tbuckley/cabot-search huggingface dataset:
Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study
Authors: Carlos Martinez, Stephan Rietbrock, Lesley Wise, Deborah Ashby, Jonathan Chick, Jane Moseley, Stephen Evans, David Gunnell
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To compare the risk of non-fatal self harm and suicide in patients taking selective serotonin reuptake inhibitors (SSRIs) with that of patients taking tricyclic antidepressants, as well as between different SSRIs and different tricyclic antidepressants. <b>Design</b> Nested case-control study. <b>Setting</b> Primary care in the United Kingdom. <b>Participants</b> 146 095 individuals with a first prescription of an antidepressant for depression. <b>Main outcome measures</b> Suicide and non-fatal self harm. <b>Results</b> 1968 cases of non-fatal self harm and 69 suicides occurred. The overall adjusted odds ratio of non-fatal self harm was 0.99 (95% confidence interval 0.86 to 1.14) and that of suicide 0.57 (0.26 to 1.25) in people prescribed SSRIs compared with those prescribed tricyclic antidepressants. We found little evidence that associations differed over time since starting or stopping treatment. We found some evidence that risks of non-fatal self harm in people prescribed SSRIs compared with those prescribed tricyclic antidepressants differed by age group (interaction P = 0.02). The adjusted odds ratio of non-fatal self harm for people prescribed SSRIs compared with users of tricylic antidepressants for those aged 18 or younger was 1.59 (1.01 to 2.50), but no association was apparent in other age groups. No suicides occurred in those aged 18 or younger currently or recently prescribed tricyclic antidepressants or SSRIs. <b>Conclusion</b> We found no evidence that the risk of suicide or non-fatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants. We found some weak evidence of an increased risk of non-fatal self harm for current SSRI use among those aged 18 or younger. However, preferential prescribing of SSRIs to patients at higher risk of suicidal behaviour cannot be ruled out.
The SV40 Large T Antigen-p53 Complexes Bind and Activate the Insulin-like Growth Factor-I Promoter Stimulating Cell Growth
Authors: Maurizio Bocchetta, Sandra Eliasz, Melissa Arakelian De Marco, Jennifer Rudzinski, Lei Zhang, Michele Carbone
Journal: Cancer Research (2008)

Inactivation of cellular p53 is a crucial step in carcinogenesis. Accordingly, p53 is inactivated in most human cancers by different mechanisms. In cells infected with DNA tumor viruses, p53 is bound to the viral tumor antigens (Tag). The current "dogma" views the Tag-p53 complexes as a way of sequestering and inactivating p53. Using primary human cells and SV40-transformed human cells, we show that in addition to inactivating p53 tumor suppressor activities, the Tag-p53 complex has growth stimulatory activities that are required for malignant cell growth. We found that in human cells, Tag-p53 complexes regulate transcription of the insulin-like growth factor I (IGF-I) gene by binding to the IGF-I promoter together with pRb and p300. Depletion of p53 leads to structural rearrangements of this multiprotein complex, resulting in IGF-I promoter transcriptional repression and growth arrest. Our data provide a novel mechanistic and biological interpretation of the p53-Tag complexes and of DNA tumor virus transformation in general. In the model we propose, p53 is not a passive inactive partner of Tag. Instead the p53-Tag complex promotes malignant cell growth through its ability to activate the IGF-I signaling pathway.
Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling
Authors: Mark Harris, Carl Aschkenasi, Carol F. Elias, Annie Chandrankunnel, Eduardo A. Nillni, Christian Bjørbæk, Joel K. Elmquist, Jeffrey S. Flier, Anthony N. Hollenberg
Journal: Journal of Clinical Investigation (2001)

