tbuckley/cabot-search huggingface dataset:
A Mitochondrial Target Sequence Polymorphism in Manganese Superoxide Dismutase Predicts Inferior Survival in Breast Cancer Patients Treated with Cyclophosphamide
Authors: Sharon A. Glynn, Brenda J. Boersma, Tiffany M. Howe, Hege Edvardsen, Stephanie B. Geisler, Julie E. Goodman, Lisa A. Ridnour, Per E. Lønning, Anne-Lise Børresen-Dale, Bjorn Naume, Vessela N. Kristensen, Stephen J. Chanock, David A. Wink, Stefan Ambs
Journal: Clinical Cancer Research (2009)

Manganese superoxide dismutase protects against oxidative damage and modulates the efficacy of chemotherapeutic drugs. A functional single-nucleotide polymorphism in codon 16 of SOD2 (rs4880), which encodes manganese superoxide dismutase, results in a substitution of valine by alanine (Val16Ala). We hypothesized that this single-nucleotide polymorphism affects breast cancer survival of patients receiving chemotherapy.Two patient populations from the United States (n = 248) and Norway (n = 340) were genotyped for Val16Ala. Kaplan-Meier survival and Cox proportional hazards regression analyses were used to examine the relationship between Val16Ala and disease-specific survival.Val16Ala was significantly associated with breast cancer outcome in both patient populations. Carriers of the Ala allele had inferior survival rates in the multivariate analysis [hazard ratio (HR), 2.44 and 95% confidence interval (95% CI), 1.11-5.37 in U.S. cohort; HR, 1.91 and 95% CI, 1.06-3.45 in Norway cohort for Ala/Ala versus Val/Val]. In an analysis of the combined cohorts, this association was significant for patients receiving adjuvant therapy (HR, 2.47; 95% CI, 1.46-4.19), but not for patients without it (HR, 1.47; 95% CI, 0.57-3.74). After further stratification by type of chemotherapy, the effect of the Ala allele was mostly restricted to cyclophosphamide-containing chemotherapy regimens (HR, 22.0; 95% CI, 5.22-92.9; Ala/Ala versus Val/Val).The Val16Ala polymorphism affects survival of patients receiving cyclophosphamide-containing chemotherapy. The findings provide the first evidence pointing toward a mechanism for cyclophosphamide resistance in breast cancer patients.
Myocardial infarction after vascular surgery: the role of prolonged, stress-induced, ST depression-type ischemia
Authors: Giora Landesberg, Morris Mosseri, Doron Zahger, Yehuda Wolf, Misha Perouansky, Haim Anner, Benjamin Drenger, Yonatan Hasin, Yacov Berlatzky, Charles Weissman
Journal: Journal of the American College of Cardiology (2001)
Calcium signalling in human spermatozoa: a specialized ‘toolkit’ of channels, transporters and stores
Authors: C. Jimenez-Gonzalez, F. Michelangeli, C.V. Harper, C.L.R. Barratt, S.J. Publicover
Journal: Human Reproduction Update (2005)

Ca2+ is a ubiquitous intracellular messenger which encodes information by temporal and spatial patterns of concentration. In spermatozoa, several key functions, including acrosome reaction and motility, are regulated by cytoplasmic Ca2+ concentration. Despite the very small size and apparent structural simplicity of spermatozoa, evidence is accumulating that they possess sophisticated mechanisms for regulation of cytoplasmic Ca2+ concentration and generation of complex Ca2+ signals. In this review, we consider the various components of the Ca2+-signalling 'toolkit' that have been characterized in somatic cells and summarize the evidence for their presence and activity in spermatozoa. In particular, data accumulated over the last few years show that spermatozoa possess one (and probably two) Ca2+ stores as well as a range of plasma membrane pumps and channels. Selective regulation of the various components of the 'toolkit' by agonists probably allows spermatozoa to generate localized Ca2+ signals despite their very small cytoplasmic volume, permitting the discrete and selective activation of cell functions.
Relationship between past airway pathology and current lung function in preschool wheezers
Authors: S. Sonnappa, C.M. Bastardo, S. Saglani, A. Bush, P. Aurora
Journal: European Respiratory Journal (2011)

