tbuckley/cabot-search huggingface dataset:
Galectin-3 Contributes to Melanoma Growth and Metastasis via Regulation of NFAT1 and Autotaxin
Authors: Russell R. Braeuer, Maya Zigler, Takafumi Kamiya, Andrey S. Dobroff, Li Huang, Woonyoung Choi, David J. McConkey, Einav Shoshan, Aaron K. Mobley, Renduo Song, Avraham Raz, Menashe Bar-Eli
Journal: Cancer Research (2012)

Melanoma is the deadliest form of skin cancer in which patients with metastatic disease have a 5-year survival rate of less than 10%. Recently, the overexpression of a β-galactoside binding protein, galectin-3 (LGALS3), has been correlated with metastatic melanoma in patients. We have previously shown that silencing galectin-3 in metastatic melanoma cells reduces tumor growth and metastasis. Gene expression profiling identified the protumorigenic gene autotaxin (ENPP2) to be downregulated after silencing galectin-3. Here we report that galectin-3 regulates autotaxin expression at the transcriptional level by modulating the expression of the transcription factor NFAT1 (NFATC2). Silencing galectin-3 reduced NFAT1 protein expression, which resulted in decreased autotaxin expression and activity. Reexpression of autotaxin in galectin-3 silenced melanoma cells rescues angiogenesis, tumor growth, and metastasis in vivo. Silencing NFAT1 expression in metastatic melanoma cells inhibited tumor growth and metastatic capabilities in vivo. Our data elucidate a previously unidentified mechanism by which galectin-3 regulates autotaxin and assign a novel role for NFAT1 during melanoma progression.
The transcription factor Ets1 is important for CD4 repression and <i>Runx3</i> up-regulation during CD8 T cell differentiation in the thymus
Authors: Monica Zamisch, Linhua Tian, Roland Grenningloh, Yumei Xiong, Kathryn F. Wildt, Marc Ehlers, I-Cheng Ho, Rémy Bosselut
Journal: The Journal of Experimental Medicine (2009)

The transcription factor Ets1 contributes to the differentiation of CD8 lineage cells in the thymus, but how it does so is not understood. In this study, we demonstrate that Ets1 is required for the proper termination of CD4 expression during the differentiation of major histocompatability class 1 (MHC I)–restricted thymocytes, but not for other events associated with their positive selection, including the initiation of cytotoxic gene expression, corticomedullary migration, or thymus exit. We further show that Ets1 promotes expression of Runx3, a transcription factor important for CD8 T cell differentiation and the cessation of Cd4 gene expression. Enforced Runx3 expression in Ets1-deficient MHC I–restricted thymocytes largely rescued their impaired Cd4 silencing, indicating that Ets1 is not required for Runx3 function. Finally, we document that Ets1 binds at least two evolutionarily conserved regions within the Runx3 gene in vivo, supporting the possibility that Ets1 directly contributes to Runx3 transcription. These findings identify Ets1 as a key player during CD8 lineage differentiation and indicate that it acts, at least in part, by promoting Runx3 expression.
Associations of Adiponectin Levels With Incident Impaired Glucose Metabolism and Type 2 Diabetes in Older Men and Women
Authors: Marieke B. Snijder, Robert J. Heine, Jacob C. Seidell, Lex M. Bouter, Coen D.A. Stehouwer, Giel Nijpels, Tohru Funahashi, Yuji Matsuzawa, Iichiro Shimomura, Jacqueline M. Dekker
Journal: Diabetes Care (2006)

Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose metabolism (IGM).The Hoorn Study is a cohort study among Caucasians, aged 50-75 years. BMI, waist-to-hip ratio (WHR), fasting glucose, 2-h glucose, triglycerides, HDL cholesterol, LDL cholesterol, alanine aminotransferase, leptin, and adiponectin were measured at baseline. Lifestyle (alcohol intake, smoking, and physical activity) was assessed by questionnaires. After a mean follow-up of 6.4 years, glucose tolerance was assessed by a 75-g oral glucose tolerance test. Analyses were performed in 1,264 subjects (584 men and 680 women) without type 2 diabetes at baseline. For analyses of incident IGM, 239 subjects with IGM at baseline and/or type 2 diabetes at follow-up were excluded.Age- and lifestyle-adjusted odds ratios and 95% CIs comparing highest with lowest adiponectin quartile were 0.52 (0.23-1.18) in men and 0.15 (0.06-0.39) in women for type 2 diabetes and 0.90 (0.51-1.61) and 0.28 (0.16-0.48) for IGM, respectively. The risks were only slightly reduced after adjustment for WHR and leptin as markers of (abdominal) adiposity. Adjustment for baseline fasting and postload glucose levels (potential mediators) substantially diminished these inverse associations with type 2 diabetes (0.79 [0.32-1.91] and 0.62 [0.21-1.81]) and with IGM (1.20 [0.61-2.35] and 0.48 [0.26-0.90]), respectively.A high adiponectin level was strongly associated with a lower risk of IGM and type 2 diabetes, particularly in women. These results suggest that adiponectin is involved in the pathophysiology linking obesity to type 2 diabetes.
Serum urate association with hypertension in young adults: analysis from the Coronary Artery Risk Development in Young Adults cohort
Authors: Angelo L Gaffo, David R Jacobs, Femke Sijtsma, Cora E Lewis, Ted R Mikuls, Kenneth G Saag
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To determine if serum urate concentration is associated with development of hypertension in young adults. <h3>Methods</h3> Retrospective cohort analysis from 4752 participants with available serum urate and without hypertension at baseline from the Coronary Artery Risk Development in Young Adults (CARDIA) study; a mixed race (African-American and White) cohort established in 1985 with 20 years of follow-up data for this analysis. Associations between baseline serum urate concentration and incident hypertension (defined as a blood pressure greater or equal to 140/90 or being on antihypertensive drugs) were investigated in sex-stratified bivariate and multivariable Cox-proportional analyses. <h3>Results</h3> Mean age (SD) at baseline was 24.8 (3.6) years for men and 24.9 (3.7) years for women. Compared with the referent category, we found a greater hazard of developing hypertension starting at 345 µmol/l (5.8 mg/dl) of serum urate for men and 214 µmol/l (3.6 mg/dl) for women. There was a 25% increase in the hazard of developing hypertension in men (HR1.25 (95% CI 1.15 to 1.36)) per each mg/dl increase in serum urate but no significant increase in women (HR 1.06 (95%CI 0.97 to 1.16)). <h3>Conclusions</h3> We found a significant independent association between higher serum urate concentrations and the subsequent hazard of incident hypertension, even at concentrations below the conventional hyperuricaemia threshold of 404 µmol/l (6.8 mg/dl).
EGFRvIII and DNA Double-Strand Break Repair: A Molecular Mechanism for Radioresistance in Glioblastoma
Authors: Bipasha Mukherjee, Brian McEllin, Cristel V. Camacho, Nozomi Tomimatsu, Shyam Sirasanagandala, Suraj Nannepaga, Kimmo J. Hatanpaa, Bruce Mickey, Christopher Madden, Elizabeth Maher, David A. Boothman, Frank Furnari, Webster K. Cavenee, Robert M. Bachoo, Sandeep Burma
Journal: Cancer Research (2009)

Glioblastoma multiforme (GBM) is the most lethal of brain tumors and is highly resistant to ionizing radiation (IR) and chemotherapy. Here, we report on a molecular mechanism by which a key glioma-specific mutation, epidermal growth factor receptor variant III (EGFRvIII), confers radiation resistance. Using Ink4a/Arf-deficient primary mouse astrocytes, primary astrocytes immortalized by p53/Rb suppression, as well as human U87 glioma cells, we show that EGFRvIII expression enhances clonogenic survival following IR. This enhanced radioresistance is due to accelerated repair of DNA double-strand breaks (DSB), the most lethal lesion inflicted by IR. The EGFR inhibitor gefitinib (Iressa) and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 attenuate the rate of DSB repair. Importantly, expression of constitutively active, myristylated Akt-1 accelerates repair, implicating the PI3K/Akt-1 pathway in radioresistance. Most notably, EGFRvIII-expressing U87 glioma cells show elevated activation of a key DSB repair enzyme, DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Enhanced radioresistance is abrogated by the DNA-PKcs-specific inhibitor NU7026, and EGFRvIII fails to confer radioresistance in DNA-PKcs-deficient cells. In vivo, orthotopic U87-EGFRvIII-derived tumors display faster rates of DSB repair following whole-brain radiotherapy compared with U87-derived tumors. Consequently, EGFRvIII-expressing tumors are radioresistant and continue to grow following whole-brain radiotherapy with little effect on overall survival. These in vitro and in vivo data support our hypothesis that EGFRvIII expression promotes DNA-PKcs activation and DSB repair, perhaps as a consequence of hyperactivated PI3K/Akt-1 signaling. Taken together, our results raise the possibility that EGFR and/or DNA-PKcs inhibition concurrent with radiation may be an effective therapeutic strategy for radiosensitizing high-grade gliomas.
Respiratory mechanics II
Authors: B. Fabry, J. Guttmann, L. Eberhard, W. Bertschmann, G. Wolff, E. Calzia, K. H. Lindner, U. Schirmer, M. Lessard, F. Lemaire, L. Brochard, J. Mancebo, I. Vallverdú, E. Bak, A. Ortiz, S. Benito, A. Net, R. Giuliani, V. M. Ranieri, L. Mascia, T. Fiore, F. Erice, Y. Salib, J. Meakins, G. Fox, S. Magder
Journal: Intensive Care Medicine (1992)
Functional ankle control of rock climbers
Authors: A Schweizer, H-P Bircher, X Kaelin, P E Ochsner
Journal: British Journal of Sports Medicine (2005)

