tbuckley/cabot-search huggingface dataset:
Secular trends in the epidemiology and outcome of Barrett's oesophagus in Olmsted County, Minnesota
Authors: M Conio
Journal: Gut (2001)

<h3>BACKGROUND</h3> The incidence of oesophageal adenocarcinoma has increased greatly. Barrett9s oesophagus is a known risk factor. <h3>AIMS</h3> To identify changes in the incidence, prevalence, and outcome of Barrett9s oesophagus in a defined population. <h3>SUBJECTS</h3> Residents of Olmsted County, Minnesota, with clinically diagnosed Barrett9s oesophagus, or oesophageal or oesophagogastric junction adenocarcinoma. <h3>METHODS</h3> Cases were identified using the Rochester Epidemiology Project medical records linkage system. Records were reviewed with follow up to 1 January 1998. <h3>RESULTS</h3> The incidence of clinically diagnosed Barrett9s oesophagus (&gt;3 cm) increased 28-fold from 0.37/100 000 person years in 1965–69 to 10.5/100 000 in 1995–97. Of note, gastroscopic examinations increased 22-fold in this same time period. The prevalence of diagnosed Barrett9s oesophagus increased from 22.6 (95% confidence interval (CI) 11.7–33.6) per 100 000 in 1987 to 82.6/100 000 in 1998. The prevalence of short segment Barrett9s oesophagus (&lt;3 cm) in 1998 was 33.4/ 100 000. Patients with Barrett9s oesophagus had shorter than expected survival but only one patient with Barrett9s oesophagus died from adenocarcinoma. Only four of 64 adenocarcinomas occurred in patients with previously known Barrett9s oesophagus. <h3>CONCLUSIONS</h3> The incidence and prevalence of clinically diagnosed Barrett9s oesophagus have increased in parallel with the increased use of endoscopy. We infer that the true population prevalence of Barrett9s oesophagus has not changed greatly, although the incidence of oesophageal adenocarcinoma increased 10-fold. Many adenocarcinomas occurred in patients without a previous diagnosis of Barrett9s oesophagus, suggesting that many people with this condition remain undiagnosed in the community.
Grg1 Acts as a Lung-Specific Oncogene in a Transgenic Mouse Model
Authors: Thaddeus Allen, Minke van Tuyl, Pratibha Iyengar, Serge Jothy, Martin Post, Ming-Sound Tsao, Corrinne G. Lobe
Journal: Cancer Research (2006)

Groucho proteins are transcriptional corepressors that are recruited to gene regulatory regions by numerous transcription factors. Long isoforms, such as Grg1, have all the domains of the prototype Drosophila Groucho. Short Groucho proteins, such as Grg5, have only the amino-terminal Q and G/P domains. We generated Grg1 and Grg5 transgenic mice and found that Grg1 overexpression induces lung adenocarcinoma, whereas Grg5 overexpression does not. Coexpression of Grg5 with Grg1 reduces tumor burden. Grg1 and Grg5 both diminish p53 protein levels; however, only Grg1 overexpression induces elevated levels of ErbB1 and ErbB2 receptor tyrosine kinases. The molecular and biological changes that accompany tumor progression in Grg1 transgenic mice closely reiterate events seen in human lung cancer. We also found that within a human lung tumor tissue array, a significant number of carcinomas overexpress Grg1/TLE1. Our data suggest that Grg1 overexpression contributes to malignancy in human lung cancers.
New developments in the endoscopic surveillance of Barrett's oesophagus
Authors: J J G H M Bergman
Journal: Gut (2005)

Patients with a Barrett’s oesophagus are at risk for developing an adenocarcinoma of the distal oesophagus. Therefore, many patients undergo endoscopic surveillance to detect dysplasia and/or cancer at an early and curable stage. However, early neoplastic lesions are difficult to identify with standard endoscopy. In addition, the low incidence of these lesions, currently estimated at 0.5% per year, reduces the cost effectiveness of the surveillance strategy. New developments, aimed at improving the efficacy of Barrett’s surveillance, focus on two areas: 1) improvement of the endoscopic detection of early neoplastic lesions; and 2) the use of alternative techniques for tissue sampling combined with molecular markers to identify patients at risk for malignant degeneration.
Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice.
Authors: I L Campbell, T W Kay, L Oxbrow, L C Harrison
Journal: Journal of Clinical Investigation (1991)

