tbuckley/cabot-search huggingface dataset:
Treatment of Obesity in Children
Authors: Albert J. Stunkard
Journal: JAMA (1990)

Two propositions about obesity are generally accepted: fat children grow into fat adults,<sup>1,2</sup>and weight lost in treatment programs is promptly regained.<sup>3</sup> It is against this background that the 10-year follow-up of treatment of obese children, reported by Epstein and colleagues<sup>4</sup>in this issue ofThe Journal, must be considered. For this study showed that obese children treated for a very short period of time (eight weekly meetings followed by six monthly meetings) showed effects of treatment 10 years later, when they were significantly less obese than children in a comparison group. How are we to explain these surprising results? Three possible explanations seem unlikely. Differential attrition between treatment and control groups is always a possibility in long-term follow-up studies, and there was some attrition in this study. The attrition, however, was limited—only 14 of 75 children became unavailable for follow-up—and it was distributed about evenly among
Toxocara-induced eosinophilic inflammation. Airway function and effect of anti-IL-5.
Authors: J Buijs, M W Egbers, W H Lokhorst, H F Savelkoul, F P Nijkamp
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The immunoinflammatory response to parasitic nematode infections and allergic diseases have some similarities, the most profound being the increases in eosinophils and serum total IgE concentration. Whether parasitic infections stimulate or inhibit allergic asthma is a matter of debate. We investigated the effect of Toxocara canis (T. canis) infection on airway function in BALB/c mice at various days post-infection. Within 24 h after infection, the trachea responded hyperreactive to carbachol stimulation. Eosinophils, and to a lesser degree lymphocytes, infiltrated the airways causing interstitial and alveolar inflammation (7 d post-infection). Concurrently with cell infiltration, the trachea became hyporesponsive to carbachol whereas the pulmonary resistance was increased and the dynamic compliance decreased. The hyporeactive response could be simulated in vitro by incubating normal tracheae with eosinophil-enriched bronchoalveolar lavage cells obtained from infected mice. The response depended on the number of cells added to the medium, a lower number causing a hyper- and a higher number a hyporeactive response. Anti-interleukin-5 (anti-IL-5) producing hybridoma cells given simultaneously with T. canis infection inhibited eosinophil infiltration in the airways but not that of lymphocytes. Anti-IL-5 treatment prevented tracheal hyporeactivity but not perivascular and peribronchial edema, increased pulmonary resistance, or decreased dynamic compliance. Treatment with isotype control antibody did not affect eosinophil number nor the observed changes in airway functions. It was concluded that T. canis-induced airway inflammation coincided with increased pulmonary resistance, decreased dynamic compliance, and perivascular/peribronchial edema. These phenomena were independent on the presence of eosinophils, whereas tracheal hyporeactivity was clearly associated with airway eosinophilia.
Book Review Contagion and Chaos: Disease, Ecology, and National Security in the Era of Globalization By Andrew T. Price-Smith. 281 pp. Cambridge, MA, MIT Press, 2009. $48 (cloth); $24 (paper). 978-0-262-16248-7 (cloth); 978-0-262-66203-1 (paper).
Authors: Jesse M. Klempner, Mark S. Klempner
Journal: New England Journal of Medicine (2009)
Cell-mediated immunity in patients with cystic fibrosis.
Authors: A Gibbons, J D Allan, A Holzel, H McFarlane
Journal: BMJ (1976)

