tbuckley/cabot-search huggingface dataset:
Trichostatin A sensitises rheumatoid arthritis synovial fibroblasts for TRAIL-induced apoptosis
Authors: A Jungel
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Histone acetylation/deacetylation has a critical role in the regulation of transcription by altering the chromatin structure. <b>Objective:</b> To analyse the effect of trichostatin A (TSA), a streptomyces metabolite which specifically inhibits mammalian histone deacetylases, on TRAIL-induced apoptosis of rheumatoid arthritis synovial fibroblasts (RASF). <b>Methods:</b> Apoptotic cells were detected after co-treatment of RASF with TRAIL (200 ng/ml) and TSA (0.5, 1, and 2 μmol/l) by flow cytometry using propidium iodide/annexin-V-FITC staining. Cell proliferation was assessed using the MTS proliferation test. Induction of the cell cycle inhibitor p21<sup>Waf/Cip1</sup> by TSA was analysed by western blot. Expression of the TRAIL receptor-2 (DR5) on the cell surface of RASF was analysed by flow cytometry. Levels of soluble TRAIL were measured in synovial fluid of patients with RA and osteoarthritis (OA) by ELISA. <b>Results:</b> Co-treatment of the cells with TSA and TRAIL induced cell death in a synergistic and dose dependent manner, whereas TRAIL and TSA alone had no effect or only a modest effect. RASF express DR5 (TRAIL receptor 2), but treatment of the cells with TSA for 24 hours did not change the expression level of DR5, as it is shown for cancer cells. TSA induced cell cycle arrest in RASF through up regulation of p21<sup>Waf1/Cip1</sup>. Levels of soluble TRAIL were significantly higher in RA than in OA synovial fluids. <b>Conclusion:</b> Because TSA sensitises RASF for TRAIL-induced apoptosis, it is concluded that TSA discloses sensitive sites in the cascade of TRAIL signalling and may represent a new principle for the treatment of RA.
Gene polymorphism for microsomal epoxide hydrolase and susceptibility to emphysema in a Japanese population
Authors: K. Takeyabu, E. Yamaguchi, I. Suzuki, M. Nishimura, N. Hizawa, Y. Kamakami
Journal: European Respiratory Journal (2000)

Recently, it was reported that gene polymorphism for microsomal epoxide hydrolase (mEPHX), an enzyme involved in the first-pass metabolism of epoxide intermediates, was associated with susceptibility to emphysema. This association was examined in a Japanese population, performing polymerase chain reaction (PCR)-based direct sequencing and restriction fragment length polymorphism assays for variant forms of mEPHX. The subjects consisted of 79 smokers with moderate to severe emphysema diagnosed by lung computed tomography scans, 58 smokers without emphysema, with a comparable smoking history, and 114 consecutive subjects who undertook annual health checkups. The allele frequency of exon 3 Tyr113 to His113, which was reported to confer slow mEPHX activity, was substantially higher in the population control group compared with that of the Caucasian control subjects in a previous study. However, neither the genotype distribution of exon 3, nor that of exon 4 His139 to Arg139, was significantly different between the two groups of smokers. These data indicate that the gene polymorphism for mEPHX is not associated with susceptibility to emphysema in the Japanese population. The discrepancy between the two studies may be explained either by racial difference or by the selection bias of subjects in the previous study, which examined those who had only mild to moderate emphysema with lung cancer or those who were clinically diagnosed as having chronic obstructive pulmonary disease.
Fiber and C-Reactive Protein in Diabetes, Hypertension, and Obesity
Authors: Dana E. King, Arch G. Mainous, Brent M. Egan, Robert F. Woolson, Mark E. Geesey
Journal: Diabetes Care (2005)

Elevated levels of C-reactive protein (CRP) have been associated with increased risk of cardiovascular disease among the general population (1–6). People with diabetes (7), hypertension (8), and obesity (9) have CRP levels that are higher than those in people without these conditions in the general population.

Previous studies indicate an inverse association between dietary fiber intake and levels of inflammatory biomarkers (10,11). Acknowledging that individuals with certain conditions (e.g., diabetes) are at higher risk for elevated CRP, it is unclear whether intake of dietary fiber may have more impact on inflammatory markers among such people. To investigate the relationship between dietary fiber and inflammatory markers in people with diabetes, hypertension, and obesity, we conducted a study using the nationally representative 1999–2002 National Health and Nutrition Examination Survey (NHANES).

