Vera Bittner, Ami Iskandrian, Prakash Deedwania
Journal: Journal of the American College of Cardiology (2011)
Adverse Effect of Lomotil Therapy in Shigellosis
Authors: Herbert L. DuPont, Richard B. Hornick
Journal: JAMA (1973)

Twenty-five men with induced shigellosis received a mixture of diphenyoxylate hydrochloride with atropine (Lomotil), placebo and oxolinic acid (Oxabid), or a second placebo in four randomly assigned treatment groups. Diarrhea was decreased by oxolinic acid or Lomotil therapy, while fever was prolonged in the group receiving only Lomotil. Two men who received Lomotil alone had fever until the drug regimen was discontinued five days later. Shigellae were eradicated from stool in four of six men treated with oxolinic acid alone, but in only one of six men receiving oxolinic acid and Lomotil. Lomotil may be contraindicated in shigellosis. Diarrhea may represent a defense mechanism when disease is caused by a bacterial pathogen that must penetrate the intestinal epithelium to produce illness where increased intestinal motility (diarrhea) may decrease contact time between the invasive bacteria and mucosal cells.
Abstract PD02-05: Comparison of fluorescence in situ hybridization (FISH) and dual-ISH (D-ISH) in the determination of HER2 status
Authors: AS Mansfield, Y Sakai, FJ Walsh, AE Wiktor, WR Sukov, A Dogan, RB Jenkins
Journal: Cancer Research (2012)

Abstract Introduction: The appropriate assessment of HER2 amplification status is critical to determining which patients should receive HER2-directed therapy. An alternative to FISH is D-ISH (Ventana Medical Systems Tucson, Arizona) which utilizes chromogenic HER2 and chromosome 17 probes. Both FISH and D-ISH utilize formalin-fixed, paraffin-embedded (FFPE) human breast cancer tissue specimens. D-ISH has two principle advantages over FISH: it can be visualized using light microscopy and after analysis the specimens can be archived. Methods: We tested 250 samples with FISH and with D-ISH. Fifty specimens were controls: 25 cases with no HER2 or CEP17anomaly and 25 cases with HER2 amplification. There were also 200 test subjects of 50 cases each of chromosome 17 aneusomy, HER2 deletion (HER2/CEP17 ratio &amp;lt;0.8), HER2 duplication (HER2/CEP17 ratio 1.3–1.8), and equivocal results (HER2/CEP17 ratios between 1.8 and 2.2). FISH (Abbott Molecular) and D-ISH analysis were performed using methods described in the appropriate clinical kit package inserts, with the following exception: Four cases with CEP17 and HER2 co-amplification were also included and for FISH analysis these cases were reflexed to the use of chromosome 17 control probe (D17S122). Results: Four samples failed testing by D-ISH. There was a 63% (155/246) concordance between FISH and D-ISH by anomaly (aneusomy, duplication, deletion, etc.) and an 83% concordance by amplification status (non-amplified, equivocal, and amplified). D-ISH detected 18 (62%) of F-ISH-amplified cases. D-ISH resulted in lower estimates of HER2/CEP17 ratios than FISH, and many cases that were equivocal by FISH were normal by D-ISH. D-ISH did not detect HER2 amplification in any of the four HER2 and CEP17 co-amplified cases. Conclusions: We observed a lower concordance rate between FISH and D-ISH than the ∼95% rate in the D-ISH package insert. This lower concordance rate is likely a result of how this study was designed: it was biased toward common chromosome 17 anomalies and difficult specimens. Such specimens comprise about 60% of our current clinical HER2 biomarker practice. D-ISH may underestimate the HER2/CEP17 ratio, or FISH may overestimate this ratio. D-ISH also does not reliably detect HER2 amplification when the centromere of chromosome 17 is also co-amplifed. Compared to FISH, in this study cohort D-ISH had a significant false negative rate for the detection of HER2 amplification. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD02-05.
Abstract 5714: Combination of glucagon-like-peptide-1 (GLP-1) receptor targeted therapy with anti-angiogenic compounds in a mouse model of neuroendocrine tumors
Authors: Andreas Wicki, Damian Wild, Annette Orleth, Christoph Rochlitz, Christoph Mamot, Gerhard Christofori
Journal: Cancer Research (2012)

