tbuckley/cabot-search huggingface dataset:
Electronic Cigarettes May Lead to Nicotine Addiction
Authors: M. Fillon
Journal: JNCI Journal of the National Cancer Institute (2015)

Are electronic cigarettes (e-cigarettes) a relatively harmless substitute for cigarettes?Or are they a Trojan horse leading to nicotine addiction and ultimately chronic smoking?Many researchers believe the latter.E-cigarettes are battery-powered devices that deliver aerosolized nicotine and kid-friendly flavored additives, such as chocolate mint, piña colada, atomic fireball candy, and even gummy bears.Designed to mimic the look and habit of smoking, the devices are marketed as a relatively benign alternative to smoking, without the tar, carbon monoxide, and other harmful ingredients adversely affecting the heart and respiratory system."Vaping," the term for using e-cigarettes, emits only a cloud of vapor-not secondhand smoke.Many people are buying into the nonsmoking allure.E-cigarettes have quickly become a marketing marvel.In the U.S., sales escalated from 50,000 devices in 2008 to 3.5 million in 2012, fulfilling every marketing executive's dream to sell a product that customers return to repeatedly.And the younger customers start, the longer they keep buying.Most smokers begin when they're young.According to the Centers for Disease Control and Prevention (CDC) in Atlanta, nearly 90% of U.S. adult smokers began smoking by the age of 18 years.These companies' pro-e-cigarette marketing strategy seems to work.In a national survey by CDC appearing in the November 28, 2014 issue of Nicotine & Tobacco Research, 4.5% of high school students said they had used e-cigarettes in the previous month, up from 1.5% in 2011 and 2.8% in 2012.
Genome interrupted: sequencing of prostate cancer reveals the importance of chromosomal rearrangements
Authors: Akash Kumar, Jay Shendure, Peter S Nelson
Journal: Genome Medicine (2011)

A recent study involving whole genome sequencing of seven prostate cancers has provided the first comprehensive assessment of genomic changes that underlie this common malignancy. Point mutations were found to be infrequent but changes in chromosome structure were common. Rearrangements were linked to chromatin organization and associated with regions involved in transcription factor binding. Novel candidate prostate cancer genes were also identified, highlighting the importance of genome sequencing to identify oncogenic changes that are otherwise invisible to detection.
Heme Is a Carbon Monoxide Receptor for Large-Conductance Ca <sup>2+</sup> -Activated K <sup>+</sup> Channels
Authors: Jonathan H. Jaggar, Anlong Li, Helena Parfenova, Jianxi Liu, Edward S. Umstot, Alejandro M. Dopico, Charles W. Leffler
Journal: Circulation Research (2005)

