tbuckley/cabot-search huggingface dataset:
Body mass index, fitness and physical activity from childhood through adolescence
Authors: Katja Pahkala, Miika Hernelahti, Olli J Heinonen, Päivi Raittinen, Maarit Hakanen, Hanna Lagström, Jorma S A Viikari, Tapani Rönnemaa, Olli T Raitakari, Olli Simell
Journal: British Journal of Sports Medicine (2012)

Background Obesity, sedentary lifestyle and poor cardiorespiratory fitness in childhood may increase the risk of health problems later in life. Purpose The authors studied the association of early childhood weight status with cardiorespiratory fitness and leisure-time physical activity (LTPA) in adolescence. The stability and associations of LTPA and fitness from childhood through adolescence were also studied. Methods Body mass index (BMI) was assessed annually since birth in a prospective, longitudinal study. The mean BMI between ages 2 and 7 years indicated weight status at preschool age. Fitness was studied with a shuttle run test at age 9 and with a maximal cycle ergometer test at age 17. The same questionnaire was used to assess LTPA at age 9, 13 and 17. Complete data on preschool BMI, LTPA at ages 13 and 17 and fitness at age 17 years was provided by 351 children, while fitness and LTPA data were available for 74 children at ages 9 and 17. Results Preschool BMI was inversely associated with fitness in adolescence independently of adolescent LTPA (p=0.0001). Children who had a high preschool BMI but whose weight status was reduced in adolescence had similar fitness in adolescence as the children with a persistently low BMI. Regardless of the fitness level in childhood, the children whose LTPA increased between age 9 and 17 had a similar adolescent fitness level as persistently active subjects. Conclusions It is important to maintain a healthy body weight and a physically active lifestyle from very childhood through adolescence to improve fitness during adolescence.
Profiling markers of prognosis in colorectal cancer.
Authors: Matthew S Lyall, Sinclair R Dundas, Stephanie Curran, Graeme I Murray
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: Colorectal cancer is one of the most common forms of cancer in developed nations and the incidence of this disease is increasing. There is a need to further stratify prognostically distinct groups of colorectal cancer, and the purpose of this study was to identify prognostically significant immunohistochemical marker profiles in colorectal cancer. EXPERIMENTAL DESIGN: In this study, a range (n = 23) of markers [pRb, p16, p21, p27, p53, proliferating cell nuclear antigen, cyclin D1, bcl-2, epidermal growth factor receptor, C-erb-B2, topoisomerase-I, liver fatty acid-binding protein, matrix metalloproteinases (MMP) 1-3, 7, 9, and 13, MT1-MMP, MT2-MMP, and tissue inhibitors of MMP 1-3] of putative prognostic significance have been investigated by immunohistochemistry on formalin-fixed, wax-embedded sections in a series (n = 90) of stage III (Dukes C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and, where relevant, the proportion of immunoreactive cells was established for each marker. RESULTS: Unsupervised two-dimensional hierarchical cluster analysis identified three distinct cluster groups (designated groups 1-3) with different marker profiles. There were significant survival differences between groups 1 and 2 (log rank = 11.48; P = 0.0007) and between groups 1 and 3 (log rank = 8.32; P = 0.0039). Multivariate analysis showed that the complete marker profile was independently the most significant prognostic factor (hazard ratio, 2.27; 95% confidence interval, 1.15-4.48; P = 0.004). CONCLUSIONS: This study has identified an immunohistochemical marker profile of colorectal cancer and showed that it is an independent indicator of prognosis in this type of cancer.
R-RAS2 overexpression in tumors of the human central nervous system
Authors: Sylvia Gutierrez-Erlandsson, Pedro Herrero-Vidal, Marcos Fernandez-Alfara, Susana Hernandez-Garcia, Sandra Gonzalo-Flores, Alberto Mudarra-Rubio, Manuel Fresno, Beatriz Cubelos
Journal: Molecular Cancer (2013)