Abstract Neuroendocrine tumors are well vascularized and express specific cell surface markers, such as somatostatin receptors and glucagon-like peptide-1 receptors (GLP-1R). Using the Rip1Tag2 transgenic mouse model of pancreatic neuroendocrine tumors, we have investigated the potential benefit of a combination of anti-angiogenic treatment with targeted internal radiotherapy. To this end, [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4, a radiopeptide that selectively binds to GLP-1R expressed on insulinoma and other neuroendocrine tumor cells, was co-administered with PTK787, an inhibitor of vascular endothelial growth factors (VEGFR). For biodistribution, Rip1Tag2 mice were pre-treated with PTK787 for 0, 3, 5 or 7 days. Subsequently, [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 was administered and the biodistribution assessed after 4 hours. For therapy, mice were injected with 1.1 MBq [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 and treated with PTK787 orally for another 7 days. Tumor volume, tumor cell apoptosis and proliferation, and microvessel density were quantified. Combination of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 and PTK787 was significantly more effective than single treatments (p&amp;lt;0.05) and reduced the tumor volume by 97% in the absence of organ damage. Pre-treatment of mice with PTK787 led to a reduction in the tumor uptake of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4, indicating that concomitant administration of PTK787 and the radiopeptide was the best approach. Thus, combination of targeted radionuclide therapy with an anti-angiogenic compound inhibiting VEGF signaling had a synergistic effect on therapy efficacy. The combination of 1.1 MBq of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 with PTK787 had the same effect on a neuroendocrine tumor as the injection of 28 MBq of the radiopeptide alone, but without any apparent side-effects, such as radiation damage of the kidneys. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5714. doi:1538-7445.AM2012-5714
HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study.
Authors: W P Castelli, J T Doyle, T Gordon, C G Hames, M C Hjortland, S B Hulley, A Kagan, W J Zukel
Journal: Circulation (1977)

The relation between coronary heart disease (CHD) prevalence and fasting lipid levels was assessed by a case-control study in five populations with a total of 6859 men and women of black, Japanese and white ancestry drawn from subjects aged 40 years and older from populations in Albany, Framingham, Evans County, Honolulu and San Francisco. In each major study group mean levels of high density lipoprotein (HDL) cholesterol were lower in persons with CHD than in those without the disease. The average difference was small -- typically 3-4 mg/dl -- but statistically significant. It was found in most age-race-sex specific groups. The inverse HDL cholesterol-CHD association was not appreciably diminished when adjusted for levels of low density lipoprotein (LDL) cholesterol and triglyceride. LDL, totoal cholesterol and triglycerides were directly related to CHD prevalence; surprisingly, these findings were less uniformly present in the various study groups than the inverse HDL cholesterol-CHD association.
An NLRP7-Containing Inflammasome Mediates Recognition of Microbial Lipopeptides in Human Macrophages
Authors: Sonal Khare, Andrea Dorfleutner, Nicole B. Bryan, Chawon Yun, Alexander D. Radian, Lucia de Almeida, Yon Rojanasakul, Christian Stehlik
Journal: Immunity (2012)
Oxygen
Authors: Yen-Sin Ang, Deepak Srivastava
Journal: Circulation Research (2014)

M ammalian hearts transition from a hypoxic in utero environment to an oxygen-rich habitat after birth, coinciding with the rapid postnatal exit of cardiomyocytes out of the cell cycle.A recent article in Cell identified a novel connection between the 2 seminal events, focusing on the accumulation of reactive oxygen species in cardiomyocytes as a major mediator of the critical neonatal cell cycle switch. Oxygen
Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor
Authors: Koji Nakabayashi, Hirotaka Matsumi, Alka Bhalla, Jeehyeon Bae, Sietse Mosselman, Sheau Yu Hsu, Aaron J.W. Hsueh
Journal: Journal of Clinical Investigation (2002)

