tbuckley/cabot-search huggingface dataset:
Apoptotic cell clearance and fibrotic lung disease
Authors: William J. Janssen, Konosuke Morimoto
Journal: European Respiratory Journal (2012)

ecognition and clearance of dying cells by phagocytes (a process known as efferocytosis) is essential for development, tissue homeostasis, and recovery from inflammation and injury.Under most circumstances, this process is so efficient that it can be difficult to detect, as illustrated by the fact that .1610 11neutrophils are eliminated from the human circulation each day in a process that leaves no obvious trace [1].Along similar lines, during communityacquired pneumonia there may be .1.16106 neutrophils per cubic millimetre of lung tissue, yet clearance of dying cells is so efficient that ,0.3% of the neutrophils in the lungs are apoptotic [2].While the consequences of apoptotic cell removal were initially thought to be immunologically silent, it is now recognised that efferocytosis can lead to the production of potent anti-inflammatory molecules, such as transforming growth factor (TGF)-b and interleukin-10, and growth factors that enhance tissue repair, such as hepatocyte growth factor (HGF) and vascular endothelial growth factor [3][4][5].It is not surprising then that intentional injection of apoptotic cells into inflamed lungs or peritonea can enhance resolution of inflammation.In this issue of the European Respiratory Journal, LEE et al. [6] build on this foundation by demonstrating that a single administration of apoptotic cells into the lungs of bleomycin-injured mice reduces acute inflammation, attenuates activation of proapoptotic caspases and ameliorates the development of fibrosis.These striking results raise two important questions.How are these effects achieved and can these results be applied to human lung disease?
Are we improving disease outcomes in IBD? A view from the epidemiology side
Authors: Corinne Gower-Rousseau, Guillaume Savoye, Jean-Frédéric Colombel, Laurent Peyrin-Biroulet
Journal: Gut (2013)

<h3>Abstract</h3> The specification of tissue identity during embryonic development requires precise spatiotemporal coordination of gene expression. Many transcription factors required for the development of organs have been identified and their expression patterns are known; however, the mechanisms through which they coordinate gene expression in time remain poorly understood. Here we show that hormone-induced transcription factor Blimp-1 participates in the temporal coordination of tubulogenesis in <i>Drosophila melanogaster</i> by regulating the expression of many genes involved in tube maturation. In particular, we demonstrate that Blimp-1 regulates the expression of genes involved in chitin deposition and F-actin organization. We show that Blimp-1 is involved in the temporal control of lumen maturation by regulating the beginning of chitin deposition. We also report that Blimp-1 represses a variety of genes involved in tracheal maturation. Finally, we reveal that the kinase Btk29A serves as a link between Blimp-1 transcriptional repression and apical extra-cellular matrix organization.
Can 6 minute walk test with continuous pulse oximetry predict nocturnal hypoxemia in chronic obstructive pulmonary disease
Authors: Mir Shad Ali, Deepak Talwar, Ritesh Singh
Journal: European Respiratory Journal (2012)

Rationale : Predictors of exercise desaturation are emphysema scores and severity on pathology and CT imaging with FEV 1 and resting SpO2 showing variable results. However, nocturnal hypoxemia predictors are less studied; hence we evaluated 6MWT with continuous pulse oximetry and spirometry indices for it.  Methods:  28 patients of COPD with nocturnal hypoxemia were prospectively evaluated at Metro Centre for Respiratory Diseases, between May to July 2011 Parameters measured1) Spirometry: Pre and Post-bronchodilator 2) Six Minute Walk test (6MWT) using continuous oximetry: baseline SpO2(SpO2 base ),minimum SpO2 (SpO2 min. ),End SpO2 (SpO2 end ),maximum heart rate (HR  max ),minimum HR (HR min )and 6 minute walk distance (6MWD) and 3) Nocturnal Oximetry: baseline, minimum & mean SpO2,% time SpO2  Results : Of 28 patients with COPD (mean age 61.42±12.04 Yrs) 20 were males. Mean SpO2 baseline at start of 6MWT was 94.3±3.23%. SpO2 min  during nocturnal oximetry was significantly correlated with SpO2 min  during 6MWT (r = 0.878; p value  end  (r = 0.552; p value =0.002)and post-bronchodilator FEV 1 (r = 0.461;p = 0.013). Time of sleep with SpO2 min. on 6MWT (r = -0.427; p value 0.024) and SpO2 base (r= -0.543;p value=0.003) but not with SpO2 end  (r= -0.269; p value = 0.166) and 6MWD (r =-0.073; p-value =0.713).  Conclusion : Baseline SpO2 and maximum desaturation during exercise on 6MWT and post- bronchodilator FEV 1  are good predictors of degree and duration of nocturnal hypoxemia in COPD. Hence such patients should be evaluated for nocturnal hypoxia.
Degradation of cartilage proteoglycan by human leukocyte granule neutral proteases--a model of joint injury. II. Degradation of isolated bovine nasal cartilage proteoglycan.
Authors: H Keiser, R A Greenwald, G Feinstein, A Janoff
Journal: Journal of Clinical Investigation (1976)

