tbuckley/cabot-search huggingface dataset:
Rhumatologie Europeenne. Revue critique de la litterature du 1 juillet, 1953, au 1 juillet, 1956
Authors: D. Preiskel
Journal: Annals of the Rheumatic Diseases (1958)

This book is undoubtedly a classic in the literature of the rheumatic diseases.It is based on a detailed study of 293 patients with rheumatoid arthritis, with clinical and laboratory data obtained according to a set plan, which was initiated in 1929 and which has been carried out with meticulous care.The previous literature is reviewed, pointing out that the term "rheumatoid arthritis" was introduced by Sir A. B. Garrod, and that his son, A. E. Garrod, published in 1890 a study of 500 cases, using control data, and giving figures for the frequency of a family history, the age and sex distribution, the aetiological significance of emotional disturbances and the influence of the menopause.The present study is a wider up-to-date record of the same type using modem methods of investigation.In discussing the diagnostic criteria used, the authors have covered the differential diagnosis of the disease in a comprehensive manner.They admit the difficulty in some cases of a clear-cut distinction between the later changes of rheumatoid and degenerative arthritis.The inclusion in the series of cases of ankylosing spondylitis is explained, but will be regretted in this country where it is considered to be a separate disease.The known high familial incidence of this condition undoubtedly alters the figures in this series, though the authors state that no conclusion can yet be drawn as to the relative influence of environment, contagion or heredity.Careful analyses are made of the effect of other illnesses, operations, injuries, occupation, and the menopause, and are compared with control material.The mode of onset and constitutional symptoms have been studied in detail and the results are of the greatest interest.Laboratory investigations have been extensive and the findings are most valuable.This detailed description of the disease by three dis- tinguished clinicians from the Massachusetts General Hospital, backed by statistical evidence compared with a control series, is one of the most authoritative studies yet published.We are promised a further report on the life history of the disease and possibly one on rational treatment.These will be awaited eagerly by all phy- sicians interested in rheumatoid arthritis.OSWALD SAVAGE
Increased Superoxide Generation Is Associated With Pulmonary Hypertension in Fetal Lambs
Authors: Lisa A. Brennan, Robin H. Steinhorn, Stephen Wedgwood, Eugenia Mata-Greenwood, Everett A. Roark, James A. Russell, Stephen M. Black
Journal: Circulation Research (2003)

Ligation of the ductus arteriosus in utero produces pulmonary hypertension and vascular remodeling in fetal and newborn lambs. However, the mechanisms producing these vascular changes are not well defined. Because reactive oxygen species (ROS) have been implicated as mediators of smooth muscle cell proliferation, we hypothesized that increased formation of ROS may be involved in the pathophysiology of pulmonary hypertension after in utero ductal ligation. Using ethidium fluorescence, we demonstrated an increase in superoxide levels after 9 days of ductal ligation compared with control lungs (P<0.05) that was localized to the adventitia and smooth muscle cells of hypertensive vessels. SOD-1 and SOD-2 protein levels and activities in lung, vein, and artery of hypertensive lambs were unchanged relative to controls after 2 days of ductal ligation. However, after 9 days, superoxide dismutase (SOD) activity was significantly decreased in arteries from ligated lambs without associated changes in SOD protein expression (P<0.05). Examination of NADPH oxidase expression as a potential source of the superoxide production indicated that the levels of p67phox, a subunit of the NADPH oxidase complex, were significantly increased in the pulmonary arteries, but not veins, from the ligated lung as early as 2 days (P<0.05). Functional analyses demonstrated that reducing superoxide levels significantly increased the NO-mediated relaxation of pulmonary arteries isolated after 9 days, but not 2 days, of ductal ligation (P<0.05). These results suggest that increased NADPH oxidase expression may increase levels of superoxide in persistent pulmonary hypertension of the newborn lung tissue, and that increased superoxide blunts vascular relaxations to exogenous NO while stimulating smooth muscle cell growth.
In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial
Authors: Thomas Jack, Martin Boehne, Bernadette E. Brent, Ludwig Hoy, Harald Köditz, Armin Wessel, Michael Sasse
Journal: Intensive Care Medicine (2012)

