tbuckley/cabot-search huggingface dataset:
Hyperhomocysteinemia Exaggerates Adventitial Inflammation and Angiotensin II−Induced Abdominal Aortic Aneurysm in Mice
Authors: Ziyi Liu, Hongzhi Luo, Lu Zhang, Yaqian Huang, Bo Liu, Kongyang Ma, Juan Feng, Jinsheng Xie, Jingang Zheng, Jing Hu, Siyan Zhan, Yi Zhu, Qingbo Xu, Wei Kong, Xian Wang
Journal: Circulation Research (2012)

Rationale: A number of epidemiological studies have suggested an association of hyperhomocysteinemia (HHcy) and abdominal aortic aneurysm (AAA), but discrepancies exist. In addition, we lack direct evidence supporting a causal role. Objective: We determined the association and contribution of HHcy to AAA formation. Methods and Results: We first performed a meta-analysis of studies involving 1489 subjects and found a strong association of HHcy and AAA (odds ratio, 7.39). Next, we used angiotensin II–infused male apolipoprotein E–deficient mice and tested whether HHcy contributes to AAA pathogenesis. Homocysteine (Hcy) supplement (1.8 g/L) in drinking water resulted in mild HHcy. Intriguingly, HHcy greatly increased the incidence of angiotensin II–induced AAA and aortic dissection in apolipoprotein E–deficient mice (vehicle versus Hcy: 50% versus 100%; P&lt;0.05 ). Histology indicated HHcy markedly exaggerated aortic adventitial inflammation. Increased levels of proinflammatory interleukin-6 and monocyte chemoattractant protein-1 were preferentially colocalized within adventitial fibroblasts in HHcy plus angiotensin II mice, which suggested the importance of adventitial fibroblasts activation in Hcy-aggravated AAA. Hcy sequentially stimulated adventitial fibroblasts transformation into myofibroblasts, secretion of interleukin-6 and monocyte chemoattractant protein-1, and consequent recruitment of monocytes/macrophages to adventitial fibroblasts, which was abolished by the NADPH oxidase inhibitor diphenyliodonium. NADPH oxidase 4, but not other homologs of NADPH oxidase, was significantly upregulated by Hcy in adventitial fibroblasts, whereas NADPH oxidase 4 small interfering RNA silencing diminished Hcy-induced adventitial fibroblasts activation. Finally, folic acid supplement (0.071 μg/g per day) markedly reduced HHcy-aggravated angiotensin II–induced AAA formation in apolipoprotein E–deficient mice. Conclusions: HHcy may aggravate AAA formation at least partially via activating adventitial fibroblast NADPH oxidase 4.
Will Hsp90 Inhibitors Prove Effective in BRAF-Mutant Melanomas?
Authors: Federica Catalanotti, David B. Solit
Journal: Clinical Cancer Research (2012)

The RAF inhibitor vemurafenib has unprecedented activity in BRAF-mutant melanomas, but resistance invariably develops. As Hsp90 is required for the stability of several of the oncoproteins that mediate RAF inhibitor resistance, inhibitors of this cellular chaperone may be effective in patients with intrinsic or acquired resistance to RAF inhibitors.
Preclinical Activity Profile and Therapeutic Efficacy of the HSP90 Inhibitor Ganetespib in Triple-Negative Breast Cancer
Authors: David A. Proia, Chaohua Zhang, Manuel Sequeira, John-Paul Jimenez, Suqin He, Neil Spector, Geoffrey I. Shapiro, Sara Tolaney, Masazumi Nagai, Jaime Acquaviva, Donald L. Smith, Jim Sang, Richard C. Bates, Iman El-Hariry
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Treatment options for patients with triple-negative breast cancer (TNBC) are largely limited to systemic chemotherapies, which have shown disappointing efficacy in the metastatic setting. Here, we undertook a comprehensive evaluation of the activity of ganetespib, a potent inhibitor of HSP90, in this malignancy. Experimental Design: The antitumor and antimetastatic activity of ganetespib was investigated using TNBC cell lines and xenograft models. Combinatorial drug analyses were performed with chemotherapeutic agents and concomitant effects on DNA damage and cell-cycle disruption were assessed in vitro; antitumor efficacy was assessed in vivo. Metabolic and objective tumor responses were evaluated in patients with metastatic TNBC undergoing ganetespib treatment. Results: Ganetespib simultaneously deactivated multiple oncogenic pathways to potently reduce cell viability in TNBC cell lines, and suppressed lung metastases in experimental models. Ganetespib potentiated the cytotoxic activity of doxorubicin via enhanced DNA damage and mitotic arrest, conferring superior efficacy to the doxorubicin–cyclophosphamide regimen in TNBC xenografts. Ganetespib also promoted mitotic catastrophe and apoptosis in combination with taxanes in vitro, and these effects translated to significantly improved combinatorial activity in vivo. Marked tumor shrinkage of metastatic lung and lymphatic lesions were seen in patients on ganetespib monotherapy. Conclusion: The preclinical activity profile and clinical evidence of tumor regression suggest that ganetespib offers considerable promise as a new therapeutic candidate to target TNBC. Clin Cancer Res; 20(2); 413–24. ©2013 AACR.
Genome-wide Analysis of CpG Island Methylation in Bladder Cancer Identified TBX2, TBX3, GATA2, and ZIC4 as pTa-Specific Prognostic Markers
Authors: Raju Kandimalla, Angela A G van Tilborg, Lucie C Kompier, Dominique J P M Stumpel, Ronald W Stam, Chris H Bangma, Ellen C Zwarthoff
Journal: European Urology (2012)
Identification of novel regulatory modules in dicotyledonous plants using expression data and comparative genomics.
Authors: Klaas Vandepoele, Tineke Casneuf, Yves Van de Peer
Journal: Genome biology (2006)

