tbuckley/cabot-search huggingface dataset:
Intima-Media Thickness in Severe Obesity
Authors: Elise Dalmas, Jean-François Kahn, Philippe Giral, Meriem Abdennour, Jean-Luc Bouillot, Soraya Fellahi, Jean-Michel Oppert, Karine Clément, Michèle Guerre-Millo, Christine Poitou
Journal: Diabetes Care (2013)

Obesity is associated with cardiovascular risk and a low-grade inflammatory state in both blood and adipose tissue (AT). Whether inflammation contributes to vascular alteration remains an open question. To test this hypothesis, we measured arterial intima-media thickness (IMT), which reflects subclinical atherosclerosis, in severely obese subjects and explored associations with systemic inflammation and AT inflammation.IMT of the carotid artery (C-IMT) and IMT of the femoral artery (F-IMT) were measured in 132 nonobese (control) subjects (BMI 22.3 kg/m2; mean age 44.8 years) and 232 subjects who were severely obese without diabetes (OB/ND; n = 146; BMI 48.3 kg/m2; age 38.2 years) or severely obese with type 2 diabetes (OB/D; n = 86; BMI 47.0; age 49.4 years). In 57 OB/ND subjects, circulating soluble E-selectin, matrix metalloproteinase 9, myeloperoxidase, soluble intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, tissue plasminogen activator inhibitor 1, cystatin C, cathepsin S, and soluble CD14 were measured in serum. AT macrophages were quantified by CD68 immunochemistry.Both C-IMT and F-IMT increased in OB/ND and OB/D patients. In OB/ND patients, age was the sole independent determinant of IMT. No significant association was found with circulating inflammation-related molecules, number of CD68+ cells, or the presence of crown-like structures in visceral or subcutaneous AT of OB/ND patients.IMT increased with severe obesity but was not influenced by the degree of systemic inflammation or AT macrophage accumulation.
Pulmonary Tumor Thrombotic Microangiopathy
Authors: Shinsuke Miyano, Shinyu Izumi, Yuichiro Takeda, Makoto Tokuhara, Makoto Mochizuki, Osamu Matsubara, Hiromi Kuwata, Nobuyuki Kobayashi, Koichiro Kudo
Journal: Journal of Clinical Oncology (2007)
Protective Effects of Tiotropium Bromide in the Progression of Airway Smooth Muscle Remodeling
Authors: Reinoud Gosens, I. Sophie T. Bos, Johan Zaagsma, Herman Meurs
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Recent findings have demonstrated that muscarinic M(3) receptor stimulation enhances airway smooth muscle proliferation to peptide growth factors in vitro. Because both peptide growth factor expression and acetylcholine release are known to be augmented in allergic airway inflammation, it is possible that anticholinergics protect against allergen-induced airway smooth muscle remodeling in vivo.We investigated the effects of treatment with the long-acting muscarinic receptor antagonist tiotropium on airway smooth muscle changes in a guinea pig model of ongoing allergic asthma.Twelve weekly repeated allergen challenges induced an increase in airway smooth muscle mass in the noncartilaginous airways. This increase was not accompanied by alterations in cell size, indicating that the allergen-induced changes were entirely from increased airway smooth muscle cell number. Morphometric analysis showed no allergen-induced changes in airway smooth muscle area in the cartilaginous airways. However, repeated ovalbumin challenge enhanced maximal contraction of open tracheal ring preparations ex vivo. This was associated with an increase in smooth muscle-specific myosin expression in the lung. Treatment with inhaled tiotropium considerably inhibited the increase in airway smooth muscle mass, myosin expression, and contractility.These results indicate a prominent role for acetylcholine in allergen-induced airway smooth muscle remodeling in vivo, a process that has been thus far considered to be primarily caused by growth factors and other mediators of inflammation. Therefore, muscarinic receptor antagonists, like the long-acting anticholinergic tiotropium bromide, could be beneficial in preventing chronic airway hyperresponsiveness and decline in lung function in allergic asthma.
Familial pulmonary veno-occlusive disease: a case report.
Authors: C G Voordes, J R Kuipers, J D Elema
Journal: Thorax (1977)

