tbuckley/cabot-search huggingface dataset:
Tpl2 kinase regulates T cell interferon-γ production and host resistance to <i>Toxoplasma gondii </i>
Authors: Wendy T. Watford, Bruce D. Hissong, Lydia R. Durant, Hidehiro Yamane, Linda M. Muul, Yuka Kanno, Cristina M. Tato, Haydeé L. Ramos, Alan E. Berger, Lisa Mielke, Marko Pesu, Benjamin Solomon, David M. Frucht, William E. Paul, Alan Sher, Dragana Jankovic, Philip N. Tsichlis, John J. O'Shea
Journal: The Journal of Experimental Medicine (2008)

Tpl2 (Tumor progression locus 2), also known as Cot/MAP3K8, is a hematopoietically expressed serine-threonine kinase. Tpl2 is known to have critical functions in innate immunity in regulating tumor necrosis factor–α, Toll-like receptor, and G protein–coupled receptor signaling; however, our understanding of its physiological role in T cells is limited. We investigated the potential roles of Tpl2 in T cells and found that it was induced by interleukin-12 in human and mouse T cells in a Stat4-dependent manner. Deficiency of Tpl2 was associated with impaired interferon (IFN)-γ production. Accordingly, Tpl2−/− mice had impaired host defense against Toxoplasma gondii with reduced parasite clearance and decreased IFN-γ production. Furthermore, reconstitution of Rag2−/− mice with Tpl2-deficient T cells followed by T. gondii infection recapitulated the IFN-γ defect seen in the Tpl2-deficient mice, confirming a T cell–intrinsic defect. CD4+ T cells isolated from Tpl2−/− mice showed poor induction of T-bet and failure to up-regulate Stat4 protein, which is associated with impaired TCR-dependent extracellular signal-regulated kinase activation. These data underscore the role of Tpl2 as a regulator of T helper cell lineage decisions and demonstrate that Tpl2 has an important functional role in the regulation of Th1 responses.
Therapy of psoriasis 1975
Authors: E. J. Van Scott
Journal: JAMA (1976)

EVER a subject for perennial reports of "breakthroughs," psoriasis recently has indeed been the recipient of several therapeutic developments that promise to provide new options to patients and their physicians harassed by this vexing disease. Among the new entries are triacetyl azauridine, with New Drug Application recently approved; mycophenolic acid, still under an Investigational New Drug application; and long-wave ultraviolet light (UV) and methoxsalen phototherapy, now scheduled for multiinstitutional evaluation over the next year. At this time it is uncertain which of the new introductions will provide solutions and which might provide additional haunting problems. <h3>Burden to Patients</h3> The issue of what constitutes appropriate therapy of psoriasis has been repetitiously controversial with each new treatment advanced over the years. The recurrent controversy seems to have its foundations in the choice of adjectives through which the disease is characterized in divergent points of view. Thus, it is seen as ei<b>See</b>
Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease
Authors: G C Donaldson
Journal: Thorax (2002)

<b>Background:</b> Chronic obstructive pulmonary disease (COPD) is characterised by both an accelerated decline in lung function and periods of acute deterioration in symptoms termed exacerbations. The aim of this study was to investigate whether these are related. <b>Methods:</b> Over 4 years, peak expiratory flow (PEF) and symptoms were measured at home daily by 109 patients with COPD (81 men; median (IQR) age 68.1 (63–74) years; arterial oxygen tension (Pao<sub>2</sub>) 9.00 (8.3–9.5) kPa, forced expiratory volume in 1 second (FEV<sub>1</sub>) 1.00 (0.7–1.3) l, forced vital capacity (FVC) 2.51 (1.9–3.0) l); of these, 32 (29 men) recorded daily FEV<sub>1</sub>. Exacerbations were identified from symptoms and the effect of frequent or infrequent exacerbations (&gt; or &lt; 2.92 per year) on lung function decline was examined using cross sectional, random effects models. <b>Results:</b> The 109 patients experienced 757 exacerbations. Patients with frequent exacerbations had a significantly faster decline in FEV<sub>1</sub> and peak expiratory flow (PEF) of –40.1 ml/year (n=16) and –2.9 l/min/year (n=46) than infrequent exacerbators in whom FEV<sub>1</sub> changed by –32.1 ml/year (n=16) and PEF by –0.7 l/min/year (n=63). Frequent exacerbators also had a greater decline in FEV<sub>1</sub> if allowance was made for smoking status. Patients with frequent exacerbations were more often admitted to hospital with longer length of stay. Frequent exacerbations were a consistent feature within a patient, with their number positively correlated (between years 1 and 2, 2 and 3, 3 and 4). <b>Conclusions:</b> These results suggest that the frequency of exacerbations contributes to long term decline in lung function of patients with moderate to severe COPD.
Impact of Lifestyle-Related Factors on All-Cause and Cause-Specific Mortality in Patients With Type 2 Diabetes
Authors: Cheng-Chieh Lin, Chia-Ing Li, Chiu-Shong Liu, Wen-Yuan Lin, Martin Mao-Tsu Fuh, Sing-Yu Yang, Cheng-Chun Lee, Tsai-Chung Li
Journal: Diabetes Care (2011)

