tbuckley/cabot-search huggingface dataset:
Canine Right and Left Ventricular Cell and Sarcomere Lengths after Banding the Pulmonary Artery
Authors: MICHAEL M. LAKS, FRED MORADY, H.J.C. SWAN
Journal: Circulation Research (1969)

Canine hearts were fixed with glutaraldehyde at zero transmural pressure 17 to 48 weeks after main pulmonary arterial banding. Tissues were taken from the trabeculae carneae at the ventricular right base, right apex, left base, and left apex. They were placed in osmium tetroxide, embedded in Epon 812, stained with Azure II methylene blue, and sectioned at ½ µ. The mean cell lengths of the hearts with main pulmonary arterial banding were greatest at the right base, 105±5 µ and left base, 103±5.7 µ. (The means ± SE are given.) The mean cell length at the left apex was 95±4 µ and that at the right apex was 92±5 µ. All were greater (P &lt;0.001) than the cell lengths of normal hearts, 71±1.5 µ. The mean sarcomere lengths of the right ventricle with main pulmonary arterial banding (right base, 2.04±0.006 µ right apex, 2.18±0.004 µ) were less than those of normal hearts (right base, 2.41±0.006 µ right apex, 2.46±0.003 µ). The mean sarcomere length of the left base with main pulmonary arterial banding (2.10±0.01 µ) was less than the normal (2.16±0.002 µ); however, the mean sarcomere length of the left apex with main pulmonary arterial banding (2.28±0.005 µ) was the same as the normal. With main pulmonary arterial banding, both the right and left ventricular cell lengths increased more at the bases than at the apexes, and the sarcomere lengths decreased in the right base, right apex, and left base.
Mast cells: bridging the gap between pre- and post-capillary pulmonary hypertension?
Authors: D. Montani, I.M. Lang
Journal: European Respiratory Journal (2011)

ccording to the current guidelines for the diagnosis and treatment of pulmonary hypertension (PH) [1,2], the Dana Point diagnostic classification separates precapillary PH, i.e.PH due to pulmonary vascular disease mainly affecting the pre-capillary arteriolar compartment (i.e.Dana Point groups 1, 3, 4 and 5), from post-capillary disease that originates distal to the capillaries and involves morphological changes in the pre-capillary compartment only occur after a significant pressure increase in the venous compartment (i.e.Dana Point group 2).Currently, a single haemodynamic parameter, i.e. wedge pressure [3], that is commonly flawed by methodological errors [4] is employed to distinguish between pre-and post-capillary disease.This distinction is vital because treatment is completely different for the two classes of disease [2], with a virtual ''therapeutic gap'' between the two disorders.For example, epoprostenol, the life-saving treatment for pulmonary arterial hypertension (PAH) [5], was shown to be detrimental in congestive heart failure [6].
Large genomic aberrations detected by SNP array are independent prognosticators of a shorter time to first treatment in chronic lymphocytic leukemia patients with normal FISH
Authors: M. Mian, A. Rinaldi, A.A. Mensah, D. Rossi, M. Ladetto, F. Forconi, R. Marasca, M. Uhr, G. Stussi, I. Kwee, F. Cavalli, G. Gaidano, E. Zucca, F. Bertoni
Journal: Annals of Oncology (2013)
Impaired lung compliance and DL,CO but no restrictive ventilatory defect in sarcoidosis
Authors: P.W. Boros, P.L. Enright, P.H. Quanjer, G.J.J.M. Borsboom, S.P. Wesolowski, R.E. Hyatt
Journal: European Respiratory Journal (2010)