A case of pulmonary veno-occlusive disease in a male infant who died at the age of 3 months is presented. Both intra- and extrapulmonary veins were involved. Two years earlier a brother had died of the same disease at the age of 8 weeks, but, in that case, the disease was restricted to the intrapulmonary veins. It is suggested that the disease may have been caused by a viral infection, the mother acting as a carrier. The simultaneous occurrence of intra- and extraparenchymal pulmonary vein occlusion indicates that some instances of isolated extraparenchymal pulmonary vein atresia or obstruction may also have been examples of pulmonary veno-occlusive disease.
Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies
Authors: Stephanie L Bielas, Jennifer L Silhavy, Francesco Brancati, Marina V Kisseleva, Lihadh Al-Gazali, Laszlo Sztriha, Riad A Bayoumi, Maha S Zaki, Alice Abdel-Aleem, Rasim Ozgur Rosti, Hulya Kayserili, Dominika Swistun, Lesley C Scott, Enrico Bertini, Eugen Boltshauser, Elisa Fazzi, Lorena Travaglini, Seth J Field, Stephanie Gayral, Monique Jacoby, Stephane Schurmans, Bruno Dallapiccola, Philip W Majerus, Enza Maria Valente, Joseph G Gleeson
Journal: Nature Genetics (2009)
DNA Methylation Array Analysis Identifies Profiles of Blood-Derived DNA Methylation Associated With Bladder Cancer
Authors: Carmen J. Marsit, Devin C. Koestler, Brock C. Christensen, Margaret R. Karagas, E. Andres Houseman, Karl T. Kelsey
Journal: Journal of Clinical Oncology (2011)

Purpose Epigenetic alterations in tissues targeted for cancer play a causal role in carcinogenesis. Changes in DNA methylation in nontarget tissues, specifically peripheral blood, can also affect risk of malignant disease. We sought to identify specific profiles of DNA methylation in peripheral blood that are associated with bladder cancer risk and therefore serve as an epigenetic marker of disease susceptibility. Methods We performed genome-wide DNA methylation profiling on participants involved in a population-based incident case-control study of bladder cancer. Results In a training set of 112 cases and 118 controls, we identified a panel of 9 CpG loci whose profile of DNA methylation was significantly associated with bladder cancer in a masked, independent testing series of 111 cases and 119 controls (P &lt; .0001). Membership in three of the most methylated classes was associated with a 5.2-fold increased risk of bladder cancer (95% CI, 2.8 to 9.7), and a model that included the methylation classification, participant age, sex, smoking status, and family history of bladder cancer was a significant predictor of bladder cancer (area under the curve, 0.76; 95% CI, 0.70 to 0.82). CpG loci associated with bladder cancer and aging had neighboring sequences enriched for transcription-factor binding sites related to immune modulation and forkhead family members. Conclusion These results indicate that profiles of epigenetic states in blood are associated with risk of bladder cancer and signal the potential utility of epigenetic profiles in peripheral blood as novel markers of susceptibility to this and other malignancies.
MHC Class-I Transgenic Mice
Authors: Bernd Arnold, Günter J. Hämmerling
Journal: Annual Review of Immunology (1991)

The introduction of cloned genes into the germline of mice has been proven to be a powerful tool to investigate the role of the respective gene products within the immune system. Here we summarize the transgenic mouse models that have been established with major histocompatibility complex (MHC) class-I genes. Foreign class-I alleles can be expressed in transgenic mice according to their normal expression patterns as authentic self molecules and can function in T-cell responses in the same way as endogenous class-I molecules. Since this is also true for most of the introduced human HLA class-I alleles, there is great interest in establishing mouse models for HLA-linked diseases. A new field of experimental approaches concerning self-tolerance has been opened by tissue specific expression of MHC antigens under specific promoters. Besides negative selection in the thymus, peripheral mechanisms could be identified that induce and maintain self-tolerance.
A Monoclonal Antibody to α1β1 Blocks Antigen-induced Airway Responses in Sheep
Authors: William M. Abraham, Ashfaq Ahmed, Irakli Serebriakov, Amie N. Carmillo, Janine Ferrant, Antonin R. de Fougerolles, Ellen A. Garber, Philip J. Gotwals, Victor E. Koteliansky, Fred Taylor, Roy R. Lobb
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The integrin α1β1 (very late antigen-1; CD49a/CD29) is a major adhesion receptor for collagen I, IV, and VI, and its induced expression on activated monocytes and lymphocytes plays a central role in their retention and activation at inflammatory sites in autoimmune pathologies. However, the role of α1β1 in allergic settings has not been explored. In this study, we show that a single 45-mg dose of aerosolized monoclonal antibody AQC2 to the α1 chain of human and sheep very late antigen-1, given 30 minutes before challenge, blocks both the allergen-induced late response and the associated airway hyperresponsiveness, functional indicators of allergen-induced inflammation, in sheep. AQC2 does not affect the early response. Consistent with these effects, AQC2 tended to reduce the cell response associated with local antigen instillation. An isotype-matched control antibody had no protective effects. Two humanized versions of AQC2, a wild-type IgG1 and an aglycosyl form of the same monoclonal antibody, which has reduced Fc receptor–mediated effector functions, are equally effective in blocking the antigen-induced late response and airway hyperresponsiveness in the sheep model. These data suggest that mononuclear leukocyte adhesion–dependent pathologies contribute to allergic lung disease and provide proof-of-concept that antagonists of α1 integrins may be useful in preventing these events.
Phosphorylation of the ryanodine receptor mediates the cardiac fight or flight response in mice
Authors: Jian Shan, Alexander Kushnir, Matthew J. Betzenhauser, Steven Reiken, Jingdong Li, Stephan E. Lehnart, Nicolas Lindegger, Marco Mongillo, Peter J. Mohler, Andrew R. Marks
Journal: Journal of Clinical Investigation (2010)