The functional outcome in preschool severe wheezers with eosinophilic airway inflammation and increased reticular basement membrane (RBM) thickness is unknown. We investigated the relationship between airway pathology at age 2 yrs and lung function at age 4–6 yrs in previous severe wheezers. Severe wheezers previously investigated by endobronchial biopsy and healthy children aged 4–6 yrs were recruited. Lung clearance index (LCI), conducting zone ventilation inhomogeneity ( S cond ), acinar ventilation inhomogeneity by multiple-breath washout, plethysmographic-specific airway resistance and exhaled nitric oxide fraction ( F eNO ) were measured. Lung function was compared between wheezers and healthy controls, and in wheezers correlated with past RBM thickness and mucosal eosinophilia (EG2+ cells). 72 healthy controls and 28 previous severe wheezers were tested. Wheezers had significantly higher median LCI (6.8 versus 6.6; p=0.001) and S cond (0.046 versus 0.016; p&lt;0.0005) than healthy controls. Past RBM thickness (r=0.474, p=0.047) and EG2+ cells (r=0.552, p=0.041) showed significant correlations with current F eNO , but no correlations were seen between past RBM thickness and current lung function. RBM thickness and EG2+ cells at age 2 yrs show a significant positive association with F eNO at age 5 yrs. Although lung function was abnormal at age 5 yrs in severe wheezers, this did not correlate with past RBM thickness.
Dyspnoea and flow-volume curve during exercise in COPD patients
Authors: A Noseda, JP Carpiaux, J Schmerber, F Valente, JC Yernault
Journal: European Respiratory Journal (1994)

The purpose of this study, in patients with chronic obstructive pulmonary disease (COPD), was to examine the relationship of dyspnoea, rated on a visual analogue scale (VAS), to 1) tidal ventilatory variables measured on exercise and 2) pre-exercise lung function. Twenty one patients (forced expiratory volume in one second (FEV1) mean (SD) 1.19 (0.32) l) were studied. During a preliminary test, the maximal workload was assessed and the upper end of the VAS was anchored. On the study day, the tidal flow-volume curve on exercise was monitored and dyspnoea was assessed serially every minute. In each individual, the relationship of dyspnoea to various tidal ventilatory variables was studied using linear regression analysis; results were reported squared correlation coefficients, slopes and dyspnoea thresholds. Subsequently, the relationship of slopes and thresholds to pre-exercise lung function was examined. In all patients, dyspnoea showed a close correlation with ventilation, tidal volume, breathing frequency and tidal flow. The tidal peak inspiratory flow was the best individual predictor of dyspnoea with a median r2 of 0.91. Patients with the poorest pre-exercise lung function exhibited the highest rates of increase in dyspnoea and the lowest thresholds, the strongest correlation being observed between the dyspnoea/ventilation slope and pre-exercise maximal peak inspiratory flow (r2 = 0.54). In conclusion, for individual COPD patients dyspnoea on exercise is closely related to inspiratory flow. The degree of pre-exercise ventilatory impairment accounts, at most, for only half of the variation in dyspnoea perception between subjects.
Value of imprint cytology for ultrasound-guided transthoracic core biopsy
Authors: R. R. Paulose, C. D. Shee
Journal: European Respiratory Journal (2005)

The aim of this study was to investigate the possible additional diagnostic information provided by imprint cytology when performing ultrasound-guided transthoracic core biopsy and to evaluate whether it could optimise the biopsy procedure. A total of 155 transthoracic core biopsies with touch imprint smears were performed under ultrasound guidance, with 127 malignant and 28 benign lesions. The imprint smears were stained using Riu's method and interpreted by a cytopathologist. These were compared with the histopathology of core biopsy specimens and the final diagnosis of malignant versus benign disease. The overall diagnostic accuracy of imprint cytology was 94% (146 out of 155). Histopathological analysis showed an overall accuracy of 94% (146 out of 155), with a sensitivity of 94% (119 out of 127) and negative predictive value of 79% (27 out of 34). The combination of these two methodologies had an increased overall accuracy and negative predictive value of 98% (152 out of 155) and 90% (28 out of 31), respectively. The results of imprint cytology and histopathology were in agreement in 143 patients (92%). In conclusion, imprint cytology of ultrasound-guided transthoracic core biopsy is a sensitive procedure for diagnosing peripheral thoracic lesions, and it may increase the diagnostic accuracy and cancer negative prediction of biopsy alone. With an on-site approach, imprint cytology may help to assess the adequacy of biopsy specimens and optimise the biopsy procedure.
The Pattern and Evolution of Looped Gene Bendability
Authors: Zhiming Dai, Yuanyan Xiong, Xianhua Dai
Journal: Molecular Biology and Evolution (2013)