Sarcoidosis is a systemic granulomatous disease with predominant manifestation in the lungs, often presenting as interstitial lung disease. Pulmonary function abnormalities in sarcoidosis include restriction of lung volumes, reduction in diffusing capacity of the lung for carbon monoxide (D(L,CO)), reduced static lung compliance (C(L,s)) and airway obstruction. The aim of the present study was to assess various lung function indices, including C(L,s) and D(L,CO), as markers of functional abnormality in sarcoidosis patients. Results from 830 consecutive patients referred for lung function tests with a diagnosis of sarcoidosis (223 in stage I, 486 in stage II and 121 in stage III) were retreospectively analysed. The mean ± sd age of the patients was 40 ± 11 yrs; 18% were active smokers and 24% were former smokers. Normal total lung capacity was found in 772 (93%) patients. Of these cases, 24.5% had a low C(L,s) and 21.5% had a low D(L,CO). At least one abnormality was observed in 39.3% of these patients, whereas, in restrictive patients, this figure was 88%. Airway obstruction was present in 11.7% of cases. Lung volumes usually remain within the normal range and measurement of either C(L,s) or D(L,CO) often reveal impaired lung function in sarcoidosis patients, even when their lung volumes are still in the normal range; these two measurements provide complementary information.
CELLULAR NEAEVI WITH PECULIAR FOAM CELLS.
Authors: E. WILSON JONES, K. V. SANDERSON
Journal: British Journal of Dermatology (1963)

Journal Article CELLULAR NEAEVI WITH PECULIAR FOAM CELLS. Get access E. WILSON JONES, E. WILSON JONES Institute of Dermatology, St. John's Hospital for Diseases of the Skin, Lisle St., London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar K. V. SANDERSON K. V. SANDERSON Institute of Dermatology, St. John's Hospital for Diseases of the Skin, Lisle St., London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 75, Issue 2, 1 February 1963, Pages 47–54, https://doi.org/10.1111/j.1365-2133.1963.tb13937.x Published: 01 February 1963
Extraintestinal Virulence Is a Coincidental By-Product of Commensalism in B2 Phylogenetic Group Escherichia coli Strains
Authors: T. Le Gall, O. Clermont, S. Gouriou, B. Picard, X. Nassif, E. Denamur, O. Tenaillon
Journal: Molecular Biology and Evolution (2007)

The selective pressures leading to the evolution and maintenance of virulence in the case of facultative pathogens are quite unclear. For example, Escherichia coli, a commensal of the gut of warm-blooded animals and humans, can cause severe extraintestinal diseases, such as septicemia and meningitis, which represent evolutionary dead ends for the pathogen as they are associated to rapid host death and poor interhost transmission. Such infectious process has been linked to the presence of so-called "virulence genes." To understand the evolutionary forces that select and maintain these genes, we focused our study on E. coli B2 phylogenetic group strains that encompass both commensal and pathogenic (extra- and intraintestinal) strains. Multilocus sequence typing (MLST), comparative genomic hybridization of the B2 flexible gene pool, and quantification of extraintestinal virulence using a mouse model of septicemia were performed on a panel of 60 B2 strains chosen for their genetic and ecologic diversity. The phylogenetic history of the strains reconstructed from the MLST data indicates the emergence of at least 9 subgroups of strains. A high polymorphism is observed in the B2 flexible gene pool among the strains with a good correlation between the MLST-inferred phylogenetic history of the strains and the presence/absence of specific genomic regions, indicating coevolution between the chromosomal background and the flexible gene pool. Virulence in the mouse model is a highly prevalent and widespread character present in all subgroups except one. Association studies reveal that extraintestinal virulence is a multigenic process with a common set of "virulence determinants" encompassing genes involved in transcriptional regulation, iron metabolism, adhesion, lipopolysaccharide (LPS) biosynthesis, and the recently reported peptide polyketide hybrid synthesis system. Interestingly, these determinants can also be viewed as intestinal colonization and survival factors linked to commensalism as they can increase the fitness of the strains within the normal gut environment. Altogether, these data argue for an ancestral emergence of the extraintestinal virulence character that is a coincidental by-product of commensalism. Furthermore, the phenotypic and genotypic markers identified in this work will allow further epidemiological studies devoted to test the niche specialization hypothesis for the B2 phylogenetic subgroups.
SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model
Authors: Maged M. Harraz, Jennifer J. Marden, Weihong Zhou, Yulong Zhang, Aislinn Williams, Victor S. Sharov, Kathryn Nelson, Meihui Luo, Henry Paulson, Christian Schöneich, John F. Engelhardt
Journal: Journal of Clinical Investigation (2008)

