tbuckley/cabot-search huggingface dataset:
Sustained Activation of Cell Adhesion Is a Differentially Regulated Process in B Lymphopoiesis
Authors: Aleksandra M. Glodek, Marek Honczarenko, Yi Le, James J. Campbell, Leslie E. Silberstein
Journal: The Journal of Experimental Medicine (2003)

It is largely unknown how hematopoietic progenitors are positioned within specialized niches of the bone marrow microenvironment during development. Chemokines such as CXCL12, previously called stromal cell–derived factor 1, are known to activate cell integrins of circulating leukocytes resulting in transient adhesion before extravasation into tissues. However, this short-term effect does not explain the mechanism by which progenitor cells are retained for prolonged periods in the bone marrow. Here we show that in human bone marrow CXCL12 triggers a sustained adhesion response specifically in progenitor (pro- and pre-) B cells. This sustained adhesion diminishes during B cell maturation in the bone marrow and, strikingly, is absent in circulating mature B cells, which exhibit only transient CXCL12-induced adhesion. The duration of adhesion is tightly correlated with CXCL12-induced activation of focal adhesion kinase (FAK), a known molecule involved in integrin-mediated signaling. Sustained adhesion of progenitor B cells is associated with prolonged FAK activation, whereas transient adhesion in circulating B cells is associated with short-lived FAK activation. Moreover, sustained and transient adhesion responses are differentially affected by pharmacological inhibitors of protein kinase C and phosphatidylinositol 3-kinase. These results provide a developmental cell stage–specific mechanism by which chemokines orchestrate hematopoiesis through sustained rather than transient activation of adhesion and cell survival pathways.
Spontaneous Pneumothorax from Secondary Sarcoma of Lung
Authors: A. B. Shaw
Journal: BMJ (1951)

CommentThe pre-operative diagnosis of torsion is seldom made; about 80% of cases are diagnosed as appendi- citis, but, considering the duration of symptoms, the patients look less toxic than do cases of appendicitis.The age incidence varies between 35 and 55 years, and the condition is twice as common in males.The three cases reported here were all those of men between 45 and 50.Cases 2 and 3 are examples of secondary torsion, the third case being associated with intraperitoneal adhe- sions, and the second with a right inguinal hernia, though there was no evidence of adhesions between the hernial sac and the omentum.No definite cause was found for torsion in Case 1, which can therefore be grouped as an example of primary or idiopathic torsion.I wish to thank Mr. T. G. I. James for his advice
Efficacy of azathioprine versus mesalazine in postoperative Crohn's disease-The Authors' response
Authors: W. Reinisch, E. F. Stange
Journal: Gut (2011)

We thank Dr Ford for his comments1 on our recent paper in Gut entitled ‘Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy multi-centre trial’.2 With regard to our power calculation assuming a difference in treatment effect of 35% in favour of azathioprine, although two previous …
Regression Models in Clinical Studies: Determining Relationships Between Predictors and Response
Authors: F. E. Harre, K. L. Lee, B. G. Pollock
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Regression Models in Clinical Studies: Determining Relationships Between Predictors and Response Get access Frank E. Harre, Jr., Frank E. Harre, Jr. 3Clinical Biostatistics, Duke University Medical CenterDurham, NC 27710;Takima West CorporationChapel Hill, NC 27514. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kerry L. Lee, Kerry L. Lee 3Clinical Biostatistics, Duke University Medical CenterDurham, NC 27710;Takima West CorporationChapel Hill, NC 27514. Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara G. Pollock Barbara G. Pollock 3Clinical Biostatistics, Duke University Medical CenterDurham, NC 27710;Takima West CorporationChapel Hill, NC 27514. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 15, 5 October 1988, Pages 1198–1202, https://doi.org/10.1093/jnci/80.15.1198 Published: 05 October 1988 Article history Received: 27 April 1988 Accepted: 08 June 1988 Published: 05 October 1988
Myocardial subcellular fractionation studies on cardiomyopathic Syrian hamsters
Authors: D. H. FITCHETT, J. SCOTT, H. R. STEPHENS, T. J. PETERS
Journal: Cardiovascular Research (1979)