To examine whether combined lifestyle behaviors have an impact on all-cause and cause-specific mortality in patients aged 30-94 years with type 2 diabetes (T2DM).Participants included 5,686 patients >30 years old with T2DM who were enrolled in a Diabetes Care Management Program at a medical center in central Taiwan before 2007. Lifestyle behaviors consisted of smoking, alcohol drinking, physical inactivity, and carbohydrate intake. The main outcomes were all-cause and cause-specific mortality. Cox proportional hazards models were used to examine the association between combined lifestyle behaviors and mortality.The mortality rate among men was 24.10 per 1,000 person-years, and that among women was 17.25 per 1,000 person-years. After adjusting for the traditional risk factors, we found that combined lifestyle behavior was independently associated with all-cause mortality and mortality due to diabetes, cardiovascular disease, and cancer. Patients with three or more points were at a 3.50-fold greater risk of all-cause mortality (95% CI 2.06-5.96) and a 4.94-fold (1.62-15.06), 4.24-fold (1.20-14.95), and 1.31-fold (0.39-4.41) greater risk of diabetes-specific, CVD-specific, and cancer-specific mortality, respectively, compared with patients with zero points. Among these associations, the combined lifestyle behavior was not significantly associated with cancer mortality.Combined lifestyle behavior is a strong predictor of all-cause and cause-specific mortality in patients with T2DM.
Interleukin-2- and Interferon Alfa-2a-Based Immunochemotherapy in Advanced Renal Cell Carcinoma: A Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)
Authors: J. Atzpodien, H. Kirchner, U. Jonas, L. Bergmann, H. Schott, H. Heynemann, P. Fornara, S.A. Loening, J. Roigas, S.C. Müller, H. Bodenstein, S. Pomer, B. Metzner, U. Rebmann, R. Oberneder, M. Siebels, T. Wandert, T. Puchberger, M. Reitz
Journal: Journal of Clinical Oncology (2004)

Purpose We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. Patients and Methods Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-α-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-α-2a and IV vinblastine. Results Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P = .0248). Both arm A (median overall survival, 25 months; P = .0440) and arm B (median overall survival, 27 months; P = .0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-α-2a–based therapies were moderately or well tolerated. Conclusion Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-α-2a–based outpatient immunochemotherapies, compared with sc-INF-α-2a/IV vinblastine.
Test accuracy is example of redundant information
Authors: A R. Henderson
Journal: BMJ (1998)

Editor—Greenhalgh's usual common sense seems to have deserted her when she discusses test accuracy.1 I,2 and others before me, have pointed out the inadequacy of test accuracy. Its use condenses two fundamental test variables—sensitivity and specificity—which apply to diseased and non-diseased populations, respectively. So what is the …
Gene Expression Profiling of Fixed Tissues Identified Hypoxia-Inducible Factor-1α, VEGF, and Matrix Metalloproteinase-2 as Biomarkers of Lymph Node Metastasis in Hepatocellular Carcinoma
Authors: Zuo-Lin Xiang, Zhao-Chong Zeng, Jia Fan, Zhao-You Tang, Hai-Ying Zeng, Dong-Mei Gao
Journal: Clinical Cancer Research (2011)