Neurodegeneration in familial amyotrophic lateral sclerosis (ALS) is associated with enhanced redox stress caused by dominant mutations in superoxide dismutase–1 (SOD1). SOD1 is a cytosolic enzyme that facilitates the conversion of superoxide (O2•–) to H2O2. Here we demonstrate that SOD1 is not just a catabolic enzyme, but can also directly regulate NADPH oxidase–dependent (Nox-dependent) O2•– production by binding Rac1 and inhibiting its GTPase activity. Oxidation of Rac1 by H2O2 uncoupled SOD1 binding in a reversible fashion, producing a self-regulating redox sensor for Nox-derived O2•– production. This process of redox-sensitive uncoupling of SOD1 from Rac1 was defective in SOD1 ALS mutants, leading to enhanced Rac1/Nox activation in transgenic mouse tissues and cell lines expressing ALS SOD1 mutants. Glial cell toxicity associated with expression of SOD1 mutants in culture was significantly attenuated by treatment with the Nox inhibitor apocynin. Treatment of ALS mice with apocynin also significantly increased their average life span. This redox sensor mechanism may explain the gain-of-function seen with certain SOD1 mutations associated with ALS and defines new therapeutic targets.
Responding to the Challenges of Primary Diabetes Care Through the National Diabetes Education Program
Authors: Kevin A. Peterson, Marie T. Brown, Elizabeth Warren-Boulton
Journal: Diabetes Care (2015)

In this issue of Diabetes Care , the article by Paddison et al. (1) provides valuable information that furthers our understanding of the primary care patient experience for people with diabetes. Using the English General Practice Patient Survey (GPPS), the authors compare the primary care experience of 85,760 survey responders with self-reported diabetes with 820,818 responders without diabetes across three domains of care delivery: access, continuity, and communication. Individuals with diabetes reported primary care experiences that were as good as or better than people without diabetes across most domains of care. The authors point out that the concept of family practice in England is not dissimilar to that of the patient-centered medical home (PCMH) articulated in the U.S. Primary care practices in both countries identify patient populations and both share some degree of financial risk for keeping their patients healthy. Despite the similarities, several findings do not broadly generalize to the U.S. health care system.

Patient satisfaction surveys reflect perceptions as well as the capabilities of a health care delivery system, but the realities faced by U.S. and U.K. patients are different. In the 2014 National Committee for Quality Assurance annual summary of assessments from U.S. health plans, 94.5% of patients reported that their doctors usually or always explained things, listened carefully, showed respect, and spent enough time, and 86.7% of patients reported that access to care was good, comparing favorably with the GPPS results (2). However, only 67.6% of these …
THE CATABOLISM OF HOMOLOGOUS AND HETEROLOGOUS 7S GAMMA GLOBULIN FRAGMENTS
Authors: Hans L. Spiegelberg, William O. Weigle
Journal: The Journal of Experimental Medicine (1965)

The catabolism of homologous and heterologous 7S gamma globulin fragments obtained by pepsin and papain digestion was studied in rabbits, guinea pigs, and mice. The elimination from the circulation of I* labeled gamma globulin fragments was followed and the urinary excretion of the total and protein-bound I* activity determined. Evidence is presented that the molecular structure responsible for the catabolism of 7S gamma globulin is located in papain fragment III. The elimination of papain fragment III was slow and closely related to the intact gamma globulin, whereas the pepsin fragment and papain fragments I and II were rapidly eliminated and catabolized in all species examined. Prolonged incubation with cysteine altered papain fragment III as shown by a rapid catabolism of a large portion of incubated fragment III within 24 hours after injection. Small amounts of intact RGG and RGG papain fragment III were excreted as protein-bound I* activity in the urine. On the other hand, large amounts of the pepsin fragment and papain fragments I and II of RGG were excreted as protein-bound I* activity in the urine. The possibility of a molecular structure present in papain fragment III, which may be responsible for tubular reabsorption in the kidney, is discussed. The rate of urinary excretion of fragments obtained from RGG was different from that of fragments obtained from gamma globulin of several other species. In general, small amounts of the pepsin fragment and papain fragment III obtained from gamma globulin other than RGG were excreted as protein-bound I* activity. The amounts of fragment I* excreted as protein-bound I* activity depended on the species in which it was injected, as well as the source of the gamma globulin. The rapid catabolism of the pepsin fragment and papain fragments I or II which bear antibody-combining sites suggest that their use for the prophylactic treatment of tetanus and diphtheria in man is limited.
Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma
Authors: Peter Borchmann, Roland Schnell, Irene Fuss, Oliver Manzke, Thomas Davis, Lionel D. Lewis, Detlev Behnke, Claudia Wickenhauser, Petra Schiller, Volker Diehl, Andreas Engert
Journal: Blood (2002)
Cytomegalovirus mononucleosis as a cause of prolonged fever and prominent weight loss in immunocompetent adults
Authors: J. Rodríguez-Baño, M.A. Muniain, M.V. Borobio, J.L. Corral, E. Ramirez, E.J. Perea, R. Perez-Cano
Journal: Clinical Microbiology and Infection (2004)
Depression: An Important Comorbidity With Metabolic Syndrome in a General Population
Authors: James A. Dunbar, Prasuna Reddy, Nathalie Davis-Lameloise, Benjamin Philpot, Tiina Laatikainen, Annamari Kilkkinen, Stephen J. Bunker, James D. Best, Erkki Vartiainen, Sing Kai Lo, Edward D. Janus
Journal: Diabetes Care (2008)