Human thyrotropin (TSH), luteotropin (LH), follitropin (FSH), and chorionic gonadotropin are members of the heterodimeric glycoprotein hormone family. The common α subunit forms noncovalent heterodimers with different β subunits. Two novel human glycoprotein hormonelike genes, α2 (A2) and β5 (B5), recently have been identified. Using a yeast two-hybrid assay, the two subunits were found as potential heterodimerization partners. Immunological analyses confirmed the heterodimerization of A2 and B5 in transfected cells and their colocalization in the anterior pituitary. Recombinant A2/B5 heterodimeric glycoproteins, purified using cation exchange and size fractionation chromatography, activated human TSH receptors, but not LH and FSH receptors, and showed high affinity to TSH receptors in a radioligand receptor assay. The heterodimer also stimulated cAMP production and thymidine incorporation by cultured thyroid cells and increased serum thyroxine levels in TSH-suppressed rats in vivo. This new heterodimeric glycoprotein hormone was named as thyrostimulin based on its thyroid-stimulating activity. The expression of thyrostimulin in the anterior pituitary known to express TSH receptors suggested a paracrine mechanism. The present discovery of a new ligand based on genomic approaches could facilitate the understanding of the physiological roles of extra-thyroid TSH receptor systems and the structural-functional basis of receptor signaling by related glycoprotein hormones.
Asymmetric Redundancy in CD4 Silencer Function
Authors: David D Duncan, Matthew Adlam, Gerald Siu
Journal: Immunity (1996)

We and others have defined a transcriptional silencer critical for the proper expression of the CD4 gene at all stages of T cell development. In this report, we use biochemical techniques to identify three different factor-binding sites within the CD4 silencer, denoted sites I, II, and III. Using transgenic analyses, we determine that although all three factor-binding sites are important for silencer activity, there is significant redundancy in that the presence of either site II alone, or the combination of sites I and III permits silencer function. Thus, our data indicate that the mechanism of function of the CD4 silencer is extremely complex. Further biochemical analyses indicate that the factor binding to site II has the same sequence specificity as a factor binding to an E box site in the CD4 enhancer; thus, a member of the bHLH factor family may be important in mediating silencer function.
A Decade of Progress in the Rh Blood-Group System
Authors: Alan Richardson Jones, Louis K. Diamond, Fred H. Allen
Journal: New England Journal of Medicine (1954)

Significance of f At present it is difficult to assess the practical importance of the antigen, but of its academic importance there can be no doubt. Perhaps the practical status of the new antigen and its corresponding antibody can best be appreciated by the realization that many examples of currently used anti-c and anti-e typing serums probably also contain anti-f, which heretofore had been undetected. The ease with which the anti-f can be isolated from these serums, together with the fact that its existence has escaped notice for several years, constitutes a strong argument in favor of the supposition that . . .
Biofeedback Therapy for Fecal Incontinence
Authors: ARNOLD WALD
Journal: Annals of Internal Medicine (1981)

Twenty-five patients (ages 10 to 79 years; average, 48 years) with fecal incontinence underwent anorectal manometry with a three-balloon system connected to a physiograph. On a basis of manometric criteria showing the presence of rectal sensation, 17 patients underwent biofeedback conditioning. Underlying disorders included irritable bowel syndrome, diabetes mellitus, anal sphincter damage from surgery or disease, and neurogenic anal dysfunction. Twelve of the 17 patients who received biofeedback training had significant improvement in bowel soiling. Follow-up periods ranged from 2 to 38 months (mean, 15 months). There were no significant differences in threshold of rectal sensation, relaxation of the internal anal sphincter, and pre- and postbiofeedback thresholds of external anal sphincter contraction between responders and nonresponders. Minimal criteria for successful treatment appeared to be ability to sense rectal distension, good motivation, and absence of significant psychological dysfunction. Biofeedback conditioning is a simple and effective technique in the treatment of selected patients with fecal incontinence.
Fogarty Balloon Catheter For Removal of Catheter Fragment in Subclavian Vein
Authors: A. P. Mathur
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Intravascular breakage and embolization of catheter fragments are being reported with increasing frequency.<sup>1</sup>Currently used polyethylene central venous catheters appear to be particularly susceptible to the shearing force of the advancing needle.<sup>1,2</sup> Complications due to retained catheter fragments include thrombosis, emboli formation, septicemia, and myocardial damage.<sup>3</sup>Prompt removal of these foreign bodies is imperative. Dotter et al<sup>1</sup>collected 29 cases from the literature in which attempts at transluminal retrieval of catheter debris from the heart and great vessels were reported. The recovery instruments included bronchoscopic forceps, urologic-type stone baskets, guide wire snares,<sup>4,5</sup>and catheter hook snares<sup>3</sup>and loop snares.<sup>1</sup>We report successful removal of a catheter embolus by means of a Fogarty balloon catheter.<sup>6</sup> <h3>Report of a Case.—</h3> A 64-year-old man was admitted with profuse rectal bleeding and a diagnosis of diverticulitis. A central venous catheter introduced into the right
Results of a Multicenter Randomized Clinical Trial of Exercise and Long-Term Survival in Myocardial Infarction Patients
Authors: Joan Dorn, John Naughton, Dai Imamura, Maurizio Trevisan
Journal: Circulation (1999)

