tbuckley/cabot-search huggingface dataset:
Association Between Catechol-<i>O</i>-Methyltransferase and Phobic Anxiety
Authors: Monica McGrath, Ichiro Kawachi, Alberto Ascherio, Graham A. Colditz, David J. Hunter, Immaculata De Vivo
Journal: American Journal of Psychiatry (2004)

The authors assessed the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and scores on the phobic anxiety scale of the Crown-Crisp Experimental Index.A total of 1,234 women completed the Crown-Crisp Experimental Index phobic anxiety scale and were genotyped for the COMT polymorphism. The authors used unconditional logistic regression to compute odds ratios and 95% confidence intervals (CIs) to evaluate the association between the COMT genotype and phobic anxiety.The mean scores for the three genotypes were statistically significantly different. Compared to the COMT Met/Met genotype, the age-adjusted odds ratio for scoring >/=6 compared to scoring 0 or 1 were 1.15 (95% CI=0.71-1.85) and 1.99 (95% CI=1.17-3.40) for the COMT Val/Met and COMT Val/Val genotypes, respectively; a significant gene dosage effect was observed.Our results suggest that the functional COMT polymorphism is associated with the development of phobic anxiety.
Evidence, Politics, and the Future of the Children’s Health Insurance Program
Authors: Marian Jarlenski
Journal: JAMA Pediatrics (2015)

The major expansion of health insurance coverage through the creation of the Children’s Health Insurance Program (CHIP) in 1997 was driven by the recognition that millions of children—those whose family incomes were too high to qualify for Medicaid but for whom other insurance was unobtainable—were falling through the cracks of the US health insurance system. At the time, CHIP appeared a bipartisan victory, representing an expansion of public insurance coverage that gave states wide latitude to contract with private plans or place limits on enrollment. 1 By 1999, all states had implemented CHIP. Since the creation of the program, states have implemented a diverse array of policy options under CHIP to serve children and have dramatically improved access to and continuity of insurance coverage for children in low-income families. In the short term, funding for CHIP is likely to be temporarily extended by Congress. In the long term, the future of CHIP should be part of a serious and bipartisan discussion among policy makers about how to best ensure access to health insurance for children in low-income families and develop a comprehensive health policy approach for children and families.
Identification of Domains of BRCA1 Critical for the Ubiquitin-Dependent Inhibition of Centrosome Function
Authors: Satish Sankaran, Lea M. Starita, Amanda M. Simons, Jeffrey D. Parvin
Journal: Cancer Research (2006)

Abstract The breast and ovarian cancer specific tumor suppressor BRCA1, bound to BARD1, has multiple functions aimed at maintaining genomic stability in the cell. We have shown earlier that the BRCA1/BARD1 E3 ubiquitin ligase activity regulates centrosome-dependent microtubule nucleation. In this study, we tested which domains of BRCA1 and BARD1 were required to control the centrosome function. In the present study, (a) we confirmed that the ubiquitination activity of BRCA1 regulates centrosome number and function in Hs578T breast cancer cells; (b) we observed that both the amino and carboxyl termini of BRCA1 are required for regulation of centrosome function in vitro; (c) an internal domain (770-1,290) is dispensable for centrosome regulation; (d) BARD1 is required for regulation of centrosome function and protein sequences within the terminal 485 amino acids are necessary for activity; and (e) BARD1 is localized at the centrosome throughout the cell cycle. We conclude that the BRCA1-dependent E3 ubiquitin ligase functions to restrain centrosomes in mammary cells, and loss of BRCA1 in the precancerous breast cell leads to centrosomal hypertrophy, a phenotype commonly observed in incipient breast cancer. (Cancer Res 2006; 66(8): 4100-7)
Sperm-Associated Antigen 9, a Novel Cancer Testis Antigen, Is a Potential Target for Immunotherapy in Epithelial Ovarian Cancer
Authors: Manoj Garg, Dipak Chaurasiya, Ritu Rana, Nirmala Jagadish, Deepika Kanojia, Namrata Dudha, Neha Kamran, Sudha Salhan, Amar Bhatnagar, Sushma Suri, Anju Gupta, Anil Suri
Journal: Clinical Cancer Research (2007)