Abstract Malignant tumors of the central nervous system (CNS) are the 10 th most frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of the RAS family of small GTPases. This raises the question as to whether other RAS family members may be affected in CNS tumors, excessively activating RAS pathways. The RAS -related subfamily of GTPases is that which is most closely related to classical Ras and it currently contains 3 members: RRAS , RRAS2 and RRAS3 . While R-RAS and R-RAS2 are expressed ubiquitously, R-RAS3 expression is restricted to the CNS. Significantly, both wild type and mutated RRAS2 (also known as TC21) are overexpressed in human carcinomas of the oral cavity, esophagus, stomach, skin and breast, as well as in lymphomas. Hence, we analyzed the expression of R-RAS2 mRNA and protein in a wide variety of human CNS tumors and we found the R-RAS2 protein to be overexpressed in all of the 90 CNS cancer samples studied, including glioblastomas, astrocytomas and oligodendrogliomas. However, R-Ras2 was more strongly expressed in low grade (World Health Organization grades I-II) rather than high grade (grades III-IV) tumors, suggesting that R-RAS2 is overexpressed in the early stages of malignancy. Indeed, R-RAS2 overexpression was evident in pre-malignant hyperplasias, both at the mRNA and protein levels. Nevertheless, such dramatic changes in expression were not evident for the other two subfamily members, which implies that RRAS2 is the main factor triggering neural transformation.
Response to Comment on: Cryer. Severe Hypoglycemia Predicts Mortality in Diabetes. Diabetes Care 2012;35:1814–1816
Authors: Philip E. Cryer
Journal: Diabetes Care (2013)

I am pleased that Kerner and Volzke (1) believe, based on their experience and assumptions, that the death rate from hypoglycemia in their patients with type 1 diabetes is lower than in the published literature. In my commentary (2) on the report of McCoy et al. (3) of a 3.4-fold higher mortality in patients with diabetes who self-reported severe hypoglycemia …
Cetuximab and First-Line Taxane/Carboplatin Chemotherapy in Advanced Non–Small-Cell Lung Cancer: Results of the Randomized Multicenter Phase III Trial BMS099
Authors: Thomas J. Lynch, Taral Patel, Luke Dreisbach, Michael McCleod, William J. Heim, Robert C. Hermann, Eugene Paschold, Nicholas O. Iannotti, Shaker Dakhil, Steven Gorton, Virginie Pautret, Martin R. Weber, Donald Woytowitz
Journal: Journal of Clinical Oncology (2010)

PURPOSE To evaluate the efficacy of cetuximab plus taxane/carboplatin (TC) as first-line treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS This multicenter, open-label, phase III study enrolled 676 chemotherapy-naïve patients with stage IIIB (pleural effusion) or IV NSCLC, without restrictions by histology or epidermal growth factor receptor expression. Patients were randomly assigned to cetuximab/TC or TC. TC consisted of paclitaxel (225 mg/m(2)) or docetaxel (75 mg/m(2)), at the investigator's discretion, and carboplatin (area under the curve = 6) on day 1 every 3 weeks for < or = six cycles; cetuximab (400 mg/m(2) on day 1, 250 mg/m(2) weekly) was administered until progression or unacceptable toxicity. The primary end point was progression-free survival assessed by independent radiologic review committee (PFS-IRRC); overall response rate (ORR), overall survival (OS), quality of life (QoL), and safety were key secondary end points. PFS and ORR assessed by investigators were also evaluated. Results Median PFS-IRRC was 4.40 months with cetuximab/TC versus 4.24 months with TC (hazard ratio [HR] = 0.902; 95% CI, 0.761 to 1.069; P = .236). Median OS was 9.69 months with cetuximab/TC versus 8.38 months with TC (HR = 0.890; 95% CI, 0.754 to 1.051; P = .169). ORR-IRRC was 25.7% with cetuximab/TC versus 17.2% with TC (P = .007). The safety profile of this combination was manageable and consistent with its individual components. CONCLUSION The addition of cetuximab to TC did not significantly improve the primary end point, PFS-IRRC. There was significant improvement in ORR by IRRC. The difference in OS favored cetuximab but did not reach statistical significance.
Induction of γδ T-lymphocyte effector functions by bisphosphonate zoledronic acid in cancer patients in vivo
Authors: Francesco Dieli, Nicola Gebbia, Fabrizio Poccia, Nadia Caccamo, Carla Montesano, Fabio Fulfaro, Carlo Arcara, Maria R. Valerio, Serena Meraviglia, Caterina Di Sano, Guido Sireci, Alfredo Salerno
Journal: Blood (2003)
Anti-CD20 Antibody Promotes Cancer Escape via Enrichment of Tumor-Evoked Regulatory B Cells Expressing Low Levels of CD20 and CD137L
Authors: Monica Bodogai, Catalina Lee Chang, Katarzyna Wejksza, Jinping Lai, Maria Merino, Robert P. Wersto, Ronald E. Gress, Andrew C. Chan, Charles Hesdorffer, Arya Biragyn
Journal: Cancer Research (2013)