Leucocytes from 26 patients with cystic fibrosis (CF) and 18 healthy controls were investigated by migration inhibition induced by a variety of antigens. In patients with CF cell-mediated immunity was found to human lung and pancreatic tissue extracts as well as to Aspergillus fumigatus, Pseudomonas aeruginosa, and food antigens but not to brain, heart, or kidney. Those patients with the severest form of the disease had the greatest impairment of cell-mediated immunity, but this impairment could be reversed by steroid treatment. Cell-mediated cytotoxicity may also be concerned in the pathogenesis of CF.
The transcription repressors Bach2 and Bach1 promote B cell development by repressing the myeloid program
Authors: Ari Itoh-Nakadai, Reina Hikota, Akihiko Muto, Kohei Kometani, Miki Watanabe-Matsui, Yuki Sato, Masahiro Kobayashi, Atsushi Nakamura, Yuichi Miura, Yoko Yano, Satoshi Tashiro, Jiying Sun, Tomokatsu Ikawa, Kyoko Ochiai, Tomohiro Kurosaki, Kazuhiko Igarashi
Journal: Nature Immunology (2014)
Wide variation in institutional transesophageal echo utilization affects its apparent value: From V.O.T.E. I
Authors: MaryAnn McLaughlin, Ravin Davidoff, Benico Barzilai, Steve Schwartz, Michael Picard, Shunichi Homma, Paul Tunick, Michael Motro, Zvi Vered, Anthony DeMaria, Howard Dittrich, Steven Goldstein, Itzhak Kronzon, David Vorchheimer, Larry Baruch, Orna David, Martin E. Goldman
Journal: Journal of the American College of Cardiology (1996)
The unacceptable face of tipping.
Authors: D C Currie, D Gaskell, P J Cole
Journal: BMJ (1987)

This type of effect is analogous with tumour chemotherapy in the sense that the greater the decrease in tumour burden the longer the remission expected.The more favourable responses obtained in Paget's disease in patients with more complete biochemical responses may reflect the ablation of an abnormal osteoclast population.This phenomenon, together with the associated clinical im- provements, suggests that indications for medical treatment will continue to increase and that treat- ment strategies for the future should include more meticulous attention to maximal suppression of disease activity.
Ethanol metabolism alters interferon gamma signaling in recombinant HepG2 cells
Authors: Natalia A. Osna, Dahn L. Clemens, Terrence M. Donohue
Journal: Hepatology (2005)

Abstract We previously showed that IFNγ signal transduction was suppressed by ethanol in recombinant HepG2 cells (VL-17A cells), which express alcohol dehydrogenase (ADH) and CYP2E1. We examined the mechanisms by which STAT1 phosphorylation is blocked by ethanol treatment in VL-17A cells. Cells were exposed to 0 or 100 mmol/L ethanol for 72 hours. STAT1 phosphorylation was determined by Western blot after 1 hour IFNγ exposure. Reduction of STAT1 phosphorylation by ethanol was prevented in the presence of 4MP, DAS, or uric acid, indicating that the oxidative products from ethanol metabolism were partly responsible for suppression of STAT1 phosphorylation. Ethanol exposure decreased STAT1 tyrosine phosphorylation, whereas serine phosphorylation on the protein was unchanged. These effects of ethanol were mimicked by the peroxynitrite (PN) donor, SIN-1, which also blocked tyrosine, but not serine phosphorylation, on STAT1. When cells expressing either ADH (VA-13 cells) or CYP2E1 (E-47 cells) were exposed to ethanol, both ADH- and CYP2E1-generated products reduced STAT1 phosphorylation. In addition, SOCS1, a negative regulator of IFNγ signaling and which is degraded by the proteasome, was stabilized by ethanol treatment, presumably because of inhibited proteasome activity. Furthermore, SIN-1 treatment elevated SOCS1 levels in VL-17A cells, indicating that PN has a role in SOCS1 elevation. In conclusion , under conditions of ethanol-elicited oxidative stress, PN prevents STAT1 phosphorylation by stabilization of SOCS1, and possibly by nitration of tyrosine residues in STAT1 protein. (Hepatology 2005;42:1109–1117.)
Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen.
Authors: B S Prabhakar, G P Allaway, J Srinivasappa, A L Notkins
Journal: Journal of Clinical Investigation (1990)

