tbuckley/cabot-search huggingface dataset:
Functional Genomic Analysis Identified Epidermal Growth Factor Receptor Activation as the Most Common Genetic Event in Oral Squamous Cell Carcinoma
Authors: Jim Jinn-Chyuan Sheu, Chun-Hung Hua, Lei Wan, Ying-Ju Lin, Ming-Tsung Lai, Hsien-Chang Tseng, Natini Jinawath, Ming-Hsui Tsai, Nai-Wen Chang, Chin-Fen Lin, Chyi-Chyang Lin, Lie-Jiau Hsieh, Tian-Li Wang, Ie-Ming Shih, Fuu-Jen Tsai
Journal: Cancer Research (2009)

Abstract A 250K single-nucleotide polymorphism array was used to study subchromosomal alterations in oral squamous cell carcinoma (OSCC). The most frequent amplification was found at 7p11.2 in 9 of 29 (31%) oral cancer patients. Minimal genomic mapping verified a unique amplicon spanning from 54.6 to 55.3 Mb on chromosome 7, which contains SEC61G and epidermal growth factor receptor (EGFR). Results from fluorescence in situ hybridization, transcriptome, and immunohistochemistry analyses indicated that the expression level of EGFR, but not of SEC61G, was up-regulated and tightly correlated with DNA copy number in 7p11.2 amplified tumors. Among the members of the erbB family, EGFR (HER1) was found to be the most frequently amplified and highly expressed gene in both human and mouse oral tumors (P &amp;lt; 0.01). Genes for downstream effectors of EGFR, including KRAS, mitogen-activated protein kinase 1, and CCND1, were also found amplified or mutated, which resulted in activation of EGFR signaling in 55% of OSCC patients. Head and neck squamous cancer cells with different EGFR expression levels showed differential sensitivity to antitumor effects of AG1478, a potent EGFR inhibitor. AG1478-induced EGFR inactivation significantly suppressed tumor development and progression in a mouse oral cancer model. Our data suggest that EGFR signaling is important in oral cancer development and that anti-EGFR therapy would benefit patients who carry the 7p11.2 amplicon in their tumors. [Cancer Res 2009;69(6):2568–76]
Prevalence of Childhood and Adult Obesity in the United States, 2011-2012
Authors: Cynthia L. Ogden, Margaret D. Carroll, Brian K. Kit, Katherine M. Flegal
Journal: JAMA (2014)

More than one-third of adults and 17% of youth in the United States are obese, although the prevalence remained stable between 2003-2004 and 2009-2010.To provide the most recent national estimates of childhood obesity, analyze trends in childhood obesity between 2003 and 2012, and provide detailed obesity trend analyses among adults.Weight and height or recumbent length were measured in 9120 participants in the 2011-2012 nationally representative National Health and Nutrition Examination Survey.In infants and toddlers from birth to 2 years, high weight for recumbent length was defined as weight for length at or above the 95th percentile of the sex-specific Centers for Disease Control and Prevention (CDC) growth charts. In children and adolescents aged 2 to 19 years, obesity was defined as a body mass index (BMI) at or above the 95th percentile of the sex-specific CDC BMI-for-age growth charts. In adults, obesity was defined as a BMI greater than or equal to 30. Analyses of trends in high weight for recumbent length or obesity prevalence were conducted overall and separately by age across 5 periods (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012).In 2011-2012, 8.1% (95% CI, 5.8%-11.1%) of infants and toddlers had high weight for recumbent length, and 16.9% (95% CI, 14.9%-19.2%) of 2- to 19-year-olds and 34.9% (95% CI, 32.0%-37.9%) of adults (age-adjusted) aged 20 years or older were obese. Overall, there was no significant change from 2003-2004 through 2011-2012 in high weight for recumbent length among infants and toddlers, obesity in 2- to 19-year-olds, or obesity in adults. Tests for an interaction between survey period and age found an interaction in children (P = .03) and women (P = .02). There was a significant decrease in obesity among 2- to 5-year-old children (from 13.9% to 8.4%; P = .03) and a significant increase in obesity among women aged 60 years and older (from 31.5% to 38.1%; P = .006).Overall, there have been no significant changes in obesity prevalence in youth or adults between 2003-2004 and 2011-2012. Obesity prevalence remains high and thus it is important to continue surveillance.
Risk of Lymphoproliferative Malignancy in Relation to Small Intestinal Histopathology Among Patients With Celiac Disease
Authors: P. Elfstrom, F. Granath, K. Ekstrom Smedby, S. M. Montgomery, J. Askling, A. Ekbom, J. F. Ludvigsson
Journal: JNCI Journal of the National Cancer Institute (2011)