Background —This study examined whether a supervised exercise program improved 19-year survival in 30- to 64-year-old male myocardial infarction patients. Methods and Results —The men (n=651) were participants in the National Exercise and Heart Disease Project, a 3-year multicenter randomized clinical trial conducted in the United States (1976–1979). The treatment group (n=315) exercised for 8 weeks in a laboratory. Thereafter, they jogged, cycled, or swam in a gymnasium/pool setting guided by an individualized target heart rate. Participants in the control group (n=319) were to maintain normal routines but not participate in any regular exercise program. Participants were followed up until their death or December 31, 1995. Cox proportional hazards analysis revealed the all-cause mortality risk estimates (95% CIs) in the exercise group compared with controls to be 0.69 (0.39 to 1.25) after an average follow-up of 3 years, 0.84 (0.55 to 1.28) after 5 years, 0.95 (0.71 to 1.29) after 10 years, 1.02 (0.79 to 1.32) after 15 years, and 1.09 (0.87 to 1.36) after 19 years. Cardiovascular disease (CVD) mortality risk estimates (95% CI) for the same follow-up periods were 0.73 (0.37 to 1.43), 0.98 (0.60 to 1.61), 1.21 (0.79 to 1.60), 1.14 (0.84 to 1.54), and 1.16 (0.88 to 1.52). However, each 1-MET increase in work capacity from baseline to the end of the original trial resulted in consistent reductions in all-cause and CVD mortality risk at each follow-up period, regardless of initial work-capacity level. Conclusions —These findings indicate exercise-program participation resulted in nonsignificantly reduced mortality risks early in the follow-up period. Benefits diminished as time since participation increased, which suggests that the protective mechanisms associated with the program may be short term. Contamination between groups over time could also explain the diminished effects, because increased work capacity provided survival benefits up to 19 years.
Primary Sclerosing Cholangitis Mimicking Choledocal Cyst Type 1 in a Young Patient
Authors: E. G. Siegel, U. R. Fölsch
Journal: Endoscopy (1999)

A choledochal cyst type I was diagnosed in a 12-year-old boy in 1984. The diagnosis was made using ultrasound and confirmed using computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP). Instead of the usual surgical treatment, endoscopic balloon dilatation of the sphincter of Oddi and the distal common bile duct was carried out using an endoscopic procedure. The patient experienced relief of symptoms, gained weight and felt healthy again. An ERCP performed in 1990, because of increasing levelsCARETof liver enzymes and clinical features of abdominal pain and fatigue, revealed typical cholangiographic findings associated with primary sclerosing cholangitis, including bile duct irregularities with diffuse narrowing and twisting of the bile ducts with localized ectatic and strictured areas. Percutaneous needle liver biopsy confirmed the diagnosis. We conclude that primary sclerosing cholangitis should be considered when interpreting ERCP films from patients who are supposed to have choledochal cysts type I.
Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation.
Authors: A B Waxman, O Einarsson, T Seres, R G Knickelbein, J B Warshaw, R Johnston, R J Homer, J A Elias
Journal: Journal of Clinical Investigation (1998)

