tbuckley/cabot-search huggingface dataset:
S26 Barriers to attendance and adherence at pulmonary rehabilitation
Authors: C. Hayton, A. Clark, A. M. Wilson
Journal: Thorax (2011)

<h3>Background</h3> Pulmonary rehabilitation (PR) is a multidisciplinary programme which has been shown to improve symptoms and exercise tolerance in patients with COPD and is recommended by national guidelines. Attendance at pulmonary rehabilitation following referral is low and many patients drop-out of the programme before completion. The aim of this study is to obtain quantitative data to assess predictors of attendance and adherence at PR. <h3>Methods</h3> We performed a retrospective analysis of a database of patients with COPD, who had been invited to attend a pulmonary rehabilitation programme over a 5-year period. Data was obtained from 727 patients. Patients were divided into three groups based on the number of sessions attended; non-attendance (0% attendance), non-adherence (1%–63% attendance), adherence (&gt;63% attendance). Data were compared between attenders vs non-attenders and adherers vs non-adherers to identify predictors (Gender, Smoking status, pack years, cohabitation, referral route, employment status, body mass index, forced expiratory volume in 1 s (FEV<sub>1</sub>), FEV<sub>1</sub>% predicted, oxygen therapy (LTOT), oxygen saturations at rest, lung information needs questionnaire*, shuttle walk distance*, previous hospitalisation and year of referral) of attendance and adherence to be identified. *Included in adherence analysis only. <h3>Results</h3> 31.8% of patients referred for PR did not attend and a further 28.3% were non-adherent. Univariate predictors of attendance were male gender (OR=1.53 95% CI (1.05 to 2.25)), cohabitation (1.77 (1.17 to 2.67)) ex-smoker (2.29 (1.50 to 3.50)). Predictors of adherence were age (64–70: OR 1.99 (1.20 to 3.30); 71–76: 2.57 (1.48 to 4.45)) ex-smoker (4.86 (3.18 to 7.41)), FEV<sub>1</sub> (higher more likely), FEV<sub>1</sub>% predicted (higher more likely), LTOT (0.54 (0.30 to 0.96)). Multiple logistic regression revealed that LTOT (OR 0.39 (0.18 to 0.84)) and cohabitation (1.84 (1.03 to 3.30)) were independent predictors of attendance. Multiple logistic regression revealed that only ex-smoker was predictive of adherence (OR 5.68 (3.33 to 9.7)). <h3>Discussion</h3> This large quantitative study has reaffirmed previous smaller observations regarding attendance at pulmonary rehabilitation. Disease severity and lack of potential supportive partner also has a negative impact on attendance. Smoking status appears to be a strong factor in predicting attendance and adherence to sessions. Contrary to previous observations, we found no association between type of professional referring and attendance at pulmonary rehabilitation.
Persistence of mucosal abnormality in ulcerative colitis.
Authors: A P Dick, L P Holt, E R Dalton
Journal: Gut (1966)

EDITORIAL COMMENT It is concluded that in the vast majority of patients with colitis, once the disease has developed, the mucosa remains permanently abnormal whether symptoms are present or not, a fact which may be related to the tendency to relapse and to the increased tendency to carcinoma of the colon.
Cellular heterogeneity of ammonium ion transport across the basolateral membrane of the hamster medullary thick ascending limb of Henle's loop.
Authors: S Tsuruoka, M Takeda, K Yoshitomi, M Imai
Journal: Journal of Clinical Investigation (1993)