Celiac disease is associated with an increased risk of malignant lymphomas. The risk of lymphoproliferative malignancies in patients with small intestinal inflammation without villous atrophy and in patients with latent celiac disease is unknown.We performed a cohort study using duodenal and jejunal biopsy data that were collected from all 28 Swedish pathology departments (July 1969 to February 2008). We identified two population-based cohorts composed of 28,989 individuals with biopsy-verified celiac disease (villous atrophy, Marsh stage 3) and 13,140 individuals with small intestinal inflammation without villous atrophy (Marsh 1 + 2) and a regional cohort of 3711 individuals with latent celiac disease (positive celiac disease serology and normal mucosa). Cancer data were obtained by linkage to the National Cancer Registry. We used Cox regression to estimate hazard ratios (HRs) for lymphoproliferative malignancy and any solid cancer among the three cohorts compared with a total of 227,911 age- and sex-matched reference individuals.Although biopsy-verified celiac disease and intestinal inflammation were associated with lymphoproliferative malignancy (for celiac disease, HR = 2.82; 95% confidence interval [CI] = 2.36 to 3.37, n = 193; for inflammation, HR = 1.81; 95% CI = 1.42 to 2.31, n = 89), latent celiac disease was not associated with lymphoproliferative malignancy (HR = 0.97; 95% CI = 0.44 to 2.14, n = 7). The absolute rates of lymphoproliferative malignancies among persons with celiac disease, small intestinal inflammation, and latent celiac disease were 70.3 per 100,000 person-years, 83.4 per 100,000 person-years, and 28.0 per 100,000 person-years, respectively. Compared with individuals with celiac disease, individuals with small intestinal inflammation or latent celiac disease were at a statistically significantly lower risk of lymphoproliferative malignancy. Risk of any solid cancer was not increased beyond the first year of follow-up in any cohort. Celiac disease was associated with Hodgkin lymphoma and both T-cell and B-cell non-Hodgkin lymphomas.The risk of lymphoproliferative malignancy in celiac disease is dependent on small intestinal histopathology, with no increased risk in latent celiac disease.
Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester.
Authors: R N DuBois, J Awad, J Morrow, L J Roberts, P R Bishop
Journal: Journal of Clinical Investigation (1994)

