tbuckley/cabot-search huggingface dataset:
Smoking Cessation and Lung Function in Mild-to-Moderate Chronic Obstructive Pulmonary Disease
Authors: PAUL D. SCANLON, JOHN E. CONNETT, LANCE A. WALLER, MURRAY D. ALTOSE, WILLIAM C. BAILEY, A. SONIA BUIST, DONALD P.TASHKIN for th e Lung Health Study Research Group
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Previous studies of lung function in relation to smoking cessation have not adequately quantified the long-term benefit of smoking cessation, nor established the predictive value of characteristics such as airway hyperresponsiveness. In a prospective randomized clinical trial at 10 North American medical centers, we studied 3,926 smokers with mild-to-moderate airway obstruction (3,818 with analyzable results; mean age at entry, 48.5 yr; 36% women) randomized to one of two smoking cessation groups or to a nonintervention group. We measured lung function annually for 5 yr. Participants who stopped smoking experienced an improvement in FEV1 in the year after quitting (an average of 47 ml or 2%). The subsequent rate of decline in FEV1 among sustained quitters was half the rate among continuing smokers, 31 ± 48 versus 62 ± 55 ml (mean ± SD), comparable to that of never-smokers. Predictors of change in lung function included responsiveness to β -agonist, baseline FEV1, methacholine reactivity, age, sex, race, and baseline smoking rate. Respiratory symptoms were not predictive of changes in lung function. Smokers with airflow obstruction benefit from quitting despite previous heavy smoking, advanced age, poor baseline lung function, or airway hyperresponsiveness. Scanlon PD, Connett JE, Waller LA, Altose MD, Bailey WC, Buist AS, Tashkin DP, for the Lung Health Study Research Group. Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease: The Lung Health Study.
How Much Scrutiny and Stress Can the Fidelis Lead Withstand?
Authors: Avi Fischer
Journal: Circulation (2011)

T he implantable cardioverter-defibrillator lead has under- gone numerous design and manufacturing changes over the last 25 years aimed at improving patient care and outcomes.It is widely accepted that implantable cardioverterdefibrillator leads, similar to pacemaker leads, have a finite life.The design of an implantable cardioverter-defibrillator lead is more complex than that of a pacemaker lead, and the propensity for failure is greater.Estimates of the rate of failure vary, but during follow-up at 10 years, the failure rate may be as high as 20%. 1 Factors that affect implantable cardioverter-defibrillator lead performance include the implanting physician, the patient, and specific characteristics related to lead design.Most lead failures are multifactorial.
Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice.
Authors: E Racila, R H Scheuermann, L J Picker, E Yefenof, T Tucker, W Chang, R Marches, N E Street, E S Vitetta, J W Uhr
Journal: The Journal of Experimental Medicine (1995)

Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.
A Bispecific Recombinant Cytotoxin (DTEGF13) Targeting Human Interleukin-13 and Epidermal Growth Factor Receptors in a Mouse Xenograft Model of Prostate Cancer
Authors: Brad J. Stish, Hua Chen, Yanqun Shu, Angela Panoskaltsis-Mortari, Daniel A. Vallera
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Overexpressed cytokine receptors are considered valid targets for new biologicals targeting prostate cancer. However, current reagents are limited in efficacy. Our goal was to determine the advantages of simultaneously targeting two established targets, epidermal growth factor receptor and interleukin-13 (IL-13) receptor, with a new bispecific cytotoxin in which both EGF and IL-13 cytokines were cloned onto the same single-chain molecule with truncated diphtheria toxin (DT390). Experimental Design: In vitro experiments measured the potency of bispecific DTEGF13 and compared its activity to its monospecific counterparts, DTEGF and DTIL13. We determined whether the presence of both cytokine ligands on the same molecule was responsible for its superior activity. In vivo, DTEGF13 was given i.t. to athymic nude mice with established PC-3 human prostate cancer tumor xenografts on their flanks. Results: In vitro, DTEGF13 was more potent than the monospecific cytotoxins against human prostate cancer lines. Enhanced activity was related to the presence of both cytokines on the same single-chain molecule and was not attributed to enhanced binding capacity. Killing was receptor specific. Cytotoxicity could be blocked with anti-EGF and anti–IL-13 antibodies. In vivo, DTEGF13, but not monospecific DTEGF or DTIL13, significantly inhibited the growth of established PC-3 tumors in nude mice (P &amp;lt; 0.0001). Conclusions: These data show for the first time that simultaneous targeting of cytokine receptors with two ligands on the same molecule has pronounced anticancer advantages. In an animal model in which human DTEGF13 is cross-reactive with mouse, DTEGF13 was highly effective in checking aggressive prostate tumor progression and was reasonably tolerated.
Integrated MicroRNA Network Analyses Identify a Poor-Prognosis Subtype of Gastric Cancer Characterized by the miR-200 Family
Authors: Fengju Song, Da Yang, Ben Liu, Yan Guo, Hong Zheng, Lian Li, Tao Wang, Jinpu Yu, Yanrui Zhao, Ruifang Niu, Han Liang, Hans Winkler, Wei Zhang, Xishan Hao, Kexin Chen
Journal: Clinical Cancer Research (2013)