Myocardial homogenates from control animals and from hamsters with hereditary cardiomyopathy were subjected to analytical subcellular fractionation and enzymic microanalysis. Animals without ventricular hypertrophy or overt heart failure were used in this study. The principal subcellular organelles were characterised by density gradient centrifugation. Apart from evidence of enhanced lysosomal and peroxisomal fragility, probably secondary to the intracellular oedema, the intracellular organelles investigated in this study were unaffected by the myopathic process. Highly significant increases in 5'-nucleotidase activity, a marker for the sarcolemma, and an increased equilibrium density of this organelle were found in the myopathic tissue. Ultrastructural studies revealed patchy myocytolysis associated with lysosomes and with more extensive invaginations of the sarcolemma. It is suggested that a primary defect in membrane composition, leading to increased cation permeability, is the underlying abnormality in the myopathic hamster.
Reducing Personal Exposure to Particulate Air Pollution Improves Cardiovascular Health in Patients with Coronary Heart Disease
Authors: Jeremy P. Langrish, Xi Li, Shengfeng Wang, Matthew M.Y. Lee, Gareth D. Barnes, Mark R. Miller, Flemming R. Cassee, Nicholas A. Boon, Ken Donaldson, Jing Li, Liming Li, Nicholas L. Mills, David E. Newby, Lixin Jiang
Journal: Environmental Health Perspectives (2012)

Air pollution exposure increases cardiovascular morbidity and mortality and is a major global public health concern.We investigated the benefits of reducing personal exposure to urban air pollution in patients with coronary heart disease.In an open randomized crossover trial, 98 patients with coronary heart disease walked on a predefined route in central Beijing, China, under different conditions: once while using a highly efficient face mask, and once while not using the mask. Symptoms, exercise, personal air pollution exposure, blood pressure, heart rate, and 12-lead electrocardiography were monitored throughout the 24-hr study period.Ambient air pollutants were dominated by fine and ultrafine particulate matter (PM) that was present at high levels [74 μg/m³ for PM(2.5) (PM with aerodynamic diamater <2.5 µm)]. Consistent with traffic-derived sources, this PM contained organic carbon and polycyclic aromatic hydrocarbons and was highly oxidizing, generating large amounts of free radicals. The face mask was well tolerated, and its use was associated with decreased self-reported symptoms and reduced maximal ST segment depression (-142 vs. -156 μV, p = 0.046) over the 24-hr period. When the face mask was used during the prescribed walk, mean arterial pressure was lower (93 ± 10 vs. 96 ± 10 mmHg, p = 0.025) and heart rate variability increased (high-frequency power: 54 vs. 40 msec², p = 0.005; high-frequency normalized power: 23.5 vs. 20.5 msec, p = 0.001; root mean square successive differences: 16.7 vs. 14.8 msec, p = 0.007). However, mask use did not appear to influence heart rate or energy expenditure.Reducing personal exposure to air pollution using a highly efficient face mask appeared to reduce symptoms and improve a range of cardiovascular health measures in patients with coronary heart disease. Such interventions to reduce personal exposure to PM air pollution have the potential to reduce the incidence of cardiovascular events in this highly susceptible population.
Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition
Authors: Ming Sun, Xiang-Hua Liu, Ke-Ming Wang, Feng-qi Nie, Rong Kong, Jin-song Yang, Rui Xia, Tong-Peng Xu, Fei-Yan Jin, Zhi-Jun Liu, Jin-fei Chen, Er-Bao Zhang, Wei De, Zhao-Xia Wang
Journal: Molecular Cancer (2014)

Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its' molecular mechanisms controlling cancer cell migration and metastasis are unclear.Expression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry.BANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression.We determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.
Mobilization of tissue kallikrein in inflammatory disease of the colon
Authors: I. J. Zeitlin, A. N. Smith
Journal: Gut (1973)

Colonic tissue was taken at operation from 10 patients with active ulcerative colitis and three patients with uncomplicated diverticular disease but with severe symptoms. Levels of kininogen, kallikrein, and kallikrein precursor were measured in blood-free tissue samples. In normal colon tissue a kininogen occurred in the muscle and none was detected in the mucosa. Kallikrein and its precursor were found in mucosa but not in muscle. In acutely inflamed tissue from ulcerative colitis patients relatively high levels of active kallikrein were detected in the underlying colonic muscle. There was little change in the level of kallikrein in inflamed mucosa or of kininogen in the muscle of these patients. No kallikrein was found in colonic muscle from patients with diverticular disease and the mucosal kallikrein level in these patients was unchanged. The findings suggest a mechanism for the formation of kinins in the wall of the colon which is present in ulcerative colitis but not in diverticular disease.
Species differences in NTM pulmonary disease (pNTM)
Authors: Steven Cowman, Charlotte Goward, Diana Bilton, Robert Wilson, Michael Loebinger
Journal: European Respiratory Journal (2013)