We conducted an analysis of the 1999–2002 NHANES (http://www.cdc.gov/nchs/nhanes.htm). Our sample was limited to participants ≥20 years of age who had valid high-sensitivity CRP measurements and dietary information (unweighted n = 7,891). The study was approved by the institutional review board at the Medical University of South Carolina.

Individuals were considered to have a previous diagnosis of diabetes or hypertension based on questions asking whether the individual had ever been told by a doctor that he or she had the condition. People with …
A Focus on PD-L1 in Human Melanoma
Authors: Peter Hersey, Stuart Gallagher
Journal: Clinical Cancer Research (2012)

Abstract Treatment of metastatic melanoma with inhibitors of the BRAF V600 oncogene in melanoma has been limited by the development of resistance. Combining the BRAF inhibitors with immunotherapy may prolong the response, but will acquisition of resistance to BRAF inhibitors also make melanoma cells resistant to immunotherapy? Clin Cancer Res; 19(3); 514–6. ©2012 AACR.
Comprehensive analysis of pseudogenes in prokaryotes: widespread gene decay and failure of putative horizontally transferred genes
Authors: Yang Liu, Paul M Harrison, Victor Kunin, Mark Gerstein
Journal: Genome biology (2004)

Pseudogenes often manifest themselves as disabled copies of known genes. In prokaryotes, it was generally believed (with a few well-known exceptions) that they were rare.We have carried out a comprehensive analysis of the occurrence of pseudogenes in a diverse selection of 64 prokaryote genomes. Overall, we find a total of around 7,000 candidate pseudogenes. Moreover, in all the genomes surveyed, pseudogenes occur in at least 1 to 5% of all gene-like sequences, with some genomes having considerably higher occurrence. Although many large populations of pseudogenes arise from large, diverse protein families (for example, the ABC transporters), notable numbers of pseudogenes are associated with specific families that do not occur that widely. These include the cytochrome P450 and PPE families (PF00067 and PF00823) and others that have a direct role in DNA transposition.We find suggestive evidence that a large fraction of prokaryote pseudogenes arose from failed horizontal transfer events. In particular, we find that pseudogenes are more than twice as likely as genes to have anomalous codon usage associated with horizontal transfer. Moreover, we found a significant difference in the number of horizontally transferred pseudogenes in pathogenic and non-pathogenic strains of Escherichia coli.
Physiological pathways and molecular mechanisms regulating uterine contractility
Authors: H. N. Aguilar, B. F. Mitchell
Journal: Human Reproduction Update (2010)

BACKGROUNDUterine contractile activity plays an important role in many and varied reproductive functions including sperm and embryo transport, implantation, menstruation, gestation and parturition. Abnormal contractility might underlie common and important disorders such as infertility, implantation failure, dysmenorrhea, endometriosis, spontaneous miscarriage or preterm birth.
Filaggrin Mutations are Associated with an Increased Risk of Infantile Food Allergy and Sensitization
Authors: T. Tan, J.A. Ellis, J.J. Koplin, P.E. Martin, T.D. Dang, M.C. Matheson, S. Dharmage, A. Lowe, M. Tang, M. Robinson, A. Ponsonby, N. Osborne, D. Hill, K.J. Allen
Journal: Journal of Allergy and Clinical Immunology (2012)
Efficacy and tolerability of rupatadine at four times the recommended dose against histamine- and platelet-activating factor-induced flare responses and <i>ex vivo</i> platelet aggregation in healthy males
Authors: M.K. Church
Journal: British Journal of Dermatology (2010)

Journal Article Efficacy and tolerability of rupatadine at four times the recommended dose against histamine‐ and platelet‐activating factor‐induced flare responses and ex vivo platelet aggregation in healthy males Get access M.K. Church M.K. Church Department of Dermatology and Allergy, Allergy Centre Charité, Charité‐Universitätsmedizin Berlin, Berlin, Germany Correspondence: Martin K. Church. E‐mail: mkc@southampton.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 6, 1 December 2010, Pages 1330–1332, https://doi.org/10.1111/j.1365-2133.2010.10029.x Published: 01 December 2010
SETBP1 and miR_4319 dysregulation in primary myelofibrosis progression to acute myeloid leukemia
Authors: Francesco Albano, Luisa Anelli, Antonella Zagaria, Nicoletta Coccaro, Paola Casieri, Angela Minervini, Giorgina Specchia
Journal: Journal of Hematology & Oncology (2012)