Hepatocellular carcinoma (HCC) most often develops in patients infected with hepatitis B or hepatitis C virus. Differential gene expression profiling is useful for investigating genes associated with lymph node metastasis (LNM). We screened genes to identify potential biomarkers for LNM in HCC.RNA was extracted from formalin-fixed specimens of paired intratumoral and peritumoral tissues of patients with lymph node-positive (n = 36) or negative (n = 36) HCC. A cDNA-mediated annealing, selection, extension, and ligation assay was done with an array of 502 known cancer-related genes to identify differentially expressed genes in 20 pairs of patients with or without LNM. Candidate biomarkers were evaluated by using immunohistochemistry and tissue microarrays in an independent cohort of 309 HCC patients who had undergone hepatectomy. Of the 309 patients, 235 (76.1%) patients were infected with hepatitis B.Compared with lymph node-negative patients, lymph node-positive patients had 17 overexpressed genes and 19 underexpressed genes in intratumoral tissues, and 25 overexpressed genes and 22 underexpressed genes in peritumoral tissues. Hypoxia-inducible factor (HIF)-1α, VEGF, and matrix metalloproteinase (MMP)-2 were selected for analysis in the cohort of 309 HCC patients. We found that intratumoral protein levels of HIF-1α, VEGF, and MMP-2 were independent risk factors for developing LNM.We identified 83 cancer genes that were differentially expressed in lymph node-positive and lymph node-negative HCC. Our findings show that the combination of intratumoral HIF-1α, VEGF, and MMP-2 may be useful as a molecular prediction model for LNM.
Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase
Authors: M. G. H. van de Sande, M. J. H. de Hair, C. van der Leij, P. L. Klarenbeek, W. H. Bos, M. D. Smith, M. Maas, N. de Vries, D. van Schaardenburg, B. A. C. Dijkmans, D. M. Gerlag, P. P. Tak
Journal: Annals of the Rheumatic Diseases (2010)

Insulin influences learning and cognition and activity in brain centers that mediate reward and motivation in humans. However, very little is known about how insulin influences excitatory transmission within brain reward centers such as the nucleus accumbens (NAc). Further, insulin dysregulation that accompanies obesity is linked to cognitive decline, depression, anxiety, and aberrant motivation that also rely on excitatory transmission in the NAc, but potential mechanisms are poorly understood. Here we show that insulin receptor activation increases presynaptic glutamate release via a previously unidentified form of opioid receptor-mediated disinhibition, whereas activation of IGF receptors by insulin decreases presynaptic glutamate release in the NAc. Furthermore, obesity results in a loss of the insulin receptor-mediated increases and a reduction in NAc insulin receptor surface expression, while preserving reductions in excitatory transmission mediated by IGF receptors. These results provide the first insights into how insulin influences excitatory transmission in the adult brain and have broad implications for the regulation of motivation and reward related processes by peripheral hormones.
Consensus statement on injury definitions and data collection procedures for studies of injuries in rugby union
Authors: Colin W Fuller, Michael G Molloy, Christian Bagate, Roald Bahr, John H M Brooks, Hilton Donson, Simon P T Kemp, Paul McCrory, Andrew S McIntosh, Willem H Meeuwisse, Kenneth L Quarrie, Martin Raftery, Preston Wiley
Journal: British Journal of Sports Medicine (2007)

Wide variations in the definitions and methodologies used for studies of injuries in rugby union have created inconsistencies in reported data and made interstudy comparisons of results difficult. The International Rugby Board established a Rugby Injury Consensus Group (RICG) to reach an agreement on the appropriate definitions and methodologies to standardise the recording of injuries and reporting of studies in rugby union. The RICG reviewed the consensus definitions and methodologies previously published for football (soccer) at a meeting in Dublin in order to assess their suitability for and application to rugby union. Following this meeting, iterative draft statements were prepared and circulated to members of the RICG for comment; a follow-up meeting was arranged in Dublin, at which time all definitions and procedures were finalised. At this stage, all authors confirmed their agreement with the consensus statement. The agreed document was presented to and approved by the International Rugby Board Council. Agreement was reached on definitions for injury, recurrent injury, non-fatal catastrophic injury, and training and match exposures, together with criteria for classifying injuries in terms of severity, location, type, diagnosis and causation. The definitions and methodology presented in this consensus statement for rugby union are similar to those proposed for football. Adoption of the proposals presented in this consensus statement should ensure that more consistent and comparable results will be obtained from studies of injuries within rugby union.
Large scale variation in Enterococcus faecalis illustrated by the genome analysis of strain OG1RF
Authors: Agathe Bourgogne, Danielle A Garsin, Xiang Qin, Kavindra V Singh, Jouko Sillanpaa, Shailaja Yerrapragada, Yan Ding, Shannon Dugan-Rocha, Christian Buhay, Hua Shen, Guan Chen, Gabrielle Williams, Donna Muzny, Arash Maadani, Kristina A Fox, Jason Gioia, Lei Chen, Yue Shang, Cesar A Arias, Sreedhar R Nallapareddy, Meng Zhao, Vittal P Prakash, Shahreen Chowdhury, Huaiyang Jiang, Richard A Gibbs, Barbara E Murray, Sarah K Highlander, George M Weinstock
Journal: Genome biology (2008)

