tbuckley/cabot-search huggingface dataset:
John ("Jack") Parsons Shillingford Robert Michael Badminton Terry Coates Christopher Charles Crampton Richard Michael Dean Desmond Stopford Mulock Enraght-Moony Eric Glyn Hughes Alfred Cecil Victor Maltby Gisela ("Gilli") Oppenheim Fredrick Shepherd Eleanor Mary Singer Barry Leonard Stone Brian Ponsford Webber Henry John ("Jack") Weldon Giles Martin James Woolley
Authors: M. Shillingford, M. N Badminton, J S Brown, D. Zuck, S. Dean, A. Enraght-Moony, D. G Hughes, T. Wilmot, K. Heymann, C W Shepherd, K. Reid, S Lieberman, B. Webber, B. Beale, D. Sage
Journal: BMJ (1999)
Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease
Authors: Emanuele Nicastro, Giusy Ranucci, Pietro Vajro, Angela Vegnente, Raffaele Iorio
Journal: Hepatology (2010)

The diagnosis of Wilson disease (WD) is challenging, especially in children. Early detection is desirable in order to avoid dramatic disease progression. The aim of our study was to re-evaluate in WD children with mild liver disease the conventional diagnostic criteria and the WD scoring system proposed by an international consensus in 2001. Forty children with WD (26 boys and 14 girls, age range = 1.1-20.9 years) and 58 age-matched and sex-matched patients with a liver disease other than WD were evaluated. Both groups were symptom-free and had elevated aminotransferases as predominant signs of liver disease. In all WD patients, the diagnosis was supported by molecular analysis, the liver copper content, or both. A receiver operating characteristic (ROC) analysis of ceruloplasmin at the cutoff value of 20 mg/dL showed a sensitivity of 95% [95% confidence interval (CI) = 83%-99.4%] and a specificity of 84.5% (95% CI = 72.6%-92.6%). The optimal basal urinary copper diagnostic cutoff value was found to be 40 μg/24 hours (sensitivity = 78.9%, 95% CI = 62.7%-90.4%; specificity = 87.9%, 95% CI = 76.7%-95%). Urinary copper values after penicillamine challenge did not significantly differ between WD patients and control subjects, and the ROC analysis showed a sensitivity of only 12%. The WD scoring system was proved to have positive and negative predictive values of 93% and 91.6%, respectively.Urinary copper excretion greater than 40 μg/24 hours is suggestive of WD in asymptomatic children, whereas the penicillamine challenge test does not have a diagnostic role in this subset of patients. The WD scoring system provides good diagnostic accuracy.
Androgen Receptor Exon 1 CAG Repeat Length and Breast Cancer in Women Before Age Forty Years
Authors: A. B. Spurdle, G. S. Dite, X. Chen, C. J. Mayne, M. C. Southey, L. E. Batten, H. Chy, L. Trute, M. R. E. McCredie, G. G. Giles, J. Armes, D. J. Venter, J. L. Hopper, G. Chenevix-Trench
Journal: JNCI Journal of the National Cancer Institute (1999)

We conducted a population-based, case-control-family study to determine whether androgen receptor (AR) exon 1 polymorphic CAG repeat length (CAGn) was a risk factor for early-onset breast cancer in the Australian population.Case subjects under 40 years of age at diagnosis of a first primary breast cancer and age-matched control subjects were interviewed to assess family history and other risk factors. AR CAGn length was determined for 368 case subjects and 284 control subjects. Distributions in the two groups were compared by linear and logistic regression, allowing adjustment for measured risk factors. All statistical tests were two-tailed.When analyzed as either a continuous or a dichotomous variable, there was no association between CAG, length and breast cancer risk, before or after adjustment for risk factors. Mean (95% confidence interval [CI]) CAGn lengths were 22.0 (21.8-22.2) for case subjects and 22.0 (21.7-22.3) for control subjects (P = .9). The frequency (95% CI) of alleles with 22 or more CAGn repeats was 0.531 (0.494-0.568) for case subjects and 0.507 (0.465-0.549) for control subjects (P = .4). After adjustment, the average effect on log OR (odds ratio) per allele was 0.16 (95% CI = -0.03 to 0.40; P = .2), and the effect of any allele was equivalent to an OR of 1.40 (95% CI = 0.94-2.09; P = .1). Stratification by family history also failed to reveal any association. Similar results were obtained when alleles were defined by other cutoff points.We found no evidence for an association between AR exon 1 CAGn length and breast cancer risk in women under the age of 40, despite having 80% power to detect modest effects.
IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation
Authors: Yijing Li, Lei Wang, Loretta Pappan, Amy Galliher-Beckley, Jishu Shi
Journal: Molecular Cancer (2012)