Experimental studies in vitro suggest that cytokines are important mediators in the pathogenesis of autoimmune insulin-dependent diabetes mellitus (IDDM). However, there is little evidence for the role of cytokines in vivo, either in humans or in the spontaneous animal models of IDDM such as the NOD mouse or BB rat. To address this question, we used the model of cyclophosphamide (CYP)-induced autoimmune diabetes in the NOD/Wehi mouse to examine for (a) the production of IFN-gamma and IL-6 from isolated islets, and (b) the effect of anti IFN-gamma or anti IL-6 monoclonal antibodies on the development of diabetes. After cyclophosphamide, the majority of these mice develop of mononuclear cell infiltrate (insulitis) which by 10-14 d is associated with beta cell destruction. IFN-gamma activity at low levels (2.7 +/- 0.3 U/ml) could be detected only in culture supernatants from islets isolated at day 7 post-cyclophosphamide. In contrast, IL-6 activity progressively increased from 457 +/- 44 U/ml at day 0 to 6,020 +/- 777 U/ml at day 10. Culture of islets with anti-CD3 monoclonal antibody resulted in a significant increase in IFN-gamma activity from 41 +/- 7 U/ml at day 0 to 812 +/- 156 U/ml at day 10. Mice given either anti-IFN-gamma or anti-IL-6 antibody had a significantly reduced (P less than 0.001) incidence of diabetes and especially with IFN-gamma, decreased severity of insulitis. We conclude that IFN-gamma and IL-6 have essential roles in the pathogenesis of pancreatic islet beta cell destruction in this model.
Migration of human inflammatory cells into the lung results in the remodeling of arachidonic acid into a triglyceride pool.
Authors: M Triggiani, A Oriente, M C Seeds, D A Bass, G Marone, F H Chilton
Journal: The Journal of Experimental Medicine (1995)

Increasing evidence suggests that the metabolism of arachidonic acid (AA) may be different in inflammatory cells isolated from blood or migrating into tissues. To explore the possibility that changes in AA metabolism between blood and tissue inflammatory cells could be due in part to a different content or distribution of AA in glycerolipid classes, we studied these parameters in six human inflammatory cells isolated from blood (eosinophils, monocytes, neutrophils, and platelets) or from the lung tissue (mast cells and macrophages). Lung cells generally had a higher total cellular content of AA than that found in the blood cells. In addition, both mast cells and macrophages had a large endogenous pool of AA associated with triglycerides (TG), containing 45 and 22% of their total cellular AA, respectively. To address the hypothesis that cells migrating into the lung had a higher cellular level of AA and a larger AA pool in TG, we studied neutrophils isolated from the bronchoalveolar lavage (BAL) of patients with adult respiratory distress syndrome. BAL neutrophils had a fourfold increase in cellular AA as compared with blood neutrophils and contained 25% of their AA in TG versus 3% in blood neutrophils. BAL neutrophils also had a higher number of cytoplasmic lipid bodies (8 +/- 3/cell) relative to blood neutrophils (2 +/- 1/cell). High concentrations of free AA were also found in the cell-free BAL fluid of adult respiratory distress syndrome patients. To explore whether changes in BAL neutrophils may be due to the exposure of the cells to high concentrations of exogenous AA found in BAL, we incubated blood neutrophils in culture with AA (10-100 microM) for 24 h. Neutrophils supplemented with AA had a 10-fold increase in the amount of AA associated with TG and a sixfold increase in the number of lipid bodies. In addition, supplementation with AA induced a dose-dependent formation of hypodense cells. Taken together, these data indicate that human inflammatory cells undergo a fundamental and consistent remodeling of AA pools as they mature or enter the lung from the blood. These biochemical and morphological changes can be mimicked in vitro by exposing the cells to high levels of AA. This mechanism may be responsible for the changes in AA mobilization and eicosanoid metabolism observed in tissue inflammatory cells.
Lymphomatoid papulosis in children: a series of 25 cases
Authors: J. Miquel, S. Fraitag, D. Hamel‐Teillac, T. Molina, N. Brousse, Y. Prost, C. Bodemer
Journal: British Journal of Dermatology (2014)

