tbuckley/cabot-search huggingface dataset:
Cytoplasmic Phospholipase A2 Levels Correlate with Apoptosis in Human Colon Tumorigenesis
Authors: Mei Dong, Michael Johnson, Anahita Rezaie, Jillian N.M. Ilsley, Masako Nakanishi, Melinda M. Sanders, Faripour Forouhar, Joel Levine, David C. Montrose, Charles Giardina, Daniel W. Rosenberg
Journal: Clinical Cancer Research (2005)

Abstract Colon cancers often display perturbations in arachidonic acid metabolism, with elevated levels of cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) production frequently observed. Whereas COX-2 and PGE2 are associated with cancer cell survival and tumor angiogenesis, arachidonic acid itself is a strong apoptotic signal that may facilitate cancer cell death. To further explore how cancer cells exploit the progrowth actions of prostaglandins while suppressing the proapoptotic actions of intracellular arachidonic acid, we determined the cytoplasmic phospholipase A2 (cPLA2) and COX-2 expression levels in a panel of human colon tumors by immunohistochemistry. Although high levels of cPLA2 and COX-2 expression are predicted to facilitate maximal prostaglandin production, tumors frequently displayed a high-COX-2/low-cPLA2 phenotype. The least represented phenotype was the high expression of cPLA2, a characteristic predicted to generate the highest levels of intracellular arachidonic acid. The potential proapoptotic role of cPLA2 was supported by a higher frequency of terminal deoxynucleotidyl transferase–mediated nick end labeling staining in cPLA2-positive tumors. Moreover, analysis of preneoplastic aberrant crypt foci from high-risk patients suggests that acquisition of the high-COX-2/low-cPLA2 phenotype may arise at an early stage of colon carcinogenesis. We additionally inhibited cPLA2 in HT-29 cells using antisense oligonucleotides. Our results indicate that cPLA2 plays an important role in tumor necrosis factor α–induced apoptosis in human colon cancer cells. Our data further support the model in which colon cancer growth is favored when intracellular arachidonic acid levels are suppressed by inhibition of cPLA2 or by a high-COX-2/low-cPLA2 phenotype.
Expression profiling of ion channel genes predicts clinical outcome in breast cancer
Authors: Jae-Hong Ko, Eun A Ko, Wanjun Gu, Inja Lim, Hyoweon Bang, Tong Zhou
Journal: Molecular Cancer (2013)

Ion channels play a critical role in a wide variety of biological processes, including the development of human cancer. However, the overall impact of ion channels on tumorigenicity in breast cancer remains controversial.We conduct microarray meta-analysis on 280 ion channel genes. We identify candidate ion channels that are implicated in breast cancer based on gene expression profiling. We test the relationship between the expression of ion channel genes and p53 mutation status, ER status, and histological tumor grade in the discovery cohort. A molecular signature consisting of ion channel genes (IC30) is identified by Spearman's rank correlation test conducted between tumor grade and gene expression. A risk scoring system is developed based on IC30. We test the prognostic power of IC30 in the discovery and seven validation cohorts by both Cox proportional hazard regression and log-rank test.22, 24, and 30 ion channel genes are found to be differentially expressed with a change in p53 mutation status, ER status, and tumor histological grade in the discovery cohort. We assign the 30 tumor grade associated ion channel genes as the IC30 gene signature. We find that IC30 risk score predicts clinical outcome (P < 0.05) in the discovery cohort and 6 out of 7 validation cohorts. Multivariate and univariate tests conducted in two validation cohorts indicate that IC30 is a robust prognostic biomarker, which is independent of standard clinical and pathological prognostic factors including patient age, lymph node status, tumor size, tumor grade, estrogen and progesterone receptor status, and p53 mutation status.We identified a molecular gene signature IC30, which represents a promising diagnostic and prognostic biomarker in breast cancer. Our results indicate that information regarding the expression of ion channels in tumor pathology could provide new targets for therapy in human cancers.
Irritable bowel syndrome
Authors: Paul Enck, Qasim Aziz, Giovanni Barbara, Adam D. Farmer, Shin Fukudo, Emeran A. Mayer, Beate Niesler, Eamonn M. M. Quigley, Mirjana Rajilić-Stojanović, Michael Schemann, Juliane Schwille-Kiuntke, Magnus Simren, Stephan Zipfel, Robin C. Spiller
Journal: Nature Reviews Disease Primers (2016)
Statins in the Prevention of Prostate Cancer Recurrence: Are Certain Biases Exaggerating the Results?
Authors: Laurent Azoulay, Samy Suissa
Journal: Journal of Clinical Oncology (2010)