Carbon monoxide (CO) is an endogenous paracrine and autocrine gaseous messenger that regulates physiological functions in a wide variety of tissues. CO induces vasodilation by activating arterial smooth muscle large-conductance Ca2+-activated potassium (BK(Ca)) channels. However, the mechanism by which CO activates BK(Ca) channels remains unclear. Here, we tested the hypothesis that CO activates BK(Ca) channels by binding to channel-bound heme, a BK(Ca) channel inhibitor, and altering the interaction between heme and the conserved heme-binding domain (HBD) of the channel alpha subunit C terminus. Data obtained using thin-layer chromatography, spectrophotometry, mass spectrometry (MS), and MS-MS indicate that CO modifies the binding of reduced heme to the alpha subunit HBD. In contrast, CO does not alter the interaction between the HBD and oxidized heme (hemin), to which CO cannot bind. Consistent with these findings, electrophysiological measurements of native and cloned (cbv) cerebral artery smooth muscle BK(Ca) channels show that CO reverses BK(Ca) channel inhibition by heme but not by hemin. Site-directed mutagenesis of the cbv HBD from CKACH to CKASR abolished both heme-induced channel inhibition and CO-induced activation. Furthermore, on binding CO, heme switches from being a channel inhibitor to an activator. These findings indicate that reduced heme is a functional CO receptor for BK(Ca) channels, introduce a unique mechanism by which CO regulates the activity of a target protein, and reveal a novel process by which a gaseous messenger regulates ion channel activity.
Comparison of the Prevalence of Wheeze, Persistent Rash and Doctor-Diagnosed Eczema in the Three South East Asian Cities of Jarkarta, Bandung and Singapore.
Authors: K. Baratawidjaja, B. Setabudiawan, Z. Munasir, N. Kurniati, T.N. Tan, D.L. Lim, B.W. Lee, H. Van Bever
Journal: Journal of Allergy and Clinical Immunology (2006)
Relation between resistance of Philadelphia-chromosome-positive acute lymphoblastic leukaemia to the tyrosine kinase inhibitor STI571 and gene-expression profiles: a gene-expression study
Authors: Wolf-K Hofmann, Sven de Vos, David Elashoff, Harald Gschaidmeier, Dieter Hoelzer, H Phillip Koeffler, Oliver G Ottmann
Journal: The Lancet (2002)
Efficacy of Alendronate in Adults with Cystic Fibrosis with Low Bone Density
Authors: Robert M. Aris, Gayle E. Lester, Melissa Caminiti, A. Denene Blackwood, Margaret Hensler, Robert K. Lark, Travis M. Hecker, Jordan B. Renner, Ursula Guillen, Sue A. Brown, Isabel P. Neuringer, Worakij Chalermskulrat, David A. Ontjes
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

As adults with cystic fibrosis (CF) have enjoyed incremental increases in longevity over the last few decades, they have also been suffering from low bone density and its clinical manifestations, fractures and kyphosis. We conducted a placebo-controlled, randomized, double-blinded trial of alendronate (10 mg/day orally) (n = 24) compared with placebo (n = 24) for 1 year in 48 patients to improve bone mineral density at the spine as the primary endpoint. All patients received 800 IU of cholecalciferol and 1,000 mg of calcium carbonate. Both groups were similar in age, sex, CF mutations, bone density T scores, renal function, and body mass index at study onset. The alendronate-treated patients gained (mean ± SD) 4.9 ± 3.0% and 2.8 ± 3.2% bone density after 1 year versus placebo, which lost (mean ± SD) 1.8 ± 4.0% and 0.7 ± 4.7%, in spine and femur bone density, respectively (p ⩽ 0.001 for the spine; p = 0.003 for the femur). Urine N-telopeptide, a bone resorption marker, levels declined in the treatment group more than in the control group (p = 0.002), consistent with the known antiresorptive effects of bisphosphonates. Alendronate was more effective than placebo in improving spine and femur bone mineral density and is a promising agent for the long-term prevention and management of bone disease in patients with CF.
Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E-cadherin in mucin core protein 5AC expression <i>in vivo</i>
Authors: H. Hata, K. Natsuga, S. Kitamura, K. Imafuku, Y. Yamaguchi, Y. Ebihara, T. Shichinohe, S. Hirano, H. Shimizu
Journal: British Journal of Dermatology (2015)

Mucin core protein (MUC) 5AC is a gel‐forming glycoprotein that is expressed in different types of tumour cells. MUC5AC expression in cultured cells is regulated through the extracellular matrix and through remodelling by other membranous proteins such as type IV collagen (COL4) and E‐cadherin. However, it has not been elucidated whether COL4 and E‐cadherin affect MUC5AC expression in tumours in vivo. Here, by analysing a single individual with concomitant neoplasms in the skin [extramammary Paget disease (EMPD)] and the stomach (gastric cancer), we show that MUC5AC expression is reduced in COL4 and membranous E‐cadherin‐expressing EMPD specimens whereas MUC5AC is not abolished in gastric cancer with COL4 negativity and E‐cadherin cytoplasmic localization. As the EMPD and gastric cancer specimens were derived from a single patient, each specimen had the same genetic background. These in vivo results support previous in vitro studies which showed that COL4 and E‐cadherin downregulated MUC5AC expression. Our study suggests that concomitant neoplasms in different organs of the same individual can serve as a strong tool for uncovering functional diversity in tumour markers in distinct cancer cells.
CD40 AND CD154 IN CELL-MEDIATED IMMUNITY
Authors: Iqbal S. Grewal, Richard A. Flavell
Journal: Annual Review of Immunology (1998)