Particulate contamination due to infusion therapy carries a potential health risk for intensive care patients.
Psychobiological Aspects of Atopic Dermatitis: An Overview
Authors: Angelika Buske-Kirschbaum, Andrea Geiben, Dirk Hellhammer
Journal: Psychotherapy and Psychosomatics (2001)

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease with increasing incidence characterized by eczematous inflammation of the skin, a chronically relapsing course and severe pruritus. In the last decade, there has been growing evidence indicating that psychological factors such as personality and stress may play an important role in the pathogenesis of AD. While there is only little consensus on an AD-specific personality profile and its etiological significance, a growing number of reports support the role of psychosocial stress in the onset and the course of AD symptomatology. However, although a close association between psychosocial stress and skin condition in AD patients has been demonstrated by several investigators, pathological models that integrate stress and its effect on atopy-relevant biological processes, e.g. immune processes, are still missing. This overview summarizes the role of immunological and psychological factors in AD pathogenesis and discusses potential psychobiological pathways of stress-related modulation of AD symptoms.
Response to Letter Regarding Article, “Smoking, Clopidogrel, and Mortality in Patients With Established Cardiovascular Disease”
Authors: Jeffrey S. Berger, Deepak L. Bhatt, Steven R. Steinhubl, Mingyuan Shao, A. Michael Lincoff, P. Gabriel Steg, Gilles Montalescot, Werner Hacke, Keith A. Fox, Eric J. Topol, Peter B. Berger
Journal: Circulation (2010)
NF-κB activation enhances cell death by antimitotic drugs in human prostate cancer cells
Authors: Ricardo Parrondo, Alicia de las Pozas, Teresita Reiner, Priyamvada Rai, Carlos Perez-Stable
Journal: Molecular Cancer (2010)

Abstract Background NF-κB is a transcription factor that promotes inhibition of apoptosis and resistance to chemotherapy. It is commonly believed that inhibition of NF-κB activity can increase sensitivity of cancer cells to chemotherapy. However, there is evidence that NF-κB activation can sensitize cells to apoptosis and that inhibition of NF-κB results in resistance to chemotherapy. In prostate cancer, it is not clear in the different cell types (androgen-dependent and castration-resistant) if activation or inhibition of NF-κB is required for stimulation of apoptosis by chemotherapy. Results Our data indicate that the response of prostate cancer (PC) cells to the antimitotic drugs docetaxel (Doc) and 2-methoxyestradiol (2ME2) is dependent on the levels of NF-κB activity. In androgen-dependent LNCaP cells, Doc and 2ME2 treatment increased the low basal NF-κB activity, as determined by Western blot analysis of phospho-IκBα/p65, NF-κB promoter reporter assays, and p65 localization. Treatment of LNCaP cells with parthenolide, a pharmacologic inhibitor of NF-κB, or introduction of dominant-negative IκBα, or an shRNA specific for p65, a component of the NF-κB heterodimer, blocked apoptosis induced by Doc and 2ME2. In castration-resistant DU145 and PC3 cells, Doc and 2ME2 had little effect on the high basal NF-κB activity and addition of parthenolide did not enhance cell death. However, the combination of Doc or 2ME2 with betulinic acid (BA), a triterpenoid that activates NF-κB, stimulated apoptosis in LNCaP and non-apoptotic cell death in DU145 and PC3 cells. Increased sensitivity to cell death mediated by the Doc or 2ME2 + BA combination is likely due to increased NF-κB activity. Conclusions Our data suggest that the combination of antimitotic drugs with NF-κB inhibitors will have antagonistic effects in a common type of PC cell typical of LNCaP. However, combination strategies utilizing antimitotic drugs with BA, an activator of NF-κB, will universally enhance cell death in PC cells, notably in the aggressive, castration-resistant variety that does not respond to conventional therapies.
Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production by human B cells.
Authors: R Yarchoan, G Tosato, R M Blaese, R M Simon, D L Nelson
Journal: The Journal of Experimental Medicine (1983)