Background:  pNTM represents a hetrogenous group of species with varying pathogenicity, making management challenging.   Aims:  To describe the distribution and clinical features of species causing pNTM.   Methods:  pNTM cases were identified and recruited from a tertiary referral clinic over 6 months. They underwent clinical assessment and lung function testing.   Results:  57 cases were recruited; their details are shown in table 1. There was significant variation in species amongst disease groups (p=0.0004) with  M. avium  complex (MAC) more common in bronchiectasis and  M. xenopi  in COPD. There was also variation between sex (p=0.024), with MAC more common in females and  M. abscessus  in men. There were no significant differences in lung function, BMI, SGRQ or the proportion requiring treatment.   Conclusion:  Species vary with underlying disease. Despite perceived differences in pathogenicity, the proportion requiring treatment did not vary significantly between species.
Paclitaxel plus carboplatin, compared with paclitaxel plus gemcitabine, shows similar efficacy while more cost-effective: a randomized phase II study of combination chemotherapy against inoperable non-small-cell lung cancer previously untreated
Authors: Y.-M. Chen, R.-P. Perng, Y.-C. Lee, J.-F. Shih, C.-S. Lee, C.-M. Tsai, J. Whang-Peng
Journal: Annals of Oncology (2002)
Fraud and Misconduct in Medical Research.
Authors: W B. Fye
Journal: Cardiovascular Research (1994)

Fraud and Misconduct in Medical Research. Get access W Bruce Fye W Bruce Fye Marshfield, WI, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 6, June 1994, Page 931, https://doi.org/10.1093/cvr/28.6.931a Published: 01 June 1994
Prognostic Factors in Meningococcal Disease
Authors: Nicolau Barquet
Journal: JAMA (1997)

<h3>Context.</h3> —Meningococcal disease is associated with significant morbidity and mortality. Development of a prognostic model based on clinical findings may be useful for identification and management of patients with meningococcal infection. <h3>Objectoves.</h3> —To construct and validate a bedside model and scoring system for prognosis in meningococcal disease. <h3>Design.</h3> —Prospective, population-based study. <h3>Setting.</h3> —Twenty-four hospitals in the metropolitan area of Barcelona, Spain. <h3>Patients.</h3> —A total of 907 patients with microbiologically proven meningococcal disease. Patients diagnosed with meningococcal disease from 1987 through 1990 were used to develop the prognostic model, and those diagnosed in 1991 and 1992 were used to validate it. <h3>Outcome Measures.</h3> —Clinical independent prognostic factors for mortality in meningococcal disease. The association between outcome and independent prognostic factors was determined by logistic regression analysis. A scoring system was constructed and tested using receiver operating characteristic curves. <h3>Results.</h3> —Among 624 patients in the derivation set, 287 (46%) were male, the mean age was 12.4 years, and 34 patients (5.4%) died. Among 283 patients in the validation set, 124 (43.8%) were male, the mean age was 12.7 years, and 17 patients (6.0%) died. In multivariate analysis, independent predictors of death were hemorrhagic diathesis (odds ratio [OR], 101; 95% confidence interval [CI], 30-333), focal neurologic signs (OR, 25; 95% CI, 7-83), and age 60 years or older (OR, 10; 95% CI, 3-34), whereas receipt of adequate antibiotic therapy prior to admission was associated with reduced likelihood of death (OR, 0.09; 95% CI, 0.02-0.4). Hemorrhagic diathesis was scored with 2 points, presence of focal neurologic signs with 1 point, age of 60 years or older with 1 point, and preadmission antibiotic therapy was scored as -1. The clinical scores of -1, 0,1,2, and 3 or more points were associated with a probability of death of 0%, 2.3%, 27.3%, 73.3%, and 100%, respectively. <h3>Conclusions.</h3> —Hemorrhagic diathesis, focal neurologic signs, and age of 60 years or older were independent predictors of death in meningococcal disease, whereas receipt of adequate antibiotic therapy was associated with a more favorable prognosis. The scoring system presented is simple, is based on findings readily available at the bedside, and may be useful to help guide aggressive therapy.
P117 Comparison of respiratory-related quality of life pulmonary rehabilitation outcomes and duration of treatment in acute and community settings: Abstract P117 Table 1.
Authors: JMS Cox, H Matthews, P Browne, A Blackburn
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> NICE guidance recommends that patients are offered between six and twelve weeks of pulmonary rehabilitation as effective treatment option for chronic obstructive pulmonary disease (NICE, 2010). While there is good evidence for programme content, evidence is less on the optimum duration or comparative efficacy in different settings. Two English NHS pulmonary rehabilitation services used different service models for COPD patients. An acute based service offered up to nine weekly sessions of pulmonary rehabilitation using a multi-disciplinary team. Another service based in a community gym offered up to ten sessions provided by respiratory nurses and a physical activity co-ordinator. We hypothesised that outcomes would not improve after eight pulmonary rehabilitation sessions and would be similar for the two services. <h3>Methods</h3> A pragmatic service evaluation with before-after design was used. Self-reported chronic respiratory questionnaires (CRQ) measuring four quality of life domains (dyspnoea, fatigue, emotional function, mastery) were completed by patients at baseline and again on completion of pulmonary rehabilitation. For each service, baseline scores were subtracted from completion scores to measure change in respiratory related quality of life outcomes and compared to minimum clinically important difference (MICD) of 0.5 (Williams <i>et al</i>, 2003). The effect of number of sessions attended by patients on respiratory outcome scores was tested using linear regression. <h3>Results</h3> Baseline and follow-up CRQ scores were available for 149 patients (89 in the acute based service). In the community based service, improvements in dyspnoea and emotion were statistically significantly greater than the MCID whereas for the acute service, improvements in emotional function and mastery were significantly greater than MCID (Table 1). The overall proportion of patients experiencing CRQ increases greater than the MCID for both services were dyspnoea: 62.4%; fatigue: 57.7%; emotional function: 61.7%; mastery: 59.1% at follow up. The effect of duration on CRQ outcomes will be reported. <h3>Conclusions</h3> A community based pulmonary rehabilitation service obtained similar CRQ outcomes to an acute based service suggesting community based services may achieve equally good outcomes to acute based services.
Paclitaxel 175 or 225 mg per Meters Squared With Carboplatin in Advanced Ovarian Cancer: A Randomized Trial
Authors: Giorgio Bolis, Giovanna Scarfone, Gianpiero Polverino, Francesco Raspagliesi, Saverio Tateo, Giovanni Richiardi, Mauro Melpignano, Massimo Franchi, Giorgia Mangili, Mauro Presti, Antonella Villa, Enrico Conta, Paolo Guarnerio, Sonia Cipriani, Fabio Parazzini
Journal: Journal of Clinical Oncology (2004)