Gene looping, defined as the physical interaction between the promoter and terminator regions of a RNA polymerase II-transcribed gene, is widespread in yeast and mammalian cells. Gene looping has been shown to play important roles in transcription. Gene-loop formation is dependent on regulatory proteins localized at the 5' and 3' ends of genes, such as TFIIB. However, whether other factors contribute to gene looping remains to be elucidated. Here, we investigated the contribution of intrinsic DNA and chromatin structures to gene looping. We found that Saccharomyces cerevisiae looped genes show high DNA bendability around middle and 3/4 regions in open reading frames (ORFs). This bendability pattern is conserved between yeast species, whereas the position of bendability peak varies substantially among species. Looped genes in human cells also show high DNA bendability. Nucleosome positioning around looped ORF middle regions is unstable. We also present evidence indicating that this unstable nucleosome positioning is involved in gene looping. These results suggest a mechanism by which DNA bendability and unstable nucleosome positioning could assist in the formation of gene loops.
p38 Triggers Late Preconditioning Elicited by Anisomycin in Heart
Authors: Ting C. Zhao, Mohiuddin M. Taher, Kristoffer C. Valerie, Rakesh C. Kukreja
Journal: Circulation Research (2001)

We investigated the role of stress-activated p38 MAP kinase (p38/SAPK-2) signaling in delayed preconditioning of the heart. Adult male out-bred ICR mice were treated with p38 activator, anisomycin (0.1 mg/kg IP), or vehicle (5% DMSO). Twenty-four hours later, hearts were perfused in Langendorff mode and subjected to 30 minutes of ischemia and 30 minutes of reperfusion. Improvement in postischemic recovery of end-diastolic pressure and reduction in infarct size was observed, which was abolished by SB203580, a specific p38 inhibitor, and pyrrolidinediethyldithiocarbamate (PDTC), the NF-κB inhibitor, but not by PD 98059, a specific inhibitor for MEK1 or 2. Transient increase in p38 phosphorylation was observed 15 minutes after anisomycin treatment which subsided by 30 minutes. Electrophoretic mobility shift assay demonstrated rapid activation of NF-κB DNA binding with anisomycin, peaking at 30 minutes. Western blot confirmed the accumulation of p50 and p65 in nuclear extracts after anisomycin treatment. Anisomycin-induced NF-κB DNA binding activity was inhibited by SB203580 and PDTC. Expression of inducible nitric oxide synthase (iNOS) mRNA, protein, and nitric oxide (NO) synthesis were enhanced in anisomycin-treated mice. SB203580 and PDTC blocked the increased expression of iNOS and increase in synthesis of NO. Selective iNOS inhibitor S -methylisothiourea abolished the protective effect of anisomycin. Furthermore, postischemic cardioprotective effect of anisomycin was absent in mice with targeted ablation of iNOS gene but not in the wild-type B6.129 mice. For the first time, these results suggest that direct pharmacological activation of p38 triggers delayed preconditioning by signaling mechanism involving NF-κB activation and synthesis of NO from iNOS.
Obesity in CKD—What Should Nephrologists Know?
Authors: Peter Stenvinkel, Carmine Zoccali, T. Alp Ikizler
Journal: Journal of the American Society of Nephrology (2013)