Abstract The possible therapeutic benefits of B-cell depletion in combating tumoral immune escape have been debated. In support of this concept, metastasis of highly aggressive 4T1 breast cancer cells in mice can be abrogated by inactivation of tumor-evoked regulatory B cells (tBreg). Here, we report the unexpected finding that B-cell depletion by CD20 antibody will greatly enhance cancer progression and metastasis. Both murine and human tBregs express low levels of CD20 and, as such, anti-CD20 mostly enriches for these cells. In the 4T1 model of murine breast cancer, this effect of enriching for tBregs suggests that B-cell depletion by anti-CD20 may not be beneficial at all in some cancers. In contrast, we show that in vivo–targeted stimulation of B cells with CXCL13-coupled CpG oligonucleotides (CpG-ODN) can block cancer metastasis by inhibiting CD20Low tBregs. Mechanistic investigations suggested that CpG-ODN upregulates low surface levels of 4-1BBL on tBregs to elicit granzyme B–expressing cytolytic CD8+ T cells, offering some explanative power for the effect. These findings underscore the immunotherapeutic importance of tBreg inactivation as a strategy to enhance cancer therapy by targeting both the regulatory and activating arms of the immune system in vivo. Cancer Res; 73(7); 2127–38. ©2013 AACR.
Decreased levels of serum soluble HLA class I antigens in HLA-B27 positive spondyloarthropathies
Authors: Eric Toussirot, Philippe Saas, J. Pariset, J. Chabod, Pierre Tiberghien, Daniel Wendling
Journal: Annals of the Rheumatic Diseases (2006)

Human leucocyte class I antigens (HLA-I) are expressed on the surface of all nucleated cells but can also be found in soluble forms. These soluble HLA-I (sHLA-I) molecules can be produced by either membrane shedding, proteolysis of the intact heavy chain, or by alternative splicing.1 They have been implicated in regulatory functions and have immunomodulatory properties.2 Increased levels of sHLA-I were found during graft rejections, in various infectious (cytomegalovirus, hepatitis B or C, HIV infection, active tuberculosis) and autoimmune diseases.3–6 In systemic lupus erythematosus and rheumatoid arthritis, levels of sHLA-I antigens correlate with disease activity.4,6 Spondyloarthropathies (SpA) are conditions closely linked to HLA-B27, a class I antigen. Thus, in this study, we evaluated the serum concentrations of sHLA-I antigens in a large cohort of patients with SpA.