Growth factors and tumor promoters have been shown to play a role in intestinal epithelial growth regulation and transformation. In this study, transforming growth factor-alpha (TGF alpha) and the tumor promoter, tetradecanoyl phorbol acetate (TPA), are shown to stimulate the production of eicosanoids by rat intestinal epithelial (RIE-1) cells in culture. A 4.5-kb mRNA, which hybridizes to the mouse cyclooxygenase-2 cDNA probe, is elevated 18-fold within 30 min after TGF alpha or TPA treatment. Stimulation of RIE-1 cells with TGF alpha leads to the increase of a protein (M(r) approximately 69,000), which binds a monospecific antibody to the mouse cyclooxygenase-2 protein. Dexamethasone markedly inhibits the increase of the 4.5-kb mRNA. Pretreatment of TGF alpha or TPA-stimulated RIE-1 cells with dexamethasone or cyclooxygenase inhibitors prevents the increase in eicosanoid production by these cells. Treatment of quiescent RIE-1 cells with TGF alpha stimulates mitogenesis. This mitogenic activity is blocked by pretreating the cells with dexamethasone or cyclooxygenase inhibitors. A mitogen-inducible cyclooxygenase gene is thus shown to be regulated by TGF alpha and TPA in rat intestinal epithelial cells. We suggest that products of an intestinal growth factor-inducible cyclooxygenase may play a role in the regulation of mitogenesis.
Disruption of Platelet-derived Chemokine Heteromers Prevents Neutrophil Extravasation in Acute Lung Injury
Authors: Jochen Grommes, Jean-Eric Alard, Maik Drechsler, Sarawuth Wantha, Matthias Mörgelin, Wolfgang M. Kuebler, Michael Jacobs, Philipp von Hundelshausen, Philipp Markart, Malgorzata Wygrecka, Klaus T. Preissner, Tilman M. Hackeng, Rory R. Koenen, Christian Weber, Oliver Soehnlein
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Acute lung injury (ALI) causes high mortality, but its molecular mechanisms and therapeutic options remain ill-defined. Gram-negative bacterial infections are the main cause of ALI, leading to lung neutrophil infiltration, permeability increases, deterioration of gas exchange, and lung damage. Platelets are activated during ALI, but insights into their mechanistic contribution to neutrophil accumulation in the lung are elusive.Objectives: To determine mechanisms of platelet-mediated neutrophil recruitment in ALI.Methods: Interference with platelet–neutrophil interactions using antagonists to P-selectin and glycoprotein IIb/IIIa or a small peptide antagonist disrupting platelet chemokine heteromer formation in mouse models of ALI.Measurements and Main Results: In a murine model of LPS-induced ALI, we uncover important roles for neutrophils and platelets in permeability changes and subsequent lung damage. Furthermore, platelet depletion abrogated lung neutrophil infiltration, suggesting a sequential participation of platelets and neutrophils. Whereas antagonists to P-selectin and glycoprotein IIb/IIIa had no effects on LPS-mediated ALI, antibodies to the platelet-derived chemokines CCL5 and CXCL4 strongly diminished neutrophil eflux and permeability changes. The two chemokines were found to form heteromers in human and murine ALI samples, positively correlating with leukocyte influx into the lung. Disruption of CCL5-CXCL4 heteromers in LPS-, acid-, and sepsis-induced ALI abolished lung edema, neutrophil infiltration, and tissue damage, thereby revealing a causal contribution.Conclusions: Taken together, our data identify a novel function of platelet-derived chemokine heteromers during ALI and demonstrate means for therapeutic interference.
Use of a dummy (pacifier) during sleep and risk of sudden infant death syndrome (SIDS): population based case-control study
Authors: De-Kun Li, Marian Willinger, Diana B Petitti, Roxana Odouli, Liyan Liu, Howard J Hoffman
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To examine the association between use of a dummy (pacifier) during sleep and the risk of sudden infant death syndrome (SIDS) in relation to other risk factors. <b>Design</b> Population based case-control study. <b>Setting</b> Eleven counties in California. <b>Participants</b> Mothers or carers of 185 infants whose deaths were attributed to SIDS and 312 randomly selected controls matched for race or ethnicity and age. <b>Main outcome measure</b> Use of a dummy during sleep determined through interviews. <b>Results</b> The adjusted odds ratio for SIDS associated with using a dummy during the last sleep was 0.08 (95% confidence interval 0.03 to 0.21). Use was associated with a reduction in risk in every category of sociodemographic characteristics and risk factors examined. The reduced risk associated with use seemed to be greater with adverse sleep conditions (such as sleeping prone or on side and sleeping with a mother who smoked), although the observed interactions were not significant. In addition, use of a dummy may reduce the impact of other risk factors for SIDS, especially those related to adverse sleep environment. For example, infants who did not use a dummy and slept prone or on their sides (<i>v</i> on their back) had an increased risk of SIDS (2.61, 1.56 to 4.38). In infants who used dummies, there was no increased risk associated with sleeping position (0.66, 0.12 to 3.59). While cosleeping with a mother who smoked was also associated with increased risk of SIDS among infants who did not use a dummy (4.5, 1.3 to 15.1), there was no such association among those who did (1.1, 0.1 to 13.4). <b>Conclusions</b> Use of a dummy seems to reduce the risk of SIDS and possibly reduces the influence of known risk factors in the sleep environment.
Problems Paying Out-of-Pocket Medication Costs Among Older Adults With Diabetes
Authors: John D. Piette, Michele Heisler, Todd H. Wagner
Journal: Diabetes Care (2004)