Lymphomatoid papulosis (LyP) is an uncommon cutaneous T-cell lymphoproliferative disorder (CTLPD) rarely encountered in children.To specify characteristics of paediatric LyP and to describe both diagnostic difficulties and the course of the disease with the experience of 10 years' follow-up.This was a retrospective, single-centre study of 25 children diagnosed with LyP according to the 2008 World Health Organization guidelines, and a clinical and pathological correlation by two experts.The mean age at onset was 7·5 years. The lesions were mostly papulonodular with frequent pruritus (40%). Mucosal involvement was sometimes observed. A single ulcerative nodule was initially suggestive of a primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Pityriasis lichenoides was associated in 36% of cases, atopic dermatitis in 28% and nonspecific infections in 28%. Complete remission was observed in 44% of cases. Through the mean follow-up of 10 years, none of our patients have experienced lymphoma occurrence. Histopathological subtype A clearly predominated (82%). A marked eosinophilic infiltrate was present in 44% of cases and a cutaneous T-gamma clone in 40%. No correlation was observed between histopathological subtype, cutaneous clone or LyP clinical course.Paediatric LyP belongs to the group of CD30-positive CTLPDs including C-ALCL. Children have to be carefully followed up lifelong, even if the prognosis appears good. The high frequencies of an associated viral infection, atopic dermatitis, marked eosinophilic infiltrate and a good outcome suggest that paediatric LyP could be considered a reactional disease rather than a malignant disorder.
Genetically engineered mesenchymal stem cell therapy using self-assembling supramolecular hydrogels
Authors: Byung Woo Hwang, Su Jin Kim, Kyeng Min Park, Hyemin Kim, Junseok Yeom, Jeong-A Yang, Hyeonseon Jeong, Hyuntae Jung, Kimoon Kim, Young Chul Sung, Sei Kwang Hahn
Journal: Journal of Controlled Release (2015)
Confounding Effects in “A Six-Gene Signature Predicting Breast Cancer Lung Metastasis”
Authors: Aedín C. Culhane, John Quackenbush
Journal: Cancer Research (2009)

Abstract The majority of breast cancer deaths result from metastases rather than from direct effects of the primary tumor itself. Recently, Landemaine and colleagues described a six-gene signature purported to predict lung metastasis risk. They analyzed gene expression in 23 metastases from breast cancer patients (5 lung, 18 non-lung) identifying a 21-gene signature. Expression of 16 of these was analyzed in primary breast tumors from 72 patients with known outcome, and six were selected that were predictive of lung metastases: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E, and FERMT1. Despite the value of such a signature, our analysis indicates that this analysis ignored potentially important confounding factors and that their signature is instead a surrogate for molecular subtype. [Cancer Res 2009;69(18):7480–5]
Distribution of glycosaminoglycans in rat renal tubular epithelium.
Authors: T Weinstein, U Gafter, A Chagnac, E Skutelsky
Journal: Journal of the American Society of Nephrology (1997)

Polyanionic constituents of the glomerular capillary wall have been previously shown to have a primary role in the control of glomerular filtration. In the study presented here, the distribution and biochemical nature of polyanionic constituents in proximal (PT) and distal (DT) tubules have been investigated as possible determinants of tubulointerstitial function. For histochemical localization of sialic acid, paraffin sections were treated with Arachis hypogaea lectin (PNA) before and after neuraminidase treatment. Electron microscopic characterization of glycosaminoglycans (GAG) was performed on thin LR-white sections, using cationic colloidal gold (CCG) as an histochemical probe, and GAG-degrading enzymes. Without neuraminidase, PNA binded to collecting ducts but not to PT or DT. Neuraminidase pretreatment resulted in intense PNA binding to the tubulointerstitial blood vessels but only in mild apical tubular binding, which implies a lack of sialoglycoconjugates in the tubular basolateral membranes. In contrast, all PT and DT showed intense CCG binding to basolateral, but not to apical, membranes. All basement membranes showed CCG labeling, with considerable variations in labeling densities between PT (124 +/- 8.8/micron 2) and DT (52 +/- 1.8/micron 2), as well as between tubules and Bowman's capsule (P < 0.0001). Heparinase III treatment induced an almost complete loss of CCG binding in all basement and basolateral membranes, whereas chondroitinase ABC treatment led to a lesser but significant loss (P < 0.0001). The results indicate that rat tubulointerstitium expresses polyanionic constituents, consisting mainly of heparan and chondroitin sulfate. The role of these anionic sites in tubular function has yet to be clarified.
Insulin-like growth factor-1 mediates stretch-induced upregulation of myostatin expression in neonatal rat cardiomyocytes
Authors: K SHYU, W KO, W YANG, B WANG, P KUAN
Journal: Cardiovascular Research (2005)