Abstract Background Transcriptional regulation plays an important role in the control of many biological processes. Transcription factor binding sites (TFBSs) are the functional elements that determine transcriptional activity and are organized into separable cis -regulatory modules, each defining the cooperation of several transcription factors required for a specific spatio-temporal expression pattern. Consequently, the discovery of novel TFBSs in promoter sequences is an important step to improve our understanding of gene regulation. Results Here, we applied a detection strategy that combines features of classic motif overrepresentation approaches in co-regulated genes with general comparative footprinting principles for the identification of biologically relevant regulatory elements and modules in Arabidopsis thaliana , a model system for plant biology. In total, we identified 80 TFBSs and 139 regulatory modules, most of which are novel, and primarily consist of two or three regulatory elements that could be linked to different important biological processes, such as protein biosynthesis, cell cycle control, photosynthesis and embryonic development. Moreover, studying the physical properties of some specific regulatory modules revealed that Arabidopsis promoters have a compact nature, with cooperative TFBSs located in close proximity of each other. Conclusion These results create a starting point to unravel regulatory networks in plants and to study the regulation of biological processes from a systems biology point of view.
Inflammatory bowel disease and refractory anaemia (myelodysplasia).
Authors: R Sahay, D R Prangnell, B B Scott
Journal: Gut (1993)

Two patients with colitis and refractory anaemia requiring multiple transfusions are described. In one the anaemia was detected at the onset of colitis before drug treatment; in the other it started after 21 years of treatment with sulphasalazine and during an exacerbation of colitis with perianal abscess for which he had just been started receiving prednisolone, cofluampicil and metronidazole. Glomerulonephritis developed two weeks after the onset of anaemia. These findings together with a recent report of four patients with Crohn9s disease and refractory anaemia suggests that the association may be more than coincidental and may be immune mediated.
VALUE OF AORTIC VALVE CALCIUM SCORE IN PREDICTING THE SUCCESS OF PERCUTANEOUS TRANSLUMINAL AORTIC VALVULOPLASTY REGARDING IMPROVEMENTS IN AORTIC VALVE AREA
Authors: Tania Anu Singh, Junsoo Alex Lee, Gaby Weissman, Zuyue Wang, Itsik Ben-Dor, Rebecca Torguson, Petros Okubagzi, Lowell Satler, Steven Goldstein, Allen Taylor, William Guy Weigold, Augusto Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2012)
Timing breast cancer surgery
Authors: S.C. Low, M.H. Galea, R.W. Blamey, Aron Goldhirsch, RichardD. Gelber, John Forbes, Karen Price, Monica Castiglione, Carl-Magnus Rudenstam, Jurij Lindtner, Anne Hacking, Hansjörg Senn, Philip Cohen
Journal: The Lancet (1991)
CELL SURFACE IMMUNOGLOBULIN
Authors: Ellen S. Vitetta, Celso Bianco, Victor Nussenzweig, Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1972)

Thymocytes, bone marrow cells, and their derived T and B cell populations were examined for the presence of Ig by the cell surface radioiodination technique. Both IgM and IgG were identified on bone marrow cells. Thymocytes and T cells had no detectable cell surface Ig. Radiolabeling of mixtures of B cells and thymocytes suggest that the method may detect as little as 250 molecules of Ig per cell. Based on these findings, we suggest that the T cell receptor for antigen is not a conventional tetrameric Ig.
Vascular permeability and transvascular fluid and protein transport in the dog lung.
Authors: J C Parker, R E Parker, D N Granger, A E Taylor
Journal: Circulation Research (1981)

