tbuckley/cabot-search huggingface dataset:
Alpha 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep.
Authors: W M Abraham, M W Sielczak, A Ahmed, A Cortes, I T Lauredo, J Kim, B Pepinsky, C D Benjamin, D R Leone, R R Lobb
Journal: Journal of Clinical Investigation (1994)

Eosinophils and T lymphocytes are thought to be involved in allergic airway inflammation. Both cells express the alpha 4 beta 1-integrin, very late antigen-4 (VLA-4, CD49d/CD29); alpha 4-integrins can promote cellular adhesion and activation. Therefore, we examined the in vivo effects of a blocking anti-alpha 4 monoclonal antibody, HP 1/2, on antigen-induced early and late bronchial responses, airway hyperresponsiveness, inflammatory cell influx, and peripheral leukocyte counts in allergic sheep. Sheep blood lymphocytes, monocytes, and eosinophils expressed alpha 4 and bound HP 1/2. In control sheep, Ascaris antigen challenge produced early and late increases in specific lung resistance of 380 +/- 42% and 175 +/- 16% over baseline immediately and 7 h after challenge, respectively, as well as airway hyperresponsiveness continuing for 14 d after antigen challenge. Treatment with HP 1/2 (1 mg/kg, i.v.) 30 min before antigen challenge did not affect the early increase in specific lung resistance but inhibited the late-phase increase at 5-8 h by 75% (P < 0.05) and inhibited the post-antigen-induced airway hyperresponsiveness at 1, 2, 7, and 14 d (P < 0.05, for each time). Intravenous HP 1/2 given 2 h after antigen challenge likewise blocked late-phase airway changes and postchallenge airway hyperresponsiveness. Airway administration of HP 1/2 (16-mg dose) was also effective in blocking these antigen-induced changes. Response to HP 1/2 was specific since an isotypic monoclonal antibody, 1E6, was ineffective by intravenous and aerosol administration. Inhibition of leukocyte recruitment did not totally account for the activity of anti-alpha 4 antibody since HP 1/2 neither diminished the eosinopenia or lymphopenia that followed antigen challenge nor consistently altered the composition of leukocytes recovered by bronchoalveolar lavage. Because airway administration of HP 1/2 was also active, HP 1/2 may have inhibited cell activation. Reduction of platelet-activating factor-induced eosinophil peroxidase release from HP 1/2-treated eosinophils supports such a mechanism. These findings indicate a role for alpha 4-integrins in processes that lead to airway late phase responses and persisting airway hyperresponsiveness after antigen challenge.
Lower oesophageal sphincter response to intravenous infusions of pentagastrin in normal subjects, antrectomised and achalasic patients.
Authors: E Corazziari, C Pozzessere, S Dani, F Anzini, A Torsoli
Journal: Gut (1978)

Lower oesophageal sphincter response to infusion of graded doses (0.003--0.050 microgram kg-1min-1) of pentagastrin was evaluated in four antrectomised patients as well as in six healthy subjects and seven achalasic patients in whom inhibition of antral gastrin release was maintained by continuous acidification (HC1 0.1 N) and aspiration of gastric antrum. In normal subjects and in antrectomised patients doses of pentagastrin required for half-maximal gastric acid secretion (0.012 microgram kg-1min-1) produced statistically significant increases of LES pressure. In achalasic patients, the infusion of pentagastrin did not affect LES pressure. These data seem to indicate that gastrin plays, at least in some degree, a physiological role in the regulation of LES tone. Insensitivity of LES to pentagastrin in achalasia suggests that the raised sphincter pressure in this disorder can not be attributed to gastrin.
Inherited palmoplantar keratoderma and sensorineural deafness associated with A7445G point mutation in the mitochondrial genome
Authors: L. Martin, A. Toutain, C. Guillen, M. Haftek, M.C. Machet, C. Toledano, B. Arbeille, G. Lorette, A. Rötig, L. Vaillant
Journal: British Journal of Dermatology (2000)