During the classic "fight-or-flight" stress response, sympathetic nervous system activation leads to catecholamine release, which increases heart rate and contractility, resulting in enhanced cardiac output. Catecholamines bind to β-adrenergic receptors, causing cAMP generation and activation of PKA, which phosphorylates multiple targets in cardiac muscle, including the cardiac ryanodine receptor/calcium release channel (RyR2) required for muscle contraction. PKA phosphorylation of RyR2 enhances channel activity by sensitizing the channel to cytosolic calcium (Ca²+). Here, we found that mice harboring RyR2 channels that cannot be PKA phosphorylated (referred to herein as RyR2-S2808A+/+ mice) exhibited blunted heart rate and cardiac contractile responses to catecholamines (isoproterenol). The isoproterenol-induced enhancement of ventricular myocyte Ca²+ transients and fractional shortening (contraction) and the spontaneous beating rate of sinoatrial nodal cells were all blunted in RyR2-S2808A+/+ mice. The blunted cardiac response to catecholamines in RyR2-S2808A+/+ mice resulted in impaired exercise capacity. RyR2-S2808A+/+ mice were protected against chronic catecholaminergic-induced cardiac dysfunction. These studies identify what we believe to be new roles for PKA phosphorylation of RyR2 in both the heart rate and contractile responses to acute catecholaminergic stimulation.
A structural study of gallstones.
Authors: P M Bills, D Lewis
Journal: Gut (1975)

A number of gallstones have been studied using methods which have not previously been applied to gallstones. In particular, the use of scanning electron microscopy and micro-x-radiography have allowed detailed observations to be made on the structure of the stones and the distribution of the various components within the stones. Large differences in structure have been shown to exist between stones having similar overall chemical compositions. In cholesterol gallstones containing calcium carbonate the crystalline nature, distribution and method of deposition of the calcium carbonate was studied and was found to vary from stone to stone. Evidence was found for the presence of fibrous material in the centre of many stones and it is possible that this material acted as a nucleus for the deposition of the other stone components.
Effect of temazepam on tracheobronchial mucus clearance.
Authors: A Hasani, M A Spiteri, D Pavia, M T Lopez-Vidriero, J E Agnew, S W Clarke
Journal: Thorax (1992)

BACKGROUND: Tracheobronchial clearance of mucus from the lungs is reduced during sleep and, usually, by the administration of opiates. It seemed possible therefore that temazepam, a widely used potent benzodiazepine, retarded clearance. METHODS: The effect of 10 mg temazepam on mucociliary clearance was studied in eight healthy volunteers, aged 18-50 (mean 30) years, in a randomised, placebo controlled, double blind, cross-over study. Six subjects were female and two male. Six were non-smokers and two were light current smokers. Clearance was assessed from the change in radio-activity in the lungs after inhalation of 5 microns diameter polystyrene particles, labelled with technetium-99m, under controlled conditions. RESULTS: Tracheobronchial clearance was reduced by 22% after temazepam by comparison with placebo during the first three hours after drug ingestion; this is the period when circulating drug concentrations are highest. CONCLUSION: Temazepam should be prescribed with caution in patients with impaired lung mucociliary transport.
Inhibition of Collagenolytic Activity and Metastasis of Tumor Cells by a Recombinant Human Tissue Inhibitor of Metalloproteinases
Authors: O. A. Alvarez, D. F. Carmichael, Y. A. DeClerck
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Inhibition of Collagenolytic Activity and Metastasis of Tumor Cells by a Recombinant Human Tissue Inhibitor of Metalloproteinases Get access Ofelia A. Alvarez, Ofelia A. Alvarez Division of Hematology-Oncology, Department of Pediatrics, Children's Hospital of Los Angeles and the University of Southern California School of MedicineLos Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar David F. Carmichael, David F. Carmichael Carmichael, Synergen, Inc.Boulder, CO Search for other works by this author on: Oxford Academic PubMed Google Scholar Yves A. DeClerck Yves A. DeClerck * Division of Hematology-Oncology, Department of Pediatrics, Children's Hospital of Los Angeles and the University of Southern California School of MedicineLos Angeles, CA * Correspondence to: Yves A. DeClerck, M.D., Division of Hematology-Oncology, Department of Pediatrics, Children's Hospital of Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90054. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 7, 4 April 1990, Pages 589–595, https://doi.org/10.1093/jnci/82.7.589 Published: 04 April 1990 Article history Received: 31 July 1989 Revision received: 06 December 1989 Accepted: 12 December 1989 Published: 04 April 1990
Functional selectin ligands mediating human CD34+ cell interactions with bone marrow endothelium are enhanced postnatally
Authors: Andrés Hidalgo, Linnea A. Weiss, Paul S. Frenette
Journal: Journal of Clinical Investigation (2002)