We used steady state lymph-to-plasma concentration ratios of six endogenous protein fractions (effective hydrodynamic radii of 37, 40, 44, 53, 100, and 120 A) to estimate pulmonary capillary permeability characteristics. Pulmonary lymph was collected from an afferent lymphatic to the left tracheobronchial lymph node, and left atrial pressure was elevated in steps until the lymphatic protein concentration obtained a constant value. Lymph flow and transvascular protein flux increased with each increase in left atrial pressure. Convective flux was the predominant mode of transport for the smaller fractions, and solvent-drag reflection coefficients increased as lymph flow increased. This dependency on lymph flow (capillary filtration) indicates a heteroporous membrane system. For lymph flows greater than five times control, the solvent-drag reflection coefficients were: 0.59 +/- 0.11, 0.52 +/- 0.06, 0.66 +/- 0.05, 0.70 +/- 0.05, 1.01 +/- 0.04, and 1.05 +/- 0.03 for the six fractions. Osmotic reflection coefficients estimated from the minimal lymph-to-plasma concentration ratios were: 0.50 +/- 0.03, 0.59 +/- 0.02, 0.67 +/- 0.04, 0.72 +/- 0.03, 0.94 +/- 0.01, and 0.96 +/- 0.01 for the six protein fractions. The osmotic reflection coefficients are consistent with a two- "pore" exchange model possessing equivalent pore radii of 80 and 200 A. Theoretical considerations indicate that only the two largest protein fractions (100 A and 120 A radii) achieved filtration-independent concentrations in pulmonary lymph, even at the highest filtration rates. This suggests that the reported osmotic reflection coefficients of the four small protein fractions underestimate their true values.
A DESCRIPTIVE STUDY ON INJURY RELATED PHYSICAL DISABILITY IN URBAN SRI LANKA
Authors: I Weerasinghe, F Pushpa, D Samath, J Sumedha
Journal: British Journal of Sports Medicine (2014)

Background Injuries remain the leading cause of death and disability among all age groups except 60 years of age or older. Road traffic accidents, occupations, sports, violence and humanitarian crisis significantly contribute to injuries. In Sri Lanka non-accident, traumatic injury, such as stepping on pressure mines, grenade and mortar blasts and trap gun accidents are common. Sri Lankans also suffer from a high rate of train mishaps. However, the magnitude of the contribution of various types of injuries to disability is still not well documented in Sri Lanka. Objective This study assessed prevalence of physical disability due to injuries among adults in Kandy Municipal Council area (KMC) in Central Sri Lanka. Design A community-based descriptive cross sectional study. Setting KMC area in Kandy, Sri Lanka. Participants 2 460 adults aged 18 to 59 years selected using cluster sampling. Main outcome measurements Physical disability was measured using a physical examination and World Health Organization Disability Assessment Schedule-Version II. An interviewer-administered questionnaire was used to reveal injury related data. Prevalence of physical disability due to injury and types of injuries were the main outcome measures. Results Prevalence of physical disability due to injuries was 0.6% (95% CI: 0.3–0.9). 13.6% (n=14) of physical disabilities were caused by injuries. Injuries reported included road traffic accidents (42.8%, n=6), falls (42.8%, n=6), war injuries (7.2%, n=1) and sports injuries (7.2%, n=1). Majority who underwent injuries were females (57.1%, n=8). There was no significant difference between males and females according to injury occurrence (P&lt;.05). Conclusion A significant proportion of physical disabilities were due to injuries. A majority of injuries occurred due to road traffic accidents while sports injuries contributed least for physical disability in the community in Sri Lanka.
Effect of abnormal liver function on vitamin E status and supplementation in adults with cystic fibrosis.
Authors: R J Stead, D P Muller, S Matthews, M E Hodson, J C Batten
Journal: Gut (1986)

