tbuckley/cabot-search huggingface dataset:
Cigarette Smoking and Adenocarcinomas of the Esophagus and Esophagogastric Junction: A Pooled Analysis From the International BEACON Consortium
Authors: Michael B. Cook, Farin Kamangar, David C. Whiteman, Neal D. Freedman, Marilie D. Gammon, Leslie Bernstein, Linda M. Brown, Harvey A. Risch, Weimin Ye, Linda Sharp, Nirmala Pandeya, Penelope M. Webb, Anna H. Wu, Mary H. Ward, Carol Giffen, Alan G. Casson, Christian C. Abnet, Liam J. Murray, Douglas A. Corley, Olof Nyrén, Thomas L. Vaughan, Wong-Ho Chow
Journal: JNCI Journal of the National Cancer Institute (2010)

Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose-response, and duration of cigarette smoking cessation.We used primary data from 10 population-based case-control studies and two cohort studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided.The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose-response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and > or =10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar.Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.
The Effect of Gene Flow on the Coalescent Time in the Human-Chimpanzee Ancestral Population
Authors: H. Innan
Journal: Molecular Biology and Evolution (2006)

The coalescent process in the human-chimpanzee ancestral population is investigated using a model, which incorporates a certain time period of gene flow during the speciation process. a is a parameter to represent the degree and time of gene flow, and the model is identical to the null model with an instantaneous species split when a=infinity. A maximum likelihood (ML) method is developed to estimate a, and its power and reliability is investigated by coalescent simulations. The ML method is applied to nucleotide divergence data between human and chimpanzee. It is found that the null model with an instantaneous species split explains the data best, and no strong evidence for gene flow is detected. The result is discussed in the view of the mode of speciation. Another ML method is developed to estimate the male-female ratio (alpha) of mutation rate, in which the coalescent process in the ancestral population is taken into account.
Asymptomatic diffuse fasciitis with eosinophilia
Authors: P. C. Avgerinos, C. S. Papadimitriou, G. Kokkini, H. M. Moutsopoulos
Journal: Annals of the Rheumatic Diseases (1982)

The case of a 70-year-old woman with asymptomatic diffuse fasciitis with eosinophilia, confirmed by biopsy, is presented.
Does <i>MDR-1</i> G2677T/A Polymorphism Really Associate with Ovarian Cancer Response to Paclitaxel Chemotherapy?
Authors: Agnieszka H. Ludwig, Jolanta Kupryjañczyk
Journal: Clinical Cancer Research (2006)

To the Editor: In the February 1, 2006 issue of Clinical Cancer Research , Green et al. ([1][1]) described an association between G2677A/T single nucleotide polymorphism of MDR-1 gene and response to paclitaxel chemotherapy. The investigators state that “the probability of responding to
Dose response inhibition in man of meal-stimulated gastric acid secretion by 15(R)-15-methyl prostaglandin E2, given orally.
Authors: A Robert, G Kane, S B Reele
Journal: Gut (1981)

15(R)-15-methyl prostaglandin E2 was given orally to healthy male volunteers. Thirty minutes later a 10% peptone meal was introduced into the stomach, and the acid response was measured by continuous intragastric titration with 0.5 N NaOH for the next two hours. The prostaglandin inhibited acid output in a dose dependent manner; the ED50 (dose inhibiting acid output by 50%) was as little as 10 micrograms per subject (or approximately 140 ng/kg). This compound is the most potent orally active inhibitor of gastric acid secretion in man that is known. It is likely that the antisecretory and cytoprotective properties shared by 15(R)-15-methyl prostaglandin E2 would be beneficial in the treatment of peptic ulcer and in preventing recurrences.
Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing
Authors: Frédéric Amant, Magali Verheecke, Iwona Wlodarska, Luc Dehaspe, Paul Brady, Nathalie Brison, Kris Van Den Bogaert, Daan Dierickx, Vincent Vandecaveye, Thomas Tousseyn, Philippe Moerman, Adriaan Vanderstichele, Ignace Vergote, Patrick Neven, Patrick Berteloot, Katrien Putseys, Lode Danneels, Peter Vandenberghe, Eric Legius, Joris Robert Vermeesch
Journal: JAMA Oncology (2015)