Objective: To evaluate whether rock climbing type exercise would be of value in rehabilitating ankle injuries to improve ankle stability and coordination. Methods: A group of 25 rock climbers was compared with a group of 26 soccer players. All were male, uninjured, and exercised three to four times a week. Active ankle stability was evaluated by one leg stand stabilometry (measurement of migration of the centre of gravity) and measurements of maximum strength of ankle isokinetic concentric flexion and extension (Cybex). Results: The rock climbers showed significantly better results in the stabilometry and greater absolute and relative maximum strength of flexion in the ankle. The soccer players showed greater absolute but not relative strength in extension. Conclusion: Rock climbing, because of its slow and controlled near static movements, may be of value in the treatment of functional ankle instability. However, it has still to be confirmed whether it is superior to the usual rehabilitation exercises such as use of the wobble board.
Isotretinoin-induced pleuritic chest pain
Authors: V. Madan, H.L. Muston, A.M. Marsland
Journal: British Journal of Dermatology (2006)

Journal Article Isotretinoin‐induced pleuritic chest pain Get access V. Madan, V. Madan Department of Dermatology, Central Manchester and Manchester Children's University Hospital NHS Trust, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, U.K. *The Dermatology Centre, Hope Hospital, Manchester, M6 8HD, U.K. E‐mail: vishalmadan@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar H.L. Muston, H.L. Muston Department of Dermatology, Central Manchester and Manchester Children's University Hospital NHS Trust, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, U.K. *The Dermatology Centre, Hope Hospital, Manchester, M6 8HD, U.K. E‐mail: vishalmadan@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar A.M. Marsland A.M. Marsland Department of Dermatology, Central Manchester and Manchester Children's University Hospital NHS Trust, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, U.K. *The Dermatology Centre, Hope Hospital, Manchester, M6 8HD, U.K. E‐mail: vishalmadan@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 2, 1 February 2007, Pages 385–386, https://doi.org/10.1111/j.1365-2133.2006.07618.x Published: 01 February 2007
Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis
Authors: Jing Ma, Haojie Li, Ed Giovannucci, Lorelei Mucci, Weiliang Qiu, Paul L Nguyen, J Michael Gaziano, Michael Pollak, Meir J Stampfer
Journal: The Lancet Oncology (2008)
Women Living Alone Have an Increased Risk to Develop Diabetes, Which Is Explained Mainly by Lifestyle Factors
Authors: Jonas Lidfeldt, Christina Nerbrand, Göran Samsioe, Carl-David Agardh
Journal: Diabetes Care (2005)