The molecular pathogenesis underlying the primary myelofibrosis (PMF) progression to acute myeloid leukemia (AML) is still not well defined. The involvement of microRNA (miRNA) is actually helping to shed light on an important issue in the occurrence of myeloproliferative neoplasms (MPNs). However, the role of intronic miRNA, derived from the intron regions of gene transcripts, has never been reported in MPNs. In this study, we describe a PMF case evolved to AML with a t(12;18)(p13;q12) rearrangement showing the downregulation of the intronic miR_4319 and the overexpression of its host gene, SET binding protein (SETBP1). A possible molecular mechanism regulating the PMF progression to AML is discussed.
Cdc42-Interacting Protein 4 Promotes Breast Cancer Cell Invasion and Formation of Invadopodia through Activation of N-WASp
Authors: Christina S. Pichot, Constadina Arvanitis, Sean M. Hartig, Samuel A. Jensen, John Bechill, Saad Marzouk, Jindan Yu, Jeffrey A. Frost, Seth J. Corey
Journal: Cancer Research (2010)

In the earliest stages of metastasis, breast cancer cells must reorganize the cytoskeleton to affect cell shape change and promote cell invasion and motility. These events require the cytoskeletal regulators Cdc42 and Rho, their effectors such as N-WASp/WAVE, and direct inducers of actin polymerization such as Arp2/3. Little consideration has been given to molecules that shape the cell membrane. The F-BAR proteins CIP4, TOCA-1, and FBP17 generate membrane curvature and act as scaffolding proteins for activated Cdc42 and N-WASp. We found that expression of CIP4, but not TOCA-1 or FBP17, was increased in invasive breast cancer cell lines in comparison with weakly or noninvasive breast cancer cell lines. Endogenous CIP4 localized to the leading edge of migrating cells and to invadopodia in cells invading gelatin. Because CIP4 serves as a scaffolding protein for Cdc42, Src, and N-WASp, we tested whether loss of CIP4 could result in decreased N-WASp function. Interaction between CIP4 and N-WASp was epidermal growth factor responsive, and CIP4 silencing by small interfering RNA caused decreased tyrosine phosphorylation of N-WASp at a Src-dependent activation site (Y256). CIP4 silencing also impaired the migration and invasion of MDA-MB-231 cells and was associated with decreased formation of invadopodia and gelatin degradation. This study presents a new role for CIP4 in the promotion of migration and invasion of MDA-MB-231 breast cancer cells and establishes the contribution of F-BAR proteins to cancer cell motility and invasion.
Fetal Cardiomyopathies
Authors: Simone R.F.F. Pedra, Jeffrey F. Smallhorn, Greg Ryan, David Chitayat, Glenn P. Taylor, Rubina Khan, Mohamed Abdolell, Lisa K. Hornberger
Journal: Circulation (2002)