▪ Abstract CD40-CD154–mediated contact-dependent signals between B and T cells are required for the generation of thymus dependent (TD) humoral immune responses. CD40-CD154 interactions are however also important in many other cell systems. CD40 is expressed by a large variety of cell types other than B cells, and these include dendritic cells, follicular dendritic cells, monocytes, macrophages, mast cells, fibroblasts, and endothelial cells. CD40- and CD154-knockout mice and antibodies to CD40 and CD154 have helped to elucidate the role of the CD40-CD154 system in immune responses. Recently published studies indicate that CD40-CD154 interactions can influence T cell priming and T cell–mediated effector functions; they can also upregulate costimulatory molecules and activate macrophages, NK cells, and endothelia as well as participate in organ-specific autoimmune disease, graft rejection, and even atherosclerosis. This review focuses on the role of the CD40-CD154 system in the regulation of many newly discovered functions important in inflammation and cell-mediated immunity.
The FitzPatrick Lectures ON GREEK MEDICINE IN ROME: Delivered at the Royal College of Physicians of London
Authors: T. C. Allbutt
Journal: BMJ (1909)

PRESIDENT.AND FELLows,-In calling me to deliver the FitzPatrick Lectures you have done me much honour; aid it would be an ill-timed however genuine a diffidence which might seem to disparage your election; I may, notwithstanding, hesitate for a moment as I regard the dignity of this place, and as I admire the services of my predecessors.In them we have had examples of wide and sound learning, of biographical skill and of anecdotal charm, which are above my hope, and I trust outside your comparisons.For such lists I am unarmed.
Antigen-specific T-cell-mediated suppression. I. Induction of L-glutamic acid(60)-L-alanine(30)-L-tyrosine(10) specific suppressor T cells in vitro requires both antigen-specific T-cell-suppressor factor and antigen
Authors: RN Germain, J Theze, JA Kapp, B Benacerraf
Journal: The Journal of Experimental Medicine (1978)