One hundred and twenty three patients …
Using Health-Related Quality of Life Measures to Predict Cardiac Function in Survivors Exposed to Anthracyclines
Authors: Jill P. Ginsberg, Avital Cnaan, Huaqing Zhao, Bernard J. Clark, Stephen M. Paridon, Alvin J. Chin, Jack Rychik, Alexa N. Hogarty, Gerald Barber, Monika Rutkowski, Thomas R. Kimball, Cynthia DeLaat, Laurel J. Steinherz, Jeffrey H. Silber
Journal: Journal of Clinical Oncology (2004)

As the number of pediatric cancer survivors increases, so does the number of survivors previously exposed to anthracyclines as part of their cancer therapy. Because screening is costly, some have suggested that health-related quality of life (HRQL) measures might be useful in focusing screening tests on those patients with cases most likely to display positive findings. This study reports on the predictive ability of HRQL measures to detect patients with abnormalities on serial cardiac testing.Using 127 patients from the ACE-Inhibitor after Anthracycline (AAA) Trial, this study compared serial measures of the Short Form-36 (SF-36; for ages > 13 years) and Child Health Questionnaire-Child Form 87 (CHQ-CF87; for ages < or = 13 years) to serial cardiac performance tests including echocardiographic shortening fraction, left ventricular end systolic wall stress (LVESWS), LVESWS-index, and maximal cardiac index (MCI; a measure of cardiac output at peak exercise).Generally, there was no clinically or statistically significant correlation between any HRQL measure and any cardiac function measure except between MCI and vitality and physical functioning. For each of these measures, the correlation between MCI was statistically significant (P < .006), but each HRQL subscale could explain no more than 7% of the variation in MCI. HRQL measures were not predictive of any other cardiac function measure.HRQL measures should not be used in isolation as a screen for cardiac function abnormalities in patients exposed to anthracylines who already have a mild degree of ventricular dysfunction. Patient history appears to be no substitute for cardiac testing in this cohort.
MASSIVE DOSES OF TRIFLUOPERAZINE IN THE TREATMENT OF COMPULSIVE RITUALS
Authors: MILTON ALTSCHULER
Journal: American Journal of Psychiatry (1962)

1. Five of twelve patients with severe compulsive rituals showed improvement in symptomatology on high doses of trifluoperazine. 2. Blood and urine studies remained stable throughout the study. 3. Minor dystonic side effects were noted that were readily reversible when the drug was decreased or discontinued.
UNG shapes the specificity of AID-induced somatic hypermutation
Authors: Pablo Pérez-Durán, Laura Belver, Virginia G. de Yébenes, Pilar Delgado, David G. Pisano, Almudena R. Ramiro
Journal: The Journal of Experimental Medicine (2012)

Secondary diversification of antibodies through somatic hypermutation (SHM) and class switch recombination (CSR) is a critical component of the immune response. Activation-induced deaminase (AID) initiates both processes by deaminating cytosine residues in immunoglobulin genes. The resulting U:G mismatch can be processed by alternative pathways to give rise to a mutation (SHM) or a DNA double-strand break (CSR). Central to this processing is the activity of uracil-N-glycosylase (UNG), an enzyme normally involved in error-free base excision repair. We used next generation sequencing to analyze the contribution of UNG to the resolution of AID-induced lesions. Loss- and gain-of-function experiments showed that UNG activity can promote both error-prone and high fidelity repair of U:G lesions. Unexpectedly, the balance between these alternative outcomes was influenced by the sequence context of the deaminated cytosine, with individual hotspots exhibiting higher susceptibility to UNG-triggered error-free or error-prone resolution. These results reveal UNG as a new molecular layer that shapes the specificity of AID-induced mutations and may provide new insights into the role of AID in cancer development.
Red Wine Polyphenols Inhibit Vascular Smooth Muscle Cell Migration Through Two Distinct Signaling Pathways
Authors: Katsuya Iijima, Masao Yoshizumi, Masayoshi Hashimoto, Masahiro Akishita, Koichi Kozaki, Junya Ako, Tokumitsu Watanabe, Yumiko Ohike, Bokyung Son, Jing Yu, Koichi Nakahara, Yasuyoshi Ouchi
Journal: Circulation (2002)