witha57%riskreduction(hazardratio,0.43;95%CI,0.25to0.73)in freedom from biochemical failure and a 43% risk reduction (hazard ratio, 0.57; 95% CI, 0.39 to 0.84) in relapse-free survival. These impressive risk reductions may have been exaggerated by certain biases. First, as reported by the authors, patients who used statins had more favorable pretreatment characteristics than nonstatin users. Thus, it seems that statin users were systematically different from nonstatin users. Although the authors adjusted for some potential confounders, it is possible that residual confounding may still be present. With such large baseline differences, techniques such as propensity scores with tight matching may be more accurate. 2 Second, patients were considered continuously exposed to statins from the time they received a prescription. This simplistic definition does not consider discontinuations, which are likely to have occurred during the long follow-up of this study. Finally, for patients who received statins at some point during follow-up, the time period between cohort entry (end of radiotherapy) and first statin prescription is called immortal because no events could have occurred during this time period. Patients experiencing an event before initiating statin therapy were necessarily included in the unexposed group. This immortal person-time period should have been accounted for as unexposed until the time of statin initiation and, subsequently, as exposed, using statistical techniques for time-dependent exposures. 3 However, given
Metronidazole and antibiotic-associated colitis.
Authors: J R Brown
Journal: BMJ (1981)

isolation of G vaginalis together with the significantly higher isolation rate among heterosexual men suggests that while gardnerella infection of the male urethra is unlikely, colonisation of this site may be an important factor in the epidemiology of "non-specific" vaginitis.This should be borne in mind when setting up and evaluating trials of therapy for this condition.
Mast cells/basophils in the peripheral blood of allergic individuals who are HIV-1 susceptible due to their surface expression of CD4 and the chemokine receptors CCR3, CCR5, and CXCR4
Authors: Yong Li, Lixin Li, Robert Wadley, Stephen W. Reddel, Jian C. Qi, Con Archis, Andrew Collins, Elizabeth Clark, Margaret Cooley, Steven Kouts, Hassan M. Naif, Mohammed Alali, Anthony Cunningham, Guang W. Wong, Richard L. Stevens, Steven A. Krilis
Journal: Blood (2001)
John T D Attenborough
Authors: J. T. D. A. B. Griffiths
Journal: BMJ (2013)

Having qualified at the age of 22, John T D Attenborough joined the army in 1943. He served in the Middle East, Italy, Holland, Germany, and finally, as staff surgeon, in Peshawar, India. In 1945, he met up with his fiancee, Frances, after a separation of two years as she had been in India and Burma with the Princess Mary’s Royal Air Force Nursing Service (PMRAFNS). They were married in Peshawar. After demobilisation in 1946, John joined the family …
Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma
Authors: Luis F. Porrata, Morie A. Gertz, David J. Inwards, Mark R. Litzow, Martha Q. Lacy, Ayalew Tefferi, Dennis A. Gastineau, Angela Dispenzieri, Stephen M. Ansell, Ivana N. M. Micallef, Susan M. Geyer, Svetomir N. Markovic
Journal: Blood (2001)
Asialoerythropoietin Prevents Contrast-Induced Nephropathy
Authors: Yukiyo Yokomaku, Toshiro Sugimoto, Shinji Kume, Shin-ichi Araki, Keiji Isshiki, Masami Chin-Kanasaki, Masayoshi Sakaguchi, Norihisa Nitta, Masakazu Haneda, Daisuke Koya, Takashi Uzu, Atsunori Kashiwagi
Journal: Journal of the American Society of Nephrology (2008)

