tbuckley/cabot-search huggingface dataset:
Airway pathology in asthma
Authors: M. Saetta, G. Turato
Journal: European Respiratory Journal (2001)

This review focuses on the major cellular and structural changes present in the airways and lung parenchyma in asthma in comparison with chronic obstructive pulmonary disease (COPD) in an attempt to underline the possible mechanisms contributing to airflow limitation in these two diseases. Both asthma and COPD are characterized by a thickening of the airway wall and by the presence of an inflammatory process, but the inflammatory cells infiltrating the airway wall differ between the two diseases. In asthma, the most striking feature is the eosinophilic infiltration, whereas, in COPD, it is the CD8 T‐lymphocytic infiltration of the airway wall. In the lung parenchyma, both diseases are characterized by an inflammatory process, whereas destruction and fibrosis of the alveolar walls occur in COPD but not in asthma. These cellular and structural changes may contribute to the development of airflow limitation (that characterizes both asthma and chronic obstructive pulmonary disease) by inducing either an increase in resistance or a decrease in driving pressure.
HER Kinase Axis Receptor Dimer Partner Switching Occurs in Response to EGFR Tyrosine Kinase Inhibition despite Failure to Block Cellular Proliferation
Authors: Anjali Jain, Elicia Penuel, Sheldon Mink, Joanna Schmidt, Amanda Hodge, Kristin Favero, Charles Tindell, David B. Agus
Journal: Cancer Research (2010)

Abstract The human epidermal receptor (HER) axis consists of a dynamic, interconnected family of receptors that make critical contributions to a number of malignancies. Therapeutics targeting epidermal growth factor receptor (EGFR) are unable to effectively inhibit tumor growth in a majority of cases. These tumors are assumed to possess primary resistance to anti-EGFR therapies, but the consequence of inhibiting EGFR in these tumors is unclear. We established isogenic cell lines by prolonged gefitinib treatment at concentrations that are in excess of that which is required for complete EGFR kinase inhibition but only minimally affected growth. Subsequently, we monitored the ligand-dependent HER profiles based on receptor expression, phosphorylation, and dimerization in conjunction with measurements of cellular susceptibility to gefitinib. Chronic EGFR kinase inhibition rapidly switched the HER network from dependence on EGFR to HER2. However, both receptors activated the critical signaling proteins AKT and mitogen-activated protein kinase, and in both cases, HER3 was the common association partner. Remarkably, the switch in receptor dimers caused diminished susceptibility to EGFR-targeted inhibitors gefitinib and cetuximab but acquired susceptibility to the HER2-targeted inhibitor pertuzumab. Overall, our study indicates that the EGFR pathway is responsive to EGFR inhibiting therapies that are not dependent on EGFR for their growth and survival, thus challenging the current definition of primary therapeutic resistance. Furthermore, EGFR kinase inhibition induces HER kinase receptors to engage in alternative dimerization that can ultimately influence therapeutic selection and responsiveness. Cancer Res; 70(5); 1989–99
Rapid molecular TB diagnosis: evidence, policy making and global implementation of Xpert MTB/RIF
Authors: Karin Weyer, Fuad Mirzayev, Giovanni Battista Migliori, Wayne Van Gemert, Lia D'Ambrosio, Matteo Zignol, Katherine Floyd, Rosella Centis, Daniela M. Cirillo, Enrico Tortoli, Chris Gilpin, Jean de Dieu Iragena, Dennis Falzon, Mario Raviglione
Journal: European Respiratory Journal (2012)

If tuberculosis (TB) is to be eliminated as a global health problem in the foreseeable future, improved detection of patients, earlier diagnosis and timely identification of rifampicin resistance will be critical. New diagnostics released in recent years have improved this perspective but they require investments in laboratory infrastructure, biosafety and staff specialisation beyond the means of many resource-constrained settings where most patients live. Xpert MTB/RIF, a new assay employing automated nucleic acid amplification to detect Mycobacterium tuberculosis, as well as mutations that confer rifampicin resistance, holds the promise to largely overcome these operational challenges. In this article we position Xpert MTB/RIF in today's TB diagnostic landscape and describe its additional potential as an adjunct to surveillance and surveys, taking into account considerations of pricing and ethics. In what could serve as a model for the future formulation of new policy on diagnostics, we trace the unique process by which the World Health Organization consulted international expertise and systematically assessed published evidence and freshly emerging experience from the field ahead of its endorsement of the Xpert MTB/RIF technology in 2010, summarise subsequent research findings and guidance on who to test and how, and provide perspectives on scaling up the new technology.
Antigen-Specific IL-13 Secretion in Children with Eosinophilic Esophagitis
Authors: Benedicte Michaud, Diana Colson, Pascale Soulaines, Sophie Candon, Marie-Alexandra Alyanakian, Jocelyne Just, Lucienne Chatenoud, Christophe Dupont
Journal: Journal of Allergy and Clinical Immunology (2013)
Lower Left Temporal Lobe MRI Volumes in Patients With First-Episode Schizophrenia Compared With Psychotic Patients With First-Episode Affective Disorder and Normal Subjects
Authors: Yoshio Hirayasu, Martha E. Shenton, Dean F. Salisbury, Chandlee C. Dickey, Iris A. Fischer, Paola Mazzoni, Tanya Kisler, Hajime Arakaki, Jun Soo Kwon, Jane E. Anderson, Deborah Yurgelun-Todd, Mauricio Tohen, Robert W. McCarley
Journal: American Journal of Psychiatry (1998)