A combination of in vitro and in vivo techniques were used to explore the mode of action of both crude and purified suppressive extracts specific for the random copolymer L-giutamic acid(60)-L-alanine(30)-L-tyrosine(10) (GAT- T(s)F) obtained from nonresponder DBA/1 (H-2(q)) mice. Normal DBA/1 spleen cells were incubated under modified Mishell-Dutton culture conditions for 2 days together with crude or purified GAT-T(s)F, and in the presence or absence of free GAT. These cells were then washed extensively and 3 × 10(6) viable cells transferred to syngeneic recipients, which were challenged at the same time with the immunogenic form of GAT complexed to methylated bovine serum albumin (GAT-MBSA). GAT-specific IgG plaque-forming cells (PFC) in the spleen were assayed 7 days later. In agreement with earlier in vitro studies on the action of GAT-T(s)F, it was demonstrated that under these conditions, low concentrations of GAT-T(s)F stimulated the development of cells which, aider transfer, are able to suppress the GAT PFC response to GAT-MBSA. The cells responsible for this suppression were shown to be T lymphocytes by using nylon wool-purified T cells for suppressor cell induction and by eliminating suppressive activity in cells cultured with crude GAT-T(s)F by treatment with anti-Thy 1.2 plus C before transfer. The suppressor T cells act in a specific manner failing to suppress significantly either anti-sheep erythrocyte or trinitrophenyl-ovalbumin primary PFC responses. For the induction of GAT-specific suppressor T cells in culture, a moiety bearing H- 2(K(q) or I(q)) determinants and also GAT, either bound to the crude GAT- T(s)F or added in nanogram amounts to antigen (GAT)-free purified GAT-T(s)F, were both required.
Relationship between Heberden's nodes and underlying radiographic changes of osteoarthritis
Authors: A Thaper
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To determine whether clinically determined Heberden's nodes (HN) and Bouchard's nodes (BN) are associated with underlying individual radiographic changes of osteoarthritis (OA). <b>Methods:</b> 232 index patients with symptomatic large joint and/or hand OA, and 257 of their first degree relatives were included. HN were graded 0–2; BN were scored as present/absent. Joint space narrowing (JSN) and osteophyte (OST) were each scored 0–3 using the OARSI atlas. A weighted κ test was used to examine intraobserver reproducibility. Odds ratio (OR) was estimated for the relationship between nodes and associated JSN and OST. <b>Results:</b> The adjusted OR of HN for underlying JSN in the same digit was 1.72 (95% CI 1.47 to 2.02), whereas for OST it was higher at 5.15 (95% CI 4.37 to 6.08). A similar trend was seen with BN and underlying OA, with OST having a higher OR (OR = 2.98, 95% CI 2.55 to 3.47) than JSN (OR = 1.62, 95% CI 1.37 to 1.91). <b>Conclusion:</b> There is a positive relationship between HN/BN and underlying radiographic changes of OA, especially OST. Nodes do appear to link pathologically to OA in interphalangeal joints.
Aiming for SDAI remission versus low disease activity at 1 year after inclusion in ESPOIR cohort is associated with better 3-year structural outcomes
Authors: Adeline Ruyssen-Witrand, Gregory Guernec, Delphine Nigon, Gabriel Tobon, Bénédicte Jamard, Anne-Christine Rat, Olivier Vittecoq, Alain Cantagrel, Arnaud Constantin
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Using data for patients with early rheumatoid arthritis (RA) from the ESPOIR cohort, we aimed to evaluate the impact of remission versus low disease activity (LDA) by the Simple Disease Activity Index (SDAI) at 1 year on 3-year structural damage assessed by the modified Sharp–van der Heijde total score (mTSS) and functional impairment assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI). <h3>Methods</h3> We included 625 patients from the ESPOIR cohort who fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and had an SDAI score at 1 year. mTSS and HAQ-DI scores were compared at 3 years for patients with SDAI remission or LDA status at 1 year. A linear mixed model was used to assess the independent effect of SDAI status at 1 year on mTSS and HAQ-DI at 3 years. <h3>Results</h3> Of the 625 patients included (mean (SD) age 48.5 (12.1) years; 491 (78.6%) were women), 121 (19.4%) were in SDAI remission and 223 (35.7%) in LDA at 1 year. The mean (SD) mTSS and HAQ-DI score at 3 years was 9.6 (9.2) and 0.23 (0.42), respectively, for patients in remission at 1 year and 15.8 (16.1) and 0.43 (0.52), respectively, for patients with LDA (both p&lt;0.05). Multivariate analysis revealed an association of remission rather than LDA status at 1 year and reduced mTSS score (p=0.005) but not HAQ-DI score (p=0.4) at 3 years. <h3>Conclusions</h3> Aiming for SDAI remission rather than LDA at 1 year leads to better radiographic outcomes at 3 years in early RA patients.
Activation of brain macrophages/microglia cells in hepatitis C infection
Authors: J. Wilkinson, M. Radkowski, J. M. Eschbacher, T. Laskus
Journal: Gut (2010)

