tbuckley/cabot-search huggingface dataset:
Cigarette smoke induces CXCL8 production by human neutrophils via activation of TLR9 receptor
Authors: E. Mortaz, I.M. Adcock, K. Ito, A.D. Kraneveld, F.P. Nijkamp, G. Folkerts
Journal: European Respiratory Journal (2009)

Chronic obstructive pulmonary disease (COPD) is a major health problem and cigarette smoke is the main risk factor for the development of COPD. The characteristic changes in airway morphology, inflammatory cell infiltration and mediator expression in COPD may result from direct effects of cigarette smoke on airway cells. Toll-like receptors (TLRs) are key elements in pathogen recognition by the host immune system. Although TLRs have been intensely studied in innate immunity and infection, their critical role in noninfectious challenges has only recently emerged. Here we investigate whether cigarette smoke induces TLR9 signalling in human neutrophils. Human neutrophils were isolated from buffy coat and exposed to cigarette smoke extract. The production of CXC chemokine ligand (CXCL)8 was measured as a functional readout and the role of TLR9 signalling was investigated. Cigarette smoke extract induced CXCL8 release via TLR9 activation in neutrophils, which was confirmed in TLR9 stably transfected human embryonic kidney 293 cells. Moreover, cigarette smoke extract upregulated the expression of TLR9 and the upregulated expression was suppressed by N-acetylcysteine. TLR9 mediates cigarette smoke-induced release of CXCL8 and this may contribute to the accumulation of neutrophils and inflammation within the airways of smokers.
Sieving characteristics of inflamed rectal mucosa
Authors: J. Rask-Madsen
Journal: Gut (1973)

The sieving characteristics of the normal and inflamed rectal mucosa are studied in three healthy volunteers and five patients with ulcerative colitis. Following rectal instillation of (125)I-polyvinylpyrrolidone (PVP), the molecular size distribution of labelled PVP in urine samples was determined by Sephadex gel filtration. The results of the study suggest that the increased permeability of the inflamed rectal mucosa to electrolytes and small hydrophilic compounds is due primarily to ultrastructural changes since only the low molecular fractions of PVP were found in the urine.
Young people's access to tobacco, alcohol, and other drugs
Authors: David Ogilvie, Laurence Gruer, Sally Haw
Journal: BMJ (2005)

Young people in the UK can easily obtain cigarettes and alcoholic drinks from a range of social and illicit commercial sources before they reach the legal minimum purchase age; many also report having access to illicit drugsPrices of alcoholic drinks and most illicit drugs, but not cigarettes, have been falling in real terms  Increasing the price of tobacco and alcohol is likely to reduce young people's demand for them  Enforcing or raising minimum purchase ages can reduce under-age sales of tobacco and alcohol, and has also been shown to reduce young peope's hazardous use of alcohol  Unenforced voluntary agreements with retailers, and intervening in illicit distribution systems, have not been shown to influence young people's use of tobacco, alcohol or other drugs.
P29. T-cell responses to oncogenic Merkel cell polyomavirus proteins distinguish Merkel cell carcinoma patients from healthy donors
Authors: L Lyngaa, NW Pedersen, D Schrama, CA Thrue, D Ibrani, O Met, P thor Straten, P Nghiem, JC Becker, SR Hadrup
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with strong evidence for viral carcinogenesis. The association of MCC with the Merkel cell polyomavirus (MCPyV) may explain the explicit immunogenicity of MCC. Indeed, MCPyV-encoded proteins are likely targets for
Older Adults With Severe, Treatment-Resistant Depression
Authors: Jürgen Unützer, Mijung Park
Journal: JAMA (2012)

Depression is a common, disabling, and costly condition encountered in older patients. Effective strategies for detection and treatment of late-life depression are summarized based on a case of a 69-year-old woman who struggled with prolonged depression. Clinicians should screen older patients for depression using a standard rating scale, initiate treatment such as antidepressant medications or evidence-based psychotherapy, and monitor depression symptoms. Patients who are not improving should be considered for psychiatric consultation and treatment changes including electroconvulsive therapy. Several changes in treatment approaches are usually needed before patients achieve complete remission. Maintenance treatment and relapse-prevention planning (summarization of early warning signs for depression, maintenance treatments such as medications, and other strategies to reduce the risk of relapse [eg, regular physical activity or pleasant activities]) can reduce the risk of relapse. Collaborative programs, in which primary care clinicians work closely with mental health specialists following a measurement-based treatment-to-target approach, are significantly more effective than typical primary care treatment.
Risks, costs, and compliance limit colorectal adenoma surveillance: lessons from a randomised trial
Authors: J N Lund
Journal: Gut (2001)