Objective:Magnetic resonance imaging (MRI) studies of schizophrenic patients have revealed structural brain abnormalities, with low volumes of gray matter in the left posterior superior temporal gyrus and in medial temporal lobe structures. However, the specificity to schizophrenia and the roles of chronic morbidity and neuroleptic treatment in these abnormalities remain unclear. Method:Magnetic resonance (1.5-T) scans were obtained from 33 patients with first-episode psychosis and 18 age-matched normal comparison subjects, all right-handed. Sixteen of the patients were diagnosed with affective disorder and 17 with schizophrenia. Results:Quantitative volumetric analysis showed that the patients with first-episode schizophrenia had significantly smaller gray matter volume in the left posterior superior temporal gyrus than did the patients with first-episode affective psychosis or the comparison subjects, with a significant left-less-than-right asymmetry. The schizophrenic patients also showed a smaller gray matter volume of the left posterior amygdala-hippocampal complex than the comparison subjects. Both the patients with schizophrenia and those with affective psychosis had significant left-less-than-right asymmetry of the posterior amygdala-hippocampal complex.Conclusions:These findings suggest that temporal lobe abnormalities are present at the first hospitalization for schizophrenia and that low volume of the left posterior superior temporal gyrus gray matter is specific to schizophrenia compared with affective disorder. Am J Psychiatry 1998; 155: 1384-1391
The use of induced sputum in clinical trials
Authors: J.C. Kips, M.D. Inman, L. Jayaram, E.H. Bel, K. Parameswaran, M.M.M. Pizzichini, I.D. Pavord, R. Djukanović, F.E. Hargreave, P.J. Sterk
Journal: European Respiratory Journal (2002)

As asthma is considered to be an inflammatory disorder of the airways, it seems logical to include an assessment of this inflammatory process as an outcome measure in clinical trials. Biopsy studies illustrate that clinical or lung function characteristics such as symptoms, peak flow variability or degree of airway responsiveness do not consistently correlate with histological alterations. Therefore, these clinical indices cannot be seen as accurate markers of airway inflammation 1–3. Conversely, repeated bronchoscopic sampling is not feasible in large­scale clinical studies. Hence there is interest in a relatively noninvasive but direct marker of airway inflammation.

Analysis of induced sputum seems to meet these criteria. Provided proper precautions are taken, induction of sputum is safe, even in patients with more severe asthma 4, 5. In addition, sputum cell counts, particularly eosinophil counts, have been well validated in terms of responsiveness to intervention. It has been argued that, in comparison with other noninvasive markers of inflammation, induced sputum offers the most balanced assessment of the degree of inflammation, being more responsive to intervention than serum eosinophil cationic protein, yet not as oversensitive as exhaled nitric oxide 6–8.

As for any outcome measure, when including induced sputum in a clinical trial, specific features of sputum analysis need to be taken into account when designing the study: 1) origin of sputum; 2) methodological aspects; 3) selection of subjects; and 4) power calculations.

The induced sputum technique samples the inflammatory cells and soluble markers present in the airway lumen of the bronchial tree, which, although reflective of, does not represent an identical situation to the local inflammatory process in the mucosa. This probably explains the poor correlation between the cellular composition of biopsy samples and sputum, bronchial wash or bronchoalveolar lavage 9–11. Therefore, …
Gastrointestinal motor mechanisms in hyperglycaemia induced delayed gastric emptying in type I diabetes mellitus.
Authors: M Samsom, L M Akkermans, R J Jebbink, H van Isselt, G P vanBerge-Henegouwen, A J Smout
Journal: Gut (1997)