Obesity, the epidemic of the 21st century, carries a markedly increased risk for comorbid complications, such as type 2 diabetes, cancer, hypertension, dyslipidemia, cardiovascular disease, and sleep apnea. In addition, obesity increases the risk for CKD and its progression to ESRD. Paradoxically, even morbid obesity associates with better outcomes in studies of ESRD patients on maintenance dialysis. Because the number of obese CKD and maintenance dialysis patients is projected to increase markedly in developed as well as low- and middle-income countries, obesity is a rapidly emerging problem for the international renal community. Targeting the obesity epidemic represents an unprecedented opportunity for health officials to ameliorate the current worldwide increase in CKD prevalence. Nephrologists need more information about assessing and managing obesity in the setting of CKD. Specifically, more precise estimation of regional fat distribution and the amount of muscle mass should be introduced into regular clinical practice to complement more commonly used practical markers, such as body mass index. Studies examining the effects of obesity on kidney disease progression and other clinical outcomes along with weight management strategies are much needed in this orphan area of research.
Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response and tolerability in a randomised phase III trial (TOPIC 2)
Authors: S. Chua, I.E. Smith, R.P. A'Hern, G.A. Coombes, T.F. Hickish, A.C. Robinson, R.W. Laing, M.E.R. O'Brien, S.R. Ebbs, A. Hong, A. Wardley, T. Mughal, M. Verrill, D. Dubois, J.M. Bliss
Journal: Annals of Oncology (2005)
Antibodies to Endothelial Cells in Borderline Hypertension
Authors: Johan Frostegård, Ruihua Wu, Caroline Gillis-Haegerstrand, Carola Lemne, Ulf de Faire
Journal: Circulation (1998)

Background —Antibodies to endothelial cells (aECs) and to cardiolipin (aCLs) are implicated in autoimmune diseases like systemic lupus erythematosus vasculitis. β 2 -Glycoprotein 1 (β2GP1) is a cofactor for aCLs. The present study investigated the possible role of aECs, aCLs, and aβ2GP1 in borderline hypertension. Methods and Results —Seventy-three men with borderline hypertension (BHT) and 73 age-matched normotensive (NT) men (diastolic blood pressure, 85 to 94 and &lt;80 mm Hg, respectively) were recruited from a population screening program. Antibody levels were determined by ELISA. Presence of carotid atherosclerosis was determined by B-mode ultrasonography, and 29 individuals had atherosclerotic plaques. BHT men had significantly higher aEC and aβ2GP1 levels of IgG class than NT control subjects ( P =0.029 and P =0.0001, respectively). aEC levels of IgM class were higher in BHT ( P =0.012), but not aβ2GP1 levels. There was no correlation between aCL levels and BHT. Individuals with atherosclerotic plaques had significantly higher aEC levels of both IgG ( P =0.042) and IgM subclasses ( P =0.018) than those without plaques, but no difference was found in aCL and aβ2GP1 levels. Endothelin and aECs of IgM class were significantly associated. Conclusions —We demonstrate the first evidence of a significant elevation of aEC and aβ2GP1 levels in borderline hypertension. These findings provide a new link between hypertension and atherosclerosis and indicate that humoral immune reactions to the endothelium may play an important role in both conditions.
Treatment Of Murine Chronic Granulomatous Disease (CGD) With The PPARγ Agonist Pioglitazone Enhances Phagocyte Mitochondrial Reactive Oxygen Species (ROS) Production and Antimicrobial Responses
Authors: Donna Bratton, S. Courtney Frasch, Kenneth Malcolm, Ruby Fernandez-Boyanapalli
Journal: Journal of Allergy and Clinical Immunology (2014)
A high body mass index has a protective effect on the amount of joint destruction in small joints in early rheumatoid arthritis
Authors: A H M van der Helm-van Mil, S M van der Kooij, C F Allaart, R E M Toes, T W J Huizinga
Journal: Annals of the Rheumatic Diseases (2007)