The Ku complex, a heterodimer of 86- and 70-kD proteins, is a nuclear DNA-binding autoantigen. However, hydrophobicity analysis of the deduced amino acid sequence of the 70-kD protein had strongly suggested that this might also be a membrane protein. In the present study, using antibodies to synthetic peptides and a polyclonal antiserum to the purified protein, we show that the 70-kD protein of the Ku complex is present in isolated plasma membranes of human cells. By indirect immunofluorescence microscopy and fluorescein-activated cell sorting, we demonstrate that this autoantigen is exposed on the cell surface. In addition, we have identified several domains of the protein that are exposed. Our study provides one of the first demonstrations of a eukaryotic, nuclear DNA-binding protein that is also on the cell membrane. Moreover, our results might help explain how autoantibodies to the Ku autoantigen could target cells for an autoimmune attack.
Microvessel development following therapeutic angiogenesis with vascular endothelial growth factor (VEGF) in a rat model of Hindlimb ischemia
Authors: S. Takeshita, T. Isshiki, Y. Miyazawa, K. Eto, M. Ochiai, E. Tanaka, H. Mori, T. Sato
Journal: Journal of the American College of Cardiology (1998)
CONJUGATED AMINO ACIDS IN PLASMA OF PATIENTS WITH UREMIA*
Authors: George W. Frimpter, David D. Thompson, E. Hugh Luckey
Journal: Journal of Clinical Investigation (1961)

In patients with renal insufficiency, the elevated plasma nonprotein nitrogen cannot be accounted for solely by the rise in the urea nitrogen (2). It is known that other nitrogenous materials such as creatinine and uric acid contribute to this elevation. Since free amino acids also contribute to the nonprotein, nonurea nitrogen of plasma, several investigators have determined the amino acid composition of plasma from both normal subjects and patients with uremia. They have shown that in uremia, concentrations of the individual plasma are normal or that such alterations in concentrations as exist are slight and probably insignificant (3-7). In addition, the total a-amino nitrogen in plasma of patients with uremia remains approximately normal (3-10). However, studies in which deproteinized plasma was hydrolyzed revealed that some anmino acids are variably increased in concentration (34). These findings suggested the presence of one or more amino acid conjugates in the plasma of patients with uremia. The investigations described in this paper were undertaken to characterize further the amino acid conjugates in the plasma of patients with uremia. The general plan of the study consisted of measurement of a-amino nitrogen in deproteinized plasma of normal subjects, and of patients with uremia before and after hydrolysis. By means
High-risk Melanoma Susceptibility Genes and Pancreatic Cancer, Neural System Tumors, and Uveal Melanoma across GenoMEL
Authors: Alisa M. Goldstein, May Chan, Mark Harland, Elizabeth M. Gillanders, Nicholas K. Hayward, Marie-Francoise Avril, Esther Azizi, Giovanna Bianchi-Scarra, D. Timothy Bishop, Brigitte Bressac-de Paillerets, William Bruno, Donato Calista, Lisa A. Cannon Albright, Florence Demenais, David E. Elder, Paola Ghiorzo, Nelleke A. Gruis, Johan Hansson, David Hogg, Elizabeth A. Holland, Peter A. Kanetsky, Richard F. Kefford, Maria Teresa Landi, Julie Lang, Sancy A. Leachman, Rona M. MacKie, Veronica Magnusson, Graham J. Mann, Kristin Niendorf, Julia Newton Bishop, Jane M. Palmer, Susana Puig, Joan A. Puig-Butille, Femke A. de Snoo, Mitchell Stark, Hensin Tsao, Margaret A. Tucker, Linda Whitaker, Emanuel Yakobson
Journal: Cancer Research (2006)

Abstract GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, c.IVS2-105A&amp;gt;G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P &amp;lt; 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available. (Cancer Res 2006; 66(20): 9818-28)
Suspected Obstructive Jaundice: A Decision Analysis of Diagnostic Strategies
Authors: JAMES M. RICHTER
Journal: Annals of Internal Medicine (1983)

Clinical decision analysis and a computer model were used to evaluate ten diagnostic strategies for the diagnosis of extrahepatic obstructive jaundice. The sensitivity, specificity, complications, and costs of currently used individual tests were used to determine the overall sensitivity, specificity, complications, and costs of each strategy at different disease prevalences. In patients with a low probability of extrahepatic obstructive jaundice (≤ 20%), the optimal strategy begins with ultrasonography, followed by a cholangiogram when dilated ducts are present. When dilated ducts are not present, patients may be observed clinically and endoscopic retrograde cholangiopancreatography is done if the jaundice does not resolve. In patients with a higher probability of extrahepatic obstructive jaundice, a cholangiogram is needed for an accurate diagnosis. In patients with a low probability of extrahepatic obstructive jaundice, the optimal strategy has an overall sensitivity of 92% and a specificity of 99%. About 40% of patients need a cholangiogram at an average cost of $1000 per patient. In patients with a higher probability of extrahepatic obstructive jaundice, the optimal strategy has an overall sensitivity of 97%, specificity of 98%, and cost of $1000 to $1200 per patient.
Three quarters of delegates drove to conference on impact of environment on health
Authors: B. Hanratty, W. Patterson
Journal: BMJ (1998)