Cancer testis antigens are a group of tumor antigens with gene expression restricted to male germ cells in the testis and in various cancerous tissues. Recently, we reported a novel testis-specific sperm-associated antigen 9 (SPAG9) gene, a new member of the c-Jun NH(2)-terminal kinase-interacting protein family, having functional role in sperm-egg fusion and mitogen-activated protein kinase signaling pathway. National Center for Biotechnology Information Blast searches revealed SPAG9 nucleotide sequence similarities with expressed sequence tags of various cancerous tissues. In an effort to examine the clinical utility of SPAG9, we investigated the SPAG9 mRNA and protein expression in epithelial ovarian cancer (EOC). Humoral immune response to SPAG9 was also evaluated in EOC patients.We determined the expression profile of SPAG9 transcript by reverse transcription-PCR and RNA in situ hybridization and SPAG9 protein expression by immunohistochemistry in EOC specimens and human ovarian cancer cell lines. Using ELISA and Western blotting, we analyzed specific antibodies for SPAG9 in sera from patients with EOC.SPAG9 mRNA and protein expression was detected in 90% of EOC tissues and in all three human ovarian cancer cell lines. Specific SPAG9 antibodies were detected in 67% of EOC patients and not in sera from healthy individuals.Our findings indicate that SPAG9 is highly expressed in EOC and immunogenic in patients. Humoral immune response against SPAG9 in early stages of EOC suggests its important role in early diagnostics. These results collectively suggest that SPAG9, a novel member of cancer testis antigen family, could be a potential target for the development of diagnostic and therapeutic methods in EOC.
Echocardiographic tissue characterization and range-gated Doppler ultrasound for the diagnosis of pulmonary embolism.
Authors: K B Sagar, T L Rhyne, L J Greenfield
Journal: Circulation (1983)

We evaluated reflection and absorption indexes of ultrasound as well as Doppler estimates of intrapulmonary blood flow for diagnosing pulmonary embolism. The pulmonary reflection coefficient (PRC), coefficient of tissue attenuation (alpha R) and range-gated blood Doppler signals were studied in 25 patients with pulmonary embolism, 19 with pneumonia, nine with atelectasis, 20 with congestive heart failure, 20 with chronic obstructive lung disease and 10 normal subjects. The PRC was significantly diminished in pulmonary embolism, pneumonia and atelectasis, but was not altered by underlying chronic obstructive lung disease or congestive heart failure. The alpha R in pulmonary embolism was 1.03 +/- 0.04 db/MHz cm, significantly lower than that for pneumonia, 1.48 +/- 0.03 db/MHz cm (p less than 0.001), but not significantly different from that for atelectasis, 0.95 +/- 0.05 db/MHz cm. Doppler signals indicating blood flow in the affected area of lung were present in only two of 25 patients with pulmonary embolism, compared with seven of nine with atelectasis and 17 of 19 with pneumonia. The combined use of PRC, alpha R and blood Doppler signals correctly diagnosed pulmonary embolism in 23 of 25 patients. Thus, ultrasound offers a reliable noninvasive method for diagnosis of pulmonary embolism.
Mitogen-Activated Protein Kinase Phosphatase-1 Is Required for Cisplatin Resistance
Authors: Zhaoqing Wang, Jing Xu, Jun-Ying Zhou, Yusen Liu, Gen Sheng Wu
Journal: Cancer Research (2006)

Abstract Mitogen-activated protein kinase (MAPK) phosphatase (MKP)-1 is a member of the MKP family that negatively regulates MAPK signaling. MKP-1 has been implicated in cell survival in response to stressful stimuli, including anticancer treatment, but its role in cisplatin resistance is not fully understood. Here, we show that cisplatin induces MKP-1 in several human cancer cell lines. Induction of MKP-1 by cisplatin was through the transcriptional mechanism regulated by extracellular signal-regulated kinase (ERK). Overexpression of MKP-1 rendered human lung cancer cells resistant to cisplatin. Conversely, down-regulation of MKP-1 by small interfering RNA silencing sensitized human lung cancer cells to cisplatin-induced cell death. Using primary mouse embryonic fibroblasts (MEF) from MKP-1 knockout mice, we show that induction of MKP-1 by cisplatin correlates with inactivation of c-Jun NH2-terminal kinase (JNK) but not ERK and p38. Furthermore, apoptosis induced by cisplatin was significant in MKP-1−/− MEFs, whereas such change was minimal in MKP-1+/+ MEFs. More importantly, cisplatin-induced cell death is inhibited by blocking JNK but not ERK and p38 activities. Collectively, our results establish a critical role of JNK in cisplatin-induced apoptosis and suggest that MKP-1 is required for cisplatin resistance. (Cancer Res 2006; 66(17): 8870-7)
Development of cockroach immunotherapy by the Inner-City Asthma Consortium
Authors: Robert A. Wood, Alkis Togias, Jeremy Wildfire, Cynthia M. Visness, Elizabeth C. Matsui, Rebecca Gruchalla, Gurjit Hershey, Andrew H. Liu, George T. O'Connor, Jacqueline A. Pongracic, Edward Zoratti, Frederic Little, Mark Granada, Suzanne Kennedy, Stephen R. Durham, Mohamed H. Shamji, William W. Busse
Journal: Journal of Allergy and Clinical Immunology (2013)
Cardioprotection Afforded by Inducible Nitric Oxide Synthase Gene Therapy Is Mediated by Cyclooxygenase-2 via a Nuclear Factor-κB–Dependent Pathway
Authors: Qianhong Li, Yiru Guo, Wei Tan, Qinghui Ou, Wen-Jian Wu, Diana Sturza, Buddhadeb Dawn, Greg Hunt, Chuanjue Cui, Roberto Bolli
Journal: Circulation (2007)

