tbuckley/cabot-search huggingface dataset:
Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo
Authors: Michael Schnoor, Frank P.L. Lai, Alexander Zarbock, Ruth Kläver, Christian Polaschegg, Dörte Schulte, Herbert A. Weich, J. Margit Oelkers, Klemens Rottner, Dietmar Vestweber
Journal: The Journal of Experimental Medicine (2011)

Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation–promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor–stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β2-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1–enriched contact areas and for transendothelial migration, the ICAM-1–mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.
Persistent Wheezing in Very Young Children Is Associated with Lower Respiratory Inflammation
Authors: MARZENA E. KRAWIEC, JAY Y. WESTCOTT, HONG WEI CHU, SILVANA BALZAR, JOHN B. TRUDEAU, L. B. SCHWARTZ, SALLY E. WENZEL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Despite advances in understanding the pathophysiology of asthma, morbidity and mortality in pediatrics continue to rise. Little is known about the initiation and chronicity of inflammation resulting in asthma in this young population. We evaluated 20 “wheezing” children (WC) (median age 14.9 mo) with a minimum of two episodes of wheezing or prolonged wheezing ⩾ 2 mo in a 6-mo period with bronchoscopy and bronchoalveolar lavage (BAL). Comparisons were made with six normal controls (NC) (median age 23.3 mo) undergoing general anesthesia for elective surgery. BAL fluid cell counts and differentials were determined. The eicosanoids, leukotriene (LT) B4, LTE4, prostaglandin (PG)E2, and 15-hydroxyeicosatetraenoic acid (HETE) and the mast cell mediators, β -tryptase and PGD2, were evaluated by enzyme immunoassay (EIA). WC had significant elevations in total BAL cells / ml (p = 0.01), as well as, lymphocytes (LYMPH, p = 0.007), macrophages / monocytes (M&M, p = 0.02), polymorphonuclear cells (PMN, p = 0.02), epithelial cells (EPI, p = 0.03), and eosinophils (EOS, p = 0.04) compared with NC. Levels of PGE2 (p = 0.0005), 15-HETE (p = 0.002), LTE4 (p = 0.04), and LTB4 (p = 0.05) were also increased in WC compared with NC, whereas PGD2 and β -tryptase were not. This study confirms that inflammation is present in the airways of very young WC and may differ from patterns seen in adults with asthma.
Comparative sequence analyses reveal sites of ancestral chromosomal fusions in the Indian muntjac genome
Authors: Vicky Tsipouri, Mary G Schueler, Sufen Hu, Nisc Comparative Sequencing Program, Amalia Dutra, Evgenia Pak, Harold Riethman, Eric D Green
Journal: Genome biology (2008)

Indian muntjac (Muntiacus muntjak vaginalis) has an extreme mammalian karyotype, with only six and seven chromosomes in the female and male, respectively. Chinese muntjac (Muntiacus reevesi) has a more typical mammalian karyotype, with 46 chromosomes in both sexes. Despite this disparity, the two muntjac species are morphologically similar and can even interbreed to produce viable (albeit sterile) offspring. Previous studies have suggested that a series of telocentric chromosome fusion events involving telomeric and/or satellite repeats led to the extant Indian muntjac karyotype. We used a comparative mapping and sequencing approach to characterize the sites of ancestral chromosomal fusions in the Indian muntjac genome. Specifically, we screened an Indian muntjac bacterial artificial-chromosome library with a telomere repeat-specific probe. Isolated clones found by fluorescence in situ hybridization to map to interstitial regions on Indian muntjac chromosomes were further characterized, with a subset then subjected to shotgun sequencing. Subsequently, we isolated and sequenced overlapping clones extending from the ends of some of these initial clones; we also generated orthologous sequence from isolated Chinese muntjac clones. The generated Indian muntjac sequence has been analyzed for the juxtaposition of telomeric and satellite repeats and for synteny relationships relative to other mammalian genomes, including the Chinese muntjac. The generated sequence data and comparative analyses provide a detailed genomic context for seven ancestral chromosome fusion sites in the Indian muntjac genome, which further supports the telocentric fusion model for the events leading to the unusual karyotypic differences among muntjac species.
Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in Healthy Volunteers: Safety, Pharmacokinetics, and Effect on the Insulin-like Growth Factor Axis
Authors: Victoria A. Brown, Ketan R. Patel, Maria Viskaduraki, James A. Crowell, Marjorie Perloff, Tristan D. Booth, Grygoriy Vasilinin, Ananda Sen, Anna Maria Schinas, Gianfranca Piccirilli, Karen Brown, William P. Steward, Andreas J. Gescher, Dean E. Brenner
Journal: Cancer Research (2010)