Starvation causes a rapid reduction in thyroid hormone levels in rodents. This adaptive response is caused by a reduction in thyrotropin-releasing hormone (TRH) expression that can be reversed by the administration of leptin. Here we examined hypothalamic signaling pathways engaged by leptin to upregulate TRH gene expression. As assessed by leptin-induced expression of suppressor of cytokine signaling-3 (SOCS-3) in fasted rats, TRH neurons in the paraventricular nucleus are activated directly by leptin. To a greater degree, they also contain melanocortin-4 receptors (MC4Rs), implying that leptin can act directly or indirectly by increasing the production of the MC4R ligand, alpha-melanocyte stimulating hormone (alpha-MSH), to regulate TRH expression. We further demonstrate that both pathways converge on the TRH promoter. The melanocortin system activates the TRH promoter through the phosphorylation and DNA binding of the cAMP response element binding protein (CREB), and leptin signaling directly regulates the TRH promoter through the phosphorylation of signal transducer and activator of transcription 3 (Stat3). Indeed, a novel Stat-response element in the TRH promoter is necessary for leptin's effect. Thus, the TRH promoter is an ideal target for further characterizing the integration of transcriptional pathways through which leptin acts.
Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells
Authors: Francesca Di Sole, Robert Cerull, Soeren Petzke, Valeria Casavola, Gerhard Burckhardt, Corinna Helmle-Kolb
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Regulation of renal apical Na+/H+ exchanger 3 (NHE3) activity by adenosine has been suggested to contribute to acute control of mammalian Na+ homeostasis. The mechanism by which adenosine controls NHE3 activity in a renal cell line was examined. The adenosine analog, N6-cyclopentyladenosine (CPA) exerts a bimodal effect on NHE3: CPA concentrations >10−8 M inactivate NHE3, whereas concentrations <10−8 M stimulate NHE3 activity. Acute CPA-induced control of NHE3 was blocked by antagonists of A1 adenosine receptors and inhibition of phospholipase C, pretreatment with BAPTA-AM (chelator of cellular calcium), and exposure to pertussis toxin. Stimulatory and to some extent also inhibitory CPA concentrations attenuated 8-bromo-cAMP and dopamine-mediated inhibition of NHE3. BAPTA eliminated the ability of a stimulatory dose of CPA to attenuate 8-bromo-cAMP–induced suppression of NHE3 activity. Upon inhibition of protein kinase C, CPA at an inhibitory dose provoked activation of NHE3, which is partially reverted by 8-bromo-cAMP and suppressed by pre-incubation with BAPTA-AM. Cytochalasin B, an actin-modifying agent, selectively prevented downregulation but did not affect upregulation of NHE3 activity by CPA. In conclusion, these observations demonstrate that (1) CPA modulates NHE3 activity by elevation of cellular Ca2+ exerting a negative control on adenylate cyclase activity, (2) protein kinase C is the determining factor leading to CPA-induced downregulation of NHE3 activity, and (3) alterations of surface NHE3 abundance may contribute to A1 adenosine receptor–dependent inhibition of NHE3 activity. E-mail: [email protected]
The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas
Authors: Chitralekha Bhattacharya, Xiaolei Wang, Dorothea Becker
Journal: Molecular Cancer (2012)

Abstract Background Despite continuous efforts to identify genes that are pivotal regulators of advanced melanoma and closely related to it, to determine which of these genes have to be blocked in their function to keep this highly aggressive disease in check, it is far from clear which molecular pathway(s) and specific genes therein, is the Achilles’ heel of primary and metastatic melanoma. In this report, we present data, which document that the DEAD-box helicase DDX11, which is required for sister chromatid cohesion, is a crucial gatekeeper for melanoma cell survival. Methods Performing immunohistochemistry and immunoblot analysis, we determined expression of DDX11 in melanoma tissues and cell lines. Following transfection of melanoma cells with a DDX11-specific siRNA, we conducted a qPCR analysis to determine downregulation of DDX11 in the transfected melanoma cells. In subsequent studies, which focused upon an analysis of fluorescently labeled as well as Giesma-stained chromosome spreads, a proliferation analysis and apoptosis assays, we determined the impact of suppressing DDX11 expression on melanoma cells representing advanced melanoma. Result The findings of the study presented herein document that DDX11 is upregulated with progression from noninvasive to invasive melanoma, and that it is expressed at high levels in advanced melanoma. Furthermore, and equally important, we demonstrate that blocking the expression of DDX11 leads not only to inhibition of melanoma cell proliferation and severe defects in chromosome segregation, but also drives melanoma cells rapidly into massive apoptosis. Conclusion To date, little is known as to whether helicases play a role in melanoma development and specifically, in the progression from early to advanced melanoma. In this report, we show that the helicase DDX11 is expressed at high levels in primary and metastatic melanoma, and that interfering with its expression leads to severe chromosome segregation defects, telomere shortening, and massive melanoma cell apoptosis. These findings suggest that DDX11 could be an important candidate for molecular targeted therapy for advanced melanoma.
Ten-year pathological study of Beall mitral valve prostheses.
Authors: K S Chang, J Fernandez, S D Cha, S S Yang
Journal: Thorax (1982)