Our aim was to investigate whether microRNAs can predict the clinical outcome of patients with gastric cancer. We used integrated analysis of microRNA and mRNA expression profiles to identify gastric cancer microRNA subtypes and their underlying regulatory scenarios.MicroRNA-based gastric cancer subtypes were identified by consensus clustering analysis of microRNA profiles of 90 gastric cancer tissues. Activated pathways in the subtypes were identified by gene expression profiles. Further integrated analysis was conducted to model a microRNA regulatory network for each subtype. RNA and protein expression were analyzed by RT-PCR and tissue microarray, respectively, in a cohort of 385 gastric cancer cases (including the 90 cases for profiling) to validate the key microRNAs and targets in the network. Both in vitro and in vivo experiments were carried out to further validate the findings.MicroRNA profiles of 90 gastric cancer cases identified two microRNA subtypes significantly associated with survival. The poor-prognosis gastric cancer microRNA subtype was characterized by overexpression of epithelial-to-mesenchymal transition (EMT) markers. This gastric cancer "mesenchymal subtype" was further validated in a patient cohort comprising 385 cases. Integrated analysis identified a key microRNA regulatory network likely driving the gastric cancer mesenchymal subtype. Three of the microRNAs (miR-200c, miR-200b, and miR-125b) targeting the most genes in the network were significantly associated with survival. Functional experiments demonstrated that miR-200b suppressed ZEB1, augmented E-cadherin, inhibited cell migration, and suppressed tumor growth in a mouse model.We have uncovered a key microRNA regulatory network that defines the mesenchymal gastric cancer subtype significantly associated with poor overall survival in gastric cancer.
Impaired inactive to active kallikrein conversion in human salt-sensitive hypertension.
Authors: C Bellini, C Ferri, A Carlomagno, S Necozione, A R Lepore, G Desideri, A Santucci
Journal: Journal of the American Society of Nephrology (1996)