Extracts of human peripheral blood polymorphonuclear leukocyte granules, and two purified proteases derived from such extracts, an elastase and a chymotrypsin-like enzyme, degrade isolated bovine nasal cartilage proteoglycan at neutral pH. Viscosity studies indicate that the leukocyte granule extracts lack hyaluronidase activity and that their degradative effect on proteoglycan at physiological pH is due entirely to proteolytic action. Sepharose 4B gel chromatography and SDS-polyacrylamide gel electrophoresis of proteoglycan fractions treated with leukocyte granule enzymes at pH 7.0 indicate that they degrade one of the proteoglycan link proteins, release a fragment from the hyaluronic acid-binding portion of the proteoglycan subunit core protein, and break down the remainder of the proteoglycan subunit molecule into peptide fragments with varying numbers of chondroitin sulfate chains. Immunodiffusion studies indicate that the antigenic determinants of the proteoglycan subunit core protein and the link proteins survive treatment with granule proteases. Similar degradation of human articular cartilage proteoglycan by granule neutral proteases can be presumed to occur, in view of the similarity of structure of human articular and bovine nasal cartilage proteoglycans. The release of granule enzymes in the course of neutrophil-mediated inflammation can thus result in the degradation of cartilage matrix proteoglycan, leading to cartilage destruction and joint injury.
Neoadjuvant chemo-radiotherapy and lymph node retrieval rates after curative resection for rectal cancers- should the same standards apply?
Authors: Philip Varghese, Zakir Mohamed, Fadlo Shaban, Talvinder Gill, Mohammed Tabaqchali, Dharmendra Garg, David Borowski, Anil Agarwal
Journal: International Journal of Surgery (2012)
Pathogenesis of gastrinomas associated with multiple endocrine neoplasia type 1
Authors: D M Pritchard
Journal: Gut (2007)

Deletion of the second allele of the tumour suppressor gene MEN1 is assoiated with development of duodenal gastrin-secreting microtumours in MEN1 

Zollinger–Ellison syndrome results from hypergastrinaemia and gastric hyperacidity. The disorder is clinically characterised by recurrent peptic ulcer disease, gastroesophageal reflux disease and, often, diarrhoea.1,2 The syndrome is caused by gastrin-secreting tumours (gastrinomas), which can arise either sporadically (approximately 70–75%) or in association with the autosomal dominant inherited condition, multiple endocrine neoplasia type 1 (MEN1; approximately 25–30%).3 The MEN1 syndrome is also associated with a range of endocrine tumours that predominantly arise in the parathyroid glands, anterior pituitary gland and pancreas.4,5 Sporadic gastrinomas are usually single and are most commonly located in the pancreas, although some are found in the duodenum. By contrast, gastrinomas found in patients with MEN1 are usually multiple and are most often located in the duodenal wall. Although multiple endocrine macrotumours and microtumours are also commonly found in the pancreas of patients with MEN1, these neoplasms usually secrete a variety of other hormones and are rarely gastrinomas.6 These observations on the location and multiplicity of tumours have implications for the surgical resection of gastrinomas, and it is now advised that even when pancreatic tumours are shown by imaging studies, duodenotomy should be performed in all cases that seem to be associated with MEN1.7,8

MEN1 is caused by germline mutations in the tumour suppressor MEN1 gene located on chromosome 11q13.9,10 This gene encodes the protein menin, whose functions have not yet been fully defined, …
Ultrasound‐Triggered Regulation of Blood Glucose Levels Using Injectable Nano‐Network
Authors: Jin Di, Jennifer Price, Xiao Gu, Xiaoning Jiang, Yun Jing, Zhen Gu
Journal: Advanced Healthcare Materials (2013)