The epithelia of the medullary thick ascending limb (MAL) consists of two cell types, high (HBC) and low basolateral conductance (LBC) cell, depending on the K+ conductance of the basolateral membrane. The NH4+ conductance distinct from the K+ conductance has been suggested to exist in the proximal tubule, MAL cell, and Xenopus oocyte. The present study was designed to examine whether there is a conductive NH4+ transport system distinct from K+ conductance in two different cell types of the hamster MAL perfused in vitro. The basolateral membrane voltage (VB) was measured by impaling cells with conventional microelectrodes. Addition of NH4+ to the bath depolarized VB in a dose-dependent manner in both cell types. The response was maintained in the absence of HCO3-. When the VB deflection elicited upon 50 mM KCl or NH4Cl in the bath (delta VBK+ or delta VBNH4+) were compared, delta VBNH4+ was almost the same as delta VBK+ in the HBC cell, whereas the former was greater than the latter in the LBC. In the HBC cell, 10 mM Ba2+ in the bath equally suppressed both delta VBK+ and delta VBNH4+, whereas in the LBC cell it suppressed delta VBK+ with a small effect on delta VBNH4+, indicating that NH4+ is transported via a pathway distinct from Ba(2+)-sensitive K+ conductance. The VB deflection by NH4+ was unaffected by addition of 0.1 mM ouabain or 10 microM 5-nitro-2-(3-phenylpropylamino)-benzoate (a Cl- channel blocker) to the bath, excluding the contribution of the Na+, K+ pump or Cl- channel. An abrupt reduction of Na+ in the bath from 200 to 20 mM did not cause any changes in VB, suggesting that a nonselective cation channel may not account for the NH4+ transport. Amiloride at 10 microM inhibited delta VBNH4+ with a higher efficacy in the LBC cell. We conclude that a rheogenic NH4+ transport system independent from the K+ conductance exists in the basolateral membrane of the LBC cell of the hamster MAL, and may play some roles in the regulation of NH4+ transport.
Cell-Mediated Autophagy Promotes Cancer Cell Survival
Authors: William J. Buchser, Thomas C. Laskow, Philip J. Pavlik, Hui-Min Lin, Michael T. Lotze
Journal: Cancer Research (2012)

Immune effector cells integrate signals that define the nature and magnitude of the subsequent response. Experimental measures for immune cell-mediated lysis of tumors or virally infected targets rely on average responses of permeability or apoptotic changes within a population of targets. Here, we examined individual target cells following interaction with lymphoid effectors. We found that human peripheral blood lymphocytes not only provide lytic signals but also promote autophagy in the remaining cells. At high effector-to-target ratios, autophagy was induced in several human tumors, as assessed by induction of LC3 puncta and diminished p62. Natural killer cells are a primary mediator of this process. In addition, target cell autophagy was enhanced by provision of interleukin (IL)-2, whereas IL-10 attenuated this effect, and cell-to-cell contact strongly enhanced lymphocyte-mediated autophagy. Although IFN-γ can induce autophagy in target cells, IFN-α acted directly on the targets or in concert with lymphocytes to diminish target autophagy in some cell types. Importantly, cell-mediated autophagy promoted resistance from treatment modalities designed to eradicate tumor cells. Our findings therefore show that the lymphocyte-induced cell-mediated autophagy promotes cancer cell survival and may represent an important target for development of novel therapies.
Interpretation of quality of life scores from the St George's Respiratory Questionnaire
Authors: M. Ferrer, C. Villasante, J. Alonso, V. Sobradillo, R. Gabriel, G. Vilagut, J.F. Masa, J.L. Viejo, C.A. Jiménez-Ruiz, M. Miravitlles
Journal: European Respiratory Journal (2002)

The aim of the study was to obtain the general population norms for the St. George's Respiratory Questionnaire (SGRQ), a specific questionnaire for respiratory diseases. The IBERPOC project was a cross-sectional study of representative samples of the general population aged between 40-69 yrs. The study sample was composed of 862 individuals. All participants considered as "probable cases" of chronic obstructive pulmonary disease (COPD) (n=460) were eligible to complete the SGRQ and among the rest of the nonprobable COPD participants (n=3,571), 10 individuals from each defined age and sex group were eligible (n=402). Weights were applied to restore general population representativity of the sample. Mean forced expiratory volume in one second (FEV1) predicted was 89.4% (SD=16.5%; range: 16-131%). Chronbach's alpha coefficients were >0.7 in the symptoms, activity and impact scales, and >0.9 in the overall scale. Symptom scale score was significantly higher among males (11.6 versus 7.8; p<0.01) and activity scale score was significantly higher among females (12.2 versus 14.6; p=0.04). In a multiple linear regression model, respiratory diseases (asthma and COPD) and FEV1 % over pred showed the strongest association with the SGRQ total score. Smoking, sex, age and education were independently associated with the total SGRQ score. These results indicate that individuals from the general population presented some of the problems that are important when measuring health-related quality of life in respiratory patients, and provide St George's Respiratory Questionnaire norms, a useful method for interpreting the St George's Respiratory Questionnaire score in a given patient or study samples.
TNF-α is a critical negative regulator of type 1 immune activation during intracellular bacterial infection
Authors: Anna Zganiacz, Michael Santosuosso, Jun Wang, Tony Yang, Lihao Chen, Maria Anzulovic, Scott Alexander, Brigitte Gicquel, Yonghong Wan, Jonathan Bramson, Mark Inman, Zhou Xing
Journal: Journal of Clinical Investigation (2004)