Patients with cystic fibrosis tend to have reduced serum concentrations of vitamin E and are therefore at risk of developing the neurological complications associated with vitamin E deficiency. Improved survival in cystic fibrosis has resulted in an increasing number of older patients who may develop hepatobiliary complications which may further impair the absorption of vitamin E. In this study the vitamin E status and results of supplementation with oral vitamin E were compared in adult patients with and without evidence of liver involvement as assessed by routine liver function tests. The serum vitamin E concentrations were reduced below normal in 24 of 25 patients. The mean serum vitamin E concentration was significantly lower (p less than 0.05) in those patients with abnormal liver function. When vitamin E status was assessed as the serum vitamin E/cholesterol ratio, however, there was no significant difference between those patients with normal and abnormal liver function. After supplementation with oral vitamin E, either 10 mg/kg/day for one month or 200 mg/day (equivalent to 3.4 to 4.4 mg/kg/day) for up to three months, there was no significant difference in the vitamin E status between the two groups. The results of this study indicate that in general, patients with cystic fibrosis and abnormal liver function do not require increased supplements of vitamin E compared with those with normal liver function.
Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking
Authors: Simeon A Boyadjiev, J Christopher Fromme, Jin Ben, Samuel S Chong, Christopher Nauta, David J Hur, George Zhang, Susan Hamamoto, Randy Schekman, Mariella Ravazzola, Lelio Orci, Wafaa Eyaid
Journal: Nature Genetics (2006)
Rheumatoid factor seropositivity is inversely associated with oral contraceptive use in women without rheumatoid arthritis
Authors: Shailaja S Bhatia, Darcy S Majka, John M Kittelson, Lezlie A Parrish, Elizabeth D Ferucci, Kevin D Deane, William P Arend, Marian Rewers, V Michael Holers, Jill M Norris
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To examine whether oral contraceptive use is associated with the presence of serum rheumatoid factor in women of reproductive age without rheumatoid arthritis. <b>Methods:</b> 304 women selected from parents of children who were at increased risk of developing type 1 diabetes were studied, because they were enriched with the human leucocyte antigen-DR4 allele, a susceptibility marker for both type 1 diabetes and rheumatoid arthritis. Participants visited a clinic where blood was drawn for rheumatoid factor testing, and exposure data were collected via questionnaires. A medical history and joint examination were performed to rule out rheumatoid arthritis. Participants and examiners were unaware of the participants' rheumatoid factor status at the time of examination and questionnaire. <b>Results:</b> Use of oral contraceptives at any time was inversely associated with rheumatoid factor positivity (adjusted odds ratio (OR) 0.2, 95% confidence interval (CI) 0.07 to 0.52) independent of age, education and smoking. Smoking ⩾20 pack-years was also associated with rheumatoid factor positivity (adjusted OR 56.38, 95% CI 4.31 to 736.98) compared with never smoking. Smoking 1–19 pack-years was not associated with a positive rheumatoid factor. <b>Conclusions:</b> Our results suggest that oral contraceptive use, and possibly cigarette smoking, act early in the development of the immune dysregulation that occurs in rheumatoid arthritis.
Affiliative bonding as a dynamical process: A view from ethology
Authors: Kosuke Itoh, Akihiro Izumi
Journal: Behavioral and Brain Sciences (2005)

Depue & Morrone-Strupinsky's (D&M-S's) implicit assumption appears to be that affiliative bonding is either strengthened or maintained with time; however, it is more realistic that it can also be weakened or destroyed by conflictive interpersonal interactions. Without specifying the mechanisms by which antagonistic stimuli deteriorate affiliative bonding, the model is incapable of accounting for the dynamics associated with this complex phenomenon.
Cellular immunity to possible synovial antigens in rheumatoid arthritis.
Authors: A D Robinson, K D Muirden
Journal: Annals of the Rheumatic Diseases (1980)

A reaction has been demonstrated between extracts of synovial cells removed from intact rheumatoid knee joints and autologous leucocytes. The cell mediated immunity test system used was leucocyte migration inhibition. Variable reactions were found with a spectrum of allogeneic extracts when donor leucocytes came from married or transfused females or transfused males. Leucocytes from healthy (nontransfused) males showed no reaction with any of the extracts. As a period of cell culture was used prior to preparation of this extract to remove nonspecific inhibitory substances, native immunoglobulins, and complexes, the data are best explained by the presence of a foreign pathogen or altered cell component in the synovial cells of these rheumatoid patients.
Short-term exercise-based program associated to CPAP improves breathing pattern and functional status after coronary artery bypass graft surgery
Authors: Camila Bianca Falasco Pantoni, Luciana Di Thommazo-Luporini, Renata Gonçalves Mendes, Flávia Cristina Rossi Caruso, Daniel Mezzalira, Othon Amaral-Neto, Aparecida Maria Catai, Audrey Borghi-Silva
Journal: European Respiratory Journal (2013)