The Epstein-Barr virus (EBV) is a herpes virus that has the capacity to infect human B cells and to induce them to secrete immunoglobulin (Ig). In the current experiments, Poisson analysis of limiting dilution cultures has been used to study the activation of human peripheral B cells by the B95-8 strain of EBV. Under the culture conditions used, 0.2-1% of peripheral blood B cells were activated by EBV to secrete IgM or IgG. In addition, when multiple replicate cultures containing limited numbers of B cells were tested for IgM and for IgG production, the precursors for IgM and IgG segregated independently; thus, individual B cell precursors matured into cells secreting IgM or IgG but not both classes of Ig. Additional experiments using limiting dilutions of EBV were undertaken to study the viral requirements for B cell activation. These studies indicated that B cell activation by EBV to produce Ig was consistent with a "one-hit" model and inconsistent with a "two-hit" model. Taken together, these results indicate that infection by one EBV virion is sufficient to induce a precursor peripheral blood B cell to secrete Ig and that only one isotype of Ig is then secreted.
Use of Electronic Health Records in U.S. Hospitals
Authors: Ashish K. Jha, Catherine M. DesRoches, Eric G. Campbell, Karen Donelan, Sowmya R. Rao, Timothy G. Ferris, Alexandra Shields, Sara Rosenbaum, David Blumenthal
Journal: New England Journal of Medicine (2009)

Despite a consensus that the use of health information technology should lead to more efficient, safer, and higher-quality care, there are no reliable estimates of the prevalence of adoption of electronic health records in U.S. hospitals.
VEGF/VEGFR-2 Upregulates EZH2 Expression in Lung Adenocarcinoma Cells and EZH2 Depletion Enhances the Response to Platinum-Based and VEGFR-2–Targeted Therapy
Authors: Erick Riquelme, Milind Suraokar, Carmen Behrens, Heather Y. Lin, Luc Girard, Monique B. Nilsson, George Simon, Jing Wang, Kevin R. Coombes, J. Jack Lee, Waun Ki Hong, John Heymach, John D. Minna, Ignacio I. Wistuba
Journal: Clinical Cancer Research (2014)

Abstract Purpose: To investigate the mechanisms of regulation and role associated with enhancer of zeste homolog 2 (EZH2) expression in lung cancer cells. Experimental Design: We investigated the mechanisms of EZH2 expression associated with the VEGF/VEGFR-2 pathway. Furthermore, we sought to determine the role of EZH2 in response of lung adenocarcinoma to platinum-based chemotherapy, as well as the effect of EZH2 depletion on VEGFR-2–targeted therapy in lung adenocarcinoma cell lines. In addition, we characterized EZH2 expression in lung adenocarcinoma specimens and correlated it with patients' clinical characteristics. Results: In this study, we demonstrate that VEGF/VEGFR-2 activation induces expression of EZH2 through the upregulation of E2F3 and hypoxia-inducible factor-1α (HIF1α), and downregulated expression of miR-101. EZH2 depletion by treatment with 3-deazaneplanocin A and knockdown by siRNA decreased the expression of EZH2 and H3K27me3, increased PARP-C level, reduced cell proliferation and migration, and increased sensitivity of the cells to treatment with cisplatin and carboplatin. In addition, high EZH2 expression was associated with poor overall survival in patients who received platinum-based adjuvant therapy, but not in patients who did not receive this therapy. Furthermore, we demonstrated for the first time that the inhibition of EZH2 greatly increased the sensitivity of lung adenocarcinoma cells to the anti–VEGFR-2 drug AZD2171. Conclusion: Our results suggest that the VEGF/VEGFR-2 pathway plays a role in regulation of EZH2 expression via E2F3, HIF1α, and miR-101. EZH2 depletion decreases the malignant potential of lung adenocarcinoma and sensitivity of the cells to both platinum-based and VEGFR-2–targeted therapy. Clin Cancer Res; 20(14); 3849–61. ©2014 AACR.
Endothelial cell transformation in primary biliary cirrhosis: A morphological and biochemical study
Authors: Christopher Babbs, Najib Y. Haboubi, Jonathan M. Mellor, Alexander Smith, Brenda P. Rowan, Thomas W. Warnes
Journal: Hepatology (1990)