Resveratrol, a naturally occurring polyphenol, has cancer chemopreventive properties in preclinical models. It has been shown to downregulate the levels of insulin-like growth factor-1 (IGF-I) in rodents. The purpose of the study was to assess its safety, pharmacokinetics, and effects on circulating levels of IGF-I and IGF-binding protein-3 (IGFBP-3) after repeated dosing. Forty healthy volunteers ingested resveratrol at 0.5, 1.0, 2.5, or 5.0 g daily for 29 days. Levels of resveratrol and its metabolites were measured by high performance liquid chromatography-UV in plasma obtained before and up to 24 hours after a dose between days 21 and 28. IGF-I and IGFBP-3 were measured by ELISA in plasma taken predosing and on day 29. Resveratrol was safe, but the 2.5 and 5 g doses caused mild to moderate gastrointestinal symptoms. Resveratrol-3-O-sulfate, resveratrol-4'-O-glucuronide, and resveratrol-3-O-glucuronide were major plasma metabolites. Maximal plasma levels and areas under the concentration versus time curve for the metabolites dramatically exceeded those for resveratrol, in the case of areas under the concentration versus time curve, by up to 20.3-fold. Compared with predosing values, the ingestion of resveratrol caused a decrease in circulating IGF-I and IGFBP-3 (P<0.04 for both), respectively, in all volunteers. The decrease was most marked at the 2.5 g dose level. The results suggest that repeated administration of high doses of resveratrol generates micromolar concentrations of parent and much higher levels of glucuronide and sulfate conjugates in the plasma. The observed decrease in circulating IGF-I and IGFBP-3 might contribute to cancer chemopreventive activity.
Factors regulating macrophage production and growth: identity of colony-stimulating factor and macrophage growth factor.
Authors: E R Stanley, M Cifone, P M Heard, V Defendi
Journal: The Journal of Experimental Medicine (1976)

The activities of a colony-stimulating factor (CSF), which stimulates granulocyte-macrophage colony formation by mouse hemopoietic cells, and macrophage growth factor (MGF), which stimulates proliferation of activated peritoneal macrophages, have been demonstrated by various criteria to reside in the same molecular species. These criteria include occurrence in various sources and copurification of the activities in mouse L-cell-conditioned medium as well as the biological, physicochemical, and antigenic properties of the activities of L-cell-conditioned medium. CSF and MGF activities of L-cell-conditioned medium are ascribable to a glycoprotein of mol wt approximately 60,000 which migrates electrophoretically with alpha-globulin. Human urinary CSF, which also possesses MGF activity, has similar properties and can be neutralized by antiserum to highly purified L-cell medium CSF. A procedure is described for the partial purification of material from L-cell medium that has activity at 1 ng/ml in both MGF and CSF assays.
A Long-term Prospective Population Pharmacokinetic Study on Imatinib Plasma Concentrations in GIST Patients
Authors: Karel Eechoute, Martin N. Fransson, An K. Reyners, Floris A. de Jong, Alex Sparreboom, Winette T.A. van der Graaf, Lena E. Friberg, Gaia Schiavon, Erik A.C. Wiemer, Jaap Verweij, Walter J. Loos, Ron H.J. Mathijssen, Ugo De Giorgi
Journal: Clinical Cancer Research (2012)