Journal Article Inherited palmoplantar keratoderma and sensorineural deafness associated with A7445G point mutation in the mitochondrial genome Get access L. Martin, L. Martin Departments of Dermatology, Dr L.Martin. E‐mail: martin@med.univ‐tours.fr Search for other works by this author on: Oxford Academic Google Scholar A. Toutain, A. Toutain Genetics and Search for other works by this author on: Oxford Academic Google Scholar C. Guillen, C. Guillen Department of Genetics, INSERM U393, Necker‐Enfants‐Malades Hospital, 149 rue de Sèvres, 75743 Paris Cedex 15, France Search for other works by this author on: Oxford Academic Google Scholar M. Haftek, M. Haftek Department of Dermatology, INSERM U346/CNRS, Edouard‐Herriot Hospital, 69437 Lyon, France Search for other works by this author on: Oxford Academic Google Scholar M.C. Machet, M.C. Machet Pathology, and Search for other works by this author on: Oxford Academic Google Scholar C. Toledano, C. Toledano Departments of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar B. Arbeille, B. Arbeille Laboratory of Electron Microscopy, Trousseau University Hospital, 37044 Tours Cedex, France Search for other works by this author on: Oxford Academic Google Scholar G. Lorette, G. Lorette Departments of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar A. Rötig, A. Rötig Department of Genetics, INSERM U393, Necker‐Enfants‐Malades Hospital, 149 rue de Sèvres, 75743 Paris Cedex 15, France Search for other works by this author on: Oxford Academic Google Scholar L. Vaillant L. Vaillant Departments of Dermatology, Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 4, 1 October 2000, Pages 876–883, https://doi.org/10.1046/j.1365-2133.2000.03797.x Published: 01 October 2000
The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group
Authors: C. H. Knowles, R. De Giorgio, R. P. Kapur, E. Bruder, G. Farrugia, K. Geboes, G. Lindberg, J. E. Martin, W. A. Meier-Ruge, P. J. Milla, V. V. Smith, J. M. Vandervinden, B. Veress, T. Wedel
Journal: Gut (2010)

<h3>Objective</h3> Guidelines on histopathological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology have been produced recently by an international working group (IWG). These addressed the important but relatively neglected areas of histopathological practice of the general pathologist, including suction rectal biopsy and full-thickness intestinal tissue. Recommendations were presented for the indications, safe acquisition of tissue, histological techniques, reporting and referral of such histological material. <h3>Design</h3> Consensual processes undertaken by the IWG and following established guideline decision group methodologies. <h3>Results and conclusion</h3> This report presents a contemporary and structured classification of gastrointestinal neuromuscular pathology based on defined histopathological criteria derived from the existing guidelines. In recognition of its origins and first presentation in London at the World Congress of Gastroenterology 2009, this has been named 'The London Classification'. The implementation of this classification should allow some diagnostic standardisation, but should necessarily be viewed as a starting point for future modification as new data become available.
Cathepsin D Is a Potential Serum Marker for Poor Prognosis in Glioma Patients
Authors: Mieko E. Fukuda, Yasuo Iwadate, Toshio Machida, Takaki Hiwasa, Yoshinori Nimura, Yuichiro Nagai, Masaki Takiguchi, Hideki Tanzawa, Akira Yamaura, Naohiko Seki
Journal: Cancer Research (2005)

Abstract Cathepsin D is an aspartyl protease involved in protein catabolism and tissue remodeling which can be secreted from cancer cells. To identify a potential serum marker for gliomas, we investigated the gene expression levels of cathepsin D in 87 tissue samples and measured the protein concentrations in sera of glioma patients. The tissue samples consisted of 43 glioblastomas, 13 anaplastic astrocytomas, 22 astrocytomas, and 9 normal brain tissues. The results of real-time quantitative reverse transcription-PCR analysis showed that cathepsin D transcript levels became significantly higher as the glioma grade advanced (P = 0.0466, glioblastoma and anaplastic astrocytoma; P = 0.0008, glioblastoma and astrocytoma; P = 0.0271, glioblastoma and normal brain tissue; unpaired t test). Immunohistochemical analysis with anti-cathepsin D antibody revealed dense and spotty staining in the tumor cells with high transcript levels. The low expression of cathepsin D significantly correlated with long survival of the glioma patients. Furthermore, the glioblastoma patients with high gene expression of cathepsin D lived significantly shorter than those with low expression (P = 0.0104, Cox-Mantel log-rank test) and frequently had leptomeningeal dissemination (P = 0.0016, χ2 test). The multivariate analysis confirmed that the cathepsin D expression level was an independent predictor for short survival (P = 0.0102, Cox proportional hazard regression model). Measurement of the serum cathepsin D concentrations by ELISA showed a significant increase in the patients with high-grade gliomas as compared with the low-grade tumors (P = 0.0081, χ2 test). These results collectively suggest that cathepsin D could be a potential serum marker for the prediction of aggressive nature of human gliomas.
Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation
Authors: Sarah Kettlewell, Francis L. Burton, Godfrey L. Smith, Antony J. Workman
Journal: Cardiovascular Research (2013)