To identify problems faced by older adults with diabetes due to out-of-pocket medication costs.In this cross-sectional national survey of 875 adults with diabetes treated with hypoglycemic medication, respondents reported whether they had underused prescription medications due to cost pressures or had experienced other financial problems associated with medication costs such as forgoing basic necessities. Respondents also described their interactions with clinicians about medication costs.A total of 19% of respondents reported cutting back on medication use in the prior year due to cost, 11% reported cutting back on their diabetes medications, and 7% reported cutting back on their diabetes medications at least once per month. Moreover, 28% reported forgoing food or other essentials to pay medication costs, 14% increased their credit card debt, and 10% borrowed money from family or friends to pay for their prescriptions. Medication cost problems were especially common among respondents who were younger, had higher monthly out-of-pocket costs, and had no prescription drug coverage. In general, few respondents, including those reporting medication cost problems, reported that their health care providers had given them information or other assistance to address medication cost pressures.Out-of-pocket medication costs pose a significant burden to many adults with diabetes and contribute to decreased treatment adherence. Clinicians should actively identify patients with diabetes who are facing medication cost pressures and assist them by modifying their medication regimens, helping them understand the importance of each prescribed medication, providing information on sources of low-cost drugs, and linking patients with coverage programs.
Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database
Authors: T Sokka, H Kautiainen, T Pincus, S Toloza, G da Rocha Castelar Pinheiro, J Lazovskis, M L Hetland, T Peets, K Immonen, J F Maillefert, A A Drosos, R Alten, C Pohl, B Rojkovich, B Bresnihan, P Minnock, M Cazzato, S Bombardieri, S Rexhepi, M Rexhepi, D Andersone, S Stropuviene, M Huisman, S Sierakowski, D Karateev, V Skakic, A Naranjo, E Baecklund, D Henrohn, F Gogus, H Badsha, A Mofti, P Taylor, C McClinton, Y Yazici
Journal: Annals of the Rheumatic Diseases (2009)

To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country.The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000.Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents.The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.
Inhibition of Cyclooxygenase-1 and -2 Expression by Targeting the Endothelin A Receptor in Human Ovarian Carcinoma Cells
Authors: Francesca Spinella, Laura Rosanò, Valeriana Di Castro, Maria Rita Nicotra, Pier Giorgio Natali, Anna Bagnato
Journal: Clinical Cancer Research (2004)

Abstract Purpose and Experimental Design: New therapies against cancer are based on targeting cyclooxygenase (COX)-2. Activation of the endothelin A receptor (ETAR) by endothelin (ET)-1 is biologically relevant in several malignancies, including ovarian carcinoma. In this tumor, the ET-1/ETAR autocrine pathway promotes mitogenesis, apoptosis protection, invasion, and neoangiogenesis. Because COX-1 and COX-2 are involved in ovarian carcinoma progression, we investigated whether ET-1 induced COX-1 and COX-2 expression through the ETAR at the mRNA and protein level in HEY and OVCA 433 ovarian carcinoma cell lines by Northern blot, reverse transcription-PCR, Western blot, and immunohistochemistry; we also investigated the activity of the COX-2 promoter by luciferase assay and the release of prostaglandin (PG) E2 by ELISA. Results: ET-1 significantly increases the expression of COX-1 and COX-2, COX-2 promoter activity, and PGE2 production. These effects depend on ETAR activation and involve multiple mitogen-activated protein kinase (MAPK) signaling pathways, including p42/44 MAPK, p38 MAPK, and transactivation of the epidermal growth factor receptor. COX-2 inhibitors and, in part, COX-1 inhibitor blocked ET-1-induced PGE2 and vascular endothelial growth factor release, indicating that both enzymes participate in PGE2 production to a different extent. Moreover, inhibition of human ovarian tumor growth in nude mice after treatment with the potent ETAR-selective antagonist ABT-627 is associated with reduced COX-2 and vascular endothelial growth factor expression. Conclusions: These results indicate that impairing COX-1 and COX-2 and their downstream effect by targeting ETAR can be therapeutically advantageous in ovarian carcinoma treatment. Pharmacological blockade of the ETAR is an attractive strategy to control COX-2 induction, which has been associated with ovarian carcinoma progression and chemoresistance.
Mechanisms of Delayed Electrical Uncoupling Induced by Ischemic Preconditioning
Authors: Sandeep K. Jain, Richard B. Schuessler, Jeffrey E. Saffitz
Journal: Circulation Research (2003)