EDITOR—A conference was organised recently in Northern and Yorkshire region to promote joint working between health and local authorities on environmental issues. As the delegates would include potential leaders of any resulting initiatives we were interested to see how they travelled to the conference. Travel information was sent out before the event, and the venue was chosen for its accessibility: it was on a bus route and a short walk from the railway station.

A question on the conference evaluation form asked about the method of transport …
Increasing GP numbers is not that simple
Authors: S. R. Thornton
Journal: BMJ (2014)

Respiratory motion can potentially reduce accuracy in anatomic and functional image fusion from multimodality systems. It can blur the uptake of small lesions and lead to significant activity underestimation. Solutions presented to date include respiration-synchronized anatomic and functional acquisitions. To increase the signal-to-noise ratio of the synchronized PET images, methods using nonrigid transformations during the reconstruction process have been proposed. In most of these methods, 4-dimensional (4D) CT images were used to derive the required deformation matrices. However, variations between acquired 4D PET and corresponding CT image series due to differences in respiratory conditions during PET and CT acquisitions have been reported. In addition, the radiation dose burden resulting from a 4D CT acquisition may not be justifiable for every patient. <b>Methods:</b> In this paper, we present a method for the generation of dynamic CT images from the combination of one reference CT image and deformation matrices obtained from the elastic registration of 4D PET images not corrected for attenuation. On the one hand, our approach eliminates the need for the acquisition of dynamic CT. On the other hand, it also ensures a good match between CT and PET images, allowing accurate attenuation correction to be performed for respiration-synchronized PET acquisitions. <b>Results:</b> The proposed method was first validated on Monte Carlo–simulated datasets, and then on patient datasets (<i>n</i> = 4) by comparing generated 4D CT images with the corresponding acquired original CT images. Different levels of PET image statistical quality were considered in order to investigate the impact of image noise in the derivation of the 4D CT series. <b>Conclusion:</b> Our results suggest that clinically relevant PET acquisition times can be used for the implementation of such an approach, making this an even more attractive solution considering the absence of the extra dose given by a standard 4D CT acquisition. Finally, this approach may be applicable to other multimodality devices such as PET/MR.
Intracoronary urokinase for intracoronary thrombus accumulation complicating percutaneous transluminal coronary angioplasty in acute ischemic syndromes.
Authors: G Schieman, B M Cohen, J Kozina, J S Erickson, R A Podolin, K L Peterson, J Ross, M Buchbinder
Journal: Circulation (1990)

Intracoronary urokinase was used to treat flow-limiting intracoronary thrombus accumulation that complicated successful percutaneous transluminal coronary angioplasty (PTCA) during acute ischemic syndromes in 48 patients who were followed up through the acute phase of their illness. The study group comprised 10 patients with unstable angina pectoris, 18 patients with an evolving acute myocardial infarction, and 20 patients with postinfarction angina. The initial mean percent coronary diameter stenosis for the entire population was 95 +/- 7% and decreased with initial PTCA to 41 +/- 20% (p less than 0.001), with improved corresponding coronary flow by Thrombolysis in Myocardial Infarction trial (TIMI) grade. However, thrombus accumulation then resulted in a significant increase in percent diameter stenosis to 83 +/- 17% (p less than 0.001); a corresponding significant reduction in coronary flow also occurred by TIMI grade. After administration of intracoronary urokinase (mean dose, 141,000 units; range, 100,000-250,000 units during an average period of 34 minutes), with additional PTCA, mean percent diameter stenosis significantly decreased to 34 +/- 17% (p less than 0.001); a correspondingly significant improvement in mean coronary flow by TIMI grade occurred to 2.9 +/- 0.2. Overall, the angiographic success rate was 90%. There were no ischemic events requiring repeat PTCA and no procedure-related myocardial infarctions or deaths before hospital discharge. One patient was referred for urgent coronary artery bypass graft surgery after a successful PTCA. Plasma fibrinogen levels were obtained in 15 patients, and in no patient was the level below normal for our laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)
35 In vivo inhibition of HBV infection by acylated pres peptides in the urokinase-type plasminogen activator (UPA) mouse model
Authors: J. Petersen, M. Dandri, M. Lütgehetmann, T. Volz, W. Mier, U. Haberkorn, F. von Weizsäcker, P. Gripon, S. Urban
Journal: Journal of Hepatology (2006)
A New Mechanism of Exogenous Hyperglyceridemia
Authors: C. J. Glueck, A. P. Kaplan, R. I. Levy, H. Greten, H. Gralnick, D. S. Fredrickson
Journal: Annals of Internal Medicine (1969)