Gene therapy with inducible nitric oxide synthase (iNOS) markedly reduces myocardial infarct size; this effect is associated with cyclooxygenase-2 (COX-2) upregulation and is ablated by COX-2 inhibitors. However, pharmacological inhibitors are limited by relative lack of specificity; furthermore, the mechanism whereby iNOS gene therapy upregulates COX-2 remains unknown. Accordingly, we used genetically engineered mice to test the hypothesis that the cardioprotection afforded by iNOS gene transfer is mediated by COX-2 upregulation via a nuclear factor (NF)-kappaB-dependent pathway.Mice received an intramyocardial injection of Av3/LacZ (LacZ group) or Av3/iNOS (iNOS group); 3 days later, myocardial infarction was produced by a 30-minute coronary occlusion followed by 4 hours of reperfusion. Among Av3/LacZ-treated mice, infarct size was similar in COX-2(-/-) and wild-type groups. iNOS gene transfer (confirmed by iNOS immunoblotting and activity assays) markedly reduced infarct size in wild-type mice but failed to do so in COX-2(-/-) mice. In transgenic mice with cardiac-specific expression of a dominant-negative mutant of IkappaB alpha (IkappaB alpha(S32A,S36A)), the upregulation of phosphorylated IkappaB alpha, activation of NF-kappaB, and cardiac COX-2 protein expression 3 days after iNOS gene therapy were abrogated, which was associated with the abolishment of the cardioprotective effects afforded by iNOS gene therapy.These data provide strong genetic evidence that COX-2 is an obligatory downstream effector of iNOS-dependent cardioprotection and that NF-kappaB is a critical link between iNOS and COX-2. Thus, iNOS imparts its protective effects, at least in part, by recruiting NF-kappaB, leading to COX-2 upregulation. However, COX-2 does not play an important cardioprotective role under basal conditions (when iNOS is not upregulated).
Ampicillin for sore throat.
Authors: E J Stokes
Journal: BMJ (1973)

Besides being free of charge, the service is readily available without a waiting list.Under these circumstances, from our 13,000 patients, we have in the first year performed 100 vasectonies; in 1972 there were 75 and this year so far the demand is again at the rate of 100 per year.Projected throughout the country these figures suggest a continuiin demand for vasectomy, approaching half a million per annum.Mrs. Waite's paper underlines the still considerable lag in meeting this demand.-I am, etc.,
Discovery of Protein Biomarkers for Renal Diseases
Authors: Stephen M. Hewitt, James Dear, Robert A. Star
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Animal models and human studies have been useful in dissecting the molecular mechanisms of renal disease and finding new disease targets; however, translation of these findings to new clinical therapeutics remains challenging. Difficulties with detecting early disease, measuring drug effectiveness, and the daunting cost of clinical trials hampers the development of new therapeutics for renal diseases. Many existing laboratory tests were discovered because of inspired recognition that a particular protein might prove useful in clinical practice. New unbiased genomic and proteomic techniques identify many constituents present in biologic samples and thus may greatly accelerate biomarker research. This review focuses on the steps needed to develop new biomarkers that are useful in laboratory and clinical investigations, with particular focus on new proteomic screening technologies. New biomarkers will speed the laboratory and clinical development of new treatments for renal diseases through mechanistic insights, diagnoses that are more refined, early detection, and enhanced proof of concept testing.
Reactome: a knowledge base of biologic pathways and processes
Authors: Imre Vastrik, Peter D'Eustachio, Esther Schmidt, Geeta Joshi-Tope, Gopal Gopinath, David Croft, Bernard de Bono, Marc Gillespie, Bijay Jassal, Suzanna Lewis, Lisa Matthews, Guanming Wu, Ewan Birney, Lincoln Stein
Journal: Genome biology (2007)