Active and inactive urinary kallikrein excretion rates were evaluated in 43 essential hypertensive men (45.4 +/- 5.6 yr) after normal-(120 mmol/day), low-(20 mmol/day), and high-(240 mmol/day) NaCl diets were given for 2 wk each. Patients were classified as salt-sensitive, salt-resistant, or counterregulating, on the basis of their blood pressure responses to the different NaCl intakes. Resulting data show that active and inactive kallikrein excretion rates were lower (P < 0.001) in salt-sensitive (active, 0.59 +/- 0.27 U/24 h; inactive, 3.45 +/- 1.31 U/24 h) than in salt-resistant (active, 1.41 +/- 0.35 U/24 h; inactive, 6.93 +/- 2.68 U/24 h) and in counterregulating hypertensive patients (active, 1.37 +/- 0.39 U/24 h; inactive, 6.32 +/- 2.58 U/24 h) after the normal NaCl diet. Salt-sensitive hypertensive patients showed also higher plasma digoxin-like substance (P < 0.001), atrial natriuretic peptide (P < 0.001), and fasting insulin (P < 0.005) levels than the other subgroups. Active kallikrein decreased after high and increased after low-NaCl intake in all groups. Inactive kallikrein varied similarly to active one in salt-resistant patients and counterregulating patients, whereas it increased during salt-loading in salt-sensitive patients. Consequently, the active/total kallikrein ratio decreased in salt-sensitive patients (from 20.2 +/- 3.5 to 5.82 +/- 1.02%, P < 0.05) when they switched from low- to high-NaCl intake, and the ratio was lower in these patients than in the other subgroups (P < 0.0001) after the high-NaCl diet. In conclusion, active and inactive kallikrein excretions after normal-NaCl intake are reduced in salt-sensitive hypertensive patients. The divergent active and inactive kallikrein responses to dietary NaCl changes in salt-sensitive patients could indicate an impairment of inactive to active kallikrein conversion during NaCl loading as a new mechanism in human salt-sensitive hypertension.
Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis
Authors: M R Law
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To determine by how much statins reduce serum concentrations of low density lipoprotein (LDL) cholesterol and incidence of ischaemic heart disease (IHD) events and stroke, according to drug, dose, and duration of treatment. <b>Design</b> Three meta-analyses: 164 short term randomised placebo controlled trials of six statins and LDL cholesterol reduction; 58 randomised trials of cholesterol lowering by any means and IHD events; and nine cohort studies and the same 58 trials on stoke. <b>Main outcome measures</b> Reductions in LDL cholesterol according to statin and dose; reduction in IHD events and stroke for a specified reduction in LDL cholesterol. <b>Results</b> Reductions in LDL cholesterol (in the 164 trials) were 2.8 mmol/l (60%) with rosuvastatin 80 mg/day, 2.6 mmol/l (55%) with atorvastatin 80 mg/day, 1.8 mmol/l (40%) with atorvastatin 10 mg/day, lovastatin 40 mg/day, simvastatin 40 mg/day, or rosuvastatin 5 mg/day, all from pretreatment concentrations of 4.8 mmol/l. Pravastatin and fluvastatin achieved smaller reductions. In the 58 trials, for an LDL cholesterol reduction of 1.0 mmol/l the risk of IHD events was reduced by 11% in the first year of treatment, 24% in the second year, 33% in years three to five, and by 36% thereafter (P &lt; 0.001 for trend). IHD events were reduced by 20%, 31%, and 51% in trials grouped by LDL cholesterol reduction (means 0.5 mmol/l, 1.0 mmol/l, and 1.6 mmol/l) after results from first two years of treatment were excluded (P &lt; 0.001 for trend). After several years a reduction of 1.8 mmol/l would reduce IHD events by an estimated 61%. Results from the same 58 trials, corroborated by results from the nine cohort studies, show that lowering LDL cholesterol decreases all stroke by 10% for a 1 mmol/l reduction and 17% for a 1.8 mmol/l reduction. Estimates allow for the fact that trials tended to recruit people with vascular disease, among whom the effect of LDL cholesterol reduction on stroke is greater because of their higher risk of thromboembolic stroke (rather than haemorrhagic stroke) compared with people in the general population. <b>Conclusions</b> Statins can lower LDL cholesterol concentration by an average of 1.8 mmol/l which reduces the risk of IHD events by about 60% and stroke by 17%.
Power Doppler sonography: synovial tissue assessment in RA
Authors: P Hrycaj
Journal: Annals of the Rheumatic Diseases (2003)

We read with interest the paper by Carotti et al that appeared in the October issue of the Annals of the Rheumatic Diseases .1 The authors investigated the usefulness of contrast enhanced power Doppler ultrasonography (PDS) in determining the vascularisation rate of the synovial pannus of patients with rheumatoid arthritis (RA). After intravenous infusion of an echo contrast (Levovist, Schering, Germany) PDS was performed on the knee joints of 42 patients with RA, who had previously been classified as having active (n=15), moderately active (n=14), and inactive knee synovitis (n=13). The results were expressed as the area underlying time-intensity curves. Highest vascularisation scores were found in patients with active synovitis (216.2 (33.4), mean (SD)), whereas lower values were found in those with moderately active (186.8 (25.8)) and inactive synovitis (169.6 (20.6)). Significant difference (p<0.01) was found between the active and the inactive group only. Also, significant correlations were found between the vascularisation scores and some indices of the disease activity. The authors concluded that PDS may be a valuable method of distinguishing between inflammatory and non-inflammatory pannus of knee joints in RA and thus may have a clinical potential for both diagnostic and therapeutic purposes.

