tbuckley/cabot-search huggingface dataset:
Long-term endurance exercise decreases antiangiogenic endostatin signalling in overweight men aged 50-60 years
Authors: K Brixius, S Schoenberger, D Ladage, H Knigge, G Falkowski, M Hellmich, C Graf, J Latsch, G l Montie, G l Prede, W Bloch
Journal: British Journal of Sports Medicine (2007)

Endurance training may decrease the risk of coronary artery disease. It has been speculated that these effects may be due to an exercise-induced stimulation of angiogenesis. The underlying mechanisms are not yet clear. Therefore, using ELISA, we investigated the plasma level of vascular endothelial growth factor (VEGF, angiogenic factor) and endostatin (antiangiogenic factor) in a group of untrained men aged 50-60 years with obesity.All men were randomised into a "running" group (training 3 times/week, 60 min each, n = 7), a "cycling" group ( training 3 times/week, 90 min each, n = 7) and a sedentary control group ( n = 7). Both training groups worked at moderate intensity (2-4 mmol/l lactate). The intervention had a duration of 6 months. Before and after this period, blood samples were taken from the participants at rest and they underwent a medical investigation.Body mass index (BMI), systolic and diastolic blood pressure, and plasma levels of VEGF and endostatin were comparable in all three groups. Endurance training significantly reduced BMI in both exercise groups (mean (SEM) before v after 29.7 (0.7) v 29.1 (0.6) kg/m2 and 31.1 (0.7) v 30.1 (0.9) kg/m2 for the running and cycling groups respectively) but not in the control group (30.0 (1.0) v 30.2 (0.8) kg/m2). Endurance training did not influence VEGF plasma level (before v after 1.3 (0.4) v 1.5 (0.2) ng/ml for the running group; 1.6 (0.3) v 1.5 (0.2) ng/ml for the cycling group; and 2.5 (0.6) v 2.1 (0.7) ng/ml for the control group). Plasma level of endostatin was significantly reduced in both exercise groups (mean (SEM) before v after: 20.9 (1.6 v 17.5 (1.0) ng/ml and 21.3 (1.4 v 18.0 (1.6) ng/ml for the running and cycling groups respectively) but not in controls (19.7 (1.3 v 17.7 (1.1 ng/ml).Endurance training may reduce the antiangiogenic mechanisms in men aged 50-60 years by reducing endostatin plasma level and this may subsequently decrease the risk of cardiovascular disease.
Autocrine Production of Interleukin-4 and Interleukin-10 Is Required for Survival and Growth of Thyroid Cancer Cells
Authors: Matilde Todaro, Monica Zerilli, Lucia Ricci-Vitiani, Miriam Bini, Mileidys Perez Alea, Ada Maria Florena, Laura Miceli, Gerolama Condorelli, Sebastiano Bonventre, Giuseppe Di Gesù, Ruggero De Maria, Giorgio Stassi
Journal: Cancer Research (2006)