The integration of an injectable insulin-encapsulated nano-network with a focused ultrasound system (FUS) can remotely regulate insulin release both in vitro and in vivo. A single subcutaneous injection of the nano-network with intermittent FUS administration facilitates reduction of the blood glucose levels in type 1 diabetic mice for up to 10 d. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Predictive factors for initial treatment response after circumferential radiofrequency ablation for Barrett's esophagus with early neoplasia: a prospective multicenter study
Authors: F. van Vilsteren, L. Alvarez Herrero, R. Pouw, D. Schrijnders, C. Sondermeijer, R. Bisschops, J. Esteban, A. Meining, H. Neuhaus, A. Parra-Blanco, O. Pech, K. Ragunath, B. Rembacken, B. Schenk, M. Visser, F. Kate, S. Meijer, J. Reitsma, B. Weusten, E. Schoon, J. Bergman
Journal: Endoscopy (2013)

Radiofrequency ablation (RFA) is safe and effective for the eradication of neoplastic Barrett's esophagus; however, occasionally there is minimal regression after initial circumferential balloon-based RFA (c-RFA). This study aimed to identify predictive factors for a poor response 3 months after c-RFA, and to relate the percentage regression at 3 months to the final treatment outcome.We included consecutive patients from 14 centers who underwent c-RFA for high grade dysplasia at worst. Patient and treatment characteristics were registered prospectively. "Poor initial response" was defined as < 50 % regression of the Barrett's esophagus 3 months after c-RFA, graded by two expert endoscopists using endoscopic images. Predictors of initial response were identified through logistic regression analysis.There were 278 patients included (median Barrett's segment C4M6). In poor initial responders (n = 36; 13 %), complete response for neoplasia (CR-neoplasia) was ultimately achieved in 86 % (vs. 98 % in good responders; P < 0.01) and complete response for intestinal metaplasia (CR-IM) in 66 % (vs. 95 %; P < 0.01). Poor responders required 13 months treatment (vs. 7 months; P < 0.01) for a median of four RFA sessions (vs. three; P < 0.01). We identified four independent baseline predictors of poor response: active reflux esophagitis (odds ratio [OR] 37.4; 95 % confidence interval [CI] 3.2 - 433.2); endoscopic resection scar regeneration with Barrett's epithelium (OR 4.7; 95 %CI 1.1 - 20.0); esophageal narrowing pre-RFA (OR 3.9; 95 %CI 1.0 - 15.1); and years of neoplasia pre-RFA (OR 1.2; 95 %CI 1.0 - 1.4).Patients with a poor initial response to c-RFA have a lower ultimate success rate for CR-neoplasia/CR-IM, require more treatment sessions, and a longer treatment period. A poor initial response to c-RFA occurs more frequently in patients who regenerate their endoscopic resection scar with Barrett's epithelium, and those with ongoing reflux esophagitis, neoplasia in Barrett's esophagus for a longer time, or a narrow esophagus.
Prospective evaluation of type 2 diabetes mellitus on the risk of primary liver cancer in Chinese men and women
Authors: W.S. Yang, X.O. Shu, J. Gao, H.L. Li, H. Cai, G. Yang, B.T. Ji, N. Rothman, Y.T. Gao, W. Zheng, Y.B. Xiang
Journal: Annals of Oncology (2013)
A systematic review of socioeconomic position in relation to asthma and allergic diseases
Authors: Eleonora Uphoff, Báltica Cabieses, Mariona Pinart, Macarena Valdés, Josep Maria Antó, John Wright
Journal: European Respiratory Journal (2014)