Unfortunately, Carotti et al did not provide any data on the sensitivity and specificity of the method used. Moreover, no figure showing distribution of the vascularisation scores in individual patients and/or confidence limits of the mean was available. This is a major problem and, in our opinion, the data presentation does not allow for any conclusions about how the PDS really performs in clinical settings. It should be emphasised that statistical significance alone is not sufficient as it could easily be achieved if there were some lower and some higher vascularisation scores in …
A comparison between the simplified erosion and narrowing score and the Sharp–van der Heijde score: post hoc analysis from the BeSt study
Authors: N B Klarenbeek, M Güler-Yüksel, D M F M van der Heijde, P J S M Kerstens, C Mallée, M L Westedt, T W J Huizinga, B A C Dijkmans, C F Allaart
Journal: Annals of the Rheumatic Diseases (2010)

The Sharp–van der Heijde method (SHS; range 0–448)1 is an often used and well-validated method to assess joint damage on x-rays in rheumatoid arthritis (RA). It is a comprehensive method that requires training, making it less feasible for clinical practice. The simplified erosion and narrowing score (SENS; range 0–86)2 scores the same joints as SHS, but without grading of damage per joint, making it quicker and easier to learn. Using SENS takes 7 min for seven sets of radiographs, compared with 25 min for seven sets using SHS.2

In earlier studies, SENS showed good reliability and responsiveness, but these studies either had no restrictions in disease duration or limited patient numbers.2–4 We aimed to compare the properties of SENS and SHS in a large group of early, intensively treated RA patients with limited joint damage during 5 years of follow-up in the BeSt (Behandel Strategieen [Treatment Strategies]) study. Details of the study have been described earlier.5

Annual radiographs of hands and feet …
Life Study: a UK-wide birth cohort study of environment, development, health, and wellbeing
Authors: Carol Dezateux, Peter Brocklehurst, Simon Burgess, Paul Burton, Anne Carey, Debbie Colson, Chris Dibben, Paul Elliott, Alan Emond, Harvey Goldstein, Hilary Graham, Frank Kelly, Rachel Knowles, David Leon, Ronan Lyons, Diane Reay, Anna Vignoles, Suzanne Walton
Journal: The Lancet (2013)
Plaque-associated endothelial dysfunction in apolipoprotein E-deficient mice on a regular diet. Effect of human apolipoprotein AI
Authors: H Crauwels
Journal: Cardiovascular Research (2003)

Apolipoprotein E-deficient mice (apoE(-/-)) on a regular diet become hypercholesterolemic and develop atherosclerosis, but endothelium-dependent relaxation remains undisturbed for up to 6 months. We investigated whether vasomotor dysfunction develops in aged apoE(-/-), whether the defect was systemic (hypercholesterolemia-dependent) or focal (plaque-related), and the effect of human apolipoprotein AI transgenesis (apoAI/E(-/-)).Arteries of apoE(-/-) (n=5), apoAI/E(-/-) (n=6) and C57Bl/6J (WT, n=4) mice (18 months) were systematically dissected for isometric tension recording and subsequent morphometry.Acetylcholine (ACh)-induced relaxation was impaired (P<0.01) in atherosclerotic segments of apoE(-/-) (26+/-14%) as compared to WT mice (93+/-2%). Similar reduced (P<0.01) responses to adenosine 5'-triphosphate (apoE(-/-) 38+/-14, WT 94+/-3%) and the calcium ionophore A23187 (apoE(-/-) 19+/-6%, WT 97+/-2%) pointed to a post-receptor defect. Indeed, responses to exogenous nitric oxide were impaired in atherosclerotic segments as well (apoE(-/-) 71+/-7%, WT 92+/-1%, P<0.05). Furthermore, relaxations inversely correlated with plaque size (ACh r(s)=-0.74, P<0.01). In adjacent plaque-free segments however, responses to ACh (apoE(-/-) 92+/-3%, WT 97+/-1%) and all other agents were preserved, despite the prolonged hypercholesterolemia. ApoAI improved vasomotor responses in atherosclerotic segments. However, negative correlations between maximal relaxation and plaque area remained in apoAI/E(-/-) mice (ACh r(s)=-0.67, P<0.01). Indeed, covariate analysis of variance did not point to direct protection of vasomotor function by apoAI when the smaller lesions were taken into account.Endothelial dysfunction in apoE(-/-) mice is not affected by hypercholesterolemia alone, but is strictly associated with plaque formation. Human apoAI transgenesis-known to raise HDL-attenuated atherogenesis, thereby indirectly improving relaxation responses in apoE(-/-) mice.
Estimation of Cigarette Smoking–Attributable Morbidity in the United States
Authors: Brian L. Rostron, Cindy M. Chang, Terry F. Pechacek
Journal: JAMA Internal Medicine (2014)