AimsAtrial fibrillation (AF) is increased in patients with heart failure resulting from myocardial infarction (MI). We aimed to determine the effects of chronic ventricular MI in rabbits on the susceptibility to AF, and underlying atrial electrophysiological and Ca2+-handling mechanisms.
Ly49 Family Receptors Are Required for Cancer Immunosurveillance Mediated by Natural Killer Cells
Authors: Megan M. Tu, Ahmad Bakur Mahmoud, Andrew Wight, Amelia Mottashed, Simon Bélanger, Mir Munir A. Rahim, Elias Abou-Samra, Andrew P. Makrigiannis
Journal: Cancer Research (2014)

According to the missing-self hypothesis, natural killer (NK) cells survey for target cells that lack MHC-I molecules. The Ly49 receptor family recognizes loss of MHC-I and is critical for educating NK cells, conferring the ability to eliminate transformed or infected cells. In this study, we evaluated their requirement in innate immune surveillance of cancer cells using genetically manipulated mice with attenuated expression of Ly49 receptors (NKC(KD)) in several models of carcinoma and metastasis. We found that NKC(KD) mice exhibited uncontrolled tumor growth and metastases. Expression of two MHC-I alleles, H-2K(b) and H-2D(b), was decreased in tumors from NKC(KD) mice in support of the likelihood of NK-mediated tumor immunoediting. These tumor cells exhibited directed alterations to their cell surface expression in response to the genetically altered immune environment to evade host recognition. Immunoediting in NKC(KD) mice was restricted to MHC-I molecules, which are ligands for Ly49 receptors, while expression of Rae-1 and Mult1, ligands for another NK cell receptor, NKG2D, were unaffected. Restoring NK cell education in NKC(KD) mice with a transgene for the inhibitory self-MHC-I receptor Ly49I restored suppression of cancer onset and growth. Interestingly, immune surveillance mediated by activating Ly49 receptors remained intact in NKC(KD) mice, as demonstrated by the ability to stimulate the NKG2D receptor with tumor cells or splenocytes expressing Rae-1. Together, our results genetically establish the integral role of Ly49 in NK cell-mediated control of carcinogenesis through MHC-I-dependent missing-self recognition.
Trunk Fat and Leg Fat Have Independent and Opposite Associations With Fasting and Postload Glucose Levels
Authors: Marieke B. Snijder, Jacqueline M. Dekker, Marjolein Visser, Lex M. Bouter, Coen D.A. Stehouwer, John S. Yudkin, Robert J. Heine, Giel Nijpels, Jacob C. Seidell
Journal: Diabetes Care (2004)

OBJECTIVE—Waist and hip circumferences have been shown to have independent and opposite associations with glucose levels. Waist circumference is positively associated with glucose levels, whereas hip circumference is negatively associated. It is unclear which tissues are involved in the pathophysiological mechanism causing these associations. The main goal was to determine which tissue in the trunk and legs, fat or lean tissue, is associated with measures of glucose metabolism. RESEARCH DESIGN AND METHODS—In 623 participants of the third examination of the Hoorn Study, whole-body dual-energy X-ray absorptiometry was performed to determine fat and lean soft-tissue mass in the trunk and legs. Fasting and 2-h postload glucose levels after 75-g oral glucose tolerance test (OGTT) were determined. After exclusion of known diabetic patients, cross-sectional analyses were performed in 275 men aged 60–87 years (140 with normal glucose metabolism, 92 with impaired glucose metabolism; and 43 with diabetes) and in 281 women (148 with normal glucose metabolism, 90 with impaired glucose metabolism, and 43 with diabetes). RESULTS—Greater trunk fat mass was associated with higher glucose levels after adjustment for age, trunk lean mass, leg lean mass, and leg fat mass. Standardized β (95% CI) in men were 0.44 (0.25–0.64) for fasting and 0.41 (0.22–0.60) for postload glucose. For women, these values were 0.49 (0.35–0.63) and 0.47 (0.33–0.61), respectively. In contrast, in the same regression models, a larger leg fat mass was associated with lower glucose levels. Standardized β in men were −0.24 (−0.43 to −0.05) and −0.12 (−0.31 to 0.07) and in women −0.24 (−0.37 to −0.10) and −0.27 (−0.40 to −0.13) for fasting and postload glucose, respectively. In these models, larger leg lean mass was also associated with lower glucose levels but was only statistically significant in men. CONCLUSIONS—If trunk fat is taken into account, accumulation of fat in the legs seems to be protective against a disturbed glucose metabolism, particularly in women. Further research is needed to unravel underlying pathophysiological mechanisms.
Colonization of Heterochromatic Genes by Transposable Elements in Drosophila
Authors: P. Dimitri
Journal: Molecular Biology and Evolution (2003)