Noninvasive prenatal testing (NIPT) for fetal aneuploidy by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a major prenatal genetic test. Similar to placental DNA, tumor DNA can be detected in the plasma, and analysis of cell-free tumor DNA can be used to characterize and monitor cancers. We show that plasma DNA profiling allows for presymptomatic detection of tumors in pregnant women undergoing routine NIPT.During NIPT in over 4000 prospective pregnancies by parallel sequencing of maternal plasma cell-free DNA, 3 aberrant genome representation (GR) profiles were observed that could not be attributed to the maternal or fetal genomic constitution. A maternal cancer was suspected, and those 3 patients were referred for whole-body diffusion-weighted magnetic resonance imaging, which uncovered an ovarian carcinoma, a follicular lymphoma, and a Hodgkin lymphoma, each confirmed by subsequent pathologic and genetic investigations. The copy number variations in the subsequent tumor biopsies were concordant with the NIPT plasma GR profiles.We show that maternal plasma cell-free DNA sequencing for noninvasive prenatal testing also may enable accurate presymptomatic detection of maternal tumors and treatment during pregnancy.
S71 Mechanisms of Lung Repair Post Injury: The Role For Non-Canonical Wnt Signalling and Planar Cell Polarity
Authors: NA Hasan, M Hind, CH Dean
Journal: Thorax (2012)

<h3>Introduction</h3> Fibrosis is a constituent of various respiratory diseases including asthma, COPD, idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension. Research shows that Wnt genes, critical for lung development, are reactivated post cellular injury and that the canonical Wnt/β-catenin pathway is mis-expressed in these diseases. The non-canonical Wnt/PCP pathway can inhibit canonical signalling and also cause co-ordinated, directional cell migration. Moreover components of this pathway are suppressed in many respiratory fibro-proliferative disorders. We investigated the role of non-canonical Wnts in a tractable model of lung repair, by comparing the rate of wound healing using either canonical Wnt4 or non-canonical Wnt5a ligands. We hypothesised that Wnt5a would exhibit a higher rate of wound healing than Wnt4, coupled with increased cytoskeleton dynamics, favouring co-ordinated and directional cell migration. <h3>Methods</h3> Confluent A549 cells were scratched with a 10µl pipette tip to induce a ‘wound’ and treated with either recombinant canonical Wnt4 or non-canonical Wnt5a, or cultured in control serum free medium. Wound area was measured at t=0, t-6 and t=24h post scratch to determine the rate of wound healing using time-lapse imaging. Phalloidin labelling and imaging was used to determine levels and distribution of F-actin at those times. <h3>Results</h3> The addition of Wnt5a healed 4 times the area either Wnt4 or Control did using concentrations that induce maximal activity at t=6 (5.49, 1.23 and 1.01×105µm2 respectively) and t=24 (8.62, 2.42 and 2.39×105µm2 respectively) hours post scratch (p&lt;1x10–7). At 0.5µg/ml Wnt5a healed 2 times the area Wnt4 did at it’s ED50 dose with Wnt4 at 5xED50, at t=6 (1.99 and 1.01 x105µm2 respectively) and t=24 (4.29 and 1.80x105µm2 respectively) hours post scratch (p&lt;0.01). Wnt5a treatment increased the frequency of focal F-actin enrichment towards the wound edge versus Wnt4 or control. <h3>Conclusion</h3> Wnt5a is more efficient at wound healing in A549 cells than Wnt4. Wnt5a associated increase in focal F-actin enrichment amplified wound healing is associated with increased cytoskeletal dynamics and directional movement. In the future, novel therapies based around Wnt5a have the potential to be used to enhance repair in fibrotic respiratory diseases.
Growth failure occurs through a decrease in insulin-like growth factor 1 which is independent of undernutrition in a rat model of colitis
Authors: A B Ballinger
Journal: Gut (2000)