The role of socioeconomic position (SEP) in the development of asthma and allergies is unclear, with some pointing to the risks of low SEP and other research pointing in the direction of higher SEP being associated with higher prevalence rates. The aim of this systematic review is to clarify associations between SEP and the prevalence of asthma and allergies. Out of 4407 records identified, 183 were included in the analysis. Low SEP was associated with a higher prevalence of asthma in 63% of the studies. Research on allergies, however, showed a positive association between higher SEP and illness in 66% of studies. Pooled estimates for the odds ratio of disease for the highest compared with the lowest SEP confirmed these results for asthma (unadjusted OR 1.38, 95% CI 1.37-1.39), allergies in general (OR 0.67, 95% CI 0.62-0.72), atopic dermatitis (unadjusted OR 0.72, 95% CI 0.61-0.83) and allergic rhinoconjunctivitis (unadjusted OR 0.52, 95% CI 0.46-0.59). Sensitivity analyses with a subsample of high-quality studies led to the same conclusion. Evidence from this systematic review suggests that asthma is associated with lower SEP, whereas the prevalence of allergies is associated with higher SEP.
Inhibition of N-Linked Glycosylation Disrupts Receptor Tyrosine Kinase Signaling in Tumor Cells
Authors: Joseph N. Contessa, Mahaveer S. Bhojani, Hudson H. Freeze, Alnawaz Rehemtulla, Theodore S. Lawrence
Journal: Cancer Research (2008)

Abstract Receptor tyrosine kinases (RTK) are therapeutic targets for the treatment of malignancy. However, tumor cells develop resistance to targeted therapies through the activation of parallel signaling cascades. Recent evidence has shown that redundant or compensatory survival signals responsible for resistance are initiated by nontargeted glycoprotein RTKs coexpressed by the cell. We hypothesized that disrupting specific functions of the posttranslational machinery of the secretory pathway would be an effective strategy to target both primary and redundant RTK signaling. Using the N-linked glycosylation inhibitor, tunicamycin, we show that expression levels of several RTKS (EGFR, ErbB2, ErbB3, and IGF-IR) are exquisitely sensitive to inhibition of N-linked glycosylation. Disrupting this synthetic process reduces both cellular protein levels and receptor activity in tumor cells through retention of the receptors in the endoplasmic reticulum/Golgi compartments. Using U251 glioma and BXPC3 pancreatic adenocarcinoma cell lines, two cell lines resistant to epidermal growth factor receptor–targeted therapies, we show that inhibiting N-linked glycosylation markedly reduces RTK signaling through Akt and radiosensitizes tumor cells. In comparison, experiments in nontransformed cells showed neither a reduction in RTK-dependent signaling nor an enhancement in radiosensitivity, suggesting the potential for a therapeutic ratio between tumors and normal tissues. This study provides evidence that enzymatic steps regulating N-linked glycosylation are novel targets for developing approaches to sensitize tumor cells to cytotoxic therapies. [Cancer Res 2008;68(10):3803–9]
Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas
Authors: Livio Trentin, Anna Cabrelle, Monica Facco, Davide Carollo, Marta Miorin, Alicia Tosoni, Paola Pizzo, Gianni Binotto, Linda Nicolardi, Renato Zambello, Fausto Adami, Carlo Agostini, Gianpietro Semenzato
Journal: Blood (2004)
Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism
Authors: A. Catharine Ross, Reza Zolfaghari
Journal: Annual Review of Nutrition (2011)

The active metabolite of vitamin A, retinoic acid (RA), is a powerful regulator of gene transcription. RA is also a therapeutic drug. The oxidative metabolism of RA by certain members of the cytochrome P450 (CYP) superfamily helps to maintain tissue RA concentrations within appropriate bounds. The CYP26 family—CYP26A1, CYP26B1, and CYP26C1—is distinguished by being both regulated by and active toward all-trans-RA (at-RA) while being expressed in different tissue-specific patterns. The CYP26A1 gene is regulated by multiple RA response elements. CYP26A1 is essential for embryonic development, whereas CYP26B1 is essential for postnatal survival as well as germ cell development. Enzyme kinetic studies have demonstrated that several CYP proteins are capable of metabolizing at-RA; however, it is likely that CYP26A1 plays a major role in RA clearance. Thus, pharmacological approaches to limiting the activity of CYP26 enzymes may extend the half-life of RA and could be useful clinically in the future.
Role of Atrial Contraction in Diastolic Pressure Elevation Induced by Rapid Pacing of Hypertrophied Canine Ventricle
Authors: Ronald D. Berger, Matthew R. Wolff, James H. Anderson, David A. Kass
Journal: Circulation Research (1995)