Abstract Reactome http://www.reactome.org , an online curated resource for human pathway data, provides infrastructure for computation across the biologic reaction network. We use Reactome to infer equivalent reactions in multiple nonhuman species, and present data on the reliability of these inferred reactions for the distantly related eukaryote Saccharomyces cerevisiae . Finally, we describe the use of Reactome both as a learning resource and as a computational tool to aid in the interpretation of microarrays and similar large-scale datasets.
Distinguishing Clinicopathologic Features of Patients with V600E and V600K <i>BRAF</i>-Mutant Metastatic Melanoma
Authors: Alexander M. Menzies, Lauren E. Haydu, Lydia Visintin, Matteo S. Carlino, Julie R. Howle, John F. Thompson, Richard F. Kefford, Richard A. Scolyer, Georgina V. Long
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Certain clinicopathologic features correlate with BRAF mutation status in melanoma including younger age and primary subtype. This study sought to determine the BRAF mutation status by age-decade and whether BRAF-mutant genotypes correlated with clinicopathologic features and outcome in patients with metastatic melanoma. Methods: A prospectively assembled cohort of Australian patients were followed from diagnosis of metastatic melanoma (N = 308). Clinicopathologic variables were correlated with BRAF mutational status, genotype, and survival. Results: Forty-six percent of patients had a BRAF mutation; 73% V600E, 19% V600K, and 8% other genotypes. An inverse relationship existed between BRAF mutation prevalence and age-decade (P &amp;lt; 0.001). All patients &amp;lt;30 years and only 25% ≥70 years had BRAF-mutant melanoma. Amongst BRAF-mutant melanoma, the frequency of non-V600E genotypes (including V600K) increased with increasing age. Non-V600E genotypes comprised &amp;lt;20% in patients &amp;lt;50 years and &amp;gt;40% in those ≥70 years. A higher degree of cumulative sun-induced damage correlated with V600K but not V600E melanoma (P = 0.002). The disease-free interval from diagnosis of primary melanoma to first distant metastasis was shorter for patients with V600K compared with V600E melanoma (17.4 vs. 39.2 months, P = 0.048), with no difference in survival thereafter. In patients BRAF tested at diagnosis of metastatic melanoma, one year survival from diagnosis of metastasis was significantly longer for patients with BRAF-mutant melanoma treated with an inhibitor (83%), than those not treated with an inhibitor (29%, P &amp;lt; 0.001), or patients with BRAF wild-type melanoma (37%, P &amp;lt; 0.001). Conclusion: Different genotypes exist within BRAF-mutant metastatic melanoma, representing biologically and clinically discrete subtypes, suggesting distinct etiology and behavior. Clin Cancer Res; 18(12); 3242–9. ©2012 AACR.
Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci
Authors: Thorsten Kurz, Sabine Hoffjan, M. Geoffrey Hayes, Dan Schneider, Raluca Nicolae, Andrea Heinzmann, Sylvija P. Jerkic, Rod Parry, Nancy J. Cox, Klaus A. Deichmann, Carole Ober
Journal: Journal of Allergy and Clinical Immunology (2006)
Suppression of lipopolysaccharide-stimulated release of tumor necrosis factor by adenosine: Evidence for A2 receptors on rat kupffer cells
Authors: Leon J. Reinstein, Steven N. Lichtman, Robert T. Currin, Jian Wang, Ronald G. Thurman, John J. Lemasters
Journal: Hepatology (1994)