TNF-α has long been regarded as a proimmune cytokine involved in antimicrobial type 1 immunity. However, the precise role of TNF-α in antimicrobial type 1 immunity remains poorly understood. We found that TNF-α–deficient (TNF–/–) mice quickly succumbed to respiratory failure following lung infection with replication-competent mycobacteria, because of apoptosis and necrosis of granuloma and lung structure. Tissue destruction was a result of an uncontrolled type 1 immune syndrome characterized by expansion of activated CD4 and CD8 T cells, increased frequency of antigen-specific T cells, and overproduction of IFN-γ and IL-12. Depletion of CD4 and CD8 T cells decreased IFN-γ levels, prevented granuloma and tissue necrosis, and prolonged the survival of TNF–/– hosts. Early reconstitution of TNF-α by gene transfer reduced the frequency of antigen-specific T cells and improved survival. TNF-α controlled type 1 immune activation at least in part by suppressing T cell proliferation, and this suppression involved both TNF receptor p55 and TNF receptor p75. Heightened type 1 immune activation also occurred in TNF–/– mice treated with dead mycobacteria, live replication-deficient mycobacteria, or mycobacterial cell wall components. Our study thus identifies TNF-α as a type 1 immunoregulatory cytokine whose primary role, different from those of other type 1 cytokines, is to keep an otherwise detrimental type 1 immune response in check.
Phosphoinositide 3-Kinase Isoforms Selectively Couple Receptors to Vascular L-Type Ca <sup>2+</sup> Channels
Authors: Nathalie Macrez, Chantal Mironneau, Valérie Carricaburu, Jean-François Quignard, Aleksei Babich, Cornelia Czupalla, Bernd Nürnberg, Jean Mironneau
Journal: Circulation Research (2001)

Heterodimeric class I phosphoinositide 3-kinase (PI3K) has been shown to be involved in the stimulation of voltage-gated Ca(2+) channels by various mediators. In this study, we bring evidences that vascular L-type Ca(2+) channels can be modulated by both tyrosine kinase-regulated class Ia and G protein-regulated class Ib PI3Ks. Purified recombinant PI3Ks increased the peak Ca(2+) channel current density when applied intracellularly. Furthermore, PI3Kalpha-, beta-, and delta-mediated stimulations of Ca(2+) channel currents were increased by preactivation by a phosphotyrosyl peptide, whereas PI3Kgamma- and beta-mediated effects were increased by Gbetagamma. In freshly isolated and cultured vascular myocytes, angiotensin II and Gbetagamma stimulated L-type Ca(2+) channel current. In contrast, platelet-derived growth factor (PDGF)-BB and the phosphotyrosyl peptide did not stimulate Ca(2+) channel current in freshly isolated cells despite the presence of endogenous PDGF receptors and PI3Kalpha and PI3Kgamma. Interestingly, when endogenous PI3Kbeta expression arose in cultured myocytes, both PDGF and phosphotyrosyl peptide stimulated Ca(2+) channels through PI3Kbeta, as revealed by the inhibitory effect of an anti-PI3Kbeta antibody. These results suggest that endogenous PI3Kbeta but not PI3Kalpha is specifically involved in PDGF receptor-induced stimulation of Ca(2+) channels and that different isoforms of PI3K regulate physiological increases of Ca(2+) influx in vascular myocytes stimulated by vasoconstrictor or growth factor.
Circulating cardiovascular disease risk factors and signaling in endothelial cell caveolae
Authors: C MINEO, P SHAUL
Journal: Cardiovascular Research (2006)