Background — Although the prenatal diagnosis of most fetal structural heart defects and dysrhythmias has been described, there is a paucity of information about cardiomyopathies (CMs) in prenatal life. Methods and Results —- To determine the pathogenic mechanisms, hemodynamic findings, and outcome of fetal CM, we reviewed the fetal echocardiograms and perinatal histories of 55 affected fetuses. Dilated CM was diagnosed in 22 cases, including 2 with congenital infections, 5 familial cases, 6 with endocardial fibroelastosis related to maternal anti-Ro/La antibodies, and 9 idiopathic cases. Thirty-three had hypertrophic CM, 7 associated with maternal diabetes, 2 with Noonan’s syndrome, 2 with α-thalassemia, 18 with twin-twin transfusion syndrome, 1 with familial hypertrophy, and 3 with idiopathic hypertrophy. Systolic dysfunction was present in all cases of dilated CM and 15 cases of hypertrophic CM. Diastolic dysfunction was present in 19 of 30 fetuses with assessment of diastolic function parameters. Significant mitral or tricuspid valve regurgitation was seen in 32 cases. Eight fetuses were hydropic and 23 had signs of early hydrops. Seven pregnancies were terminated. Of 46 continued pregnancies with follow-up, 29 (63%) died perinatally. The presence of systolic dysfunction, diastolic dysfunction, and significant atrioventricular valve regurgitation were identified as risk factors for mortality. By multiple logistic regression, diastolic dysfunction was associated with an 8-fold increased risk relative to the other parameters. Conclusions — Fetal CM has a broad spectrum of intrinsic and extrinsic causes. A poor outcome is observed in many affected fetuses. Diastolic dysfunction in fetal CM is associated with the highest risk of mortality.
Clonal Origin of Metastatic Testicular Teratomas
Authors: Timothy D. Jones, Mingsheng Wang, Ming-Tse Sung, Shaobo Zhang, Thomas M. Ulbright, John N. Eble, Stephen D. Beck, Richard S. Foster, John J. Anagnostou, Clay Conner, Liang Cheng
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Testicular teratomas in adult patients are histologically diverse tumors that frequently coexist with other germ cell tumor (GCT) components. These mixed GCTs often metastasize to retroperitoneal lymph nodes where multiple GCT elements are frequently present in the same metastatic lesion. Neither the genetic relationships among the different components in metastatic lesions nor the relationships between primary and metastatic GCT components have been elucidated. Experimental Design: We examined metastases from 31 patients who underwent primary retroperitoneal lymph node dissection for metastatic testicular GCT. All patients had metastatic mature teratoma with one or more other GCT components. This study included a total of 72 metastatic GCT components and 16 primary GCT components from 31 patients. Genomic DNA samples from each component were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. Loss of heterozygosity (LOH) assays for seven microsatellite polymorphic markers on chromosomes 1p36 (D1S1646), 9p21 (D9S171 and IFNA), 9q21 (D9S303), 13q22-q31 (D13S317), 18q22 (D18S543), and 18q21 (D18S60) were done to assess clonality. Results: Twenty-nine of 31 (94%) cases showed allelic loss in one or more components of the metastatic GCTs. Twenty-nine of 31 mature teratomas showed allelic loss in at least one of seven microsatellite polymorphic markers analyzed. The frequency of allelic loss in informative cases of metastatic mature teratoma was 27% (8 of 30) with D1S1646, 34% (10 of 29) with D9S171, 37% (10 of 27) with IFNA, 27% (8 of 30) with D9S303, 46% (13 of 28) with D13S317, 26% (7 of 27) with D18S543, and 36% (10 of 28) with D18S60. Completely concordant allelic loss patterns between the mature teratoma and all of the other metastatic GCT components were seen in 26 of 29 cases in which the mature teratoma component showed LOH. Nearly identical allelic loss patterns were seen in the three remaining cases. In six cases analyzed, LOH patterns of each metastatic component were compared with each GCT component of the primary testicular tumor. In all six cases, each primary and metastatic component showed an identical pattern of allelic loss. Conclusion: Our data support the common clonal origin of metastatic mature teratomas with other components of metastatic testicular GCTs and with each component of the primary tumor.
Cisplatin, Irinotecan, and Bevacizumab for Untreated Extensive-Stage Small-Cell Lung Cancer: CALGB 30306, a Phase II Study
Authors: Neal E. Ready, Arkadiusz Z. Dudek, Herbert H. Pang, Lydia D. Hodgson, Stephen L. Graziano, Mark R. Green, Everett E. Vokes
Journal: Journal of Clinical Oncology (2011)

The efficacy of cisplatin, irinotecan, and bevacizumab was evaluated in patients with extensive-stage small-cell lung cancer (ES-SCLC).
A Processed Pseudogene Codes for a New Antigen Recognized by a Cd8+ T Cell Clone on Melanoma
Authors: Agnès Moreau-Aubry, Soizic Le Guiner, Nathalie Labarrière, Marie-Claude Gesnel, Francine Jotereau, Richard Breathnach
Journal: The Journal of Experimental Medicine (2000)