Hematopoietic progenitor cells (HPCs) can home to the bone marrow (BM) after a simple intravenous injection, but the adhesive mechanisms mediating the initial interactions of human HPCs with the BM endothelium have not been evaluated in vivo. Using fluorescence intravital microscopy and homing assays in NOD/SCID mice, we show that endothelial selectins are necessary for human adult CD34+ cell homing, since rolling on BM endothelium and retention in the BM compartment are drastically reduced (>90%) in endothelial selectin–deficient NOD/SCID mice. Comparative analyses of CD34+ cells collected from adults and from cord blood (CB) reveal that neonatal cells display reduced rolling fractions compared with adult CD34+ cells obtained from peripheral blood or BM, suggesting abnormal selectin ligand function on neonatal progenitors. Flow cytometric and intravital microscopy studies suggest that this defect results from nonfunctional P-selectin ligand on a subset (∼30%) of neonatal CD34+ cells. Further analyses indicate that P-selectin glycoprotein ligand-1 (PSGL-1) is expressed in a nonfunctional form among neonatal CD34+ cells that do not bind P-selectin and that this subset is enriched in primitive CD34+CD38lo/– progenitors. These results underscore the potential to improve homing of CB CD34+ cells to the BM by manipulation of selectins and their ligands.
A Modeling Approach to Explain Mutually Exclusive and Co-Occurring Genetic Alterations in Bladder Tumorigenesis
Authors: Elisabeth Remy, Sandra Rebouissou, Claudine Chaouiya, Andrei Zinovyev, François Radvanyi, Laurence Calzone
Journal: Cancer Research (2015)

Relationships between genetic alterations, such as co-occurrence or mutual exclusivity, are often observed in cancer, where their understanding may provide new insights into etiology and clinical management. In this study, we combined statistical analyses and computational modeling to explain patterns of genetic alterations seen in 178 patients with bladder tumors (either muscle-invasive or non-muscle-invasive). A statistical analysis on frequently altered genes identified pair associations, including co-occurrence or mutual exclusivity. Focusing on genetic alterations of protein-coding genes involved in growth factor receptor signaling, cell cycle, and apoptosis entry, we complemented this analysis with a literature search to focus on nine pairs of genetic alterations of our dataset, with subsequent verification in three other datasets available publicly. To understand the reasons and contexts of these patterns of associations while accounting for the dynamics of associated signaling pathways, we built a logical model. This model was validated first on published mutant mice data, then used to study patterns and to draw conclusions on counter-intuitive observations, allowing one to formulate predictions about conditions where combining genetic alterations benefits tumorigenesis. For example, while CDKN2A homozygous deletions occur in a context of FGFR3-activating mutations, our model suggests that additional PIK3CA mutation or p21CIP deletion would greatly favor invasiveness. Furthermore, the model sheds light on the temporal orders of gene alterations, for example, showing how mutual exclusivity of FGFR3 and TP53 mutations is interpretable if FGFR3 is mutated first. Overall, our work shows how to predict combinations of the major gene alterations leading to invasiveness through two main progression pathways in bladder cancer.
Prevalence and Management of Diabetes and Associated Risk Factors by Regions of Thailand
Authors: Wichai Aekplakorn, Jesse Abbott-Klafter, Amorn Premgamone, Bodi Dhanamun, Chalermchai Chaikittiporn, Virasakdi Chongsuvivatwong, Thanaruk Suwanprapisa, Weerayuth Chaipornsupaisan, Siriwat Tiptaradol, Stephen S. Lim
Journal: Diabetes Care (2007)