Red wine polyphenols (RWPs) have been shown to have an antiatherogenic activity mainly through antioxidative effects on LDL oxidation. Although vascular smooth muscle cell (SMC) migration is critical to atherosclerosis formation, the effect of RWPs on SMC migration has not been elucidated. In this study, we investigated whether RWPs could affect the migration of cultured SMCs stimulated by growth factors.RWP concentration dependently inhibited platelet-derived growth factor (PDGF)-BB-induced and serum-induced SMC migration in wounding assay and Boyden chamber assay. However, these inhibitory effects of RWPs were not seen in serum-stimulated vascular endothelial cell migration in either assay. Moreover, specific inhibitors of phosphatidylinositol-3' kinase (PI3K) and p38 mitogen-activated protein kinase (p38(MAPK)), but not of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), reduced PDGF-BB-induced SMC migration. To elucidate the signaling mechanism underlying the RWP effects, we investigated the effects of RWPs on the activity of PI3K and the phosphorylation of MAPK pathways in PDGF-BB-stimulated SMCs. RWPs inhibited the PI3K activity and p38(MAPK) phosphorylation, but not ERK1/2 phosphorylation, in a concentration-dependent manner. Moreover, the phosphorylation of MKK3/6, an upstream kinase of p38(MAPK), was also inhibited by RWP treatment in a concentration-dependent manner, suggesting that the inhibitory effect of RWPs on the p38(MAPK) pathway works upstream of MKK3/6. The concentration-effect relationship of RWPs necessary for the inhibition of PI3K and p38(MAPK) pathways was similar to that of cell migration assays.RWPs inhibit the SMC migration through the inhibition of 2 distinct signaling pathways and thus exert antiatherogenic actions.
Effect of high-dose intravenous immunoglobulin in delayed pressure urticaria
Authors: G. Dawn, M. Urcelay, A. Ah-Weng, S.M. O'Neill, W.S. Douglas
Journal: British Journal of Dermatology (2003)