Abstract The mechanism of diastolic pressure elevation induced by acute rapid pacing in pressure-load hypertrophied left ventricles (LVs) remains incompletely understood. It has been ascribed to abnormalities of coronary flow, metabolism, and calcium cycling. However, rapid pacing also alters the timing of atrial and ventricular stimulation relative to the diastolic filling period, and this could also influence diastolic pressures. To test the role of such mechanical factors, LV pressure-volume hemodynamics were measured in closed-chested anesthetized dogs during and after abrupt cessation of rapid atrial pacing. Twenty-one dogs were studied: 6 dogs with LV hypertrophy (LVH) induced by perinephritic hypertension, 5 sham-operated normotensive dogs, and 10 acute normotensive control dogs. In LVH dogs, but not in sham-operated or control dogs, end-diastolic pressure rose progressively with increasing heart rate from 5.6±3.1 mm Hg at baseline to 22.6±8.1 mm Hg at 220 beats per minute. In all hearts, rapid pacing shifted the timing of left atrial contraction so that it occurred near the onset of LV filling rather than at end diastole. However, in LVH hearts, early LV diastolic pressure and peak atrial pressure were also markedly elevated. Most striking, immediately after terminating the pacing, diastolic pressure declined to near baseline. This rapid pressure decline occurred just when atrial systole would have ensued and before ventricular activation would have followed had pacing continued. Thus, diastolic pressure elevation resolved before a change in ventricular pacing rate. The role of atrial contraction was further explored by simultaneous atrioventricular pacing. This shifted the time of atrial systole so that it occurred during LV isovolumic contraction, while maintaining the identical LV pacing rate. This change eliminated the diastolic pressure elevation found previously. Further analysis revealed that the pressure increase during rapid pacing was not due simply to partial LV filling imposed on a relaxing ventricle or to hypertension or an intact pericardium. These data indicate that mechanical effects of atrioventricular interaction play an important role in tachycardia-induced diastolic dysfunction in this model of LVH and can be more causative than ischemia or metabolic factors in this setting.
Occupational exposure to chemical substances and time to pregnancy: a systematic review
Authors: Claudia A. Snijder, Egbert te Velde, Nel Roeleveld, Alex Burdorf
Journal: Human Reproduction Update (2012)

Fertility problems are an important health issue, as 10–15% of couples have difficulties conceiving. Reproductive function is thought to be compromised by lifestyle behaviours, but environmental contaminants and work-related factors are also thought to play a role. The objective of this review was to systematically summarize the available evidence concerning the influence of occupational exposure to chemicals on time to pregnancy (TTP). A structured search on occupational exposure to chemicals and TTP was carried out in PubMed and Embase. Studies were included if TTP was used as outcome measure and exposure to chemicals at the job level was described. In total, 49 studies were included in this review. Studies varied widely in characterization of exposure, hampering a meta-analytic approach across all studies. For lead, strong indications for adverse effects on TTP were present, supporting the mandatory provisions for pregnant women being exposed to lead in many countries. These indications were also found for pesticide exposure, and one could argue that couples working in agriculture or horticultural trades must be informed about the risks of pesticide exposure. Epidemiologic evidence on other chemicals, such as organic solvents, and other metals remains equivocal, hampering clear counselling of couples who are trying to become pregnant. Despite some uncertainties in the evidence base, it may still be prudent to advise against lead and pesticide exposure at the workplace for couples trying to conceive. This review also identifies several priorities for future studies in the field of occupational epidemiology.
The geographic spread of infectious diseases
Authors: Robert Smith
Journal: The Lancet Infectious Diseases (2010)

The spread of disease throughout cities, countries, and the world relies on the spatial nature of transmission. Urban cities might face very different effects to rural communities, depending on the nature of the disease. Infections might cluster or they might move rapidly through modern transportation networks. At a smaller scale, an individual's social and travel networks might cause them to encounter infected individuals in a variety of ways.
Desmopressin Therapy for Massive Hemoptysis Associated with Severe Leptospirosis
Authors: Laurent Pea, Laurent Roda, Véronique Boussaud, Bernard Lonjon
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Massive hemoptysis in patients with severe leptospirosis is often resistant to conventional therapies and can rapidly become fatal. Desmopressin is a fast-acting blood-saving agent used in various hereditary and acquired clotting disorders. We used desmopressin infusions to treat massive pulmonary hemorrhage in six leptospirosis patients with respiratory failure, shock, and multiple organ dysfunction. Hemoptysis ceased rapidly in every case, and five patients finally recovered. Two additional patients with less severe hemoptysis were also successfully treated.