Strategies to prevent contrast-induced nephropathy (CIN) are suboptimal. Erythropoietin was recently found to be cytoprotective in a variety of nonhematopoietic cells, so it was hypothesized that the nonhematopoietic erythropoietin derivative asialoerythropoietin would prevent CIN. Nephropathy was induced in rats by injection of the radiocontrast medium Ioversol in addition to inhibition of prostaglandin and nitric oxide synthesis. Administration of a single dose of asialoerythropoietin before the induction of nephropathy significantly attenuated the resulting renal dysfunction and histologic renal tubular injury. Contrast-induced apoptosis of renal tubular cells was inhibited by asialoerythropoietin both in vivo and in vitro, and this effect was blocked by a Janus kinase 2 (JAK2) inhibitor in vitro. Furthermore, phospho-JAK2/signal transducer and activator of transcription 5 (STAT5) and heat-shock protein 70 increased after injection of asialoerythropoietin, suggesting that the effects of asialoerythropoietin may be mediated by the activation of the JAK2/STAT5 pathway. Overall, these findings suggest that asialoerythropoietin may have potential as a new therapeutic approach to prevent CIN given its ability to preserve renal function and directly protect renal tissue.
The Impact of a Decade of Changing Treatment on Rates of Severe Hypoglycemia in a Population-Based Cohort of Children With Type 1 Diabetes
Authors: Max K. Bulsara, C. D’Arcy J. Holman, Elizabeth A. Davis, Timothy W. Jones
Journal: Diabetes Care (2004)

OBJECTIVE—To determine the impact of changes to treatment on the incidence of severe hypoglycemia and its risk factors in a large population-based cohort of children with type 1 diabetes. RESEARCH DESIGN AND METHODS—The cohort consisted of 1,335 children (age at entry 9.5 ± 4.3 years [mean ± SD], range 0–18), yielding 6,928 patient-years of data. The mean follow-up period was 4.7 ± 3.1 years (range 0–10.7). Prospective assessment of severe hypoglycemia (an event leading to loss of consciousness or seizure) and associated clinical factors and outcomes was made between 1992 and 2002. Patients were reviewed every 3 months. Data were analyzed using the negative binomial regression model. RESULTS—A total of 944 severe events were recorded. The incidence of severe hypoglycemia increased significantly by 29% per year for the first 5 years but appeared to plateau over the last 5 years. The overall average HbA1c significantly decreased (by 0.2% per year) over the whole follow-up period. An increased risk of severe hypoglycemia was associated with lower HbA1c, younger age, higher insulin dose, male sex, and lower parental socioeconomic status. Of insulin therapies, only pump treatment was associated with reduced rates of severe hypoglycemia. CONCLUSIONS—Severe hypoglycemia remains a major problem for children and adolescents with type 1 diabetes. Recent approaches to therapy may be allowing a degree of improved control without the expected increased risk of severe hypoglycemia but further monitoring will be important.
Synovectomy of the Knee in Rheumatoid Arthritis
Authors: J. Stevens, G. A. Whitefield
Journal: Annals of the Rheumatic Diseases (1966)

<h3></h3> Sunday, April 2, 2006 - 3:15 to 5:15 pm Room 274/276 - Moscone Convention Center Organizer Name: Virginia M. Miller, PhD <i>Mayo Clinic College of Medicine,</i> Rochester, Minnesota Karim Benzerara, PhD Stanford University John C. Lieske, MD Mayo Clinic College of Medicine Neva Ciftcioglu, PhD National Aeronautics and Space Administration Johnson Space Center Neal Chen, MD Indiana University School of Medicine Linda Demer, MD, PhD School of Medicine University of California, Los Angeles Discussant: Howard H.T. Hsu, PhD Department of Pathology University of Kansas <i>Abstract:</i> It is becoming increasingly clear that the pathophysiology of calcification within diseased human tissues is complex. Inflammation appears to be associated with many calcific processes, including advanced atherosclerosis, nephrolithiasis, and calciphylaxis of end-stage renal disease. In all three instances characteristic cellular responses could potentially either mediate or ameliorate the calcific response. Increasingly, microorganisms are being identified as an unexpected cause of disease, with a recent well-known example being the association of <i>H. pylori</i> and peptic ulcer. The possibility that microorganisms contribute to pathologic calcification and the associated inflammation is, however, controversial. This symposium will examine evidence for three possible but not mutually exclusive mechanisms of pathologic calcification: (1) processes that drive and influence <i>inorganic</i> crystallization; (2) the mechanisms by which cells mediate crystallization, including cell transdifferentiation; and (3) evidence for the presence of calcifying microorganisms within diseased human kidneys and arteries. The program will conclude with a panel discussion led by a moderator who will comment on divergent points from the perspective of a pathologist.
The risk of chronic traumatic brain injury in professional boxing: change in exposure variables over the past century
Authors: H Clausen, P McCrory, V Anderson
Journal: British Journal of Sports Medicine (2005)