In the USA and many other countries, endoscopic surveillance of colorectal adenoma patients is now widely practised. However, the optimal frequency and mode of such surveillance are not yet established. The aim of this trial was to compare surveillance at one, two, or five year intervals using either flexible sigmoidoscopy or colonoscopy.Analysis of a randomised trial of flexible sigmoidoscopy and colonoscopy over one, two, or five years after stratification for "high" or "low" risk of recurrent adenomas. The trial started in 1984.A total of 776 patients were stratified into "high" (n=307) and "low" (n=469) recurrence risk groups and randomised to flexible sigmoidoscopy or colonoscopy at varying intervals. Only 81 recurrent adenomas (30/81 were >1 cm in diameter) were detected in the 2307 person years of follow up within the surveillance study. Adenoma recurrence was significantly higher in the high risk group (relative rate 1.82; 95% confidence interval 1.2-2.9) but recurrence rates per 1000 person years were low and not significantly different in those surveyed by colonoscopy or flexible sigmoidoscopy. Loss to follow up was greatest in those having an annual examination compared with two or five yearly surveillance examinations. Despite surveillance, invasive cancer developed in four patients compared with an expected value of 9.12 for the general population in England (p=0.10); of these four patients who developed cancers, only one was detected by surveillance examination.Adenoma recurrence rates were much lower than expected in both high and low risk groups. This suggests that endoscopic surveillance should be targeted at high risk groups. A surveillance interval of five years was as effective as shorter intervals in terms of cancer prevention, and was associated with similar compliance to two yearly examinations.
Treatment of Chronic Lymphocytic Leukemia: Achieving Minimal Residual Disease–Negative Status As a Goal
Authors: Emili Montserrat
Journal: Journal of Clinical Oncology (2005)

For many years, primum non nocere (“First, do no harm”) dictated the treatment of patients with chronic lymphocytic leukemia (CLL). This approach came from the idea that, in most cases, CLL had an indolent course (a frequently unfortunate misconception) and that there were no effective therapies for this disease (regrettably, true). However, in the 1970s, the development of staging systems and other prognostic factors allowed the identification of subsets of patients with different outcomes ranging from a normal life span to a short survival. This advance, coupled with the appearance of more effective therapies, renewed
Remnant Lipoprotein Particles Induce Apoptosis in Endothelial Cells by NAD(P)H Oxidase–Mediated Production of Superoxide and Cytokines via Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Activation
Authors: Hwa Kyoung Shin, Yong Ki Kim, Ki Young Kim, Jeong Hyun Lee, Ki Whan Hong
Journal: Circulation (2004)

Remnant lipoprotein particles (RLPs), products of lipolytic degradation of triglyceride-rich lipoprotein derived from VLDL, exert atherogenesis. In this study, we observed how RLPs induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) and cilostazol prevented cell death.RLPs were isolated from the plasma of hyperlipidemic patients by use of an immunoaffinity gel mixture of anti-apolipoprotein A-1 and anti-apolipoprotein B-100 monoclonal antibodies. RLPs (50 microg/mL) significantly increased superoxide formation in HUVECs associated with elevated gp91phox mRNA and protein expression and Rac1 translocation, accompanied by increased production of tumor necrosis factor (TNF)-alpha and interleukin-1beta, DNA fragmentation, and cell death. Cilostazol (1 to 100 micromol/L) significantly suppressed not only NAD(P)H oxidase-dependent superoxide production but also TNF-alpha and interleukin-1beta release and restored viability. RLPs activated a lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which was not inhibited by cilostazol. Treatment of HUVECs with monoclonal antibody for LOX-1 attenuated RLP-mediated production of superoxide, TNF-alpha, and interleukin-1beta and DNA fragmentation.RLPs stimulated NAD(P)H oxidase-dependent superoxide formation and induction of cytokines in HUVECs via activation of LOX-1, consequently leading to reduction in cell viability with DNA fragmentation, and cilostazol exerts a cell-protective effect by suppressing these variables.
Paracetamol use in early life and asthma: prospective birth cohort study
Authors: A. J. Lowe, J. B. Carlin, C. M. Bennett, C. S. Hosking, K. J. Allen, C. F. Robertson, C. Axelrad, M. J. Abramson, D. J. Hill, S. C. Dharmage
Journal: BMJ (2010)