Exogenous hypertriglyceridemia in two patients with systemic lupus erythematosus and one with lymphoma was associated with depression of plasma postheparin lipolytic activity and specifically the activity of triglyceride lipase and monoglyceride hydrolase. Larger doses of heparin elevated plasma lipolytic enzyme activities into the normal range and promoted clearing of chylomicrons. Resistance to the action of heparin was also seen in the coagulation system in vivo and in vitro by lack of prolongation of thrombin and coagulation times. IgG isolated from plasma of the patients with lupus and IgA: IgM from the lymphoma patient preferentially bound 3H-heparin, and removal of IgM from the latter fraction caused loss of binding activity. Preincubation of heparin with these fractions depressed the effect of heparin on release of rat adipose tissue lipoprotein lipase and prolongation of the thrombin time in vitro. The association of heparin-binding immunoglobulins with exogenous hyperlipoproteinemia adds support to a role of endogenous heparin in the maintenance of tissue lipolysis and the removal of triglycerides from plasma.
Cytokine profiles in spontaneously regressing basal cell carcinomas
Authors: D.A. Wong, G.A. Bishop, M.A. Lowes, B. Cooke, R.ST.C. Barnetson, G.M. Halliday
Journal: British Journal of Dermatology (2000)

Background Basal cell carcinomas (BCCs) can cause considerable morbidity due to their ability to enlarge progressively and to destroy underlying tissues. However, some BCCs may undergo spontaneous regression in the absence of therapy capable of inducing antineoplastic effects. Histological criteria for this process have been described, and previous studies have suggested that it may be mediated by infiltrating activated CD4-positive T cells. Objectives The purpose of this study was to compare the expression of cytokines in actively regressing and non-regressing BCCs, to ascertain if active regression is associated with a particular cytokine profile. Methods Reverse transcriptase–polymerase chain reaction, a sensitive, quantitative technique allowing analysis of multiple cytokines from small tumour samples, was used. Results Interferon (IFN)-γ was significantly elevated in actively regressing BCCs compared with non-regressing BCCs. Furthermore, interleukin (IL)-2, tumour necrosis factor (TNF)-β and CD3δ tended to be elevated in actively regressing tumours, although not to statistically significant levels. IFN-γ, IL-2, IL-10, TNF-β, granulocyte-macrophage colony-stimulating factor and Fas ligand showed strong positive correlations with CD3δ, indicating an association between infiltrating T cells and these cytokines. Conclusions These findings support a role for T-helper 1 type cytokines in mediating spontaneous regression of BCCs.
Trefoil Peptides in the Defense of the Gastrointestinal Tract
Authors: A G Plaut
Journal: New England Journal of Medicine (1997)

Microorganisms and other agents continually threaten the intestinal mucosa, calling for the gut to prevent damage, restore epithelium in regions in which cells are lost, and suppress inflammation. How does the intestine tackle these problems? Although cytokines deep in the lamina propria moderate immune responses and inflammatory injury, other repair factors operate on the apical side of the epithelial cells — the front line where mucosa and the outside world really interact. Since restoration of epithelial continuity occurs early in mucosal healing, agents that help reseal mucosal wounds must undoubtedly influence cell proliferation and perhaps accelerate the migration of proliferating . . .