Abstract Background IL-1β is a pleiotropic pro-inflammatory cytokine and its up-regulation is closely associated with various cancers including gastrointestinal tumors. However, it remains unclear how IL-1β may contribute to the initiation and development of these inflammation-associated cancers. Here we investigated the role of IL-1β in colon cancer stem cell (CSC) development. Methods Using self-renewal assay, soft-agar assay, invasion assay, real-time PCR analysis, immunoblot assay and shRNA knockdown, we determined the effects of IL-1β on cancer stem cell development and epithelial-mesenchymal transition (EMT) in human primary colon cancer cells and colon cancer cell line HCT-116. Results We found that IL-1β can increase sphere-forming capability of colon cancer cells in serum-free medium. IL-1β-induced spheres displayed an up-regulation of stemness factor genes (Bmi1 and Nestin) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activator Zeb1 was increased in IL-1β-induced spheres, indicating that there might be a close association between EMT and IL-1β-induced CSC self-renewal. Indeed, IL-1β treatment led to EMT of colon cancer cells with loss of E-cadherin, up-regulation of Zeb1, and gain of the mesenchymal phenotype. Furthermore, shRNA-mediated knockdown of Zeb1 in HCT-116 cells reversed IL-1β-induced EMT and stem cell formation. Conclusion Our findings indicate that IL-1β may promote colon tumor growth and invasion through activation of CSC self-renewal and EMT, and Zeb1 plays a critical role in these two processes. Thus, IL-1β and Zeb1 might be new therapeutic targets against colon cancer stem cells.
Community pulmonary rehabilitation after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease: randomised controlled study
Authors: William D-C Man, Michael I Polkey, Nora Donaldson, Barry J Gray, John Moxham
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To evaluate the effects of an early community based pulmonary rehabilitation programme after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease (COPD). <b>Design</b> A single centre, randomised controlled trial. <b>Setting</b> An inner city, secondary and tertiary care hospital in London. <b>Participants</b> 42 patients admitted with an acute exacerbation of COPD. <b>Intervention</b> An eight week, pulmonary rehabilitation programme for outpatients, started within 10 days of hospital discharge, or usual care. <b>Main outcome measures</b> Incremental shuttle walk distance, disease specific health status (St George9s respiratory questionnaire, SGRQ; chronic respiratory questionnaire, CRQ) and generic health status (medical outcomes short form 36 questionnaire, SF-36) at three months after hospital discharge. <b>Results</b> Early pulmonary rehabilitation, compared with usual care, led to significant improvements in median incremental shuttle walk distance (60 metres, 95% confidence interval 26.6 metres to 93.4 metres, P = 0.0002), mean SGRQ total score (−12.7, −5.0 to −20.3, P = 0.002), all four domains of the CRQ (dyspnoea 5.5, 2.0 to 9.0, P = 0.003; fatigue 5.3, 1.9 to 8.8, P = 0.004; emotion 8.7, 2.4 to 15.0, P = 0.008; and mastery 7.5, 4.2 to 10.7, P &lt; 0.001) and the mental component score of the SF-36 (20.1, 3.3 to 36.8, P = 0.02). Improvements in the physical component score of the SF-36 did not reach significance (10.6, −0.3 to 21.6, P = 0.057). <b>Conclusion</b> Early pulmonary rehabilitation after admission to hospital for acute exacerbations of COPD is safe and leads to statistically and clinically significant improvements in exercise capacity and health status at three months.
Clinical Application of an Integrated 3-Phase Mapping Technique for Localization of the Site of Origin of Idiopathic Ventricular Tachycardia
Authors: Heidi A. P. Peeters, Arne SippensGroenewegen, Eric F. D. Wever, Hemanth Ramanna, André C. Linnenbank, Mark Potse, Cornelis A. Grimbergen, Norbert M. van Hemel, Richard N. W. Hauer, Etienne O. Robles de Medina
Journal: Circulation (1999)