<h3>BACKGROUND</h3> Linear growth retardation is a frequent complication of inflammatory bowel disease in children. The precise mechanisms causing growth failure are not known. <h3>AIMS</h3> To determine the relative contribution of reduced calorie intake and inflammation to linear growth delay and to determine the effect of inflammation on the hypothalamic-pituitary-growth axis. <h3>METHODS</h3> Linear growth was assessed in prepubertal rats with trinitrobenzenesulphonic acid (TNBS) induced colitis, in healthy free feeding controls, and in a pair-fed group (i.e. healthy animals whose daily food intake was matched to the colitic group thereby distinguishing between the effects of undernutrition and inflammation). <h3>RESULTS</h3> Changes in length over five days in the TNBS colitis and pair-fed groups were 30% and 56%, respectively, of healthy free feeding controls. Linear growth was significantly reduced in the colitic group compared with the pair-fed group. Nutritional supplementation in the colitic group increased weight gain to control values but did not completely reverse the growth deficit. Plasma interleukin 6 (IL-6) concentrations were sixfold higher in the colitic group compared with controls. Plasma concentrations of insulin-like growth factor 1 (IGF-1) but not growth hormone (GH) were significantly lower in the colitic compared with the pair-fed group. Administration of IGF-1 to the colitic group increased plasma IGF-1 concentrations and linear growth by approximately 44–60%. <h3>CONCLUSIONS</h3> It seems likely that approximately 30–40% of linear growth impairment in experimental colitis occurs as a direct result of the inflammatory process which is independent of undernutrition. Inflammation acts principally at the hepatocyte/IGF-1 level to impair linear growth. Optimal growth in intestinal inflammation may only be achieved by a combination of nutritional intervention and anticytokine treatment.
A Single Amino Acid Determines the Immunostimulatory Activity of Interleukin 10
Authors: Yaozhong Ding, Lihui Qin, Serguei V. Kotenko, Sidney Pestka, Jonathan S. Bromberg
Journal: The Journal of Experimental Medicine (2000)

Cellular interleukin 10s (cIL-10s) of human and murine origin have extensive sequence and structural homology to the Epstein-Barr virus BCRF-I gene product, known as viral IL-10 (vIL-10). Although these cytokines share many immunosuppressive properties, vIL-10 lacks several of the immunostimulatory activities of cIL-10 on certain cell types. The molecular and cellular bases for this dichotomy are not currently defined. Here, we show that the single amino acid isoleucine at position 87 of cIL-10 is required for its immunostimulatory function. Substitution of isoleucine in cIL-10 with alanine, which corresponds to the vIL-10 residue, abrogates immunostimulatory activity for thymocytes, mast cells, and alloantigenic responses while preserving immunosuppressive activity for inhibition of interferon γ production and prolongation of cardiac allograft survival. Conversely, substitution of alanine with isoleucine in vIL-10 converts it to a cIL-10–like molecule with immunostimulatory activity. This single conservative residue alteration significantly affects ligand affinity for receptor; however, affinity changes do not necessarily alter specific activities for biologic responses in a predictable fashion. These results suggest complex regulation of IL-10 receptor–ligand interactions and subsequent biological responses. These results demonstrate that vIL-10 may represent a captured and selectively mutated cIL-10 gene that benefits viral pathogenesis by leading to ineffective host immune responses. The ability to manipulate the activity of IL-10 in either a stimulatory or suppressive direction may be of practical value for regulating immune responses for disease therapy, and of theoretical value for determining what aspects of IL-10 activity are important for normal T cell responses.
Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer
Authors: A.H.G. Hansma, H.J. Broxterman, I. van der Horst, Y. Yuana, E. Boven, G. Giaccone, H.M. Pinedo, K. Hoekman
Journal: Annals of Oncology (2005)
Elevated CSF Cytokines in the Jarisch-Herxheimer Reaction of General Paresis
Authors: Larry E. Davis, Ryan Oyer, J. David Beckham, Kenneth L. Tyler
Journal: JAMA Neurology (2013)