Detailed pathological studies are reported on 20 cloth-covered Beall mitral valve prostheses, which had to be removed for valve failure nine months to 10 years after implantation. Results in all patients except one indicated that there was a progressive and persistent granulomatous reaction that continued up to at least 10 years. Although the rate of tissue ingrowth into the valve decreased with time, the total volume of tissue formation increased. Cloth wear and disruption and deformity of the teflon discs was frequently seen. In these 20 valves the desired result--namely, the complete and smooth endothelialisation of the prosthesis--was certainly not achieved.
Foregut duplication cyst presenting as neonatal respiratory distress and haemoptysis.
Authors: D P Burgner, R Carachi, T J Beattie
Journal: Thorax (1994)

Rhazes was born at Ray near modern Teheran in 864 AD. He wrote over 200 scientific treatises, many of which had a major impact on European medicine. His best known manuscript is <i>Liber Continens</i>, a medical encyclopedia. Herein are described Rhazes's contributions to neurology, focusing on his description of cranial and spinal cord nerves and his clinical case reports, which illustrate his use of neuroanatomy to localize lesions. Relevant passages from facsimiles of the manuscripts <i>Kitab al-Hawi</i> (<i>Liber Continens</i>) and <i>Al-Mansuri Fi At-Tibb</i> (<i>Liber Al Mansoori</i>) were translated, reviewed, and used as references. In addition, Medline, Web, and manuscript searches on Rhazes and the history of medieval and Islamic medicine and neurology were conducted. Rhazes stated that nerves had motor or sensory functions, describing 7 cranial and 31 spinal cord nerves. He assigned a numerical order to the cranial nerves from the optic to the hypoglossal nerves. He classified the spinal nerves into 8 cervical, 12 thoracic, 5 lumbar, 3 sacral, and 3 coccygeal nerves. Rhazes showed an outstanding clinical ability to localize lesions, prognosticate, and describe therapeutic options and reported clinical observations, emphasizing the link between the anatomic location of a lesion and the clinical signs. Rhazes was a pioneer in applied neuroanatomy. He combined a knowledge of cranial and spinal cord nerve anatomy with an insightful use of clinical information to localize lesions in the nervous system.
Calcified tendinitis: a review.
Authors: G Faure, G Daculsi
Journal: Annals of the Rheumatic Diseases (1983)

Calcified tendinitis in clinical practiceCalcified tendinitis is a common disorder.Many names have been used to describe it: some of them, such as 'calcific periarthritis', emphasise the extra-articular site of the deposit; others, such as 'periarticular apatite deposition', mention the nature of the compound found in the calcification; and more recent ones, such as
Microvolt T-Wave Alternans and the Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction
Authors: Daniel M. Bloomfield, J. Thomas Bigger, Richard C. Steinman, Pearila B. Namerow, Michael K. Parides, Anne B. Curtis, Elizabeth S. Kaufman, Jorge M. Davidenko, Timothy S. Shinn, John M. Fontaine
Journal: Journal of the American College of Cardiology (2005)
Results of non invasive ventilation in patients with acute hypercapnic ventilatory failure and obesity hypoventilation syndrome (OHS)
Authors: Jesus Fernando Sanchez Gomez, Virginia Almadana Pacheco, Ana Gomez Bastero Fernandez, Patricia Guerrero Zamora, Jose Maria Benitez Moya, Agustin Valido Morales, Teodoro Montemayor Rubio
Journal: European Respiratory Journal (2012)

Background:  The NIV is used in patients with OHS presenting with hypercapnic respiratory failure. Few studies examine the evolution and impact after starting this therapy in this patient group.  Objective:  - Evaluate the result of NIV started in obese patients in acute hypercapnic respiratory failure and its prognosis consequences.  - Assess the impact of long-term NIV.  Material and Methods:  Observational study with consecutive inclusion of obese patients with acute hypercapnic respiratory failure treated with NIV from Feb 08 to Jun 11.  Results:  At the moment of discharge no differences were observed in commorbidities, clinical data an blood gases between patients with or without NIV treatment. Patients discharged with NIV had tolerated better and had more total hours of use with BiPAP than those discharged without it.  Compliance measured at 3 months of onset and the last recorded was 4.51±3,30 hours and 5.12±3,42 hours daily.  Conclusions:  1.- Non invasive ventilation is an effective tool for treating patients with obesity-hypoventilation syndrome and hypercapnic respiratory failure.  2.-Patients who received home treatment with NIV survived longer than those who didn9t. This forces us to review NIV treatment at discharge.
Alveolar nitric oxide<i>versus</i>measures of peripheral airway dysfunction in severe asthma
Authors: I. H. van Veen, P. J. Sterk, R. Schot, S. A. Gauw, K. F. Rabe, E. H. Bel
Journal: European Respiratory Journal (2006)