Cigarette smoking has been found to harm nearly every bodily organ and is a leading cause of preventable disease, but current estimates of smoking-attributable morbidity by condition for the United States are generally unavailable.To estimate the burden of major medical conditions attributable to cigarette smoking in the United States.The disease burden of smoking was estimated using population-attributable risk calculations, taking into account the uncertainty of estimates. Population estimates came from 2009 US Census Bureau data and smoking prevalence, disease prevalence, and disease relative risk estimates came from National Health Interview Survey data for surveyed adults from 2006 through 2012. National Health and Nutrition Examination Survey spirometry data obtained from medical examination of surveyed adults from 2007 through 2010 was used to adjust for underreporting of chronic obstructive pulmonary disease.Smoking status was assessed from self-reported National Health Interview Survey data.The number of adults 35 years and older who had had a major smoking-attributable disease by sex and condition and the total number of these conditions were estimated for the United States in 2009.Using National Health Interview Survey data, we estimated that 6.9 million (95% CI, 6.5-7.4 million) US adults had had a combined 10.9 million (95% CI, 10.3-11.5 million) self-reported smoking-attributable medical conditions. Using chronic obstructive pulmonary disease prevalence estimates obtained from National Health and Nutrition Examination Survey self-reported and spirometry data, we estimated that US adults had had a combined 14.0 million (95% CI, 12.9-15.1 million) smoking-attributable conditions in 2009.We estimate that US adults have had approximately 14 million major medical conditions that were attributable to smoking. This figure is generally conservative owing to the existence of other diseases and medical events that were not included in these estimates. Cigarette smoking remains a leading cause of preventable disease in the United States, underscoring the need for continuing and vigorous smoking-prevention efforts.
AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function
Authors: Laura L. Dugan, Young-Hyun You, Sameh S. Ali, Maggie Diamond-Stanic, Satoshi Miyamoto, Anne-Emilie DeCleves, Aleksander Andreyev, Tammy Quach, San Ly, Grigory Shekhtman, William Nguyen, Andre Chepetan, Thuy P. Le, Lin Wang, Ming Xu, Kacie P. Paik, Agnes Fogo, Benoit Viollet, Anne Murphy, Frank Brosius, Robert K. Naviaux, Kumar Sharma
Journal: Journal of Clinical Investigation (2013)

Diabetic microvascular complications have been considered to be mediated by a glucose-driven increase in mitochondrial superoxide anion production. Here, we report that superoxide production was reduced in the kidneys of a steptozotocin-induced mouse model of type 1 diabetes, as assessed by in vivo real-time transcutaneous fluorescence, confocal microscopy, and electron paramagnetic resonance analysis. Reduction of mitochondrial biogenesis and phosphorylation of pyruvate dehydrogenase (PDH) were observed in kidneys from diabetic mice. These observations were consistent with an overall reduction of mitochondrial glucose oxidation. Activity of AMPK, the major energy-sensing enzyme, was reduced in kidneys from both diabetic mice and humans. Mitochondrial biogenesis, PDH activity, and mitochondrial complex activity were rescued by treatment with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). AICAR treatment induced superoxide production and was linked with glomerular matrix and albuminuria reduction in the diabetic kidney. Furthermore, diabetic heterozygous superoxide dismutase 2 (Sod2+/–) mice had no evidence of increased renal disease, and Ampka2–/– mice had increased albuminuria that was not reduced with AICAR treatment. Reduction of mitochondrial superoxide production with rotenone was sufficient to reduce AMPK phosphorylation in mouse kidneys. Taken together, these results demonstrate that diabetic kidneys have reduced superoxide and mitochondrial biogenesis and activation of AMPK enhances superoxide production and mitochondrial function while reducing disease activity.