Background —Radiofrequency (RF) catheter ablation provides curative treatment for idiopathic ventricular tachycardia (VT). Methods and Results —Nineteen consecutive patients with an idiopathic VT underwent RF catheter ablation. An integrated 3-phase mapping approach was used, consisting of the successive application of online 62-lead body surface QRS integral mapping, directed regional paced body surface QRS integral mapping, and local activation sequence mapping. Mapping phase 1 was localization of the segment of VT origin by comparing the VT QRS integral map with a database of mean paced QRS integral maps. Mapping phase 2 was body surface pace mapping during sinus rhythm in the segment localized in phase 1 until the site at which the paced QRS integral map matched the VT QRS integral map was identified (ie, VT exit site). Mapping phase 3 was local activation sequence mapping at the circumscribed area identified in phase 2 to identify the site with the earliest local endocardial activation (ie, site of VT origin). This site became the ablation target. Ten VTs were ablated in the right ventricular outflow tract, 2 at the basal LV septum, and 7 at the midapical posterior left ventricle. A high long-term ablation success (mean follow-up duration, 14±9 months) was achieved in 17 of the 19 patients (89%) with a low number of RF pulses (mean, 3.3±2.2 pulses per patient). Conclusions —This prospective study shows that integrated 3-phase mapping for localization of the site of origin of idiopathic VT offers efficient and accurate localization of the target site for RF catheter ablation.
Targeted Modulation of MGMT: Clinical Implications
Authors: Lili Liu, Stanton L. Gerson
Journal: Clinical Cancer Research (2006)

Abstract O6-Methylguanine DNA methyltransferase (MGMT) has been studied for &amp;gt;20 years as a gene that is associated with the mutagenicity and cytotoxicity induced by either methylating carcinogens or alkylating (methylating and chloroethylating) therapeutic agents. Pioneering studies of alkylating agents identified alkylated guanine at the O6 position, the substrate of MGMT, as a potentially promutagenic and lethal toxic DNA lesion. MGMT plays a prominent role in DNA adduct repair that limits the mutagenic and cytotoxic effect of alkylating agents. Because of its role in cancer etiology and chemotherapy resistance, MGMT is of particular interest. In this article, the clinical effect of MGMT expression and targeted modulation of MGMT will be summarized.
Association of Autism With Induced or Augmented Childbirth in North Carolina Birth Record (1990-1998) and Education Research (1997-2007) Databases
Authors: Simon G. Gregory, Rebecca Anthopolos, Claire E. Osgood, Chad A. Grotegut, Marie Lynn Miranda
Journal: JAMA Pediatrics (2013)

One in 88 children in the United States is diagnosed as having autism spectrum disorder. Significant interest centers on understanding the environmental factors that may contribute to autism risk.To examine whether induced (stimulating uterine contractions prior to the onset of spontaneous labor) and/or augmented (increasing the strength, duration, or frequency of uterine contractions with spontaneous onset of labor) births are associated with increased odds of autism.We performed an epidemiological analysis using multivariable logistic regression modeling involving the North Carolina Detailed Birth Record and Education Research databases. The study featured 625,042 live births linked with school records, including more than 5500 children with a documented exceptionality designation for autism.Induced or augmented births.Autism as assessed by exceptionality designations in child educational records.Compared with children born to mothers who received neither labor induction nor augmentation, children born to mothers who were induced and augmented, induced only, or augmented only experienced increased odds of autism after controlling for potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth year. The observed associations between labor induction/augmentation were particularly pronounced in male children.Our work suggests that induction/augmentation during childbirth is associated with increased odds of autism diagnosis in childhood. While these results are interesting, further investigation is needed to differentiate among potential explanations of the association including underlying pregnancy conditions requiring the eventual need to induce/augment, the events of labor and delivery associated with induction/augmentation, and the specific treatments and dosing used to induce/augment labor (e.g., exogenous oxytocin and prostaglandins).
Estrogen protects against airway inflammation via upregulation of SLPI and downregulation of IL-33
Authors: Christina Draijer, Machteld N. Hylkema, Catherine M. Greene, Pieter A. Klok, Wim Timens, Dirkje S. Postma, Barbro N. Melgert
Journal: European Respiratory Journal (2012)