Abstract Although CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass does not seem to be affected by such expression. We have recently shown that thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly purified thyroid cancer cells were completely refractory to CD95-induced apoptosis despite the consistent expression of Fas-associated death domain and caspase-8. The analysis of potential molecules able to prevent caspase-8 activation in thyroid cancer cells revealed a remarkable up-regulation of cellular FLIPL (cFLIPL) and PED/PEA-15, two antiapoptotic proteins whose exogenous expression in normal thyrocytes inhibited the death-inducing signaling complex of CD95. Additionally, small interfering RNA FLIP and PED antisense sensitized thyroid cancer cells to CD95-mediated apoptosis. Exposure of normal thyrocytes to IL-4 and IL-10 potently up-regulated cFLIP and PED/PEA-15, suggesting that these cytokines are responsible for thyroid cancer cell resistance to CD95 stimulation. Moreover, treatment with neutralizing antibodies against IL-4 and IL-10 or exogenous expression of suppressor of cytokine signaling-1 of thyroid cancer cells resulted in cFLIP and PED/PEA-15 down-regulation and CD95 sensitization. More importantly, prolonged IL-4 and IL-10 neutralization induced cancer cell growth inhibition and apoptosis, which were prevented by blocking antibodies against CD95 ligand. Altogether, autocrine production of IL-4 and IL-10 neutralizes CD95-generated signals and allows survival and growth of thyroid cancer cells. Thus, IL-4 and IL-10 may represent key targets for the treatment of thyroid cancer. (Cancer Res 2006; 66(3): 1491-9)
TNFerade Biologic, an Adenovector With a Radiation-Inducible Promoter, Carrying the Human Tumor Necrosis Factor Alpha Gene: A Phase I Study in Patients With Solid Tumors
Authors: Neil Senzer, Sridhar Mani, Alexander Rosemurgy, John Nemunaitis, Casey Cunningham, Chandan Guha, Natalia Bayol, Michelle Gillen, Karen Chu, Camilla Rasmussen, Henrik Rasmussen, Donald Kufe, Ralph Weichselbaum, Nader Hanna
Journal: Journal of Clinical Oncology (2004)

TNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy.TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 x 10(7) particle units [pu] to 4 x 10(11) pu) in patients with solid tumors being treated with radiation.Thirty-six patients were assessable for toxicity and 30 for tumor response. Most frequent TNFerade-related toxicities were fever (22%), injection site pain (19%), and chills (19%). No dose-limiting toxicities were observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response (five complete responses, nine partial responses, and seven minimal responses). In four of five patients with synchronous lesions, a differential response between lesions treated with TNFerade + radiation compared with radiation only was observed.This is the first human study with TNFerade and radiation. The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade.
Possible involvement of interferon alfa in the pathogenesis of fever in systemic lupus erythematosus.
Authors: Y Kanayama, T Kim, H Inariba, N Negoro, M Okamura, T Takeda, T Inoue
Journal: Annals of the Rheumatic Diseases (1989)

Serum concentrations of interferon alfa, interleukin 1, and tumour necrosis factor alpha were measured in 25 untreated patients with systemic lupus erythematosus (SLE). A close correlation was found between serum concentrations of interferon alfa and the degree of fever, while no significant correlations were found between fever and interleukin 1 or tumour necrosis factor alpha. These results suggest the possible involvement of interferon alfa in the pathogenesis of fever in SLE.
Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes.
Authors: S D Wright, S C Silverstein
Journal: The Journal of Experimental Medicine (1983)

We have measured the release of H2O2 from granulocytes, monocytes, and macrophages during spreading on ligand-coated culture surfaces. While IgG-coated surfaces stimulate vigorous release of H2O2, neither C3b- nor C3bi-coated surfaces promoted appreciable release of H2O2 despite full ligation of C3b and C3bi receptors. We also measured release of H2O2 from cultured monocytes spreading on surfaces coated with both fibronectin and C3. Under such circumstances, the C3 receptors elicit a strong phagocytic response, but no H2O2 release was recorded. We conclude that the C3b and C3bi receptors of monocytes and granulocytes do not signal the generation of toxic oxygen intermediates from these cells.
Role of Variability in Microvascular Resistance on Fractional Flow Reserve and Coronary Blood Flow Velocity Reserve in Intermediate Coronary Lesions
Authors: Martijn Meuwissen, Steven A. J. Chamuleau, Maria Siebes, Carl E. Schotborgh, Karel T. Koch, Robbert J. de Winter, Matthijs Bax, Angelina de Jong, Jos A. E. Spaan, Jan J. Piek
Journal: Circulation (2001)