In liver grafts that will fail as a result of storage injury, reperfusion activates Kupffer cells. Overproduction of tumor necrosis factor by activated Kupffer cells may cause primary graft nonfunction, multiple organ failure and, eventually, death of graft recipients. Carolina rinse solution, adenosine, nisoldipine, pentoxifylline and prostaglandin E 1 reduce graft failure from storage/reperfusion injury. To test the hypothesis that these agents act by suppressing cytokine release by activated Kupffer cells, we assessed the effect of each drug on tumor necrosis factor released from cultured rat Kupffer cells stimulated with lipopolysaccharide. Adenosine, nisoldipine and prostaglandin E 1 each suppressed lipopolysaccharide-stimulated tumor necrosis factor release. The adenosine A 2 receptor agonists. 5-n-ethylcarboxamidadenosine, 2-chloro-adenosine and R-phenylisopropyl adenosine also blocked tumor necrosis factor release in a potency suggestive of A 2 receptor activity. Xanthine amine congener, a specific A 1 receptor antagonist, failed to reverse the suppression by adenosine of tumor necrosis factor release, whereas CGS15943A, an A 2 receptor antagonist, did reverse suppression by adenosine and 5-n-ethylcarboxamidadenosine. CGS15943A had no effect on suppression of lipopolysaccharide-stimulated tumor necrosis factor release by nisoldipine or prostaglandin E 1 . Dibutyryl-cyclicAMP also suppressed tumor necrosis factor release. Adenosine, 5-n-ethylcarboxamidadenosine, prostaglandin E 1 and pentoxifylline increased cyclicAMP levels in cultured Kupffer cells, but nisoldipine did not. We conclude that (a) adenosine A 2 receptors exist on Kupffer cells, (b) the suppression of tumor necrosis factor release by adenosine occurs by way of a cyclicAMP-dependent adenosine A 2 receptor mechanism, (c) prostaglandin E 1 and nisoldipine also suppress tumor necrosis factor release but do not act through adenosine receptors and (d) because agents that suppress tumor necrosis factor release by Kupffer cells also reduce graft failure after liver transplantation, activation of Kupffer cells and release of tumor necrosis factor may be involved in storage/reperfusion injury to liver grafts. (Hepatology 1994;19:1445-1452.)
Training volume, androgen use and serum creatine kinase activity.
Authors: K Häkkinen, M Alén
Journal: British Journal of Sports Medicine (1989)

Serum creatine kinase (CK) activities were investigated in elite male strength athletes (n = 20) during normal weight training and bodybuilding training (one training session per day), during high volume strength training (two sessions per day) and during strength training (one session per day) with the use of high dose synthetic androgens (five athletes in each subgroup). The findings demonstrated that the increase in serum CK was highest in the subgroup using androgens. These results suggest that strength training with the use of androgenic steroids leads to higher serum CK activities than normal strength training.
Cost effectiveness of ward based non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease: economic analysis of randomised controlled trial
Authors: P K Plant
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the cost effectiveness of standard treatment with and without the addition of ward based non-invasive ventilation in patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease. <b>Design:</b> Incremental cost effectiveness analysis of a randomised controlled trial. <b>Setting:</b> Medical wards in 14 hospitals in the United Kingdom. <b>Participants:</b> The trial comprised 236 patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease and mild to moderate acidosis (pH 7.25-7.35) secondary to respiratory failure. The economic analysis compared the costs of treatment that these patients received after randomisation. <b>Main outcome measure:</b> Incremental cost per in-hospital death. <b>Results:</b> 24/118 died in the group receiving standard treatment and 12/118 in the group receiving non-invasive ventilation (P=0.05). Allocation to the group receiving non-invasive ventilation was associated with a reduction in costs of £49 362 ($78 741; €73 109), mainly through reduced use of intensive care units. The incremental cost effectiveness ratio was −£645 per death avoided (95% confidence interval −£2310 to £386), indicating a dominant (more effective and less costly) strategy. Modelling of these data indicates that a typical UK hospital providing a non-invasive ventilation service will avoid six deaths and three to nine admissions to intensive care units per year, with an associated cost reduction of £12 000–53 000 per year. <b>Conclusions:</b> Non-invasive ventilation is a highly cost effective treatment that both reduced total costs and improved mortality in hospital. <h3>What is already known on this topic</h3> Non-invasive ventilation reduces the need for intubation and mortality in hospital in patients with acute exacerbations of chronic obstructive pulmonary disease and acute respiratory failure The procedure is feasible in the ward or intensive care environment <h3>What this study adds</h3> Non-invasive ventilation given on wards reduces the need for intubation by 44% and halves mortality in hospital in patients with chronic obstructive pulmonary disease and mild to moderate acidosis The early use of non-invasive ventilation on the ward reduces costs and improves outcomes compared with traditional medical treatment The main cost saving is in preventing the use of intensive care facilities