Hyperglycaemia delays gastric emptying, both in healthy controls and in patients with diabetes mellitus. The effect of hyperglycaemia on antroduodenal motility in diabetes has not yet been studied.To investigate the gastrointestinal motor mechanisms involved in the hyperglycaemia induced retardation of gastric emptying in patients with type I diabetes mellitus and autonomic neuropathy. In eight diabetic patients antroduodenal manometry was performed simultaneously with scintigraphic measurement of emptying of a mixed solid-liquid meal, during euglycaemia (5-8 mmol/l glucose) and hyperglycaemia (16-19 mmol/l glucose), on separate days, in random order.Hyperglycaemia decreased the cumulative antral motility index from 38.3 (range 24.2-47.6) to 30.8 (range 17.3-38.1) (p = 0.025) and reduced the number of antral pressure waves propagated over > or = 4.5 cm (p = 0.04). Duodenal phase III-like activity was seen irrespective of the glycaemic state (in three patients during euglycaemia and in four patients during hyperglycaemia). Hyperglycaemia significantly affected gastric emptying of the solid meal: it prolonged the lag phase from 20.0 minutes to 28.5 minutes (P = 0.02), increased the 50% emptying time from 73.5 minutes to 104.5 minutes (p = 0.03), and increased the percentage of isotope remaining in the stomach after 120 minutes from 33.5% to 46.5% (p = 0.02). The cumulative antral motility index was correlated with the 50% emptying time (r = 0.75, p = 0.02) during euglycaemia, but not during hyperglycaemia (r = 0.28, P = 0.31). Liquid emptying was not influenced by the blood glucose concentration.Hyperglycaemia reduces postprandial antral contractile activity and its organisation in patients with type I diabetes and autonomic neuropathy. These changes in antroduodenal motility are likely to constitute the mechanism through which gastric emptying of solids is delayed during high blood glucose concentrations in these diabetic patients.
An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance.
Authors: L J Baier, J C Sacchettini, W C Knowler, J Eads, G Paolisso, P A Tataranni, H Mochizuki, P H Bennett, C Bogardus, M Prochazka
Journal: Journal of Clinical Investigation (1995)

The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimulated glucose uptake rate, a higher mean insulin response to oral glucose and a mixed meal, and a higher mean fat oxidation rate compared with Pimas who were homozygous for the alanine-encoding allele. Since the FABP2 threonine-encoding allele was found to be associated with insulin resistance and increased fat oxidation in vivo, we further analyzed the FABP2 gene products for potential functional differences. Titration microcalorimetry studies with purified recombinant protein showed that the threonine-containing protein had a twofold greater affinity for long-chain fatty acids than the alanine-containing protein. We conclude that the threonine-containing protein may increase absorption and/or processing of dietary fatty acids by the intestine and thereby increase fat oxidation, which has been shown to reduce insulin action.
The role of per cent predicted 6-min walk distance in pulmonary arterial hypertension
Authors: W-T.N. Lee, A.J. Peacock, M.K. Johnson
Journal: European Respiratory Journal (2010)

Absolute 6-min walk distance (6MWD) predicts mortality in pulmonary arterial hypertension (PAH), but varies greatly between normal individuals due to physiological factors such as age, sex, height and weight. The % predicted 6MWD adjusts for these factors and may predict mortality more reliably. The aim of the study was to compare the strength of mortality prediction by absolute and % predicted 6MWD in PAH at baseline and on treatment. % predicted 6MWD was calculated using four different reference equations in 137 PAH patients (idiopathic and connective tissue disease associated) diagnosed between November 2000 and November 2009. Cox proportional hazards and receiver-operating characteristic (ROC) analyses were used to compare the prognostic strength of absolute and % predicted 6MWD. % predicted 6MWD was predictive of all-cause mortality at baseline (hazard ratio 0.74-0.83 per 10% increase; p<0.05) and on treatment (0.67-0.75 per 10% increase; p<0.01), but each respective area under the ROC curve was not different from that of absolute 6MWD for predicting 2-yr mortality at baseline (absolute versus % predicted: 0.74 versus 0.71-0.75) or on treatment (0.77 versus 0.72-0.78). In conclusion, % predicted 6MWD may help clinicians interpret the 6-min walk test, but its prognostic value is not superior to that of absolute 6MWD.
Commitment and Differentiation of Osteoclast Precursor Cells by the Sequential Expression of C-Fms and Receptor Activator of Nuclear Factor κb (Rank) Receptors
Authors: Fumio Arai, Takeshi Miyamoto, Osamu Ohneda, Tomohisa Inada, Tetsuo Sudo, Kenneth Brasel, Takashi Miyata, Dirk M. Anderson, Toshio Suda
Journal: The Journal of Experimental Medicine (1999)

Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor κB (RANK), and have demonstrated that RANK expression in early-stage of precursor cells (c-Fms+RANK−) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms+RANK+) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK–RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.
Medical survey of female boxing in Italy in 2002-2003
Authors: M Bianco, A Pannozzo, C Fabbricatore, N Sanna, M Moscetti, V Palmieri, P Zeppilli
Journal: British Journal of Sports Medicine (2005)

Background: Female boxing has been permitted in Italy since 2001. According to the latest Italian laws, athletes applying to become boxers have to pass a pre-participation medical examination. Objective: To collect novel medical information from the pre-participation visits and mandatory pre-competition and post-competition examinations for all fights involving Italian female boxers in 2002–2003. Methods: A retrospective study on all official female boxing competitions in Italy from January 2002 to October 2003 was conducted. A prospective study on 28 amateur female boxers was also carried out. Results: Retrospective study: data from 664 examinations were collected. Pre-match examinations were negative. After competitions, 19/645 visits showed some injuries, with mild, soft tissue facial lesions, epistaxis, and hand-wrist problems being the most common. Prospective study: no major lesions were found during the study. One fibroadenoma, one ovarian cyst, and one intramural uterine myoma were found. One boxer was referred to a neurologist because of non-specific electroencephalographic (EEG) abnormalities, which persisted six months later. On a re-admission examination, which was needed because of a contest that was stopped because the referee judged that she was receiving blows to the head that were dangerous, one boxer showed non-specific EEG alterations and nystagmus. A cerebral magnetic resonance imaging scan was normal. She was allowed to participate in competitions again when her EEG returned to normal and clinical signs disappeared. Deviation of the nasal septum was quite common (68%). No major eye injuries were reported. Conclusion: Probably because of the correct preventive medical approach, female boxing is much safer than expected, and no major lesions (requiring hospital admission) were reported. Any lesions to the breast and reproductive system could not be considered to be boxing related.
Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling
Authors: Ming Chang Hu, Mingjun Shi, Han Jun Cho, Beverley Adams-Huet, Jean Paek, Kathy Hill, John Shelton, Ansel P. Amaral, Christian Faul, Masatomo Taniguchi, Myles Wolf, Markus Brand, Masaya Takahashi, Makoto Kuro-o, Joseph A. Hill, Orson W. Moe
Journal: Journal of the American Society of Nephrology (2014)

Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency—genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor–23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1–, angiotensin II–, or high phosphate–induced fibrosis and abolished TGF-β1– or angiotensin II–induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor–23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging.
Oestrogen/Progestogen Oral Contraception and Blood Clotting: A Long-term Follow-up
Authors: L. Poller, J. M. Thomson, W. Thomas
Journal: BMJ (1971)

In a long-term study of women taking the combined oestrogen/progestogen oral contraceptives Ortho-Novin and Norinyl-1 the follow-up has been continued for three years and four years respectively.Acceleration of both "intrinsic" and "extrinsic" clotting tests and of specific factor VII and X assays, reported previously at the nine-month stage, persisted throughout the period of study. Acceleration of Chandler's tube platelet aggregation and hypercoagulable thrombelastographic patterns were recorded. There was, however, no evidence of a cumulative effect after the first nine months.
Polypectomy Rate: A Surrogate for Adenoma Detection Rate Varies by Colon Segment, Gender, and Endoscopist
Authors: Tushar D. Gohel, Carol A. Burke, Pavan Lankaala, Amareshwar Podugu, Ravi Pokala Kiran, Prashanthi N. Thota, Rocio Lopez, Madhusudhan R. Sanaka
Journal: Clinical Gastroenterology and Hepatology (2013)
Human G Protein–Coupled Receptor Gpr-9-6/Cc Chemokine Receptor 9 Is Selectively Expressed on Intestinal Homing T Lymphocytes, Mucosal Lymphocytes, and Thymocytes and Is Required for Thymus-Expressed Chemokine–Mediated Chemotaxis
Authors: Brian A. Zabel, William W. Agace, James J. Campbell, Heidi M. Heath, David Parent, Arthur I. Roberts, Ellen C. Ebert, Nasim Kassam, Shixin Qin, Maria Zovko, Gregory J. LaRosa, Li-Li Yang, Dulce Soler, Eugene C. Butcher, Paul D. Ponath, Christina M. Parker, David P. Andrew
Journal: The Journal of Experimental Medicine (1999)

TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein-coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti-GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory alpha4beta7(high) intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen-positive (CLA(+)) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic alpha4beta7(-)CLA(-) memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti-GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response.
Epitope Mapping of the Main Four Shrimp Allergens and Comparison of IgE Recognition Between Children and Adults
Authors: R. Ayuso, S. Sanchez-Garcia, J. Lin, M. Ibáñez, C. Blanco, T. Carrillo, M. Goldis, L. Bardina, H.A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2010)