Fractional flow reserve (FFR) and coronary blood flow velocity reserve (CFR) represent physiological quantities used to evaluate coronary lesion severity and to make clinical decisions. A comparison between the outcomes of both diagnostic techniques has not been performed in a large cohort of patients with intermediate coronary lesions.FFR and CFR were assessed in 126 consecutive patients with 150 intermediate coronary lesions (between 40% and 70% diameter stenosis by visual assessment). Agreement between outcomes of FFR and CFR, categorized at cut-off values of 0.75 and 2.0, respectively, was observed in 109 coronary lesions (73%), whereas discordant outcomes were present in 41 lesions (27%). In 26 of these 41 lesions, FFR was <0.75 and CFR>or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034).Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement.
Erosions versus joint space narrowing in rheumatoid arthritis: what do we know?
Authors: D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2011)

Both erosions and joint space narrowing (JSN) are aspects of structural damage in rheumatoid arthritis. Most information is available on structural damage as one concept. However, the differential aspect of the effects on bone and cartilage could yield interesting information. Comparative information of these aspects can be based only on radiographic data on erosions and JSN. Both erosions and JSN are the consequence of inflammation, and their progression is inhibited by drugs that inhibit inflammation. These two processes often occur in parallel but joints in which erosions are present show a preference for progression of erosions and, to a lesser extent, development of JSN. The reverse is true for joints with JSN present, where there is a preference for worsening of JSN over development of erosions. Repair is possible for erosions as well as JSN and this is related to the absence of inflammation and effective treatment (especially methotrexate in combination with a tumour necrosis factor blocker).
Nonadherence in hemodialysis: Associations with mortality, hospitalization, and practice patterns in the DOPPS
Authors: Rajiv Saran, Jennifer L Bragg-Gresham, Hugh C Rayner, David A Goodkin, Marcia L Keen, Paul C Van Dijk, Kiyoshi Kurokawa, Luis Piera, Akira Saito, Shunichi Fukuhara, Eric W Young, Philip J Held, Friedrich K Port
Journal: Kidney International (2003)
Dietary regimen and performance of high intensity ergometer exercise.
Authors: J A White, S Harridge, D Stensil, A Wyeth
Journal: British Journal of Sports Medicine (1988)

The influence of preceding diet (mixed, MD; carbohydrate CD; protein PD) on performance during high intensity endurance cycling was examined in six middle distance runners. Subjects undertook cycle ergometer exercise at a workload equivalent to 80% VO2 max until exhaustion following each of the three dietary regimens. Dietary analyses were performed using a computerised evaluation technique and cardiorespiratory, blood glucose and lactate responses to exercise were measured along with exercise time to exhaustion. Significant differences in carbohydrate and protein intakes were noted between respective diets as well as significantly higher total energy intake in MD (P less than 0.05). A significant relationship was observed between carbohydrate intake and exercise time to exhaustion (r = 0.59, P less than 0.05). No significant differences were noted in cardiorespiratory measures or blood glucose response after exhaustive exercise between the three dietary regimens but peak blood lactate concentration was lower following PD (P less than 0.05). Total time to exhaustion was significantly higher on CD (1070.0 +/- 106.7 s) than on PD (642.5 +/- 84.3 s, P less than 0.01). Performance time on MD (895.7 +/- 84.3 s) did not differ significantly for performance time on either CD or PD. It was concluded that dietary manipulation significantly improves exercise time to exhaustion during short term, high intensity cycling.
Islet-cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance?
Authors: Daniël H. van Raalte, Kelly A.A. Kwa, Renate E. van Genugten, Maarten E. Tushuizen, Jens J. Holst, Carolyn F. Deacon, John M. Karemaker, Robert J. Heine, Andrea Mari, Michaela Diamant
Journal: Metabolism (2012)
Pre-implantation genetic diagnosis in pulmonary arterial hypertension due to<i>BMPR2</i>mutation: Figure 1–
Authors: Nelly Frydman, Julie Steffann, Barbara Girerd, René Frydman, Arnold Munnich, Gérald Simonneau, Marc Humbert
Journal: European Respiratory Journal (2012)