Acute lung injury is a frequent and treatment-limiting consequence of therapy with hyperoxic gas mixtures. To determine if IL-11 is protective in oxygen toxicity, we compared the effects of 100% O2 on transgenic mice that overexpress IL-11 in the lung and transgene (-) controls. IL-11 markedly enhanced survival in 100% O2 with 100% of transgene (-) animals dying within 72-96 h and > 90% of transgene (+) animals surviving for more than 10 d. This protection was associated with markedly diminished alveolar-capillary protein leak, endothelial and epithelial membrane injury, lipid peroxidation, and pulmonary neutrophil recruitment. Significant differences in copper zinc superoxide dismutase and catalase activities were not noted and the levels of total, reduced and oxidized glutathione were similar in transgene (+) and (-) animals. Glutathione reductase, glutathione peroxidase, and manganese superoxide dismutase activities were slightly higher in transgene (+) as versus (-) mice after 100% O2 exposure, and IL-11 diminished hyperoxia-induced expression of IL-1 and TNF. Hyperoxia also caused cell death with DNA fragmentation in the lungs of transgene (-) animals and IL-11 markedly diminished this cell death response. These studies demonstrate that IL-11 markedly diminishes hyperoxic lung injury. They also demonstrate this protection is associated with small changes in lung antioxidants, diminished hyperoxia-induced IL-1 and TNF production, and markedly suppressed hyperoxia-induced DNA fragmentation.
The subtleties of intestinal metaplasia
Authors: R ROUZIER
Journal: Gut (2001)

See article on page 73 

Even if its incidence has decreased due to the influence of environmental and nutritional factors, gastric carcinoma remains a major concern because of its very poor prognosis. Screening for precancerous conditions, including intestinal metaplasia, is one method of improving the prognosis of gastric carcinoma. Nevertheless, the implications for the use of endoscopic surveillance in patients with intestinal metaplasia of the stomach are still unknown.

As suggested by Grotzinger et al in this issue of Gut ,1 molecular changes (gain or loss of protein expression) are undoubtedly the first sign of metaplasia; the use of …
EXERCISE IMPAIRS MYOCARDIAL FUNCTION ASSESSED BY MAGNETIC RESONANCE IMAGING IN SUBJECTS WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY
Authors: Jørg Saberniak, Nina Hasselberg, Sebastian Sarvari, Margareth Ribe, Rasmus Borgquist, Pyotr Platonov, Hans-Jørgen Smith, Thor Edvardsen, Kristinaz Haugaa
Journal: Journal of the American College of Cardiology (2014)
What Is the Benefit of Increasing the Sulfonylurea Dose?
Authors: Svante Stenman, Arne Melander, Per-Henrik Groop, Leif C. Groop
Journal: Annals of Internal Medicine (1993)

Objective: To study the clinical benefit of increasing the dose of the sulfonylurea, glipizide, from 10 to 40 mg per day. Design: A placebo-controlled, double-blind, cross-over study. Setting: An outpatient clinic at the Helsinki University Hospital, Finland. Patients: Twenty-three patients with non–insulin-dependent diabetes mellitus. Methods: Patients were given glipizide in three different dose schedules for 3 months each: 10 mg in the morning or 10 mg or 20 mg in the morning and the evening. Glycemic control was followed by HbA1c measurements and blood glucose monitoring at home. Beta cell function was assessed by measuring insulin responses to a test meal. Results: Mean home-monitored blood glucose was 12.4 mmol/L during placebo treatment, and it was 9.6, 9.2, and 8.9 mmol/L after treatment with glipizide, 10, 20, or 40 mg, respectively. The levels of blood glucose and HbA1c differed after all treatment groups from placebo (P < 0.001) but not among themselves. The insulin response to a test meal was greatest after 10 mg of glipizide and weakest after 40 mg/d (P = 0.02 compared with the 10-mg dose). All treatments stimulated insulin secretion more than placebo (P < 0.001). Conclusions: Increasing the glipizide dose to more than 10 mg once daily produces little or no benefit and may reduce β-cell function.