As a further step toward understanding transposable element–host genome interactions, we investigated the molecular anatomy of introns from five heterochromatic and 22 euchromatic protein-coding genes of Drosophila melanogaster. A total of 79 kb of intronic sequences from heterochromatic genes and 355 kb of intronic sequences from euchromatic genes have been used in Blast searches against Drosophila transposable elements (TEs). The results show that TE-homologous sequences belonging to 19 different families represent about 50% of intronic DNA from heterochromatic genes. In contrast, only 0.1% of the euchromatic intron DNA exhibits homology to known TEs. Intraspecific and interspecific size polymorphisms of introns were found, which are likely to be associated with changes in TE-related sequences. Together, the enrichment in TEs and the apparent dynamic state of heterochromatic introns suggest that TEs contribute significantly to the evolution of genes located in heterochromatin.
?-Adrenergic stimulation produces a decrease of cardiac contractility ex vivo in mice overexpressing the human ?-adrenergic receptor
Authors: G TAVERNIER, G TOUMANIANTZ, M ERFANIAN, M HEYMANN, K LAURENT, D LANGIN, C GAUTHIER
Journal: Cardiovascular Research (2003)

Objectives: The regulation of cardiac function by catecholamines involves three populations of β-adrenoceptor (β-AR). β1- and β2-AR stimulations produce an increase in contractility and β3-AR stimulation mediates a negative inotropic effect in human ventricular muscle. Because of the lack of suitable animal models, we have generated transgenic mice with cardiac-specific expression of the human β3-AR (TGβ3 mice). Methods: TGβ3 mice were produced by microinjection of the human β3-AR under the control of the α myosin heavy chain promoter. Phenotypic analyses comprised β3-AR mRNA and protein determinations, histological studies, electrocardiogram, contractility and cyclic nucleotide measurements. Results: TGβ3 mice presented no histological evidence of myocyte hypertrophy or fibrogenesis. In basal conditions, TGβ3 mice were characterized by an increase in heart rate and an acceleration of twitch parameters without modification of its amplitude. β3-AR agonists (CL 316243, SR 58611A) decreased contractility at low concentrations (1–100 nM). At high concentrations, the negative inotropic effect was abolished. Pretreatment with nadolol, a β1/β2-AR blocker, blunted the rebound in peak tension elicited by β3-AR agonists suggesting a non-specific action of these compounds on β1- and β2-AR. The involvement of β3-AR in the negative inotropic effect was confirmed by the pretreatment with bupranolol, a non-selective β-AR antagonist, which fully abolished the effects of SR 58611A. The negative inotropic effect was associated with an increase in intracellular cGMP level. Conclusions: We conclude that cardiac overexpression of β3-AR in mice reproduces ex vivo the negative inotropic effects obtained with β3-AR stimulation in human ventricular tissues.
αvβ3-dependent cross-presentation of matrix metalloproteinase–2 by melanoma cells gives rise to a new tumor antigen
Authors: Emmanuelle Godefroy, Agnes Moreau-Aubry, Elisabeth Diez, Brigitte Dreno, Francine Jotereau, Yannick Guilloux
Journal: The Journal of Experimental Medicine (2005)

A large array of antigens that are recognized by tumor-specific T cells has been identified and shown to be generated through various processes. We describe a new mechanism underlying T cell recognition of melanoma cells, which involves the generation of a major histocompatibility complex class I–restricted epitope after tumor-mediated uptake and processing of an extracellular protein—a process referred to as cross-presentation—which is believed to be restricted to immune cells. We show that melanoma cells cross-present, in an αvβ3-dependent manner, an antigen derived from secreted matrix metalloproteinase–2 (MMP-2) to human leukocyte antigen A*0201-restricted T cells. Because MMP-2 activity is critical for melanoma progression, the MMP-2 peptide should be cross-presented by most progressing melanomas and represents a unique antigen for vaccine therapy of these tumors.
Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis
Authors: Y Ogura
Journal: Gut (2003)