Abstract Background Enterococcus faecalis has emerged as a major hospital pathogen. To explore its diversity, we sequenced E. faecalis strain OG1RF, which is commonly used for molecular manipulation and virulence studies. Results The 2,739,625 base pair chromosome of OG1RF was found to contain approximately 232 kilobases unique to this strain compared to V583, the only publicly available sequenced strain. Almost no mobile genetic elements were found in OG1RF. The 64 areas of divergence were classified into three categories. First, OG1RF carries 39 unique regions, including 2 CRISPR loci and a new WxL locus. Second, we found nine replacements where a sequence specific to V583 was substituted by a sequence specific to OG1RF. For example, the iol operon of OG1RF replaces a possible prophage and the vanB transposon in V583. Finally, we found 16 regions that were present in V583 but missing from OG1RF, including the proposed pathogenicity island, several probable prophages, and the cpsCDEFGHIJK capsular polysaccharide operon. OG1RF was more rapidly but less frequently lethal than V583 in the mouse peritonitis model and considerably outcompeted V583 in a murine model of urinary tract infections. Conclusion E. faecalis OG1RF carries a number of unique loci compared to V583, but the almost complete lack of mobile genetic elements demonstrates that this is not a defining feature of the species. Additionally, OG1RF's effects in experimental models suggest that mediators of virulence may be diverse between different E. faecalis strains and that virulence is not dependent on the presence of mobile genetic elements.
Underreporting Exacerbation of Chronic Obstructive Pulmonary Disease in a Longitudinal Cohort
Authors: Lisa Langsetmo, Robert W. Platt, Pierre Ernst, Jean Bourbeau
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Unreported exacerbations and failure to seek medical attention may have consequences on the health of patients with chronic obstructive pulmonary disease.Objectives: This study aims to determine the incidence of reported and unreported exacerbations, to identify predictors of reporting, and to compare the impact of reported and unreported exacerbations on health status.Methods: The study is based on a multicenter Canadian cohort of patients with chronic obstructive pulmonary disease.Measurements and Main Results: Patients completed a daily diary from which exacerbations were defined as a worsening of at least one key symptom (dyspnea, sputum amount, sputum color) recorded on at least 2 consecutive days. Patients were asked to contact the study center if there was a sustained worsening of symptom. Reported exacerbations were events that led to contacting study center or health care visit. The study enrolled 421 patients. The overall incidence of diary exacerbations was 2.7 per person per year, but only 0.8 per person per year was reported. Predictors of reporting included age (HR [hazard ratio], 0.90; 95% confidence interval [CI], 0.81–0.98 per 5-yr increase), FEV1% predicted (HR, 0.84; 95% CI, 0.70–0.99 per 10% increase), number of symptoms at onset (HR, 1.59; 95% CI, 1.37–1.84 per additional symptom), and time of the week (HR, 0.35; 95% CI, 0.22–0.56 weekend vs. weekday). There was a clinically important decline in health status for 52% of patients with reported exacerbation and 43% with unreported exacerbations.Conclusions: This study has shown that less than one-third of the exacerbations were reported. The number of symptoms at onset was the most important predictor of reporting an exacerbation, and both reported and unreported exacerbations had an impact on health status.
DRAGO (KIAA0247), a New DNA Damage–Responsive, p53-Inducible Gene That Cooperates With p53 as Oncosuppressor
Authors: Federica Polato, Paolo Rusconi, Stefano Zangrossi, Federica Morelli, Mattia Boeri, Alberto Musi, Sergio Marchini, Vittoria Castiglioni, Eugenio Scanziani, Valter Torri, Massimo Broggini
Journal: JNCI Journal of the National Cancer Institute (2014)