Objectives: To determine if boxing exposure has changed over time and hence if current professional boxers are at the same risk of developing chronic traumatic brain injury (CTBI) as historical controls. Design: Literature review of published studies and analysis of data of active professional boxers. Subjects: Professional boxers in the United Kingdom and Australia. Main outcome measures: Boxing history and participation in sparring and professional bouts. Results: Since the 1930s, the average duration of a professional boxer’s career has dropped from 19 years to five years, and the mean number of career bouts has reduced from 336 to 13. This is despite no significant decline in participation rates from 1931 until 2002. Conclusions: The incidence of boxing related CTBI will diminish in the current era of professional boxing because of the reduction in exposure to repetitive head trauma and increasing medical monitoring of boxers, with preparticipation medical and neuroimaging assessments resulting in the detection of early and potentially pre-symptomatic cases of CTBI.
Evolution, the criterion problem, and complexity
Authors: Stephen M. Colarelli
Journal: Behavioral and Brain Sciences (2000)

Cultural and dual-inheritance models of evolution present ambiguities not typically present in biological evolution. Criteria and the ability to specify the adaptive value of a trait or cultural practice become less clear. When niche construction is added, additional challenges and ambiguities arise. Its dynamic nature increases the difficulty of identifying adaptations, tracing the causal path between a trait and its function, and identifying the links between environmental demands and the development of adaptations.
Laser angioplasty with a contact probe for the treatment of peripheral vascular disease
Authors: E PILGER, J LAMMER, R KLEINERT, W ASCHER, H BERTUCH
Journal: Cardiovascular Research (1988)

Percutaneous transluminal laser angioplasty was carried out for the dilatation of 30 completely occluded peripheral arterial segments and three subtotal stenoses. A neodymium-YAG laser and an optical fibre delivery system with a sapphire tip were used. All three arterial stenoses and 26 of the 30 occluded arterial segments were successfully dilated. In 20 patients additional dilatation was carried out with a balloon catheter. Laser angioplasty failed to recanalise four occlusions, and vessel leakage without clinical consequences occurred in one patient. Reocclusion occurred within 48 h in two patients and after five months in one patient during a follow up period of at least six months. It is concluded that percutaneous transluminal laser angioplasty using direct contact with a sapphire tip is highly effective (89% success rate) in reopening peripheral vascular occlusions. The procedure is safe, and reocclusion of vessels is rare during the six month follow up period.
A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial)
Authors: P. Quartier, F. Allantaz, R. Cimaz, P. Pillet, C. Messiaen, C. Bardin, X. Bossuyt, A. Boutten, J. Bienvenu, A. Duquesne, O. Richer, D. Chaussabel, A. Mogenet, J. Banchereau, J.-M. Treluyer, P. Landais, V. Pascual
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> To assess the efficacy of the interleukin 1 receptor antagonist anakinra in systemic-onset juvenile idiopathic arthritis (SJIA). <h3>Methods</h3> A multicentre, randomised, double-blind, placebo-controlled trial was conducted. The primary objective was to compare the efficacy of a 1-month treatment with anakinra (2 mg/kg subcutaneous daily, maximum 100 mg) with a placebo between two groups each with 12 patients with SJIA. Response was defined by a 30% improvement of the paediatric American College of Rheumatology criteria for JIA, resolution of systemic symptoms and a decrease of at least 50% of both C-reactive protein and erythrocyte sedimentation rate compared with baseline. After month 1 (M1), patients taking placebo were switched to anakinra. Secondary objectives included tolerance and efficacy assessment for 12 months, and analyses of treatment effect on blood gene expression profiling. <h3>Results</h3> At M1, 8/12 responders were receiving anakinra and 1 responder receiving placebo (p=0.003). Ten patients from the placebo group switched to anakinra; nine were responders at M2. Between M1 and M12, six patients stopped treatment owing to an adverse event (n=2), lack of efficacy (n=2) or a disease flare (n=2). Blood gene expression profiling at enrolment and at 6 months9 follow-up showed one set of dysregulated genes that reverted to normal values in the clinical responders and a different set, including interferon (IFN)-inducible genes, that was induced by anakinra. <h3>Conclusions</h3> Anakinra treatment is effective in SJIA, at least in the short term. It is associated with normalisation of blood gene expression profiles in clinical responders and induces a de novo IFN signature. Trial Registration Number: NCT00339157.
Cardiopulmonary exercise testing following hay exposure challenge in farmer's lung
Authors: M Schwaiblmair, T Beinert, C Vogelmeier, G Fruhmann
Journal: European Respiratory Journal (1997)