Imatinib minimal (trough) plasma concentrations after one month of treatment have shown a significant association with clinical benefit in patients with gastrointestinal stromal tumors (GIST). Considering that a retrospective pharmacokinetic analysis has also suggested that imatinib clearance increases over time in patients with soft tissue sarcoma and GIST, the primary aim of this study was to assess systemic exposure to imatinib at multiple time points in a long-term prospective population pharmacokinetic study. As imatinib is mainly metabolized in the liver, our secondary aim was to elucidate the potential effects of the volume of liver metastases on exposure to imatinib.Full pharmacokinetic blood sampling was conducted in 50 patients with GIST on the first day of imatinib treatment, and after one, six, and 12 months. In addition, on day 14, and monthly during imatinib treatment, trough samples were taken. Pharmacokinetic analysis was conducted using a compartmental model. Volume of liver metastases was assessed by computed tomographic (CT) imaging.After 90 days of treatment, a significant decrease in imatinib systemic exposure of 29.3% compared with baseline was observed (P < 0.01). For every 100 cm(3) increase of metastatic volume, a predicted decrease of 3.8% in imatinib clearance was observed.This is the first prospective pharmacokinetic study in patients with GIST, showing a significant decrease of approximately 30% in imatinib exposure after long-term treatment. This means that future "trough level - clinical benefit" analyses should be time point specific. GIST liver involvement, however, has a marginal effect on imatinib clearance.
A Model to Predict the Severity of Acute Pancreatitis Based on Serum Level of Amylase and Body Mass Index
Authors: Arthi Kumaravel, Tyler Stevens, Georgios I. Papachristou, Venkata Muddana, Amit Bhatt, Peter Junwoo Lee, Jordan Holmes, Rocio Lopez, David C. Whitcomb, Mansour A. Parsi
Journal: Clinical Gastroenterology and Hepatology (2015)
A Novel RET Kinase–β-Catenin Signaling Pathway Contributes to Tumorigenesis in Thyroid Carcinoma
Authors: Taranjit S. Gujral, Wendy van Veelen, Douglas S. Richardson, Shirley M. Myers, Jalna A. Meens, Dennis S. Acton, Mireia Duñach, Bruce E. Elliott, Jo W.M. Höppener, Lois M. Mulligan
Journal: Cancer Research (2008)

Abstract The RET receptor tyrosine kinase has essential roles in cell survival, differentiation, and proliferation. Oncogenic activation of RET causes the cancer syndrome multiple endocrine neoplasia type 2 (MEN 2) and is a frequent event in sporadic thyroid carcinomas. However, the molecular mechanisms underlying RET's potent transforming and mitogenic signals are still not clear. Here, we show that nuclear localization of β-catenin is frequent in both thyroid tumors and their metastases from MEN 2 patients, suggesting a novel mechanism of RET-mediated function through the β-catenin signaling pathway. We show that RET binds to, and tyrosine phosphorylates, β-catenin and show that the interaction between RET and β-catenin can be direct and independent of cytoplasmic kinases, such as SRC. As a result of RET-mediated tyrosine phosphorylation, β-catenin escapes cytosolic down-regulation by the adenomatous polyposis coli/Axin/glycogen synthase kinase-3 complex and accumulates in the nucleus, where it can stimulate β-catenin–specific transcriptional programs in a RET-dependent fashion. We show that down-regulation of β-catenin activity decreases RET-mediated cell proliferation, colony formation, and tumor growth in nude mice. Together, our data show that a β-catenin–RET kinase pathway is a critical contributor to the development and metastasis of human thyroid carcinoma. [Cancer Res 2008;68(5):1338–46]
Mast Cell Tryptases and Airway Remodeling
Authors: CHRISTIAN P. SOMMERHOFF
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Section:ChooseTop of pageAbstract <<HUMAN TRYPTASE FAMILYSTRUCTURE OF β -TRYPTASE ...REGULATION OF TRYPTASE BY...INTERACTION WITH SUBSTRAT...CONSEQUENCES OF TRYPTASE ...CONCLUSIONSReferencesCITING ARTICLES
<i>De Minimis</i>Risk: A Proposal for a New Category of Research Risk
Authors: Rosamond Rhodes, Jody Azzouni, Stefan Bernard Baumrin, Keith Benkov, Martin J. Blaser, Barbara Brenner, Joseph W. Dauben, William J. Earle, Lily Frank, Nada Gligorov, Joseph Goldfarb, Kurt Hirschhorn, Rochelle Hirschhorn, Ian Holzman, Debbie Indyk, Ethylin Wang Jabs, Douglas P. Lackey, Daniel A. Moros, Sean Philpott, Matthew E. Rhodes, Lynne D. Richardson, Henry S. Sacks, Abraham Schwab, Rhoda Sperling, Brett Trusko, Arnulf Zweig
Journal: The American Journal of Bioethics (2011)