<h3>Objectives</h3> Hepatitis C virus (HCV) infection is commonly associated with cognitive dysfunction. Viral sequences and proteins were previously found in brain macrophage/microglia cells. The aim of the current study was to determine whether HCV infection affects the expression of key cytokines and chemokines in these cells. <h3>Methods</h3> Autopsy brain tissue from 15 patients was studied; 7 patients were HCV positive and 8 were HCV negative. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (anti-CD68) and separated by laser capture microscopy. Transcripts representing 25 various cytokines and chemokines were measured by real-time quantitative PCR. <h3>Results</h3> Compared with HCV-negative controls, HCV-positive patients demonstrated significantly higher levels of proinflammatory cytokines interleukin 1α (IL-1α), IL-1β, tumour necrosis factor α (TNFα), IL-12 and IL-18. HCV infection was also associated with increased transcription of chemokines IL-8, IL-16 and interferon-inducible protein 10 (IP-10). Type 1 interferon (IFN) activation was suggested by increased concentrations of IFNβ and myxovirus resistance protein A (MxA) transcripts. Similar results were obtained when CD68-positive/HCV-positive cells were compared with CD68-positive/HCV-negative cells in each of the 7 HCV-infected patients. <h3>Conclusion</h3> Evidence was found for activation of brain macrophages/microglia cells in autopsy brain tissue from HCV-positive patients. These findings could relate to the common presence of neurocognitive dysfunction among patients with chronic hepatitis C.
Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma
Authors: A Barreca, C Martinengo, L Annaratone, L Righi, A Chiappella, M Ladetto, A Demurtas, L Chiusa, A Stacchini, N Crosetto, A van Oudenaarden, R Chiarle
Journal: Blood Cancer Journal (2014)

Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel single-molecule RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells, we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples. Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients.
Memories of Chicago
Authors: John M. Clark
Journal: Annals of Internal Medicine (2007)

On Being a Doctor7 August 2007Memories of ChicagoJohn M. Clark, MDJohn M. Clark, MDFrom St. Petersburg, FL 33703.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-3-200708070-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail For me, it all began one autumn day in 1950, during my third year of medical school. We had studied obstetrics for a full semester, after which the University of Wisconsin sent us, in small groups, to spend a month at a place called “The Chicago Maternity Center.” It was located on the corner of Maxwell Street and Newberry Avenue, on the south side of Chicago, which we considered to be a slum and a no-man's-land.The building was an old warehouse with beds on the second floor and a telephone dispatching office on the first. During our first night ... Author, Article, and Disclosure InformationAffiliations: From St. Petersburg, FL 33703.Corresponding Author: John M. Clark, MD, 4091 13th Way NE, St. Petersburg, FL 33703; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 August 2007Volume 147, Issue 3Page: 211KeywordsAmbulancesChildrenMemoryOverweightSafetySleepWalking ePublished: 7 August 2007 Issue Published: 7 August 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Diabetic Retinopathy and the Risk of Coronary Heart Disease
Authors: Ning Cheung, Jie Jin Wang, Ronald Klein, David J. Couper, A. Richey Sharrett, Tien Y. Wong
Journal: Diabetes Care (2007)

OBJECTIVE— We sought to examine the relation of diabetic retinopathy to incident coronary heart disease (CHD). RESEARCH DESIGN AND METHODS— A population-based, prospective cohort study consisting of 1,524 middle-aged individuals with type 2 diabetes without prevalent CHD and stroke at baseline was conducted. Diabetic retinopathy signs were graded from retinal photographs according to the Early Treatment for Diabetic Retinopathy Study severity scale. Incident CHD events (myocardial infarction, fatal CHD, or coronary revascularization) were identified and validated following standardized protocols. RESULTS— In our study, 214 (14.7%) participants had diabetic retinopathy. Over an average follow-up of 7.8 years, there were 209 (13.7%) incident CHD events. After controlling for age, sex, race, study center, fasting glucose, A1C, duration of diabetes, blood pressure, antihypertensive treatment, cigarette smoking, BMI, and lipid profile, the presence of diabetic retinopathy was associated with a twofold higher risk of incident CHD events (hazard rate ratio [HR] 2.07 [95% CI 1.38–3.11]) and a threefold higher risk of fatal CHD (3.35 [1.40–8.01]). Further adjustments for inflammatory markers, carotid artery intima-media thickness, or nephropathy had minimal impact on the association. The increased risk of CHD was significant in both men (1.89 [1.08–3.31]) and women (2.16 [1.16–4.02]) with diabetic retinopathy. CONCLUSIONS— In individuals with type 2 diabetes, the presence of retinopathy signifies an increased CHD risk, independent of known risk factors. Our data support the role of microvascular disease in the pathogenesis of CHD in diabetes.