There is a recognized association among depression, diabetes, and cardiovascular disease. The aim of this study was to examine in a sample representative of the general population whether depression, anxiety, and psychological distress are associated with metabolic syndrome and its components.Three cross-sectional surveys including clinical health measures were completed in rural regions of Australia during 2004-2006. A stratified random sample (n = 1,690, response rate 48%) of men and women aged 25-84 years was selected from the electoral roll. Metabolic syndrome was defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale and psychological distress by the Kessler 10 measure.Metabolic syndrome was associated with depression but not psychological distress or anxiety. Participants with the metabolic syndrome had higher scores for depression (n = 409, mean score 3.41, 95% CI 3.12-3.70) than individuals without the metabolic syndrome (n = 936, mean 2.95, 95% CI 2.76-3.13). This association was also present in 338 participants with the metabolic syndrome and without diabetes (mean score 3.37, 95% CI 3.06-3.68). Large waist circumference and low HDL cholesterol showed significant and independent associations with depression.Our results show an association between metabolic syndrome and depression in a heterogeneous sample. The presence of depression in individuals with the metabolic syndrome has implications for clinical management.
Childhood Trauma Associated With Smaller Hippocampal Volume in Women With Major Depression
Authors: Meena Vythilingam, Christine Heim, Jeffrey Newport, Andrew H. Miller, Eric Anderson, Richard Bronen, Marijn Brummer, Lawrence Staib, Eric Vermetten, Dennis S. Charney, Charles B. Nemeroff, J. Douglas Bremner
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects. METHOD: Study participants were 32 women with current unipolar major depressive disorder—21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse—and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects’ diagnoses. RESULTS: The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects. CONCLUSIONS: A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder.
Downregulation of Protein Kinase Cδ Activity Enhances Endothelial Cell Adaptation to Hypoxia
Authors: Yukitaka Shizukuda, Armin Helisch, Ryoji Yokota, J. Anthony Ware
Journal: Circulation (1999)

Background —Although protein kinase C (PKC) has been implicated in ischemic cell death, the role of individual PKC isoenzymes in the response of endothelial cells (ECs) to hypoxia is unknown. Methods and Results —To test the effect of hypoxia on the activity of individual PKC isoenzymes, human ECs were exposed to 95% N 2 with 5% CO 2 for 24 hours. This severe hypoxia reduced PKCδ specific activity in both human umbilical vein ECs (HUVECs) and a HUVEC-derived EC line (ECVs) significantly (80.5±5.7% and 55.5±8.6% of normoxia controls, respectively); the activities of PKCα and PKCε were unchanged. The protein levels of PKCα, PKCδ, and PKCε were unchanged by hypoxia. To determine whether PKCδ downregulation by hypoxia was linked to EC function, ECVs in which PKCδ was stably overexpressed (PKCδ-ECs) were exposed to hypoxia. A significant increase in cell death was observed in PKCδ-ECs compared with controls (5.8±0.6% versus 2.3±0.4% at 24 hours, 13.2±1.2% versus 4.1±0.4% at 48 hours, P &lt;0.05) during hypoxia. Neither the DNA laddering assay nor TUNEL staining revealed an increase in apoptosis of PKCδ-ECs exposed to hypoxia, suggesting a hypoxia-induced increase in nonapoptotic cell death of PKCδ-ECs. Inhibition of NO synthase with N G -monomethyl- l -arginine (L-NMMA) affected neither the decline in PKCδ activity nor the EC death induced by hypoxia. Conclusions —PKCδ activity is decreased by hypoxia by a mechanism that does not involve NO synthase; this downregulation appears to enhance EC survival during hypoxia by decreasing nonapoptotic cell death.
Correction to: Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression. Ann Oncol 2006; 17: 1625–1630
Authors: R.A. Soo, J. Wu, A. Aggarwal, Q. Tao, W. Hsieh, T. Putti, K.B. Tan, W.L. Soon, Y.F. Lai, B. Mow, S. Hsu, K.S. Loh, L. Tan, P. Tan, B.-C. Goh
Journal: Annals of Oncology (2007)
Antioxidant Improves Smooth Muscle Sarco/Endoplasmic Reticulum Ca <sup>2+</sup> -ATPase Function and Lowers Tyrosine Nitration in Hypercholesterolemia and Improves Nitric Oxide–Induced Relaxation
Authors: Takeshi Adachi, Reiko Matsui, Shanqin Xu, Michael Kirber, Harold L. Lazar, Victor S. Sharov, Christian Schöneich, Richard A. Cohen
Journal: Circulation Research (2002)