Airway epithelium (AE) can modify airway responses through production of anti-inflammatory mediators like secretory leukoprotease inhibitor (SLPI) and pro-inflammatory mediators like IL-33. Estrogen can modulate AE responses and we therefore investigated how estrogen affects severity of airway inflammation and SLPI and IL-33 production in mice.  Female balb/c mice were ovariectomized (OVX) or sham-treated and received a 0.1 mg estrogen (E2) pellet at OVX or not (all groups n=8). Four weeks after OVX, mice were sensitized i.p. with OVA and alum on days 1 and 7 and challenged with 1% OVA on days 14-20. On day 21, allergic inflammation (OVA-specific IgE, eosinophils) and production of IL-33 and SLPI were assessed.  Ablating estrogen significantly increased airway inflammation as compared to sham-treated mice. Treating OVX mice with E2 significantly reduced the higher airway inflammation induced by OVX as judged from lower eosinophil numbers in lung and lower OVA-specific IgE levels in serum. In the parenchyma of E2-treated OVX mice we found more type II alveolar epithelial cells (AECII) expressing SLPI than in nontreated OVX mice, which correlated with higher SLPI levels in lung. The number of AECII producing IL-33 on the other hand was lower in E2-treated OVX mice as compared to nontreated OVX mice.  This study shows that estrogen protects female mice against the development of airway inflammation and this is associated with higher SLPI and lower IL-33 production by AECII. We therefore postulate that estrogen has a protective effect on asthma development through induction of anti-inflammatory SLPI production and inhibition of pro-inflammatory IL-33 production by AECII.
HIV-1 Cell to Cell Transfer across an Env-induced, Actin-dependent Synapse
Authors: Clare Jolly, Kirk Kashefi, Michael Hollinshead, Quentin J. Sattentau
Journal: The Journal of Experimental Medicine (2004)

Direct cell–cell transfer is an efficient mechanism of viral dissemination within an infected host, and human immunodeficiency virus 1 (HIV-1) can exploit this mode of spread. Receptor recognition by HIV-1 occurs via interactions between the viral surface envelope glycoprotein (Env), gp120, and CD4 and a chemokine receptor, CCR5 or CXCR4. Here, we demonstrate that the binding of CXCR4-using HIV-1–infected effector T cells to primary CD4+/CXCR4+ target T cells results in rapid recruitment to the interface of CD4, CXCR4, talin, and lymphocyte function–associated antigen 1 on the target cell, and of Env and Gag on the effector cell. Recruitment of these membrane molecules into polarized clusters was dependent on Env engagement of CD4 and CXCR4 and required remodelling of the actin cytoskeleton. Transfer of Gag from effector to target cell was observed by 1 h after conjugate formation, was independent of cell–cell fusion, and was probably mediated by directed virion fusion with the target cell. We propose that receptor engagement by Env directs the rapid, actin-dependent recruitment of HIV receptors and adhesion molecules to the interface, resulting in a stable adhesive junction across which HIV infects the target cell.
Association of tissue factor activity with the surface of cultured cells.
Authors: J R Maynard, C A Heckman, F A Pitlick, Y Nemerson
Journal: Journal of Clinical Investigation (1975)