Click to increase image sizeClick to decrease image size Acknowledgments This article derives from the "Human Microbiome and the Social Fabric" working group. Our views on the ethical, legal, and social implications of human microbiome research evolved over two years of discussion. They will be presented in a forthcoming volume to be published by Oxford University Press. Our work was funded by 1R01HG004856-01 as a component of the Human Microbiome Project, a National Institutes of Health (NIH) Common Fund initiative. We are grateful to Drs. Mark Babyatsky, Erwin Bottinger, and Marie Teil for their contribution to the group's education during the early stages of this project.
Prospective study of type 2 diabetes and cognitive decline in women aged 70-81 years
Authors: Giancarlo Logroscino, Jae Hee Kang, Francine Grodstein
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To examine the association of type 2 diabetes with baseline cognitive function and cognitive decline over two years of follow up, focusing on women living in the community and on the effects of treatments for diabetes. <b>Design</b> Nurses9 health study in the United States. Two cognitive interviews were carried out by telephone during 1995-2003. <b>Participants</b> 18 999 women aged 70-81 years who had been registered nurses completed the baseline interview; to date, 16 596 participants have completed follow up interviews after two years. <b>Main outcome measures</b> Cognitive assessments included telephone interview of cognitive status, immediate and delayed recalls of the East Boston memory test, test of verbal fluency, delayed recall of 10 word list, and digit span backwards. Global scores were calculated by averaging the results of all tests with z scores. <b>Results</b> After multivariate adjustment, women with type 2 diabetes performed worse on all cognitive tests than women without diabetes at baseline. For example, women with diabetes were at 25-35% increased odds of poor baseline score (defined as bottom 10% of the distribution) compared with women without diabetes on the telephone interview of cognitive status and the global composite score (odds ratios 1.34, 95% confidence interval 1.14 to 1.57, and 1.26, 1.06 to 1.51, respectively). Odds of poor cognition were particularly high for women who had had diabetes for a long time (1.52, 1.15 to 1.99, and 1.49, 1.11 to 2.00, respectively, for 15 years9 duration). In contrast, women with diabetes who were on oral hypoglycaemic agents performed similarly to women without diabetes (1.06 and 0.99), while women not using any medication had the greatest odds of poor performance (1.71, 1.28 to 2.281, and 1.45, 1.04 to 2.02) compared with women without diabetes. There was also a modest increase in odds of poor cognition among women using insulin treatment. All findings were similar when cognitive decline was examined over time. <b>Conclusions</b> Women with type 2 diabetes had increased odds of poor cognitive function and substantial cognitive decline. Use of oral hypoglycaemic therapy, however, may ameliorate risk.
Physical Activity and Preventing Weight Gain in Women—Reply
Authors: I-Min Lee
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Corrigendum to: Altered Na+/Ca2+-exchanger activity due to downregulation of Na+/K+-ATPase 2-isoform in heart failure
Authors: F. Swift, J. A. K. Birkeland, N. Tovsrud, U. H. Enger, J. M. Aronsen, W. E. Louch, I. Sjaastad, O. M. Sejersted
Journal: Cardiovascular Research (2008)

[ Cardiovascular Research 2008;78:71–78;doi:10.1093/cvr/cvn013]

In the print issue of Cardiovascular Research Volume 78 Number 1 (April 2008), there was an error in the colours of Figure 7C in this article following corruption of the file …
Functions of peripheral-blood monocytes and granulocytes in cutaneous T-cell lymphoma
Authors: L. HAMMINGA, P.C.J. LEIJH, A. BLUSSE OUD ALBLAS, W.A. VLOTEN, R. FURTH
Journal: British Journal of Dermatology (1982)