Delayed pressure urticaria (DPU) is difficult to treat. High-dose intravenous immunoglobulin (IVIG) has been found to be effective in treating patients with autoimmune chronic urticaria.To report the effect of IVIG on eight patients with severe unremitting DPU.IVIG was administered at a dose of 2 g kg-1 over 2-3 days on an in-patient basis. The response to treatment was assessed subjectively and recorded as remission, improved or unchanged. An autologous serum skin test (ASST) was performed in seven patients.Three of eight patients achieved remission; two after one infusion and one after three infusions. Two patients improved. Three patients remained unchanged; of these, two declined further treatment after two infusions, and one failed to improve after six infusions at monthly intervals. Four of seven patients had positive ASST; three responded to IVIG. Two developed delayed positive ASST; both responded to IVIG. Of three patients with negative ASST, two responded.IVIG induced remission or improved symptoms in five of eight patients with DPU with severe unremitting disease who had failed to respond to other therapies or were controlled only with systemic corticosteroids. Those who responded did so with three or fewer infusions. ASST is not a reliable predictor of response to IVIG.
Metformin use and mortality in patients with advanced chronic kidney disease: national, retrospective, observational, cohort study
Authors: Szu-Chun Hung, Yu-Kang Chang, Jia-Sin Liu, Ko-Lin Kuo, Yu-Hsin Chen, Chih-Cheng Hsu, Der-Cherng Tarng
Journal: The Lancet Diabetes & Endocrinology (2015)
Airway Wall Thickening and Emphysema Show Independent Familial Aggregation in Chronic Obstructive Pulmonary Disease
Authors: Bipen D. Patel, Harvey O. Coxson, Sreekumar G. Pillai, Alvar G. N. Agustí, Peter M. A. Calverley, Claudio F. Donner, Barry J. Make, Nestor L. Müller, Stephen I. Rennard, Jørgen Vestbo, Emiel F. M. Wouters, Melanie P. Hiorns, Yasutaka Nakano, Patricia G. Camp, Paola V. Nasute Fauerbach, Nicholas J. Screaton, Edward J. Campbell, Wayne H. Anderson, Peter D. Paré, Robert D. Levy, Stephen L. Lake, Edwin K. Silverman, David A. Lomas
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families.Objectives: To determine whether airway wall thickening and emphysema (1) make independent contributions to the severity of COPD and (2) show independent aggregation in families of individuals with COPD.Methods: Index cases with COPD and their smoking siblings underwent spirometry and were offered high-resolution computed tomography scans of the thorax to assess the severity of airway wall thickening and emphysema.Measurements and Main Results: A total of 3,096 individuals were recruited to the study, of whom 1,159 (519 probands and 640 siblings) had technically adequate high-resolution computed tomography scans without significant non–COPD-related thoracic disease. Airway wall thickness correlated with pack-years smoked (P ≤ 0.001) and symptoms of chronic bronchitis (P < 0.001). FEV1 (expressed as % predicted) was independently associated with airway wall thickness at a lumen perimeter of 10 mm (P = 0.0001) and 20 mm (P = 0.0013) and emphysema at −950 Hounsfield units (P < 0.0001). There was independent familial aggregation of both the emphysema (adjusted odds ratio, 2.1; 95% confidence interval, 1.1–4.0; P ≤ 0.02) and airway disease phenotypes (P < 0.0001) of COPD.Conclusions: Airway wall thickening and emphysema make independent contributions to airflow obstruction in COPD. These phenotypes show independent aggregation within families of individuals with COPD, suggesting that different genetic factors influence these disease processes.
Resynchronization of Separated Rat Cardiomyocyte Fields With Genetically Modified Human Ventricular Scar Fibroblasts
Authors: Daniël A. Pijnappels, John van Tuyn, Antoine A.F. de Vries, Robert W. Grauss, Arnoud van der Laarse, Dirk L. Ypey, Douwe E. Atsma, Martin J. Schalij
Journal: Circulation (2007)

Nonresponse to cardiac resynchronization therapy is associated with the presence of slow or nonconducting scar tissue. Genetic modification of scar tissue, aimed at improving conduction, may be a novel approach to achieve effective resynchronization. Therefore, the feasibility of resynchronization with genetically modified human ventricular scar fibroblasts was studied in a coculture model.An in vitro model was used to study the effects of forced expression of the myocardin (MyoC) gene in human ventricular scar fibroblasts (hVSFs) on resynchronization of 2 rat cardiomyocyte fields separated by a strip of hVSFs. Furthermore, the effects of MyoC expression on the capacity of hVSFs to serve as pacing sites were studied. MyoC-dependent gene activation in hVSFs was examined by gene and immunocytochemical analysis. Forced MyoC expression in hVSFs decreased dyssynchrony, expressed as the activation delay between 2 cardiomyocyte fields (control hVSFs 27.6+/-0.2 ms [n=11] versus MyoC-hVSFs 3.6+/-0.3 ms [n=11] at day 8, P<0.01). Also, MyoC-hVSFs could be stimulated electrically, which resulted in simultaneous activation of the 2 adjacent cardiomyocyte fields. Forced MyoC expression in hVSFs led to the expression of various connexin and cardiac ion channel genes. Intracellular measurements of MyoC-hVSFs coupled to surrounding cardiomyocytes showed strongly improved action potential conduction.Forced MyoC gene expression in hVSFs allowed electrical stimulation of these cells and conferred the ability to conduct an electrical impulse at high velocity, which resulted in resynchronization of 2 separated cardiomyocyte fields. Both phenomena appear mediated mainly by MyoC-dependent activation of genes that encode connexins, strongly enforcing intercellular electrical coupling.