Alveolar nitric oxide (NO) is a measure of peripheral airway inflammation in asthma, potentially associated with disease severity. The relationship between alveolar NO and physiological tests of peripheral airway (dys)function has not been investigated. The present authors hypothesised that peripheral airway inflammation and dysfunction are inter-related and associated with asthma severity. Alveolar NO was compared between 17 patients with mild-to-moderate asthma and 14 patients with severe asthma and related to total lung capacity (TLC), residual volume (RV)/TLC, thoracic gas volume (FRC), slope of the single breath nitrogen washout curve (dN 2 ), closing capacity (CC)/TLC and fall in forced vital capacity at the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second. In patients with severe asthma, strong correlations were found between alveolar NO and RV/TLC % pred, FRC % pred, dN 2 , and CC/TLC. Patients with oral steroid-dependent asthma had higher alveolar NO levels (2.7 ppb) compared with the other patients with severe (0.6 ppb) and mild-to-moderate asthma (0.3 ppb). The present authors conclude that alveolar nitric oxide is closely related to parameters of peripheral airway dysfunction in patients with severe asthma, and that oral steroid-dependent asthmatics have more peripheral airway disease than nonsteroid-dependent asthmatics. This suggests that patients on chronic oral steroid treatment have more extensive disease and require additional anti-inflammatory treatment to better target the peripheral airways.
Pathobiology of biliary epithelia and cholangiocarcinoma: Proceedings of the Henry M. and Lillian Stratton basic research single-topic conference
Authors: Alphonse E. Sirica, Michael H. Nathanson, Gregory J. Gores, Nicholas F. LaRusso
Journal: Hepatology (2008)

In June 2008, the American Association for the Study of Liver Diseases (AASLD) sponsored the Henry M. and Lillian Stratton Basic Research Single-Topic Conference on the Pathobiology of Biliary Epithelia and Cholangiocarcinoma, which was held in Atlanta, GA. Attendees from 12 different countries participated in this conference, making it a truly international scientific event. Both oral and poster presentations were given by multidisciplinary experts, who highlighted important areas of current basic and translational research on biliary epithelial cell biology and pathophysiology, and on the etiology, cellular and molecular pathogenesis, and target-based therapy of cholangiocarcinoma. The specific goals and objectives of the conference were: (1) to advance knowledge of basic and molecular mechanisms underlying developmental and proliferative disorders of the biliary tract; (2) to foster a better and more comprehensive understanding of mechanisms regulating biliary epithelial (cholangiocyte) growth and transport, signaling, cell survival, and abnormalities that result in disease; and (3) to understand basic mechanisms of cholangiocarcinoma development and progression, with the added goal of identifying and exploiting potentially critical molecular pathways that may be targeted therapeutically. A number of interrelated themes emerged from the oral and poster sessions that affected current understandings of the complex organization of transcriptional and signaling mechanisms that regulate bile duct development, hepatic progenitor cell expansion, cholangiocyte secretory functions and proliferation, and mechanisms of cholangiocarcinogenesis and malignant cholangiocyte progression. Most notable were the critical questions raised as to how best to exploit aberrant signaling pathways associated with biliary disease as potential targets for therapy.
Polymorphism of the Serotonin Transporter Gene and Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease
Authors: Saadia Eddahibi, Ari Chaouat, Nicholas Morrell, Elie Fadel, Claire Fuhrman, Anne-Sophie Bugnet, Philippe Dartevelle, Bruno Housset, Michel Hamon, E. Weitzenblum, Serge Adnot
Journal: Circulation (2003)