Granulocyte and monocyte functions (phagocytosis, intracellular killing, chemokinesis and chemotaxis) and the opsonic and chemotactic activity of the serum of twenty-two patients with cutaneous T-cell lymphoma were assessed. Granulocyte functions were within the normal control range in most cases. The monocyte functions showed more variation in the test results; in six out of twenty-two patients intracellular killing of Staphylococcus aureus was depressed and in four out of ten patients a disturbance in monocyte chemotaxis was found. Two patients with a decreased chemotactic response also had an impaired capacity to kill S. aureus. No correlation was found between the cell disturbance and susceptibility to infection, stage of the disease, or clinical course in these patients.
NF-κB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF
Authors: Bae Keun Park, Honglai Zhang, Qinghua Zeng, Jinlu Dai, Evan T Keller, Thomas Giordano, Keni Gu, Veena Shah, Lei Pei, Richard J Zarbo, Laurie McCauley, Songtao Shi, Shaoqiong Chen, Cun-Yu Wang
Journal: Nature Medicine (2006)
T cell receptor V gene usage by human T cells stimulated with the superantigen streptococcal M protein.
Authors: M A Tomai, J A Aelion, M E Dockter, G Majumdar, D G Spinella, M Kotb
Journal: The Journal of Experimental Medicine (1991)

M proteins, the major virulence factor of group A streptococci, have been implicated in the pathogenesis of acute rheumatic fever (ARF) and other streptococcal related autoimmune diseases. A 22-kD fragment of M type 5 protein is a potent stimulant of human T cells and has recently been shown by our laboratory to belong to the newly designated family of superantigens. Using flow cytometry and the polymerase chain reaction, we demonstrate that this molecule reacts with subsets of human T cells expressing specific T cell receptor (TCR) V beta elements, namely V beta 2, 4, and 8. We employed similar techniques to analyze the TCR V alpha usage of pep M5-stimulated T cells. These studies revealed that the preferential usage of particular V alpha elements is not specific for the superantigen; rather, it may reflect the repertoire of the individual being tested. The expansion of a large number of T cells bearing specific TCR V beta sequences by M protein may account for its role in mediating the pathogenesis of post-streptococcal diseases. Furthermore, the preferential usage of TCR V alpha elements in certain individuals may be an important factor that predisposes them to development of self-reactivity.
RETURN OF EPIDEMIC A1 (H1N1) INFLUENZA VIRUS
Authors: V.M Zhdanov, L.Ya Zakstelskaya, V.I Isachenko, V.I Reznik, V.P Andreyev, D.K Lvov, M.A Yakhno, N.A Braude, T.V Pysina, R.Ya Podchernyaeva
Journal: The Lancet (1978)
Early-life risk factors for chronic nonrespiratory diseases
Authors: Archana Chacko, David O. Carpenter, Leonie Callaway, Peter D. Sly
Journal: European Respiratory Journal (2014)

We have witnessed a change in disease patterns contributing to the global burden of disease, with a shift from early childhood deaths due to the classic infectious communicable diseases to years lived with disability from chronic noncommunicable diseases. In both developing and developed countries, the years lived with disability attributable to chronic disease have increased: cardiovascular diseases by 17.7%; chronic respiratory disease by 8.5%; neurological conditions by 12.2%; diabetes by 30.0%; and mental and behavioural disorders by 5.0% over the past 20 years. Recognition of the contribution made by adverse environmental exposures in early life to noncommunicable diseases in later life is increasing. These early-life exposures appear to contribute to both chronic respiratory and chronic nonrespiratory diseases. In this State of the Art article, we aim to examine early-life environmental exposures that have an epidemiological association with chronic nonrespiratory diseases, such as obesity and type II diabetes, cardiovascular disease, and neurocognitive and behavioural problems. We will highlight the potential overlap in environmental risks with respiratory diseases, and point out knowledge gaps and research opportunities.