Plasmacytoid dendritic cells (pDC), as major producers of IFN-α, are thought not only to be pivotal in antiviral immunity, but also to limit allergic inflammation. In this study, we delineate the role of pDC in a mouse model of respiratory syncytial virus (RSV)-induced airway inflammation. Bone marrow-derived pDC generated high levels of IFN-α upon RSV infection, and the percentage of pDC expressing MHC class II and maturation-associated costimulatory molecules was increased. However, their weak Ag-presenting capacity was not enhanced. Furthermore, pDC induced marked levels of IL-10 in T cell cultures irrespective of infection. In vivo, numbers of pDC in the lung increased early after RSV infection and remained elevated throughout the inflammatory phase and the resolution phase of infection. Depletion of pDC resulted in increases in peak RSV titers, pulmonary inflammation, and airway hyperresponsiveness. In contrast, adoptive transfer of activated pDC to the airways reduced RSV copy numbers. In conclusion, RSV infection induces activation of murine pDC with robust IFN-α production, limiting replication and accelerating elimination of RSV. In addition to this innate response, pDC also may play an immune regulatory role in reducing pulmonary inflammation and inhibiting the development of airway hyperresponsiveness.
Electrospinning of collagen nanofibers: Effects on the behavior of normal human keratinocytes and early-stage wound healing
Authors: Kyong Su Rho, Lim Jeong, Gene Lee, Byoung-Moo Seo, Yoon Jeong Park, Seong-Doo Hong, Sangho Roh, Jae Jin Cho, Won Ho Park, Byung-Moo Min
Journal: Biomaterials (2005)
Efficacy of Fractionated Stereotactic Reirradiation in Recurrent Gliomas: Long-Term Results in 172 Patients Treated in a Single Institution
Authors: Stephanie E. Combs, Christoph Thilmann, Lutz Edler, Jürgen Debus, Daniela Schulz-Ertner
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) performed as reirradiation in 172 patients with recurrent low- and high-grade gliomas. Patients and Methods Between 1990 and 2004, 172 patients with recurrent gliomas were treated with FSRT as reirradiation in a single institution. Seventy-one patients suffered from WHO grade 2 gliomas. WHO grade 3 gliomas were diagnosed in 42 patients, and 59 patients were diagnosed with glioblastoma multiforme (GBM). The median time between primary radiotherapy and reirradiation was 10 months for GBM, 32 months for WHO grade 3 tumors, and 48 months for grade 2 astrocytomas. FSRT was performed with a median dose of 36 Gy in a median fractionation of 5 × 2 Gy/wk. Results Median overall survival after primary diagnosis was 21 months for patients with GBM, 50 months for patients with WHO grade 3 gliomas, and 111 months for patients with WHO grade 2 gliomas. Histologic grading was the strongest predictor for overall survival, together with the extent of neurosurgical resection and age at primary diagnosis. Median survival after reirradiation was 8 months for patients with GBM, 16 months for patients with grade 3 tumors, and 22 months for patients with low-grade gliomas. Only time to progression and histology were significant in influencing survival after reirradiation. Progression-free survival after FSRT was 5 months for GBM, 8 months for WHO grade 3 tumors, and 12 months for low-grade gliomas. Conclusion FSRT is well tolerated and may be effective in patients with recurrent gliomas. Prospective studies are warranted for further evaluation.
Kinetics of thrombopoiesis
Authors: Laurence A. Harker
Journal: Journal of Clinical Investigation (1968)

Measurements of megakaryocyte number, volume, nuclear number, and cytoplasmic granulation were compared in animals with induced thrombocytosis, normal platelet counts, and induced thrombocytopenia for 4- and 10-day periods. Thrombopoiesis, as measured by megakaryocytic mass and (35)S incorporation into platelets, appeared to be regulated by the demand for circulating platelets. In addition, two mechanisms were operative in the alteration of thrombopoiesis. The first mechanism involved the regulation of endomitosis in the immature megakaryocytes which in turn determined the subsequent volume of platelet-producing cytoplasm. The second mechanism regulated the number of megakaryocytes formed from the precursor, "stem cell," compartment.
The impact of budesonide/formoterol on the airway transcriptome in COPD
Authors: Yaron Gesthalter, Katrina Steiling, Marc Lenburg, Avrum Spira, Frank Schembri
Journal: European Respiratory Journal (2014)

We have recently described COPD-associated gene-expression differences in bronchial airway epithelium that define a COPD field of injury. In this study, we sought to validate our COPD gene-expression signature and identify gene-expression changes associated with inhaled budesonide/formoterol (BUD/FORM; Symbicort ® ; 160/4.5 mcg x 2 puffs bid) in COPD patients.  Methods: Current and former smokers with (n=15) and without (n=13) COPD were enrolled and underwent baseline collection of bronchial epithelium via bronchoscopy. Re-sampling was performed on 10 COPD subjects after initiation of BUD/FORM therapy (median 97 days). RNA was hybridized to arrays. A linear model adjusting for age was used to identify gene expression changes associated with baseline COPD status, while changes associated with therapy were found using a paired t-test within COPD subjects. Relationships with previously published signatures were assessed using GSEA.  Results: Expression levels of 496 genes were altered at baseline in COPD subjects (p  Conclusions: Our study shows that components of the COPD-associated alterations in airway gene-expression are reversible following short-term budesonide/formoterol treatment. This suggests that the airway field of injury in COPD is dynamic with therapy, raising the possibility that molecular profiles in the relatively accessible airway epithelium may serve as markers of therapeutic efficacy.