Objectives: Myostatin, a negative regulator of muscle growth, is increased in hypertrophied and infarcted heart. However, the mechanism of regulation is not known. Mechanical stress is an important regulatory factor for cardiomyocyte growth. The aim of the study was to investigate the effect of cyclic stretch on the expression of myostatin gene in cardiomyocytes.
Ileostomy and excisional surgery for chronic inflammatory disease of the colon: A survey of one hospital region: Part I Results and complications of surgery
Authors: J. K. Ritchie
Journal: Gut (1971)

Four hundred and fifty-three patients who underwent ileostomy and excisional large bowel surgery for chronic inflammatory disease at two teaching hospitals and 35 non-teaching hospitals within the North East Metropolitan Hospital Region during the years 1955-66 were surveyed through a study of hospital case records. The surgical results and complications are presented in part I; a study of the health of these patients after their discharge from hospital is made in part II in an attempt to answer the question posed by many ileostomists, `Are we as healthy as other people?9
Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation
Authors: C.ézar E. Mesas, Carlo Pappone, Christopher C.E. Lang, Filippo Gugliotta, Takeshi Tomita, Gabriele Vicedomini, Simone Sala, Gabriele Paglino, Simone Gulletta, Amedeo Ferro, Vincenzo Santinelli
Journal: Journal of the American College of Cardiology (2004)
Perturbation of Cullin Deneddylation via Conditional Csn8 Ablation Impairs the Ubiquitin–Proteasome System and Causes Cardiomyocyte Necrosis and Dilated Cardiomyopathy in Mice
Authors: Huabo Su, Jie Li, Suchithra Menon, Jinbao Liu, Asangi R. Kumarapeli, Ning Wei, Xuejun Wang
Journal: Circulation Research (2010)

Rationale: Ubiquitin–proteasome system (UPS) dysfunction has been implicated in cardiac pathogenesis. Understanding how cardiac UPS function is regulated will facilitate delineating the pathophysiological significance of UPS dysfunction and developing new therapeutic strategies. The COP9 (constitutive photomorphogenesis mutant 9) signalosome (CSN) may regulate the UPS, but this has not been tested in a critical vertebrate organ. Moreover, the role of CSN in a postmitotic organ and the impact of cardiomyocyte-restricted UPS dysfunction on the heart have not been reported. Objective: We sought to determine the role of CSN-mediated deneddylation in UPS function and postnatal cardiac development and function. Methods and Results: Cardiomyocyte-restricted Csn8 gene knockout (CR-Csn8KO) in mice was achieved using a Cre-LoxP system. CR-Csn8KO impaired CSN holocomplex formation and cullin deneddylation and resulted in decreases in F-box proteins. Probing with a surrogate misfolded protein revealed severe impairment of UPS function in CR-Csn8KO hearts. Consequently, CR-Csn8KO mice developed cardiac hypertrophy, which rapidly progressed to heart failure and premature death. Massive cardiomyocyte necrosis rather than apoptosis appears to be the primary cause of the heart failure. This is because (1) massive necrotic cell death and increased infiltration of leukocytes were observed before increased apoptosis; (2) increased apoptosis was not detectable until overt heart failure was observed; and (3) cardiac overexpression of Bcl2 failed to ameliorate CR-Csn8KO mouse premature death. Conclusions: Csn8/CSN plays an essential role in cullin deneddylation, UPS-mediated degradation of a subset of proteins, and the survival of cardiomyocytes and, therefore, is indispensable in postnatal development and function of the heart. Cardiomyocyte-restricted UPS malfunction can cause heart failure.
Development of the CAT-ANX: A Computerized Adaptive Test for Anxiety
Authors: Robert D. Gibbons, David J. Weiss, Paul A. Pilkonis, Ellen Frank, Tara Moore, Jong Bae Kim, David J. Kupfer
Journal: American Journal of Psychiatry (2013)