p53 influences genomic stability, apoptosis, autophagy, response to stress, and DNA damage. New p53-target genes could elucidate mechanisms through which p53 controls cell integrity and response to damage.DRAGO (drug-activated gene overexpressed, KIAA0247) was characterized by bioinformatics methods as well as by real-time polymerase chain reaction, chromatin immunoprecipitation and luciferase assays, time-lapse microscopy, and cell viability assays. Transgenic mice (94 p53(-/-) and 107 p53(+/-) mice on a C57BL/6J background) were used to assess DRAGO activity in vivo. Survival analyses were performed using Kaplan-Meier curves and the Mantel-Haenszel test. All statistical tests were two-sided.We identified DRAGO as a new p53-responsive gene induced upon treatment with DNA-damaging agents. DRAGO is highly conserved, and its ectopic overexpression resulted in growth suppression and cell death. DRAGO(-/-) mice are viable without macroscopic alterations. However, in p53(-/-) or p53(+/-) mice, the deletion of both DRAGO alleles statistically significantly accelerated tumor development and shortened lifespan compared with p53(-/-) or p53(+/-) mice bearing wild-type DRAGO alleles (p53(-/-), DRAGO(-/-) mice: hazard ratio [HR] = 3.25, 95% confidence interval [CI] = 1.7 to 6.1, P < .001; p53(+/-), DRAGO(-/-) mice: HR = 2.35, 95% CI = 1.3 to 4.0, P < .001; both groups compared with DRAGO(+/+) counterparts). DRAGO mRNA levels were statistically significantly reduced in advanced-stage, compared with early-stage, ovarian tumors, but no mutations were found in several human tumors. We show that DRAGO expression is regulated both at transcriptional-through p53 (and p73) and methylation-dependent control-and post-transcriptional levels by miRNAs.DRAGO represents a new p53-dependent gene highly regulated in human cells and whose expression cooperates with p53 in tumor suppressor functions.
Essential Hypertension, Progressive Renal Disease, and Uric Acid
Authors: Richard J. Johnson, Mark S. Segal, Titte Srinivas, Ahsan Ejaz, Wei Mu, Carlos Roncal, Laura G. Sánchez-Lozada, Michael Gersch, Bernardo Rodriguez-Iturbe, Duk-Hee Kang, Jaime Herrera Acosta
Journal: Journal of the American Society of Nephrology (2005)

Hypertension and hypertension-associated ESRD are epidemic in society. The mechanisms responsible for renal progression in mild to moderate hypertension and those groups most at risk need to be identified. Historic, epidemiologic, clinical, and experimental studies on the pathogenesis of hypertension and hypertension-associated renal disease are reviewed and an overview/hypothesis for the mechanisms involved in renal progression is presented. There is increasing evidence that hypertension may exist in one of two forms/stages. The first stage, most commonly observed in early or borderline hypertension, is characterized by salt-resistance, normal or only slightly decreased GFR, relatively normal or mild renal arteriolosclerosis, and normal renal autoregulation. This group is at minimal risk for renal progression. The second stage, characterized by salt-sensitivity, renal arteriolar disease, and blunted renal autoregulation, defines a group at highest risk for the development of microalbuminuria, albuminuria, and progressive renal disease. This second stage is more likely to be observed in blacks, in subjects with gout or hyperuricemia, with low level lead intoxication, or with severe obesity/metabolic syndrome. The two major mechanistic pathways for causing impaired autoregulation at mild to moderate elevations in BP appear to be hyperuricemia and/or low nephron number. Understanding the pathogenetic pathways mediating renal progression in hypertensive subjects should help identify those subjects at highest risk and may provide insights into new therapeutic maneuvers to slow or prevent progression.
Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer.
Authors: Xian-Zhong Ding, Rene Hennig, Thomas E Adrian
Journal: Molecular Cancer (2003)

The essential fatty acids, linoleic acid and arachidonic acid play an important role in pancreatic cancer development and progression. These fatty acids are metabolized to eicosanoids by cyclooxygenases and lipoxygenases. Abnormal expression and activities of both cyclooxygenases and lipoxygenases have been reported in pancreatic cancer. In this article, we aim to provide a brief summary of (1) our understanding of the roles of these enzymes in pancreatic cancer tumorigenesis and progression; and (2) the potential of using cyclooxygenase and lipoxygenase inhibitors for pancreatic cancer treatment and prevention.
THE ASSESSMENT OF MERIT OF SUN-PROTECTING PREPARATIONS
Authors: WALTER KOCH
Journal: British Journal of Dermatology (1947)

Journal Article THE ASSESSMENT OF MERIT OF SUN‐PROTECTING PREPARATIONS Get access WALTER KOCH, M.D., Ph.D. WALTER KOCH, M.D., Ph.D. Department of Hygiene, Hebrew University, Jerusalem Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 59, Issue 8-9, 1 August 1947, Pages 309–312, https://doi.org/10.1111/j.1365-2133.1947.tb10911.x Published: 01 August 1947