There is increasing interest in the changes of the endothelial lining of the hepatic sinusoids during the development of chronic liver disease. In this study we looked for evidence of hepatic sinusoidal endothelial cell transformation and basement membrane production in patients with primary biliary cirrhosis. Morphological transformation to vascular-type endothelial cells, as evidenced by the development of positive immunohistochemical staining for factor VIII-related antigen, was seen at the interface between portal tracts or fibrous septae and hepatic parenchyma; the most marked changes were observed in patients with established cirrhosis. Increased immunohistochemical staining for the basement membrane components type IV collagen and laminin was also found in a similar distribution. Raised serum levels of hyaluronic acid, a glycosaminoglycan metabolized by normal hepatic endothelial cells, were found in most patients and correlated strongly with advancing histological stage. Furthermore, significant positive correlations were found between serum hyaluronic acid and serum levels of laminin and type IV collagen. The unique structure of the normal endothelial lining of the hepatic sinusoids is important in the maintenance of hepatic function. Our data show that significant changes in endothelial cell structure and function occur in primary biliary cirrhosis and appear to be a contributing factor to the progression of the disease. Further studies are needed to determine the extent and importance of these changes in other forms of chronic liver disease.(HEPATOLOGY 1990; 11:723-729.)
Serum Concentrations of Antibodies Against Vaccine Toxoids in Children Exposed Perinatally to Immunotoxicants
Authors: Carsten Heilmann, Esben Budtz-Jørgensen, Flemming Nielsen, Birger Heinzow, Pál Weihe, Philippe Grandjean
Journal: Environmental Health Perspectives (2010)

Polychlorinated biphenyls (PCBs) may cause immunotoxic effects, but the detailed dose-response relationship and possible vulnerable time windows of exposure are uncertain. In this study we applied serum concentrations of specific antibodies against childhood vaccines as sentinels of immunotoxicity.The main objective was to assess the possible dependence of antibody concentrations against diphtheria and tetanus toxoids in children with regard to prenatal and postnatal PCB exposures.From a cohort of 656 singleton births formed in the Faroe Islands during 1999-2001, children were invited for examination with assessment of serum antibody concentrations at 5 years (before and after a booster vaccination) and at 7 years of age. Total PCB concentrations were determined in serum from ages 5 and 7 years, and data were also available on PCB concentrations in maternal pregnancy serum, maternal milk, and, for a subgroup, the child's serum at 18 months of age.A total of 587 children participated in the examinations at ages 5 and/or 7 years. At age 5 years, before the booster vaccination, the antidiphtheria antibody concentration was inversely associated with PCB concentrations in milk and 18-month serum. Results obtained 2 years later showed an inverse association of concentrations of antibodies against both toxoids with PCB concentrations at 18 months of age. The strongest associations suggested a decrease in the antibody concentration by about 20% for each doubling in PCB exposure. At age 5 years, the odds of an antidiphtheria antibody concentration below a clinically protective level of 0.1 IU/L increased by about 30% for a doubling in PCB in milk and 18-month serum.Developmental PCB exposure is associated with immunotoxic effects on serum concentrations of specific antibodies against diphtheria and tetanus vaccinations. The immune system development during the first years of life appears to be particularly vulnerable to this exposure.
1204 THE PEPSI PROJECT: HCV RESISTANCE SCREENING AND PREDICTION OF PI-CONTAINING THERAPY OUTCOME
Authors: A.M. Sirkoski, S. Sierra, N. Qurishi, B. Bagel, E.S. Schelhorn, T. Lengauer, A. Erhardt, T. Goeser, S. Esser, D. Häussinger, J. Timm, S. Ciesek, S. Scholte, U. Protzer, R. Kaiser
Journal: Journal of Hepatology (2013)
Apoptosis of Cardiac Myocytes in Gsα Transgenic Mice
Authors: Yong-Jian Geng, Yoshihiro Ishikawa, Dorothy E. Vatner, Thomas E. Wagner, Sanford P. Bishop, Stephen F. Vatner, Charles J. Homcy
Journal: Circulation Research (1999)