The authors developed a computerized adaptive test for anxiety that decreases patient and clinician burden and increases measurement precision.A total of 1,614 individuals with and without generalized anxiety disorder from a psychiatric clinic and community mental health center were recruited. The focus of the present study was the development of the Computerized Adaptive Testing-Anxiety Inventory (CAT-ANX). The Structured Clinical Interview for DSM-IV was used to obtain diagnostic classifications of generalized anxiety disorder and major depressive disorder.An average of 12 items per subject was required to achieve a 0.3 standard error in the anxiety severity estimate and maintain a correlation of 0.94 with the total 431-item test score. CAT-ANX scores were strongly related to the probability of a generalized anxiety disorder diagnosis. Using both the Computerized Adaptive Testing-Depression Inventory and the CAT-ANX, comorbid major depressive disorder and generalized anxiety disorder can be accurately predicted.Traditional measurement fixes the number of items but allows measurement uncertainty to vary. Computerized adaptive testing fixes measurement uncertainty and allows the number and content of items to vary, leading to a dramatic decrease in the number of items required for a fixed level of measurement uncertainty. Potential applications for inexpensive, efficient, and accurate screening of anxiety in primary care settings, clinical trials, psychiatric epidemiology, molecular genetics, children, and other cultures are discussed.
Noninvasive Assessment of Plaque Characteristics With Multislice Computed Tomography Coronary Angiography in Symptomatic Diabetic Patients
Authors: Gabija Pundziute, Joanne D. Schuijf, J. Wouter Jukema, Eric Boersma, Arthur J.H.A. Scholte, Lucia J.M. Kroft, Ernst E. van der Wall, Jeroen J. Bax
Journal: Diabetes Care (2007)

OBJECTIVE—Cardiovascular events are high in patients with type 2 diabetes, whereas their risk stratification is more difficult. The higher risk may be related to differences in coronary plaque burden and composition. The purpose of this study was to evaluate whether differences in the extent and composition of coronary plaques in patients with and without diabetes can be observed using multislice computed tomography (MSCT). RESEARCH DESIGN AND METHODS—MSCT was performed in 215 patients (86 [40%] with type 2 diabetes). The number of diseased coronary segments was determined per patient; each diseased segment was classified as showing obstructive (≥50% luminal narrowing) disease or not. In addition, plaque type (noncalcified, mixed, and calcified) was determined. Plaque characteristics were compared in patients with and without diabetes. Regression analysis was performed to assess the correlation between plaque characteristics and diabetes. RESULTS—Patients with diabetes showed significantly more diseased coronary segments than nondiabetic patients (4.9 ± 3.5 vs. 3.9 ± 3.2, P = 0.03) with more nonobstructive (3.7 ± 3.0 vs. 2.7 ± 2.4, P = 0.008) plaques. Relatively more noncalcified (28 vs. 19%) and calcified (49 vs. 43%) and less mixed (23 vs. 38%) plaques were observed in patients with diabetes (P &amp;lt; 0.0001). Diabetes correlated with the number of diseased segments and nonobstructive, noncalcified, and calcified plaques. CONCLUSIONS—Differences in coronary plaque characteristics on MSCT were observed between patients with and without diabetes. Diabetes was associated with higher coronary plaque burden. More noncalcified and calcified plaques and less mixed plaques were observed in diabetic patients. Thus, MSCT may be used to identify differences in coronary plaque burden, which may be useful for risk stratification.
Anchoring Junctions As Drug Targets: Role in Contraceptive Development
Authors: Dolores D. Mruk, Bruno Silvestrini, C. Yan Cheng
Journal: Pharmacological Reviews (2008)

In multicellular organisms, cell-cell interactions are mediated in part by cell junctions, which underlie tissue architecture. Throughout spermatogenesis, for instance, preleptotene leptotene spermatocytes residing in the basal compartment of the seminiferous epithelium must traverse the blood-testis barrier to enter the adluminal compartment for continued development. At the same time, germ cells must also remain attached to Sertoli cells, and numerous studies have reported extensive restructuring at the Sertoli-Sertoli and Sertoli-germ cell interface during germ cell movement across the seminiferous epithelium. Furthermore, the proteins and signaling cascades that regulate adhesion between testicular cells have been largely delineated. These findings have unveiled a number of potential "druggable" targets that can be used to induce premature release of germ cells from the seminiferous epithelium, resulting in transient infertility. Herein, we discuss a novel approach with the aim of developing a nonhormonal male contraceptive for future human use, one that involves perturbing adhesion between Sertoli and germ cells in the testis.