Pre-implantation genetic diagnosis in pulmonary arterial hypertension due to BMPR2 mutationTo the Editors:Pulmonary arterial hypertension (PAH) is a rare and severe condition that may present as familial/heritable disease [1-3].In recent years, there have been considerable advances in the management of PAH and disease-specific therapies have improved survival rates [3][4][5].Nevertheless, PAH remains a devastating disease with progressively debilitating symptoms and high mortality even in the modern management era [6,7].
Targeting of gut specific leucocyte recruitment in IBD by vedolizumab
Authors: Bertus Eksteen
Journal: Gut (2014)

IBD is characterised by an inappropriate immune response to our own gut microbiota in the setting of a genetically susceptible individual. The consequence of this dysregulated process is activation of the innate immune system which in turn produces cytokines such as tumour necrosis factor α (TNFα) and activation of the adaptive immune system with subsequent recruitment of pro-inflammatory T and B cells to the colon or small bowel. This in turn leads to further amplification of pro-inflammatory cytokines release which bind to cognate receptors and activation of intercellular pathway such as JAK and STAT to mediate tissue inflammation. The mainstay of treatment for individuals with moderate to severe disease UC or Crohn's disease has been therapeutic targeting of the pro-inflammatory cytokine, TNFα. Unfortunately, a significant proportion of individuals will be refractory to these medications or eventually lose efficacy. This has widened the search for other pathways that might be targeted to treat IBD. The most advanced of these treatments are the integrin inhibitors that target trafficking of lymphocytes to the gut.1

The maintenance of gut immunity is critically dependent on regional immune responses that are generated in the gut-associated lymphoid tissues. Dendritic cells (DCs) are positioned within the lamina propria in close relation to the enterocytes to continuously monitor the micro environment for potential antigens. Once an antigen is detected, gut DCs migrate to the mesenteric lymph nodes and the Peyer's patches. Within these secondary lymphoid tissues, DCs imprint on naive T and B cells’ knowledge of the antigen to generate an appropriate immune response. DC–lymphocyte priming conveys recognition of the antigen and the shape of the immune response required such as a …
Progression Risk, Urinary Protein Excretion, and Treatment Effects of Angiotensin-Converting Enzyme Inhibitors in Nondiabetic Kidney Disease
Authors: David M. Kent, Tazeen H. Jafar, Rodney A. Hayward, Hocine Tighiouart, Marcia Landa, Paul de Jong, Dick de Zeeuw, Giuseppe Remuzzi, Anne-Lise Kamper, Andrew S. Levey
Journal: Journal of the American Society of Nephrology (2007)

It is unclear whether patients with nondiabetic kidney disease benefit from angiotensin-converting enzyme inhibitor (ACEI) therapy when they are at low risk for disease progression or when they have low urinary protein excretion. With the use of a combined database from 11 randomized, clinical trials (n = 1860), a Cox proportional hazards model, based on known predictors of risk and the composite outcome kidney failure or creatinine doubling, was developed and used to stratify patients into equal-sized quartiles of risk. Outcome risk and treatment effect were examined across various risk strata. Use of this risk model for targeting ACEI therapy was also compared with a strategy based on urinary protein excretion alone. Control patients in the highest quartile of predicted risk had an annualized outcome rate of 28.7%, whereas control patients in the lowest quartile of predicted risk had an annualized outcome rate of 0.4%. Despite the extreme variation in risk, there was no variation in the degree of benefit of ACEI therapy (P = 0.93 for the treatment x risk interaction). Significant interaction was detected between baseline urine protein and ACEI therapy (P = 0.003). When patients were stratified according to their baseline urinary protein excretion, among the subgroup of patients with proteinuria > or =500 mg/d, significant treatment effect was seen across all patients with a measurable outcome risk, including those at relatively low risk (1.7% annualized risk for progression). However, there was no benefit of ACEI therapy among patients with proteinuria <500 mg/d, even among higher risk patients (control outcome rate 19.7%). Patients with nondiabetic kidney disease vary considerably in their risk for disease progression, but the treatment effect of ACEI does not vary across risk strata. Patients with proteinuria <500 mg/d do not seem to benefit, even when at relatively high risk for progression.
MET Receptor Sequence Variants R970C and T992I Lack Transforming Capacity
Authors: Jeffrey W. Tyner, Luke B. Fletcher, Ellen Q. Wang, Wayne F. Yang, Michael L. Rutenberg-Schoenberg, Carol Beadling, Motomi Mori, Michael C. Heinrich, Michael W. Deininger, Brian J. Druker, Marc M. Loriaux
Journal: Cancer Research (2010)