OBJECTIVE— The purpose of this study was to assess the role of household conditions for the progression to diabetes in women with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS— A total of 461 women, aged 50–64 years, with IGT defined by an oral glucose tolerance test, had baseline advice on physical exercise, diet, smoking, and alcohol habits. Physical examination, blood tests, and questionnaires were completed at baseline and after 2.5 years. Household status was categorized into living alone or with a partner, other adults, or children. RESULTS— Women living alone had a 2.68-fold increased risk (95% CI 1.02–7.05) of developing diabetes after adjustments for biological risk factors. Further stepwise adjustments for education, occupation, subjective mental health, exercise, diet, and alcohol showed remaining significant odds ratios (ORs), decreasing from 3.26 (1.19–8.96) to 3.03 (1.02–8.99). However, when smoking status was added, the OR became nonsignificant, 2.07 (0.62–6.88). More women who lived alone smoked and did not reduce their daily cigarette consumption compared with women in other household conditions. At follow-up, women living alone had reduced their alcohol consumption and were more often abstainers and fewer had healthy dietary habits or had improved their diet. Physical exercise did not differ among the groups. Separate analyses of any other household status did not show any excess risk for development of diabetes. CONCLUSIONS— Women living alone had a higher risk to progress from IGT to diabetes, mostly explained by smoking, alcohol, and dietary habits. Household conditions should be accounted for when assessing future risk for diabetes.
Claudin-10 Expression Level is Associated with Recurrence of Primary Hepatocellular Carcinoma
Authors: Siu Tim Cheung, Ka Ling Leung, Ying Chi Ip, Xin Chen, Daniel Y. Fong, Irene O. Ng, Sheung Tat Fan, Samuel So
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Hepatocellular carcinoma (HCC) patients with the same clinicopathologic features can have remarkably different disease outcomes after curative hepatectomy. To address this issue, we evaluated the cDNA microarray gene expression profiles of HCCs and identified claudin-10 expression level was associated with disease recurrence. The aim of the current study is to validate the microarray data by an alternative research method applicable for routine practice. Experimental Design: Quantitative reverse transcription–PCR (RT-PCR) was used to validate the microarray data on claudin-10 expression level. The assay was repeated on a separate HCC sample set to consolidate the prognostic significance of claudin-10. Results: Claudin-10 expression level by quantitative RT-PCR and by microarray measurement showed a high concordance (r = 0.602, P &amp;lt; 0.001). Quantitative RT-PCR was repeated on a separate HCC sample set and the association of claudin-10 expression with recurrence was again confirmed (hazard ratio, 1.2; 95% confidence interval, 1.0-1.4; P = 0.011). By multivariable Cox regression analysis, claudin-10 expression and pathologic tumor-node-metastasis stage were independent factors for prediction of disease recurrence. Conclusion: Claudin-10 expression of HCC can be used as a molecular marker for disease recurrence after curative hepatectomy.
Inhibition by Phytohemagglutinin of DNA Synthesis in Cultured Mouse Lymphomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Peter B. Dent
Journal: JNCI Journal of the National Cancer Institute (1971)

Crude extracts of a variety of plants possess agglutinins for both normal and malignant cells. Phytohemagglutinin (PHA), the most widely used plant lectin, both stimulates macromolecular synthesis and causes agglutination of normal lymphoid cells. We showed that PHA, at concentrations stimulating DNA synthesis in normal mouse splenic lymphocytes, inhibited DNA synthesis in cultured Gross ascites lymphoma cells. The inhibition was partially reversible and affected RNA as well as DNA synthesis. Another plant lectin, pokeweed mitogen, did not inhibit lymphoma cells but did inhibit DNA synthesis in myeloma cells. Evidence presented suggests that neoplastic cells have an increased density of mitogen receptor sites on their surface. The specificities of the receptor sites on lymphoid tumors may be related to the differentiation influences which characterize the thymus-dependent and the thymus-independent developmental pathways. While the precise mechanism of the inhibitory action of PHA on lymphoid cells is not known, it may be qualitatively identical to, but quantitatively an exaggeration of, its stimulatory action on normal lymphoid cells.
C-reactive protein level and microbial aetiology in patients hospitalised with acute exacerbation of COPD
Authors: Tristan W. Clark, Marie-Jo Medina, Sally Batham, Martin D. Curran, Surendra Parmar, Karl G. Nicholson
Journal: European Respiratory Journal (2014)