Antioxidants improve endothelial function in hypercholesterolemia (HC); however, whether this includes improvement of the vascular smooth muscle response to NO is unknown. NO relaxes arteries, in part, by stimulating Ca 2+ uptake via sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA) in aortic smooth muscle, and HC impairs SERCA function and the response to NO. HC induces oxidative stress, which could impair SERCA function. To study the effect of antioxidants, which are known to improve endothelium-dependent relaxation in HC, smooth muscle SERCA activity and NO-induced relaxation were studied in rabbits fed normal chow or a 0.5% cholesterol diet for 13 weeks. The antioxidant t -butylhydroxytoluene (BHT, 1%) was mixed with the HC diet in the last 3 weeks. HC impaired acetylcholine- and NO-induced relaxation, and these were restored by BHT. After inhibiting SERCA with thapsigargin, no difference existed in NO-induced relaxation among the three groups. Reduced aortic SERCA activity in HC was restored by BHT without changing SERCA protein expression. 3-Nitrotyrosine was notably increased in the media of the HC aorta, where it colocalized with SERCA. Tyrosine-nitrated SERCA protein was immunoprecipitated in the aortas of HC rabbits, where it was decreased by BHT, and it was also detected in the aortas of atherosclerotic humans. Thus, the antioxidant reverses impaired smooth muscle SERCA function in HC, and this is correlated with the improved relaxation to NO. These beneficial effects may depend on reducing the direct effects on SERCA of reactive oxygen species that are augmented in HC.
Stable RNA Interference–Mediated Suppression of Cyclophilin A Diminishes Non–Small-Cell Lung Tumor Growth <i>In vivo</i>
Authors: Brandon A. Howard, Ryohei Furumai, Michael J. Campa, Zahid N. Rabbani, Zeljko Vujaskovic, Xiao-Fan Wang, Edward F. Patz
Journal: Cancer Research (2005)

Abstract Cyclophilin A (CypA) was recently reported to be overexpressed in non–small-cell lung cancer, and represents a potentially novel therapeutic target. To determine the role of CypA in oncogenesis, stable RNA interference (RNAi)–mediated knockdown of CypA was established in two non–small-cell lung cancer cell lines (ADLC-5M2 and LC-103H), and these cells were grown as xenografts in severe combined immunodeficient mice. Tumor cell proliferation, apoptosis, and angiogenesis were measured by Ki67, terminal deoxyribonucleotidyl transferase–mediated dUTP nick-end labeling, and CD31 immunohistochemistry, respectively. Tumor glucose metabolism was assessed by fluorodeoxyglucose positron emission tomography imaging. Knockdown of CypA correlated in vivo with slower growth, less fluorodeoxyglucose uptake, decreased proliferation, and a greater degree of apoptosis in the tumors. These results establish the relevance of CypA to tumor growth in vivo, specifically to proliferation and apoptosis. Elucidation of the precise role of CypA in these pathways may lead to new targeted therapies for lung cancer.