Background: Coronary artery bypass graft (CABG) results in severe alterations of lung function and reduced exercise tolerance. Continuous positive airway pressure (CPAP) has been used as an effective support to decrease the negative effects of CABG. Ventilatory assistance has shown powerful adjunct to physical exercise in chronic diseases. However, it is unknown if CPAP can positively impact CABG patients during exercise.  Aim: To evaluate the CPAP effectiveness as adjunct of inpatient rehabilitation program (IRP) during the first walking exercise (prior rest and exercise) on breathing pattern (BP) and functional status after CABG surgery.  Methods: 27 patients were randomized to IRP (n=14) or IRP+CPAP (n=13). IRP consisted of an early mobilization with progressive exercises with or without CPAP application (10-12 cmH2O). The outcomes measures included BP variables, assessed by respiratory inductive plethysmography (Lifeshirt system), time limit of exercise, and peripheral oxygen saturation.  Results: CPG presented higher tolerance of walking exercise compared to IRP, higher values of tidal volume and ventilation, lower values of %RCi and % RCe during rest and walking exercise, and higher SpO2 values at the end of walking, compared to CG. The intragroup analysis for both groups revealed increases in BF and decrease in respiratory times during walking, compared to rest.  Conclusion: CPAP can positively impact BP, ventilatory function and exercise tolerance when associated to IRP after CABG. This may constitute a feasible and effective approach to rehabilitation in these patients.  Financial Support: FAPESP (2009/01842-0 and 2009/54194-5).
Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study
Authors: Ching-Hon Pui, Deqing Pei, Elaine Coustan-Smith, Sima Jeha, Cheng Cheng, W Paul Bowman, John T Sandlund, Raul C Ribeiro, Jeffrey E Rubnitz, Hiroto Inaba, Deepa Bhojwani, Tanja A Gruber, Wing H Leung, James R Downing, William E Evans, Mary V Relling, Dario Campana
Journal: The Lancet Oncology (2015)
Verifying quality and safety in health informatics services
Authors: M. Rigby, J. Forsstrom, R. Roberts, J. Wyatt
Journal: BMJ (2001)

Information and its handling and transmission form an essential part of health care and are reflected in professional standards.Automated information systems in health care-health informatics services-will improve these functions and bring new opportunities through the harnessing of modern information and communications technologies.Thus, computer support is now essential in many parts of medicine, the US Institute of Medicine has long espoused the value of computerised patient records, 1 and many countries have developed strategies on this topic, and there are countless health related internet sites.However, as new information and communication technologies in health bring new opportunities, they also bring new risks.Emphasis has rightly been placed on ensuring appropriate levels of confidentiality in electronic information systems-to the point that the highly exacting requirements being demanded by independent commentators and professional bodies 2 are difficult to satisfy without jeopardising the functioning of core services 3 4 or the interests of the most vulnerable groups. 5In contrast, much less thought has been given so far to ensuring the appropriateness of the design and integrity of functioning of health informatics services.
Association of RNASEL Variants with Prostate Cancer Risk in Hispanic Caucasians and African Americans
Authors: Stacie J. Shook, Joke Beuten, Kathleen C. Torkko, Teresa L. Johnson-Pais, Dean A. Troyer, Ian M. Thompson, Robin J. Leach
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The RNASEL gene at 1q25 has been identified as a hereditary prostate cancer susceptibility gene, but to date, no study has investigated the role of RNASEL variants in Hispanic Caucasian men with prostate cancer. Experimental Design: Two RNASEL common variants, located at amino acids 462 and 541, were genotyped in non-Hispanic Caucasian, Hispanic Caucasian, and African American prostate cancer cases and controls. Results: The RNASEL 462 AA genotype was found to increase prostate cancer risk over 4-fold in Hispanic Caucasians [odds ratio (OR), 4.43; 95% confidence interval (95% CI), 1.68-11.68; P = 0.003] and over 10-fold in African Americans (OR, 10.41; 95% CI, 2.62-41.40; P = 0.001) when compared with the GG genotype. Analysis of the RNASEL 541 variant showed that Hispanic Caucasian patients with the GG genotype had a statistically significant increase in their risk for developing prostate cancer when compared with the TT and GT genotypes (OR, 1.91; 95% CI, 1.16-3.14; P = 0.01). A common G-T haplotype for the combination of the RNASEL 462 and 541 variants was found to occur more frequently in controls compared with cases in African Americans (P = 0.04) but not in non-Hispanic Caucasians or Hispanic Caucasians. Conclusions: This is the first study that investigates the association of prostate cancer risk with RNASEL variants in Hispanic men. Our data support the role of RNASEL as a predisposition gene for prostate cancer and showed a significant association between the RNASEL 462 variant and prostate cancer risk in African Americans and Hispanic Caucasians.