The M88.7 T cell clone recognizes an antigen presented by HLA B*1302 on the melanoma cell line M88. A cDNA encoding this antigen (NA88-A) was isolated using a library transfection approach. Analysis of the genomic gene's sequence identified it is a processed pseudogene, derived from a retrotranscript of mRNA coding for homeoprotein HPX42B. The NA88-A gene exhibits several premature stop codons, deletions, and insertions relative to the HPX42B gene. In NA88-A RNA, a short open reading frame codes for the peptide MTQGQHFLQKV from which antigenic peptides are derived; a stop codon follows the peptide's COOH-terminal Val codon. Part of the HPX42B mRNA's 3′ untranslated region codes for a peptide of similar sequence (MTQGQHFSQKV). If produced, this peptide can be recognized by M88.7 T cells. However, in HPX42B mRNA, the peptide's COOH-terminal Val codon is followed by a Trp codon. As a result, expression of HPX42B mRNA does not lead to antigen production. A model is proposed for events that participated in creation of a gene coding for a melanoma antigen from a pseudogene.
Ophthalmia Neonatorum: Diagnosis and Treatment—Why Not Prevention?
Authors: E. Russell Alexander
Journal: JAMA (1986)

We are reminded by the thorough study of Rapoza and colleagues<sup>1</sup>that chlamydial conjunctivitis is an important cause of ophthalmia neonatorum. In fact, it was not clear that any other of the broad range of bacterial and viral agents sought were causes of conjunctivitis. Only in the instance of ten cases from which<i>Haemophilus influenzae</i>was isolated was there any clear-cut evidence of an etiologic role. A striking finding was the low sensitivity of the Giemsa stain in comparison with previous studies of neonatal chlamydial conjunctivitis. In previous studies,<sup>2</sup>tissue cultures, Giemsa stains, and polyclonal fluorescent antibody smears appeared to be equally effective in diagnosis. Unfortunately, the methodologies are not comparable. In the current study, the Giemsa smear was made from the second swab after it had been used to prepare a direct immunofluorescent monoclonal antibody smear. In previous studies, the comparison was with a smear prepared from
Composite Spirometric–Computed Tomography Outcome Measure in Early Cystic Fibrosis Lung Disease
Authors: Terry E. Robinson, Ann N. Leung, William H. Northway, Francis G. Blankenberg, Frandics P. Chan, Daniel A. Bloch, Tyson H. Holmes, Richard B. Moss
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

With the advent of therapies aimed at young patients with cystic fibrosis, who have mildly reduced pulmonary function, the need for improved outcome measures that discriminate treatment effects has become important. Pulmonary function measurements or chest high-resolution computed tomography (HRCT) scores have been separately used to assess interventions. We evaluated these modalities separately and together during a treatment study to develop a more sensitive outcome measure. In a 1-year trial, 25 children randomized either to daily Pulmozyme or to normal saline aerosol were evaluated at randomization and at 3 and 12 months. Outcome variables were pulmonary function test (PFT) results, a global HRCT score, and a composite score incorporating PFTs and HRCT scoring. Regression analyses with generalized estimating equations permitted estimation of the difference in treatment effect between groups over time for each outcome. The largest difference in treatment effects observed at 12 months, measured by the percentage change from baseline, were with the composite total and maximal CT/PFT scores (35.4 and 30.4%), compared with mean forced expiratory flow during the middle half of the FVC (FEF25-75%) (13.0%) and total and maximal global HRCT scores (6.2%, 7.2%). The composite total and maximal CT/PFT scores were the most sensitive outcome measures for discriminating a treatment effect in children with cystic fibrosis with normal or mildly reduced pulmonary function during a 1-year trial of Pulmozyme.
Coronary Microvascular Endothelial Stunning After Acute Pressure Overload in the Conscious Dog Is Caused by Oxidant Processes
Authors: Shintaro Kinugawa, Heiner Post, Pawel M. Kaminski, Xiaoping Zhang, Xiaobin Xu, Harer Huang, Fabio A. Recchia, Manuel Ochoa, Michael S. Wolin, Gabor Kaley, Thomas H. Hintze
Journal: Circulation (2003)

Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation.In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning [ES]). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(-8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%), losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin.Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.
Diabetes Prevention in the Real World: Effectiveness of Pragmatic Lifestyle Interventions for the Prevention of Type 2 Diabetes and of the Impact of Adherence to Guideline Recommendations: A Systematic Review and Meta-analysis. Diabetes Care 2014;37:922–933
Authors: Alison J. Dunkley, Danielle H. Bodicoat, Colin J. Greaves, Claire Russell, Thomas Yates, Melanie J. Davies, Kamlesh Khunti
Journal: Diabetes Care (2014)

In the print version of the article cited above, the 12-month weight loss data reported for the study by Katula et al., 2011 (ref. 42) are incorrect. This was due to an error in Table 2 of the original published version of the article by Katula et al., which wrongly specified pounds …