To determine if use of paracetamol in early life is an independent risk factor for childhood asthma.Prospective birth cohort study.Melbourne Atopy Cohort Study.620 children with a family history of allergic disease, with paracetamol use prospectively documented on 18 occasions from birth to 2 years of age, followed until age 7 years.The primary outcome was childhood asthma, ascertained by questionnaire at 6 and 7 years. Secondary outcomes were infantile wheeze, allergic rhinitis, eczema, and skin prick test positivity.Paracetamol had been used in 51% (295/575) of children by 12 weeks of age and in 97% (556/575) by 2 years. Between 6 and 7 years, 80% (495/620) were followed up; 30% (148) had current asthma. Increasing frequency of paracetamol use was weakly associated with increased risk of childhood asthma (crude odds ratio 1.18, 95% confidence interval 1.00 to 1.39, per doubling of days of use). However, after adjustment for frequency of respiratory infections, this association essentially disappeared (odds ratio 1.08, 0.91 to 1.29). Paracetamol use for non-respiratory causes was not associated with asthma (crude odds ratio 0.95, 0.81 to 1.12).In children with a family history of allergic diseases, no association was found between early paracetamol use and risk of subsequent allergic disease after adjustment for respiratory infections or when paracetamol use was restricted to non-respiratory tract infections. These findings suggest that early paracetamol use does not increase the risk of asthma.
Concussion sans frontières
Authors: J Dvorak, P McCrory, M Aubry, M Molloy, L Engebretsen
Journal: British Journal of Sports Medicine (2009)

There is now overwhelming evidence that regular physical activity has important and wide-ranging health benefits. These range from reduced risk of chronic diseases such as heart disease, type 2 diabetes, and some cancers to enhanced function and preservation of function with age. As a member of the geriatric set, I am personally delighted that there is strong emerging evidence that activity delays cognitive decline and is good for brain health as well as having extensive benefits for the rest of the body.

I believe that evidence supports the conclusion that physical inactivity is one of the most important public health problems of the 21st century, and may even be the most important. This is not to deny the relevance of other health issues; and certainly we need to pay much more attention to healthful eating habits, smoking prevention and cessation programmes, and state-of-the art and evidence-based preventive medical care. My overriding concern is that the crucial importance of physical activity is undervalued and underappreciated by many individuals in public health and clinical medicine. Figure …
Familial Non-VHL Clear Cell (Conventional) Renal Cell Carcinoma: Clinical Features, Segregation Analysis, and Mutation Analysis of <i>FLCN</i>
Authors: Emma R. Woodward, Christopher Ricketts, Pip Killick, Sophie Gad, M.R. Morris, Fred Kavalier, Shirley V. Hodgson, Sophie Giraud, Brigitte Bressac-de Paillerets, Cyril Chapman, Bernard Escudier, Farida Latif, Stéphane Richard, Eamonn R. Maher
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Familial renal cell carcinoma (RCC) is genetically heterogeneous. The most common histopathologic subtype of sporadic and familial RCC is clear cell (cRCC) and von Hippel-Lindau (VHL) disease is the most common cause of inherited cRCC. Familial cRCC may also be associated with chromosome 3 translocations and has recently been described in patients with Birt-Hogg-Dube (BHD) syndrome, caused by germline FLCN mutation. Fewer than 20 kindreds with familial cRCC without VHL disease or a constitutional translocation have been described. The purpose of this investigation was to define the clinical and genetic features of familial non-VHL cRCC (FcRCC) and to evaluate whether unrecognized BHD syndrome might be present in patients with apparent nonsyndromic RCC susceptibility. Experimental Design: We analyzed the clinical features of, and undertook segregation analysis in, 60 kindreds containing two or more cases of RCC (at least one confirmed case of cRCC) and no evidence of an RCC susceptibility syndrome. We also undertook FLCN analysis to evaluate whether unrecognized BHD syndrome might be present in 69 patients with apparent nonsyndromic RCC susceptibility. Results: FcRCC was characterized by an earlier age at onset than sporadic cases and more frequent occurrence of bilateral or multicentric tumors. Segregation analysis showed autosomal dominant inheritance with sex- and age-dependent penetrance. A germline FLCN mutation was detected in 3 of 69 (4.3%) patients with apparent nonsyndromic RCC susceptibility. Conclusions: We describe the clinical and genetic features of the largest series of FcRCC and recommend these patients be offered FLCN analysis, in addition to constitutional cytogenetic and VHL analysis.
A novel druglike spleen tyrosine kinase binder prevents anaphylactic shock when administered orally
Authors: Elsa Mazuc, Bruno O. Villoutreix, Odile Malbec, Thomas Roumier, Sébastien Fleury, Jean-Paul Leonetti, David Dombrowicz, Marc Daëron, Pierre Martineau, Piona Dariavach
Journal: Journal of Allergy and Clinical Immunology (2008)
Brain Metastases (Bm) in Patients with Egfr Mutations – a Review of Incidence and Outcomes
Authors: J.A. King, B. Macadam, J. Cope, N. Bayman, F.H. Blackhall, P. Burt, R. Califano, A. Chittalia, C. Faivre-Finn, L. Lee, L. Pemberton, H. Sheikh, P.D. Taylor, A. Wallace, Y. Summers
Journal: Annals of Oncology (2014)
Calcium Antagonist Lacidipine Slows Down Progression of Asymptomatic Carotid Atherosclerosis
Authors: Alberto Zanchetti, M. Gene Bond, Michael Hennig, Albrecht Neiss, Giuseppe Mancia, Cesare Dal Palù, Lennart Hansson, Bruno Magnani, Karl-Heinz Rahn, John L. Reid, Josè Rodicio, Michel Safar, Lothar Eckes, Paolo Rizzini
Journal: Circulation (2002)