To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer.Patients with histologically confirmed epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized, multicenter study. Women were randomly assigned to treatment with (1) carboplatin at the dose (in milligrams) corresponding to the following formula: target area under the free carboplatin plasma concentration versus time curve (AUC) = 6 x (glomerular filtration rate + 25) mg/m(2) (AUC6) plus paclitaxel 175 mg/m(2) for six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m(2) for six cycles every 21 days. A total of 502 women entered the study.Pathologic complete response was documented in 132 patients (63.8%) in the 175 mg/m(2) group and in 127 cases (55.7%) in the 225 mg/m(2) group (chi(2) P =.090). The 4-year progression-free survival rate was 41.5% (SE = 3.5) in the 175-mg group and 39.2% (SE = 3.5) in the 225-mg group. The corresponding 4-year survival rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths), respectively.This randomized trial suggests that paclitaxel 175 mg/m(2) plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m(2) plus carboplatin AUC6.
Stem cell transplantation for chronic myeloid leukemia in children
Authors: Kate Cwynarski, Irene A. G. Roberts, Simona Iacobelli, Anja van Biezen, Ronald Brand, Agnes Devergie, Jaak M. Vossen, Mahmoud Aljurf, William Arcese, Franco Locatelli, Giorgio Dini, Dietrich Niethammer, Dietger Niederwieser, Jane F. Apperley
Journal: Blood (2003)
Engineered Culture Models for Studies of Tumor-Microenvironment Interactions
Authors: David W. Infanger, Maureen E. Lynch, Claudia Fischbach
Journal: Annual Review of Biomedical Engineering (2013)

Heterogeneous microenvironmental conditions play critical roles in cancer pathogenesis and therapy resistance and arise from changes in tissue dimensionality, cell-extracellular matrix (ECM) interactions, soluble factor signaling, oxygen as well as metabolic gradients, and exogeneous biomechanical cues. Traditional cell culture approaches are restricted in their ability to mimic this complexity with physiological relevance, offering only partial explanation as to why novel therapeutic compounds are frequently efficacious in vitro but disappoint in preclinical and clinical studies. In an effort to overcome these limitations, physical sciences-based strategies have been employed to model specific aspects of the cancer microenvironment. Although these strategies offer promise to reveal the contributions of microenvironmental parameters on tumor initiation, progression, and therapy resistance, they, too, frequently suffer from limitations. This review highlights physicochemical and biological key features of the tumor microenvironment, critically discusses advantages and limitations of current engineering strategies, and provides a perspective on future opportunities for engineered tumor models.