The Jarisch-Herxheimer reaction (JHR) is a well-recognized transient worsening of signs and symptoms occurring soon after the first dose of an appropriate antibiotic for several spirochetal infections. The pathogenesis of this reaction is poorly understood. In this case study of cerebrospinal fluid (CSF) cytokines, we aimed to improve understanding of the pathogenesis of JHR in patients with neurosyphilis who develop transient neurologic signs.Four hours after receiving penicillin for general paresis, a 55-year-old man developed a severe JHR characterized by fever, tachycardia, hypertension, obtundation, seizures, and a neutrophilia lasting 18 hours. Cerebrospinal fluid obtained at the peak of the JHR demonstrated a switch from a mild lymphophilia to a moderate neutrophilia. He had markedly elevated CSF interleukin (IL) 8 and likely elevated IL-1β, IL-10, and IL-15 levels, which returned to normal in follow-up CSF examination results.To our knowledge, this is the first report of elevated CSF cytokines in a patient with a JHR, which possibly contributed to the neurologic signs of JHR. Further studies on the innate inflammatory response during episodes of acute infection and inflammation are needed to develop targeted therapies to modulate this system, which could, in turn, improve future outcomes and modify the JHR.
Intrarenal Antigens Activate CD4+ Cells via Co-stimulatory Signals from Dendritic Cells
Authors: Kristy L. Edgtton, Joshua Y. Kausman, Ming Li, Kim O'Sullivan, Cecilia Lo, Paul Hutchinson, Hideo Yagita, Stephen R. Holdsworth, A. Richard Kitching
Journal: Journal of the American Society of Nephrology (2008)

Dendritic cells in the kidney take up antigens, but little is known about their role in providing co-stimulatory signals for the activation of CD4(+) cells. This study examined the phenotype of dendritic cells in the renal interstitium and in the lymph node draining the kidney before and after intrarenal ovalbumin injection. After intrarenal injection of the antigen, expression of the co-stimulatory molecules CD86 and programmed cell death ligand 1 (PD-L1) increased on renal dendritic cells, whereas expression of only CD86 increased on dendritic cells of the draining lymph node. The activation and proliferation of antigen-specific CD4(+) cells in the lymph node were assessed by transfer of naïve, fluorescently labeled ovalbumin-specific T cell receptor transgenic cells to mice before antigen administration. Blocking both CD86 and CD80 profoundly inhibited CD4(+) cell proliferation, but CD86 was the dominant CD28 ligand in the early proliferative response of CD4(+) cells. Conversely, activation of PD-1, the receptor expressed on CD4(+) cells that binds PD-L1 and PD-L2, reduced the proliferation of CD4(+) cells in the draining lymph node. Comparing subcutaneous and intrarenal administration of antigen, it was found that CD4(+) cell activation was slower and the effects of combined CD80 and CD86 blockade were more profound when antigen was presented via the kidney compared with the skin. In summary, renal dendritic cells take up antigen and participate in the control of antigen-specific CD4(+) cell proliferation by upregulating co-stimulatory molecules such as CD86 that stimulate CD4(+) cell proliferation and by signaling through PD-1, which prevents an inappropriately exuberant immune response.
Ventilatory response to hypercarbia in newborns of smoking and substance abusing mothers
Authors: Kamal Ali, Ravindra Bhat, Kim Wolff, Simon Hannam, Gerrard Rafferty, Anne Greenough
Journal: European Respiratory Journal (2012)

Infants of smoking and substance abusing mothers have an increased risk of sudden infant death. A possible explanation for the association is that such infants have neurodevelopmental abnormalities which adversely affect the control of ventilation.   Aims : To test the hypothesis that infants of substance abusing mothers (SA) and of smoking mothers (SM) compared to infants of non substance abusing, non-smoking mothers (controls) would have a poorer ventilatory response to hypercarbia.   Methods : Infants were assessed before maternity/neonatal unit discharge. Respiratory flow (and tidal volume) was measured using a pneumotachograph inserted into a face mask placed over the infant9s mouth and nose. The ventilatory responses to three levels of inspired carbon dioxide (baseline = 0%, 2% and 4% CO 2 ) were assessed.   Results : 8 SA, 15 SM and 15 control infants were assessed. The birth weight of the controls was higher than the SA and SM infants (p=0.01). At baseline SA infants had a higher respiratory rate (p=0.03) and minute volume (p=0.049) compared to controls and SM infants (Table). Both the SA and SM infants had a lower respiratory response to 2% (p=0.02) and 4% (p=0.004) CO 2    Conclusion : These results are consistent with infants of smoking and substance abusing mothers having a dampened ventilatory response to hypercarbia.
Creation and disruption of protein features by alternative splicing -- a novel mechanism to modulate function.
Authors: Michael Hiller, Klaus Huse, Matthias Platzer, Rolf Backofen
Journal: Genome biology (2005)