Abstract —The stimulatory GTP-binding protein Gsα transmits signals from catecholamine receptors to activate adenylyl cyclase and thereby initiate a cascade leading to cardiac chronotropy and inotropy. Transgenic mice overexpressing the Gs α subunit (Gsα) selectively in their hearts exhibit increased cardiac contractility in response to β-adrenergic receptor stimulation. However, with aging, these mice develop a cardiomyopathy. This study sought morphological and biochemical evidence that overexpression of Gsα is associated with increased myocyte apoptosis in the older animals and to determine whether such overexpression can promote apoptosis of isolated neonatal cardiac myocytes exposed to β-adrenergic receptor agonists. In the hearts of 15- to 18-month-old Gsα transgenic mice, histochemistry and electron microscopy illustrated the existence of numerous myocytes with abnormal nuclei embedded in collagen-rich connective tissue. Terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL, for in situ labeling of DNA breaks) demonstrated that ≈0.6% of myocyte nuclei contained fragmented DNA. Agarose gel electrophoresis provided further biochemical evidence of apoptosis by showing internucleosomal DNA fragmentation. Cultured cardiac myocytes from newborn Gsα transgenic mice showed increased TUNEL staining and internucleosomal DNA fragmentation compared with wild-type controls when treated with the β-agonist isoproterenol. Thus, enhanced activation of β-adrenergic signaling by overexpression of Gsα in the hearts of transgenic mice induces apoptosis of cardiac myocytes. This represents a potential mechanism that may contribute to the development of cardiomyopathy in this model.
A gene expression signature for recent onset rheumatoid arthritis in peripheral blood mononuclear cells
Authors: N Olsen
Journal: Annals of the Rheumatic Diseases (2004)

In previous studies the presence of a distinct gene expression pattern has been shown in peripheral blood cells from patients with autoimmune disease.To determine whether other specific signatures might be used to identify subsets of these autoimmune diseases and whether gene expression patterns in early disease might identify pathogenetic factors.Peripheral blood mononuclear cells were acquired from patients with rheumatoid arthritis (RA) and analysed by microarrays containing over 4300 named human genes. Patients with RA for <2 years were compared with subjects with longstanding RA (average duration 10 years) and with patients with other immune or autoimmune diagnoses.Cluster analyses permitted separation of the patients with early RA (ERA) from those with longstanding disease. Comparison with other patient groups suggested that the ERA signature showed some overlap with that seen in the normal immune response to viral antigen as well as with a subset of patients with systemic lupus erythematosus.The ERA signature may reflect, in part, a response to an unknown infectious agent. Furthermore, shared features with some lupus patients suggest that common aetiological factors and pathogenetic pathways may be involved in these two autoimmune disorders.
Chylothorax, chylopericardium and lymphoedema – the presenting features of signet‐ring cell carcinoma
Authors: N. Mogulkoc, B. Önal, N. Okyay, Ö. Günel, Ü. Bayindir
Journal: European Respiratory Journal (1999)

This report describes a patient with chylous pleural and pericardial effusions in conjunction with severe lymphoedema resembling elephantiasis. The chylous effusions and generalized lymphoedema were associated with a signet-ring cell carcinoma.
Pituitary Pigmentary Hormones
Authors: J. David Brown
Journal: JAMA (1978)

Pituitary control of pigmentation has been known for more than 60 years. Since 1969, β-melanocyte-stimulating hormone (β-MSH) has been accepted as the main pituitary pigmentary hormone in man. Its "constant companionship" with adrenocorticotrophic hormone (ACTH) has also been repeatedly demonstrated. Current investigations challenge both of these concepts. Human β-MSH immunoreactivity has been shown to be actually due to β-lipotropic hormone (β-LPH), a larger molecule that within itself contains the entire amino acid sequence of β-MSH. Human β-MSH does not exist in vivo; it is merely an extraction artifact formed by enzymatic degradation of β-LPH. It would appear likely that β-LPH, not β-MSH, is the constant companion of ACTH. (<i>JAMA</i>240:1273-1278, 1978)