OBJECTIVE—The aim of this study was to determine the prevalence of diabetes and impaired fasting glucose (IFG) and their association with cardiovascular risk factors and to evaluate the management of blood glucose, blood pressure, and cholesterol in individuals with diabetes by geographical regions of Thailand. RESEARCH DESIGN AND METHODS—With the use of a stratified, multistage sampling design, data from a nationally representative sample of 37,138 individuals aged ≥15 years were collected using questionnaires, physical examination, and blood samples. RESULTS—The prevalence of diabetes and IFG weighted to the national 2004 population was 6.7% (6.0% in men and 7.4% in women) and 12.5% (14.7% in men and 10.4% in women), respectively. Diabetes was more common in urban than in rural men but otherwise prevalence was relatively uniform across geographical regions. In more than one-half of those with diabetes, the disease had not been previously diagnosed, although the majority of those with diabetes were treated with oral antiglycemic agents or insulin. The prevalence of associated risk factors was high among individuals with diabetes as well as those with IFG. Two-thirds of those with diabetes and concomitant high blood pressure (≥130/80 mmHg) were not aware that they had high blood pressure, and &amp;gt;70% of those with diabetes and concomitant high cholesterol (total cholesterol ≥6.2 mmol/l) were not aware that they had high cholesterol. CONCLUSIONS—The prevalences of diabetes and IFG were uniformly high in all regions. Improvements in prevention, diagnosis, and treatment of diabetes and associated risk factors are required if the health burden of diabetes in Thailand is to be averted.
Extramedullary plasmacytoma: Clinical behaviour and response to treatment
Authors: M. Soesan, A. Paccagnella, V. Chiarion-Sileni, L. Salvagno, A. Fornasiero, G. Sotti, P.-L. Zorat, A. Favaretto, M. Fiorentino
Journal: Annals of Oncology (1992)
A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging
Authors: Matilde Murga, Samuel Bunting, Maria F Montaña, Rebeca Soria, Francisca Mulero, Marta Cañamero, Youngsoo Lee, Peter J McKinnon, Andre Nussenzweig, Oscar Fernandez-Capetillo
Journal: Nature Genetics (2009)
Common variable immunodeficiency and natural killer cell lymphopenia caused by Ets-binding site mutation in the IL-2 receptor γ (IL2RG) gene promoter
Authors: Anita Chandra, Fang Zhang, Kimberly C. Gilmour, David Webster, Vincent Plagnol, Dinakantha S. Kumararatne, Siobhan O. Burns, Sergey Nejentsev, Adrian J. Thrasher
Journal: Journal of Allergy and Clinical Immunology (2015)

Patients with severe combined immunodeficiency (SCID) of a classical phenotype present within the first year of life with life-threatening infections and failure to thrive.1 The X-linked T−B+ natural killer (NK)− form of SCID is the most frequent type (44% to 46%) and is a consequence of mutations in the IL-2 receptor γ (IL2RG) gene (OMIM 308380), which encodes the common cytokine receptor γ chain (γc).2 The γc acts as a signal-transducing subunit of cytokine receptors that are essential in the ontogeny and function of T, B, and NK cells, namely IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21.
The CD8 Population in CD4-deficient Mice Is Heavily Contaminated with MHC Class II–restricted T Cells
Authors: Aaron J. Tyznik, Joseph C. Sun, Michael J. Bevan
Journal: The Journal of Experimental Medicine (2004)

In experiments to study the impact of deficiency in CD4+ T cell help on the magnitude of CD8+ cytotoxic T cell response to pathogens, it was noted that in CD4 gene knockout mice, the CD8 population made significant responses to several nominally major histocompatibility complex (MHC) class II–restricted epitopes in addition to the expected responses to MHC class I–restricted epitopes. A similar response by CD8+ T cells to class II–restricted epitopes was not observed in wild-type mice, or in mice that had been acutely depleted of CD4+ T cells just before the immunization. Coincident with this unexpected response to class II–restricted epitopes, it was also observed that the CD8+ response to the class I–restricted epitopes was consistently lower in CD4−/− mice than in wild-type mice. Further experiments suggested that these two observations are linked and that the CD8 population in CD4−/− mice may contain a majority of T cells that were actually selected by recognition of MHC class II molecules in the thymus. These results have implications for understanding CD4 versus CD8 lineage commitment in the thymus, and for the practical use of CD4−/− mice as models of helper deficiency.