The serotonin transporter (5-HTT) is involved in the pulmonary artery smooth muscle hyperplasia that leads to pulmonary hypertension (PH). Because hypoxia and 5-HTT gene polymorphism control 5-HTT expression, we examined 5-HTT gene polymorphism and PH in hypoxemic patients with advanced chronic obstructive pulmonary disease (COPD).In 103 patients with COPD recruited in France (n=67) and the UK (n=36), we determined 5-HTT gene polymorphism and pulmonary artery pressure (PAP) measured during right heart catheterization (France) or Doppler echocardiography (UK). Ninety-eight subjects from the 2 countries served as control subjects. The distribution of 5-HTT gene polymorphism did not differ between patients and control subjects. In patients carrying the LL genotype, which is associated with higher levels of 5-HTT expression in pulmonary artery smooth muscle cells than the LS and SS genotypes, PH was more severe than in LS or SS patients. Mean PAP values in patients from France with the LL, LS, and SS genotypes were 34+/-3, 23+/-1, and 22+/-2 mm Hg (mean+/-SEM), respectively (P<0.01). Corresponding systolic PAP values in the UK were 40+/-3, 28+/-3, and 24+/-3 mm Hg, respectively (P<0.01). Compared with control subjects, platelet 5-HTT protein was increased in COPD patients in proportion to the hypoxemia level, and strong 5-HTT immunostaining was observed in remodeled pulmonary arteries from COPD patients.5-HTT gene polymorphism appears to determine the severity of PH in hypoxemic patients with COPD. Because PH is an important prognostic factor in this disease, recognition of patients at risk for PH should be helpful in managing COPD.
<i>STAT3</i>Mutations in the Hyper-IgE Syndrome
Authors: Steven M. Holland, Frank R. DeLeo, Houda Z. Elloumi, Amy P. Hsu, Gulbu Uzel, Nina Brodsky, Alexandra F. Freeman, Andrew Demidowich, Joie Davis, Maria L. Turner, Victoria L. Anderson, Dirk N. Darnell, Pamela A. Welch, Douglas B. Kuhns, David M. Frucht, Harry L. Malech, John I. Gallin, Scott D. Kobayashi, Adeline R. Whitney, Jovanka M. Voyich, James M. Musser, Cristina Woellner, Alejandro A. Schäffer, Jennifer M. Puck, Bodo Grimbacher
Journal: New England Journal of Medicine (2007)

The hyper-IgE syndrome (or Job's syndrome) is a rare disorder of immunity and connective tissue characterized by dermatitis, boils, cyst-forming pneumonias, elevated serum IgE levels, retained primary dentition, and bone abnormalities. Inheritance is autosomal dominant; sporadic cases are also found.
A Novel Pharmacologic Activity of Ketorolac for Therapeutic Benefit in Ovarian Cancer Patients
Authors: Yuna Guo, S. Ray Kenney, Linda Cook, Sarah F. Adams, Teresa Rutledge, Elsa Romero, Tudor I. Oprea, Larry A. Sklar, Edward Bedrick, Charles L. Wiggins, Huining Kang, Lesley Lomo, Carolyn Y. Muller, Angela Wandinger-Ness, Laurie G. Hudson
Journal: Clinical Cancer Research (2015)

Abstract Purpose: We previously identified the R-enantiomer of ketorolac as an inhibitor of the Rho-family GTPases Rac1 and Cdc42. Rac1 and Cdc42 regulate cancer-relevant functions, including cytoskeleton remodeling necessary for tumor cell adhesion and migration. This study investigated whether administration of racemic (R,S) ketorolac after ovarian cancer surgery leads to peritoneal distribution of R-ketorolac, target GTPase inhibition in cells retrieved from the peritoneal cavity, and measureable impact on patient outcomes. Experimental Design: Eligible patients had suspected advanced-stage ovarian, fallopian tube or primary peritoneal cancer. Secondary eligibility was met when ovarian cancer was confirmed and optimally debulked, an intraperitoneal port was placed, and there were no contraindications for ketorolac administration. R- and S-ketorolac were measured in serum and peritoneal fluid, and GTPase activity was measured in peritoneal cells. A retrospective study correlated perioperative ketorolac and ovarian cancer–specific survival in ovarian cancer cases. Results: Elevated expression and activity of Rac1 and Cdc42 was detected in ovarian cancer patient tissues, confirming target relevance. Ketorolac in peritoneal fluids was enriched in the R-enantiomer and peritoneal cell GTPase activity was inhibited after ketorolac administration when R-ketorolac was at peak levels. After adjusting for age, AJCC stage, completion of chemotherapy, and neoadjuvant therapy, women given perioperative ketorolac had a lower hazard of death (HR, 0.30; 95% confidence interval, 0.11–0.88). Conclusions: Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, potentially contributing to the observed survival benefit in women who received ketorolac. Clin Cancer Res; 21(22); 5064–72. ©2015 AACR.