Both viruses and bacteria are thought to cause exacerbations of chronic obstructive pulmonary disease (COPD); however, the relative importance of each remains uncertain. C-reactive protein (CRP) levels increase during exacerbations but the relationship with aetiology is not established. We aimed to explore the relationship between serum CRP and the rate of detection of viruses and bacteria. This was a prospectively recruited, observational study of patients hospitalised with exacerbations of COPD. Nasopharyngeal swabs were tested for respiratory viruses by reverse transcriptase-PCR. Sputum and blood were collected for bacterial culture and urine tested for pneumococcal antigen. CRP levels were measured on sera. CRP and other factors associated with viral, bacterial or mixed detection were assessed using multiple logistic regression analysis. 264 patients with exacerbations of COPD were studied: 26% tested positive for respiratory viruses only, 13% had bacteria only, 12% had mixed viral/bacterial detection, and 49% had no pathogens detected. CRP level and temperature were strongly associated with viral detection rate (p&lt;0.001 and p=0.004, respectively) and mixed viral/bacterial detection rate (p=0.02 and p=0.03, respectively) on multivariate analysis. Bacterial detection rate was not associated with CRP level or body temperature. This study supports the role of viruses as important aetiological agents causing exacerbations of COPD.
High glucose induces cardiac insulin-like growth factor I resistance in ventricular myocytes: role of Akt and ERK activation
Authors: J Ren
Journal: Cardiovascular Research (2003)

Objective: Cardiac resistance to IGF-1 occurs in diabetes and is attributed to cardiac dysfunction in diabetes. However, the mechanism of action responsible for cardiac IGF-1 resistance is still unknown. This study was designed to examine the impact of high glucose on IGF-1-induced contractile response and activation of serine-threonine kinase Akt as well as extracellular signal-regulated kinase (ERK1/2) in cardiac myocytes. Methods: Isolated adult rat ventricular myocytes were cultured for 12–18 h in a serum-free medium containing either normal (NG, 5.5 mM) or high (HG, 25.5 mM) glucose. Mechanical properties were evaluated using an IonOptix MyoCam® system. Myocytes were electrically stimulated at 0.5 Hz and contractile properties analyzed included peak shortening (PS), time-to-PS (TPS) and time-to-90% relengthening (TR90). Intracellular Ca2+-induced Ca2+ release was measured as fura-2 fluorescence intensity change (ΔFFI). Protein levels of total and phosphorylated Akt and ERK1/2, indicators of Akt and ERK1/2 activation, IGF-1 receptors (pro-IGF-1R and IGF-1Rα) as well as the glucose transporter GLUT4 were assessed by Western blot. Results: IGF-1 (10−10–10−6 M) elicited a dose-dependent increase in PS and ΔFFI in myocytes maintained in NG medium. However, IGF-1 induced a negative response on PS and ΔFFI in HG myocytes. The IGF-1-induced responses in NG or HG myocytes were blunted by the IGF-1 receptor antagonist H-1356. Western blot analysis revealed that IGF-1Rα but not pro-IGF-1R was reduced in HG myocytes. While IGF-1 (10−6 M) upregulated total Akt protein levels in both NG and HG myocytes, it only induced a significant activation of Akt in NG but not HG myocytes. IGF-1 elicited comparable ERK1/2 activation in both NG and HG myocytes. Conclusion: These results suggest that the cardiac IGF-1 resistance in diabetes is likely attributed, at least in part, to reduced IGF-1R and attenuated IGF-1-induced Akt phosphorylation under elevated extracellular glucose.
Cardiac Arrest Outside of a Hospital
Authors: Hein J.J. Wellens, Anton P. Gorgels, Hans de Munter
Journal: Circulation (2003)

n the western world, one-fifth of all deaths occur suddenly and unexpectedly, 1 ventricular fibrillation being a frequent mechanism.It happens approximately 300 000 times per year both in the United States and in Europe. 2 This problem continues to haunt us, for we know that restoring normal heart rhythm by a defibrillation shock not only saves the life of the victim, but is often followed by many years of satisfactory living. Can We Recognize the Victim Before the Event?Much effort has been put into recognizing the person at high risk of dying suddenly and is clearer in the case of a previous life-threatening arrhythmia or successful resuscitation from circulatory arrest.In such patients, death from a new arrhythmic episode can be prevented by implanting a defibrillator.Accurate risk stratification is much more difficult in the large group of patients with known heart disease but without a history of a life-threatening arrhythmia. 3atients characterized by a previous myocardial infarction and poor left ventricular function, with or without nonsustained ventricular arrhythmias, can profit from a defibrillator implant, as shown by studies such as the Multicenter Automatic Defibrillator Implantation Trial-I (MADIT I), the Multicenter Unstable Tachycardia Trial (MUSTT), and MA-DIT II. 4 -6 However, only 10% of sudden cardiac arrest victims have such a high-risk profile. 1,