In patients experiencing an acute episode of hypersensitivity pneumonitis (HP), the alveoli and interstitium show a marked inflammation. The effects of this infiltration with effector cells on gas exchange and the cardiopulmonary system are not well characterized, and there are no data regarding cardiopulmonary exercise testing during hypersensitivity pneumonitis. The aim of this study was to gain new insights into the pathophysiology of acute farmer's lung using cardiopulmonary exercise testing. Cardiopulmonary exercise testing was performed in patients who had farmer's lung (n=21) before and 4 h after a standardized exposure with mouldy hay. Farmers who were asymptomatic for this condition (n=15) served as controls. At baseline, patients who had farmer's lung had a decreased breathing reserve and a greater alveolar to arterial oxygen difference. Following exposure, all of these patients developed hypersensitivity pneumonitis. Compared to the asymptomatic farmers, they showed an increase of alveolar to arterial oxygen difference and functional dead space ventilation during exercise and a reduction of the breathing reserve. In addition, 40% of the asymptomatic farmers demonstrated a pathological increase of the alveolar to arterial oxygen difference during exercise following exposure. In conclusion, our data signify that acute hypersensitivity pneumonitis induces significant changes in pulmonary gas exchange during exercise. Cardiopulmonary exercise testing may help to identify individuals with possible subclinical farmer's lung disease.
Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer
Authors: Sofia Torres, Rubén A. Bartolomé, Marta Mendes, Rodrigo Barderas, M. Jesús Fernandez-Aceñero, Alberto Peláez-García, Cristina Peña, María Lopez-Lucendo, Roi Villar-Vázquez, Antonio García de Herreros, Felix Bonilla, J. Ignacio Casal
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Cancer-associated fibroblasts (CAF) are essential components of the stroma that play a critical role in cancer progression. This study aimed to identify novel CAFs markers that might contribute to the invasion and the prognosis of colorectal cancer. Experimental Design: The azoxymethane/dextran sodium sulfate mouse model of sporadic colon cancer represents an adequate source for the isolation of CAFs and normal fibroblasts. By using the explants technique, we purified CAFs and normal fibroblasts from colon tissues. Whole-cell extracts and supernatants were subjected to in-depth quantitative proteomic analysis by tandem mass spectrometry. Further validations of upregulated proteins in CAFs were carried out by chemokine microarray and immunohistochemical analyses of mouse and human tissues. Results: Using a fold-change of 1.4 or more, we found 132 and 125 differentially expressed proteins in whole-cell extracts and supernatants, respectively. We found CAFs-associated proinflammatory and desmoplastic signatures. The proinflammatory signature was composed of several cytokines. Among them, CCL2 and CCL8 caused an increase in migration and invasion of colorectal cancer KM12 cells. The desmoplastic signature was composed of 30 secreted proteins. In mouse and human samples, expression of LTBP2, CDH11, OLFML3, and, particularly, FSTL1 was significantly increased in the tumoral stroma, without significant expression in the cancer epithelial cells. The combination of CALU and CDH11 stromal expression showed a significant association with disease-free survival and poor prognosis. Conclusion: We have identified LTBP2, CDH11, OLFML3, and FSTL1 as selective biomarkers of cancer stroma, and CALU and CDH11 as candidate stromal biomarkers of prognostic significance in colon cancer. Clin Cancer Res; 19(21); 6006–19. ©2013 AACR.
Smooth-Muscle–Specific Gene Transfer with the Human Maxi-K Channel Improves Erectile Function and Enhances Sexual Behavior in Atherosclerotic Cynomolgus Monkeys
Authors: George J. Christ, Karl-Erik Andersson, Koudy Williams, Weixin Zhao, Ralph D'Agostino, Jay Kaplan, Tamer Aboushwareb, James Yoo, Giulia Calenda, Kelvin P. Davies, Rani S. Sellers, Arnold Melman
Journal: European Urology (2008)