Most cardiovascular events associated with hypertension are complications of atherosclerosis. Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering.The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind trial in 2334 patients with hypertension that compared the effects of a 4-year treatment based on either lacidipine or atenolol on an index of carotid atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in far walls of common carotids and bifurcations (CBM(max)). This index has been shown by epidemiological studies to be predictive of cardiovascular events. A significant (P<0.0001) effect of lacidipine was found compared with atenolol, with a treatment difference in 4-year CBM(max) progression of -0.0227 mm (intention-to-treat population) and -0.0281 mm (completers). The yearly IMT progression rate was 0.0145 mm/y in atenolol-treated and 0.0087 mm/y in lacidipine-treated patients (completers, 40% reduction; P=0.0073). Patients with plaque progression were significantly less common, and patients with plaque regression were significantly more common in the lacidipine group. Clinic blood pressure reductions were identical with both treatments, but 24-hour ambulatory systolic/diastolic blood pressure changes were greater with atenolol (-10/-9 mm Hg) than with lacidipine (-7/-5 mm Hg). No significant difference between treatments was found in any cardiovascular events, although the relative risk for stroke, major cardiovascular events, and mortality showed a trend favoring lacidipine.The greater efficacy of lacidipine on carotid IMT progression and number of plaques per patient, despite a smaller ambulatory blood pressure reduction, indicates an antiatherosclerotic action of lacidipine independent of its antihypertensive action.
Interleukin-17 and Type 17 Helper T Cells
Authors: Pierre Miossec, Thomas Korn, Vijay K. Kuchroo
Journal: New England Journal of Medicine (2009)

Type 17 helper T cells (Th17) — a third class of T cells — and their major cytokine, interleukin-17, are essential for the defense against certain fungi, extracellular bacteria, and Mycobacterium tuberculosis. Defective control of Th17 cells and production of interleukin-17 are prominent in chronic inflammation and several immunoinflammatory disorders. Monoclonal antibodies against cytokines produced by Th17 cells are being investigated in clinical trials.
Demonstration of an imbalance between coronary perfusion and excessive load as a mechanism of ischemia during stress in patients with aortic stenosis.
Authors: M L Smucker, C L Tedesco, S B Manning, R M Owen, M D Feldman
Journal: Circulation (1988)