Electrical uncoupling of cardiac myocytes during ischemia is delayed by ischemic preconditioning. This presumably adaptive response may limit development of arrhythmia substrates. To elucidate responsible mechanisms, we studied isolated, perfused rat hearts subjected to a standard preconditioning protocol of 3 cycles of 3 minutes of global no-flow ischemia each followed by 5 minutes of reperfusion before a 30-minute interval of ischemia. Changes in coupling were monitored by measuring whole-tissue resistance. Changes in phosphorylation and subcellular distribution of connexin43 (Cx43) were defined by quantitative immunoblotting and confocal microscopy. Preconditioning caused a 34% decrease in the maximal rate of uncoupling and delayed the time to plateau in uncoupling. Dephosphorylation of Cx43, known to occur during uncoupling induced by ischemia, was dramatically decreased in preconditioned hearts. Translocation of Cx43 from gap junctions to the cytosol, also known to occur during ischemia, was reduced by >5-fold in preconditioned hearts. The KATP channel blockers glybenclamide and 5-hydroxydecanoate prevented these effects in preconditioned hearts, whereas the KATP channel agonist diazoxide mimicked these effects in nonpreconditioned hearts. Intracellular translocation of Cx43 was blocked, but Cx43 dephosphorylation was not blocked during ischemia in preconditioned hearts treated with the PKC inhibitors chelerythrine and calphostin C. Uncoupling during ischemia was accelerated by PKC and KATP channel inhibition. Thus, delayed uncoupling in preconditioned hearts is likely related to diminished dephosphorylation and intracellular redistribution of Cx43 during prolonged ischemia. Both of these effects are regulated by activation of KATP channels, whereas PKC plays a role in internalization of Cx43.
No serological indications that systemic lupus erythematosus is linked with exposure to human parvovirus B19
Authors: A. Bengtsson
Journal: Annals of the Rheumatic Diseases (2000)

Infectious agents like parvovirus have been implicated as exogenous factors that could trigger onset of systemic lupus erythematosus (SLE). A number of case reports describing a SLE-like presentation of acute human parvovirus B19 infection have been published, but no systematic investigation of the actual seroprevalence in epidemiologically defined SLE populations has previously been reported.Sera from 99 SLE patients from a defined area in Southern Sweden, representing 88% of all new SLE cases 1981-1995 within the Lund-Orup Health Care district with 175 000 adult inhabitants (> 15 years of age), and sera from 99 age and sex matched healthy controls were investigated for the presence of IgG parvovirus antibodies. Two different commercially available EIA kits were used; one using E coli synthesised parvovirus VP1/VP2 antigen, and one using baculovirus derived parvovirus VP2 antigen.The EIA using baculovirus derived antigen was more sensitive and surprisingly the controls were more often positive than the SLE patients were (79% versus 65%, chi(2) p=0.027). No difference between the groups was seen with the EIA using E coli derived antigen (46% versus 49%). Titration experiments indicated that the discordance between the two tests was a matter of sensitivity rather than specificity.No evidence was found of human parvovirus B19 infection being more prevalent among SLE patients. On the contrary, in one of the parvovirus EIAs the controls were more often positive than the SLE patients were.
Evaluation of the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention
Authors: Hans-Peter Bestehorn, Franz-Josef Neumann, Heinz Joachim Büttner, Peter Betz, Peter Stürzenhofecker, Eberhard von Hodenberg, Antoine Verdun, Laszlo Levai, Jean Pierre Monassier, Helmut Roskamm
Journal: Journal of the American College of Cardiology (2004)