Alternative splicing often occurs in the coding sequence and alters protein structure and function. It is mainly carried out in two ways: by skipping exons that encode a certain protein feature and by introducing a frameshift that changes the downstream protein sequence. These mechanisms are widespread and well investigated.Here, we propose an additional mechanism of alternative splicing to modulate protein function. This mechanism creates a protein feature by putting together two non-consecutive exons or destroys a feature by inserting an exon in its body. In contrast to other mechanisms, the individual parts of the feature are present in both splice variants but the feature is only functional in the splice form where both parts are merged. We provide evidence for this mechanism by performing a genome-wide search with four protein features: transmembrane helices, phosphorylation and glycosylation sites, and Pfam domains.We describe a novel type of event that creates or removes a protein feature by alternative splicing. Current data suggest that these events are rare. Besides the four features investigated here, this mechanism is conceivable for many other protein features, especially for small linear protein motifs. It is important for the characterization of functional differences of two splice forms and should be considered in genome-wide annotation efforts. Furthermore, it offers a novel strategy for ab initio prediction of alternative splice events.
Late-breaking abstract: Alternative indications for the use of endobronchial valves
Authors: Beatriz Amat, Juan-Manuel Corcoles, Silvia Coves, Ana Camarasa, José Manuel León, Krysztof Kurowski, Lorena Aguilar, Arantxa Mena, Graciela Fajardo
Journal: European Respiratory Journal (2014)

Endobronchial valves (IBV Valve System, Olympus) were primarily designed for endoscopic lung volume reduction being later used in cases of persistent air leaks due to bronchopleural fistula. However, to date the use of these valves in patients with bronchial stump has not been described.  PATIENTS AND METHODS: We treated 4 patients with endobronchial valves. Three had pneumothorax and the fourth case was a patient with a bronchial stump fistula which could not be solved with glue and silver nitrate. All four cases were men with a mean-age of 74(67-78)years.  RESULTS  The four patients received 6 valves. The first patient presented bilateral tension pneumothorax after heart surgery and was treated with several chest tubes, pleurodesis and surgical procedures, all of which were unsuccessful. He was finally treated with two valves, solving the persistent air-leak. Two patients presented spontaneous pneumothorax, but due to comorbidities surgery was contraindicated. The fourth patient had a bronchial stump after lobectomy due to lung cancer and refused a new intervention involving thoracostomy. This last patient was treated with sealant twice and several times with silver nitrate without success. Finally, the patient was treated with a 7 mm valve, achieving complete stoppage of the air leak. All the patients improved within 24-hours of the procedure and were discharged in the following 6(2-710) days without no complications related to the intervention after a 6-month follow up(6-24).  CONCLUSION: The use of endobronchial valves in patients with spontaneous pneumothorax with high-risk for intervention or after surgery, as well as in cases of bronchial stump after lobectomy is a safe and effective alternative to solve air leakage.
Successful hyposensitization treatment in atopic eczema: results of a trial in monozygotic twins
Authors: J. RING
Journal: British Journal of Dermatology (1982)

Two sisters (monozygotic twins) suffering from severe atopic eczema with pronounced seasonal exacerbation during spring and early summer were treated with subcutaneous injections of either grass pollen extract or saline. After 2 years of preseasonal treatment the skin symptoms improved significantly in the patient treated with grass pollen extract, while the placebo produced minimal change in her twin. The therapeutic effect was paralleled by a greater decrease in total scrum IgE (from 4,200 to 1,370 ku/l) in the pollen-treated patient (compared with 3,500 to 2,580 ku/l in the control twin).
Elevated white blood cell count is associated with higher mortality in patients with acute coronary syndromes independent of other cardiac markers: a TACTICS - TIMI 18 Substudy
Authors: Marc S. Sabatine, David A. Morrow, Sabina A. Murphy, Laura A. Demopoulos, Peter M. DiBattiste, Carolyn H. McCabe, Christopher P. Cannon, Eugene Braunwald, Michael Gibson
Journal: Journal of the American College of Cardiology (2002)