<b>Background and aims:</b> Genetic variation in NOD2 has been associated with susceptibility to Crohn's disease (CD) and specifically with ileal involvement. The reason for the unique association of NOD2 mutations with ileal disease is unclear. To identify a possible link, we tested expression of NOD2 in intestinal tissue of CD patients and controls. <b>Patients and methods:</b> Fifty five specimens of ileum or colon from 21 CD patients, seven ulcerative colitis (UC) patients, and five controls with pathology other than CD or UC were stained for NOD2 using an immunoperoxidase method. <b>Results:</b> Using a monoclonal antibody against NOD2 developed in our laboratory, we detected uniform expression of NOD2 in terminal ileum Paneth cells from controls and patients as well as in metaplastic Paneth cells in the colon. Mechanical purification showed enriched expression of NOD2 mRNA in ileal crypts. In Paneth cells, NOD2 was located in the cytosol in close proximity to the granules that contain antimicrobial peptides. We detected minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium from both CD patients and controls. <b>Conclusions:</b> These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease. The impaired capacity of CD associated mutations to sense luminal bacteria may result in increased susceptibility to certain gut microbes.
Young Patients With Non–Germinal Center B-Cell–Like Diffuse Large B-Cell Lymphoma Benefit From Intensified Chemotherapy With ACVBP Plus Rituximab Compared With CHOP Plus Rituximab: Analysis of Data From the Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association Phase III Trial LNH 03-2B
Authors: Thierry Jo Molina, Danielle Canioni, Christiane Copie-Bergman, Christian Recher, Josette Brière, Corinne Haioun, Françoise Berger, Christophe Fermé, Marie-Christine Copin, Olivier Casasnovas, Catherine Thieblemont, Tony Petrella, Karen Leroy, Gilles Salles, Bettina Fabiani, Franck Morschauser, Nicolas Mounier, Bertrand Coiffier, Fabrice Jardin, Philippe Gaulard, Jean-Philippe Jais, Hervé Tilly
Journal: Journal of Clinical Oncology (2014)

To determine whether any tumor biomarkers could account for the survival advantage observed in the LNH 03-2B trial among patients with diffuse large B-cell lymphoma (DLBCL) and low-intermediate risk according to the International Prognostic Index when treated with dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) compared with standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP).Using immunohistochemistry, expression of CD10, BCL6, MUM1, MYC, and BCL2 and coexpression of MYC/BCL2 were examined. The interaction effects between each biomarker and treatment arm on survival were studied in a restricted model and a full model incorporating clinical parameters.Among the 379 patients analyzed in the trial, 229 tumors were evaluable for germinal center B-cell-like (GCB)/non-GCB subclassification according to the Hans algorithm. Among all the biomarkers, only the interaction between the Hans algorithm and the treatment arm was significant for progression-free survival (PFS) and overall survival (OS) in univariable (PFS, P = .04; OS, P = .01) and multivariable (PFS, P = .03; OS, P = .01) analyses. Non-GCB tumors predicted worse PFS (hazard ratio [HR], 3.21; 95% CI, 1.29 to 8.00; P = .01) and OS (HR, 6.09; 95% CI, 1.37 to 27.03; P = .02) among patients treated with R-CHOP compared with patients who received R-ACVBP, whereas there were no significant survival differences between these regimens among patients with GCB tumors.The survival benefit related to R-ACVBP over R-CHOP is at least partly linked to improved survival among patients with non-GCB DLBCL. Therefore, the Hans algorithm could be considered a theragnostic biomarker for selecting young patients with DLBCL who can benefit from an intensified R-ACVBP immunochemotherapy regimen.
Role of Computed Tomography and Magnetic Resonance Imaging for Deep Venous Thrombosis and Pulmonary Embolism
Authors: Jeffrey P. Kanne, Tasneem A. Lalani
Journal: Circulation (2004)

During the 1990s, computed tomography (CT) and magnetic resonance (MR) imaging underwent extensive technological advancement and expanded clinical use in patients with venous thromboembolic disease, particularly with regard to evaluation of the pulmonary vasculature. In many institutions, helical (spiral) CT pulmonary angiography has become the initial imaging study of choice to evaluate patients with suspected pulmonary embolism, supplanting ventilation/perfusion scintigraphy. In addition, CT venography of the pelvis and lower extremities is often incorporated into the CT angiography protocol to identify or exclude concurrent deep venous thrombosis. MR pulmonary angiography and MR venography are second-line diagnostic tools because of their higher cost, limited availability, and other logistical constraints. As the technology improves and becomes more widely available, MR imaging may play a greater role in the evaluation of patients with venous thromboembolic disease.