Abstract High-throughput sequencing promises to accelerate the discovery of sequence variants, but distinguishing oncogenic mutations from irrelevant “passenger” mutations remains a major challenge. Here we present an analysis of two sequence variants of the MET receptor (hepatocyte growth factor receptor) R970C and T992I (also designated R988C and T1010I). Previous reports indicated that these sequence variants are transforming and contribute to oncogenesis. We screened patients with chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), colorectal cancer, endometrial cancer, thyroid cancer, or melanoma, as well as individuals without cancer, and found these variants at low frequencies in most cohorts, including normal individuals. No evidence of increased phosphorylation or transformative capacity by either sequence variant was found. Because small-molecule inhibitors for MET are currently in development, it will be important to distinguish between oncogenic sequence variants and rare single-nucleotide polymorphisms to avoid the use of unnecessary, and potentially toxic, cancer therapy agents. Cancer Res; 70(15); 6233–7. ©2010 AACR.
Long-Term Results of a Randomized Trial of Surgery With or Without Preoperative Chemotherapy in Esophageal Cancer
Authors: William H. Allum, Sally P. Stenning, John Bancewicz, Peter I. Clark, Ruth E. Langley
Journal: Journal of Clinical Oncology (2009)

OEO2 is a randomized, controlled trial of preoperative chemotherapy in patients undergoing radical surgery for esophageal cancer. Random assignment was to surgery alone (S) or to two cycles of combination cisplatin and fluorouracil before surgery (CS). Initial results reported in 2002 demonstrated an advantage for both disease-free and overall survival in the CS group. The analysis has now been updated after a median follow-up of 6 years.OEO2 recruited 802 patients, 400 on CS and 402 on S. The nature of the first recurrence event and cause of death are detailed. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test. Survival by extent of resection is presented.There were 655 deaths, 335 for S and 320 for CS. The survival benefit has been maintained with a hazard ratio (HR) of 0.84 (95% CI, 0.72 to 0.98; P = .03) which in absolute terms is a 5-year survival of 23.0% for CS compared with 17.1% for S. The treatment effect is consistent in both adenocarcinoma and squamous cell carcinoma. The first disease-free survival event was macroscopic residual disease from incomplete resection (R2) or no resection in 26.4% of the S group versus 14.3% of the CS P < .001. Three-year survival by type of resection was R0 42.4%, R1 was 18.0%, and R2 was 8.6%.Long-term follow-up confirms that preoperative chemotherapy improves survival in operable esophageal cancer and should be considered as a standard of care.
Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia
Authors: Ana Flávia Tibúrcio Ribeiro, Marta Pratcorona, Claudia Erpelinck-Verschueren, Veronika Rockova, Mathijs Sanders, Saman Abbas, Maria E. Figueroa, Annelieke Zeilemaker, Ari Melnick, Bob Löwenberg, Peter J. M. Valk, Ruud Delwel
Journal: Blood (2012)
Dialyzer reuse and the treatment of patients with end-stage renal disease by hemodialysis.
Authors: P L Kimmel, G J Mishkin
Journal: Journal of the American Society of Nephrology (1998)

Journal of the American Society of Nephrology : JASN 9(11):p 2153-2156, November 1998. | DOI: 10.1681/ASN.V9112153