Caveolae are a subset of lipid rafts that are prevalent on the plasma membrane of endothelial cells. They compartmentalize signal transduction molecules which regulate multiple endothelial functions including the production of nitric oxide (NO) by the caveolae resident enzyme endothelial NO synthase (eNOS). Recent studies have demonstrated that circulating factors known to modify cardiovascular disease risk regulate signaling in endothelial cell caveolae. In particular, high density lipoprotein (HDL) maintains the lipid environment in caveolae, thereby promoting the retention and function of eNOS in the domain, and it also causes direct activation of eNOS via scavenger receptor type BI (SR-BI)-induced kinase signaling. Estrogen binding to estrogen receptors (ER) in caveolae also activates eNOS, and this occurs through G protein and kinase activation. Discrete domains within SR-BI and ER mediating signal initiation in caveolae have been identified. Counteracting the promodulatory actions of HDL and estrogen, C-reactive protein (CRP) antagonizes eNOS through FcgammaRIIB and PP2A, which dephosphorylates and inactivates the enzyme. The endothelial cell functions modified by these processes include the regulation of monocyte adhesion and endothelial cell migration. Thus, signaling events in caveolae invoked by known circulating cardiovascular disease risk factors have major impact on endothelial cell phenotypes of importance to cardiovascular health and disease.
Early afterdepolarizations and triggered activity in rabbit cardiac Purkinje fibers recovering from ischemic-like conditions. Role of acidosis.
Authors: G J Rozanski, R C Witt
Journal: Circulation (1991)

BACKGROUND The mechanisms underlying repetitive activity during reperfusion of ischemic myocardium are thought to include triggered responses elicited at short pacing cycle lengths. The potential to generate repetitive responses at longer pacing cycle lengths under similar conditions, however, has not been explored. Thus, the present study examined the role of cycle length on the cellular electrical changes produced during recovery from ischemic-like conditions and identified the major component precipitating nondriven, repetitive activity. METHODS AND RESULTS Transmembrane potentials were recorded in vitro from isolated rabbit Purkinje fibers exposed to hypoxia (defined as PO2 less than 30 mm Hg, high [K+]o, and zero glucose) plus lactic acidosis (pH 6.7) for 45 minutes and during recovery in normal Tyrode's solution (pH 7.4). Compared with control, action potential duration (90% repolarization) during recovery increased transiently by 40.9 +/- 11.8 and 241.0 +/- 51.1 msec at respective basic cycle lengths of 1,000 and 3,000 msec (both p less than 0.005). In 81% of preparations, action potential prolongation was accompanied by early afterdepolarizations and triggered activity generated from low (positive to -40 mV) or high (negative to -40 mV) membrane potentials. In 62% of experiments, brief periods of abnormal automaticity also occurred. Triggered responses were 1) unaffected by 1 microM ryanodine, 2) abolished by pacing at short basic cycle lengths or by exposing tissues to 2.5 micrograms/ml lidocaine, and 3) more easily induced at long basic cycle lengths or by superfusing 2.5 micrograms/ml quinidine. When tissues were conditioned with hypoxia alone (pH 7.4), action potential prolongation on recovery was comparatively small, and nondriven responses did not develop. Conversely, addition of 10-20 microM amiloride to the hypoxic, acidic test solution augmented recovery-induced action potential prolongation. CONCLUSIONS We conclude that acidosis, as a component of ischemia, plus slow pacing frequencies may mediate the genesis of early afterdepolarizations and triggered activity in Purkinje fibers on recovery, long after extracellular pH has been restored to normal. These data may have clinical relevance to the mechanisms of reperfusion arrhythmias in the intact human heart.
Markers of systemic inflammation in psoriasis: a systematic review and meta-analysis
Authors: E.A. Dowlatshahi, E.A.M van der Voort, L.R. Arends, T. Nijsten
Journal: British Journal of Dermatology (2013)

Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)-1β, IL-6, IL-10, C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, E-selectin and tumour necrosis factor (TNF)-α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random-effects model. Seventy-eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL-6 [d = 1·32, 95% confidence interval (CI) 0·83–1·81], CRP (d = 1·83, 95% CI 0·76–2·90), TNF-α (d = 1·32, 95% CI 0·86–1·79), E-selectin (d = 1·78, 95% CI 1·32–2·25) and ICAM-1 (d = 1·77, 95% CI 1·15–2·39). The SMD between cases and controls for IL-1β and IL-10 was not significant. Age had a significant effect on the SMD for IL-6 and TNF-α. For IL-6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy.
Nephrogenic Systemic Fibrosis
Authors: Peter Marckmann, Lone Skov, Kristian Rossen, Anders Dupont, Mette Brimnes Damholt, James Goya Heaf, Henrik S. Thomsen
Journal: Journal of the American Society of Nephrology (2006)

Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75 d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P < 0.0001). Seven (54%) patients became severely disabled, and one died 21 mo after exposure. No other exposure/event than gadodiamide that was common to more than a minority of the patients could be identified. These findings indicate that gadodiamide plays a causative role in nephrogenic systemic fibrosis.
Mothers of Premature Babies
Authors: D. H. Garrow, D. MacCarthy, E. R. Rue
Journal: BMJ (1970)

SIR,-Little seems to have been said about the position of the medical assistant if the Government's decisions on the Review Body's report take effect.A medical assistant must have spent at least two years as a registrar before appointment, and many will have been senior registrars.Yet it is now proposed that he should start at C2,415 when a second year registrar gets £2,472, a 3rd year registrar C2,616, and a first year senior registrar £2,760.Not only does a medical assistant give the benefit of more experience and takes less time off for study than the junior doctor but now he is to get substantially less pay for doing it.If the consultants' pay position demands action how much more does that of the medical assistant-and yet I have not even heard it mentioned.-Iam, etc.,
The Receptor-Type Protein Tyrosine Phosphatase J Antagonizes the Biochemical and Biological Effects of RET-Derived Oncoproteins
Authors: Angela Iervolino, Rodolfo Iuliano, Francesco Trapasso, Giuseppe Viglietto, Rosa Marina Melillo, Francesca Carlomagno, Massimo Santoro, Alfredo Fusco
Journal: Cancer Research (2006)

Abstract Thyroid cancer is frequently associated with the oncogenic conversion of the RET receptor tyrosine kinase. RET gene rearrangements, which lead to the generation of chimeric RET/papillary thyroid carcinoma (PTC) oncogenes, occur in PTC, whereas RET point mutations occur in familial multiple endocrine neoplasia type 2 (MEN2) and sporadic medullary thyroid carcinomas (MTC). We showed previously that the expression of the receptor-type protein tyrosine phosphatase J (PTPRJ) is suppressed in neoplastically transformed follicular thyroid cells. We now report that PTPRJ coimmunoprecipitates with wild-type RET and with the MEN2A-associated RET(C634R) oncoprotein but not with the RET/PTC1 and RET-MEN2B isoforms. Using mutated forms of PTPRJ and RET-MEN2A, we show that the integrity of the respective catalytic domains is required for the PTPRJ/RET-MEN2A interaction. PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels. In line with this finding, adoptive PTPRJ expression reduced the oncogenic activity of RET(C634R) in an in vitro focus formation assay of NIH3T3 cells. As expected from the coimmunoprecipitation results, the RET(M918T) oncoprotein, which is associated to MEN2B and sporadic MTC, was resistant to the dephosphorylating activity of PTPRJ. Taken together, these findings identify RET as a novel substrate of PTPRJ and suggest that PTPRJ expression levels may affect tumor phenotype associated with RET/PTC1 and RET(C634R) mutants. On the other hand, resistance to PTPRJ may be part of the mechanism of RET oncogenic conversion secondary to the M918T mutation. (Cancer Res 2006; 66(12): 6280-7)
Aberrant telomere structure is characteristic of resistant chronic lymphocytic leukaemia cells
Authors: T Brugat, N Gault, I Baccelli, J Maës, A Roborel de Climens, F Nguyen-Khac, F Davi, H Merle-Béral, E Gilson, M Goodhardt, J Delic
Journal: Leukemia (2009)