Tissue factor occurs in a dormant state on the surface of cultured normal human fibroblasts and WISH 1 amnion cells. The activity of undisturbed monolayers or cells lifted with brief trypsin treatment (0.125 per cent trypsin for 1 min) increases up to 60-fold upon prolonged digestion with dilute trypsin (0.0025 per cent trypsin for 30 min); activity appears subsequent to cell detachment. Up to 70 per cent of the total cellular tissue factor becomes active under these conditions and is released from the cells. The ruthenium red staining coat of the cells is lost during detachment, but cell viability (more than 90 per cent exclude trypan blue) and cell morphology do not change during the subsequent development of tissue factor activity. Furthermore, less than 10 percent of four intracellular enzymes and less than 20 per cent of two plasma membrane enzymes are released during this period of time. We therefore conclude that cells in culture do have tissue factor activity, that it exists in a latent form, and that total cell disruption is not necessary for this activity to initiate blood coagulation.
Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity
Authors: Clodagh C. O'Shea, Leisa Johnson, Bridget Bagus, Serah Choi, Cory Nicholas, Annie Shen, Larry Boyle, Kusum Pandey, Conrado Soria, John Kunich, Yuqiao Shen, Gaston Habets, Dave Ginzinger, Frank McCormick
Journal: Cancer Cell (2004)
Extensive Trans-Specific Polymorphism at the Mating Type Locus of the Root Decay Fungus Heterobasidion
Authors: Linda T.A. van Diepen, Åke Olson, Katarina Ihrmark, Jan Stenlid, Timothy Y. James
Journal: Molecular Biology and Evolution (2013)

Incompatibility systems in which individuals bearing identical alleles reject each other favor the maintenance of a diversity of alleles. Mushroom mating type loci (MAT) encode for dozens or hundreds of incompatibility alleles whose loss from the population is greatly restricted through negative frequency selection, leading to a system of alleles with highly divergent sequences. Here, we use DNA sequences of homeodomain (HD) encoding genes at the MAT locus of five closely related species of the root rot basidiomycete Heterobasidion annosum sensu lato to show that the extended coalescence time of MAT alleles greatly predates speciation in the group, contrasting loci outside of MAT that show allele divergences largely consistent with the species phylogeny with those of MAT, which show rampant trans-species polymorphism. We observe a roughly 6-fold greater genealogical depth and polymorphism of MAT compared with non-MAT that argues for the maintenance of balanced polymorphism for a minimum duration of 24 My based on a molecular-clock calibrated species phylogeny. As with other basidiomycete HD genes, balancing selection appears to be concentrated at the specificity-determining region in the N-terminus of the protein based on identification of codons under selection and the absence of recombination within the region. However, the elevated polymorphism extends into the nonspecificity determining regions as well as a neighboring non-MAT gene, the mitochondrial intermediate peptidase (MIP). In doing so, increased divergence should decrease recombination among alleles and as a by-product create incompatibilities in the functional domains not involved in allele recognition but in regulating sexual development.
Selection Bias in the Use of Thrombolytic Therapy in Acute Myocardial Infarction
Authors: Marc A. Pfeffer
Journal: JAMA (1991)

<h3>Objective.</h3> —To determine whether clinical selection for thrombolytic therapy for acute myocardial infarction results in a skewed population for subsequent adverse cardiovascular events. <h3>Design.</h3> —A comparison of the clinical features of the patients in the Survival and Ventricular Enlargement Study who either had or had not received thrombolytic therapy was conducted in both univariate and multiple logistic regression analyses. <h3>Setting.</h3> —Hospitalized patients experiencing acute myocardial infarction from 112 broadly representative, private, academic, and government hospitals in the United States and Canada. <h3>Patients.</h3> —All patients in the Survival and Ventricular Enlargement Study had had a recent myocardial infarction (&lt;16 days) and had a left ventricular ejection fraction of 40% or less. <h3>Intervention.</h3> —Thrombolytic therapy was administered to 733 patients and was not given to 1498. <h3>Main Outcome Measures.</h3> —The comparisons with respect to use of thrombolytic therapy were formulated after the completion of enrollment and indicated that the majority of patients did not receive thrombolytic therapy. <h3>Results.</h3> —The 1498 (67.1%) patients who did not receive thrombolytic therapy were at higher risk (older age, lower functional capacity, greater likelihood of a history of prior myocardial infarction, angina, diabetes, and hypertension) for subsequent cardiovascular events and, as anticipated, were more likely to have concomitant gastrointestinal and neurological diseases. A multiple logistic regression analysis indicated that older age, prior myocardial infarction, impaired functional status, employment status, diabetes, and neurological diseases were predictors of use of thrombolytic therapy. <h3>Conclusion.</h3> —Although the Survival and Ventricular Enlargement Study population was selected for left ventricular dysfunction, the majority of patients who currently are judged clinically as unsuitable for thrombolytic therapy have a higher risk for adverse cardiovascular events. (<i>JAMA</i>. 1991;266:528-532)