Patients with aortic stenosis are susceptible to myocardial ischemia during hemodynamic stress, which may be caused by two mechanisms. First, vascular abnormalities inherent in myocardial hypertrophy may impair coronary vasodilation, limiting the ability to increase coronary blood flow to meet increased metabolic demands. Second, aortic stenosis itself may cause an imbalance between oxygen supply and demand during hemodynamic stress by decreasing aortic pressure (decreasing coronary perfusion or oxygen supply) and increasing left ventricular pressure (increasing oxygen demand). By decreasing aortic valve gradient without immediately altering ventricular hypertrophy, aortic balloon valvuloplasty offers the opportunity to distinguish these mechanisms. We hypothesized that aortic valvuloplasty would improve the balance between myocardial oxygen supply and demand, especially during isoproterenol infusion. Nine patients undergoing aortic balloon valvuloplasty were assessed at baseline and during isoproterenol infusion (5 +/- 2 micrograms/min, mean +/- SD) before and after valvuloplasty. Valvuloplasty increased myocardial oxygen supply. After valvuloplasty, isoproterenol decreased diastolic pressure time index (DPTI) less and increased coronary sinus blood flow more than before valvuloplasty (-630 +/- 367 vs. -292 +/- 224 mm Hg.sec/min, p = 0.02 and 53 +/- 137 vs. 179 +/- 145 ml/min, p = 0.001, respectively). Valvuloplasty also decreased oxygen demand, decreasing systolic pressure time index (SPTI) from 4,135 +/- 511 to 3,021 +/- 492 mm Hg.sec/min (p = 0.0002). Valvuloplasty improved the balance between myocardial oxygen supply and demand, increasing baseline DPTI:SPTI, decreasing aortocoronary sinus oxygen content difference (0.51 +/- 0.15 to 0.68 +/- 0.14, p = 0.005 and 96 +/- 14 to 78 +/- 15 ml O2/l, p = 0.002, respectively), and decreasing myocardial lactate production during isoproterenol infusion (mean lactate extraction fraction, -0.26 +/- 0.40 to 0.14 +/- 0.17; p = 0.01). We conclude that aortic valvuloplasty improves the balance between myocardial oxygen supply and demand during hemodynamic stress induced by isoproterenol infusion. We speculate that the clinical improvement, which often occurs in these patients after valvuloplasty despite persistence of hemodynamically "critical" aortic stenosis, is in part attributable to immediate improvement in the myocardial oxygen supply:demand ratio.
REMARKS on CIRRHOSIS of the LIVER, with ESPECIAL REFERENCE to its OCCURRENCE in CHILDREN, and to the MODE of DEATH in CIRRHOSIS with JAUNDICE
Authors: J. M. Clarke
Journal: BMJ (1894)

CIRRHOSIS OF THE LIVER.[CAL JOURN 140T the amount of the sugar present must be taken into account.The fluid obtained from the organ must be titrated before and after hydration with sulphuric acid.In making such an estimation the organ was extracted with alcohol, and the extract divided into two parts: the sugar in one half was esti- mated at once with the ammonio-cupric test; the other half was treated with sulphuric acid, and titrated again.If the second estimation gave a higher figure, it was a proof that the sugar in the organ was a sugar differing from glucose, and approaching nearer to maltose.Experiments with cold blooded animals, in whom post-mortem changes were slow, gave, as might be seen from the tables, exactly similar re- sults, that is to say, the amount of sugar in the liver and other structures was practically the same.At the conclusion of his lectures, Dr. Pavy demonstrated lantern slides of ozazones from various sources, among others from certain organs, from beef tea, and from peptonised meat.
Microarray analysis of phosphatase gene expression in human melanoma
Authors: L. McArdle, M.M. Rafferty, K. Satyamoorthy, G.M. Maelandsmo, P.A. Dervan, M. Herlyn, D.J. Easty
Journal: British Journal of Dermatology (2005)

Tyrosine phosphate is abnormally elevated in malignant melanoma, and this has been interpreted to reflect the activity of oncogenic protein tyrosine kinases. However, elevation may also arise due to decreased protein tyrosine phosphatase (PTP) expression.To survey phosphatase gene expression in melanoma cell lines, a benign naevus and normal melanocytes: we searched for downregulation of phosphatase gene expression in malignant cells that may indicate a role as melanoma suppressor genes.Microarray analysis was used to compare gene expression for 133 phosphatase genes, comprising 39 PTPs, 16 dual-specificity phosphatases (DSPs), 47 serine/threonine phosphatases and 31 acid/alkaline and lipid-based phosphatases. Northern blotting analysis was used to study gene expression in human melanoma biopsies.There was decreased expression of four DSP genes (including PTEN); eight receptor PTP genes were downregulated in melanoma, among which were PTP-KAPPA and PTP-PI (consistent with our previous data). In addition, PTP-RF/LAR was downregulated in 13 of 22 metastatic melanomas.The expression of multiple PTP receptors is decreased in melanoma; this may be a mechanism which stimulates autonomous growth in advanced melanoma.