tbuckley/cabot-search huggingface dataset:
The effect of cigarette smoking on BAL protein profile
Authors: Paola Rottoli, Claudia Landi, Elena Bargagli, Alfonso Carleo, Carmela Olivieri, Pasquale Di Sipio, Rosa Metella Refini, Luca Bini
Journal: European Respiratory Journal (2012)

BACKGROUND: BAL proteomic analysis gives a panorama of the complex network of proteins of different origin and function and their modifications at alveolar level, simultaneously providing new information about events in the alveolar microenvironment and insights into lung physiology and pathology. In this study we applied the proteomic approach to the study of BAL in order to evaluate the effect of smoking exposure to BAL protein composition.  AIM: Aim of this study was to investigate qualitative and quantitative differences in BAL protein profiles from cigarette smoker and no-smoker healthy subjects.  METHODS: BAL samples were obtained by 10 healthy never-smoker and 8 asymptomatic smoker subjects. After centrifugation, dialysis and denaturation of samples, BAL samples were analyzed by two-dimensional electrophoresis and proteins differentially expressed were identified by mass spectrometry.  RESULTS: 20 BAL proteins were differently expressed: 15 were up-regulated in smokers and 5 proteins were up-regulated in never-smokers. Among these proteins some were involved in immune-regulation, host defense (i.e.Pulmonary Surfactant-associated protein A2), apoptosis, inflammatory responses (i.e. α-1-antichymotrypsin) and oxidant/antioxidant balance (i.e. Glutathione S transferase P and Annexin A5).  CONCLUSION: In healthy subjects smoking exposure modifies the expression of several BAL proteins implicated in the regulation of crucial biological activities (such as oxidant/antioxidant balance, inflammation and tissue matrix turnover) potentially involved in the pathogenesis of several smoke-induced lung diseases.
International, Randomized, Placebo-Controlled, Double-Blind Phase III Study of Motesanib Plus Carboplatin/Paclitaxel in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer: MONET1
Authors: Giorgio V. Scagliotti, Ihor Vynnychenko, Keunchil Park, Yukito Ichinose, Kaoru Kubota, Fiona Blackhall, Robert Pirker, Rinat Galiulin, Tudor-Eliade Ciuleanu, Oleksandr Sydorenko, Mircea Dediu, Zsolt Papai-Szekely, Natividad Martinez Banaclocha, Sheryl McCoy, Bin Yao, Yong-jiang Hei, Francesco Galimi, David R. Spigel
Journal: Journal of Clinical Oncology (2012)

We evaluated whether motesanib (a selective oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) combined with carboplatin/paclitaxel improved overall survival (OS) versus chemotherapy alone in patients with nonsquamous non-small-cell lung cancer (NSCLC) and in the subset of patients with adenocarcinoma.Patients with stage IIIB/IV or recurrent nonsquamous NSCLC (no prior systemic therapy for advanced disease) were randomly assigned 1:1 to carboplatin (area under the curve, 6 mg/ml · min) and paclitaxel (200 mg/m(2)) intravenously for up to six 3-week cycles plus either motesanib 125 mg (arm A) or placebo (arm B) once daily orally. OS was the primary end point. Secondary end points included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), and association between placental growth factor (PLGF) change and OS.A total of 1,090 patients with nonsquamous NSCLC were randomly assigned (arms A/B, n = 541 of 549); of those, 890 had adenocarcinoma (n = 448 of 442). Median OS in arms A and B was 13.0 and 11.0 months, respectively (hazard ratio [HR], 0.90; 95% CI, 0.78 to 1.04; P = .14); median OS for the adenocarcinoma subset was 13.5 and 11.0 months, respectively (HR, 0.88; 95% CI, 0.75 to 1.03; P = .11). In descriptive analyses (arms A v B), median PFS was 5.6 months versus 5.4 months (P = < .001); ORR was 40% versus 26% (P < .001). There was no association between PLGF change and OS in arm A. The incidence of grade ≥ 3 AEs (arms A and B, 73% and 59%, respectively) and grade 5 AEs (14% and 9%, respectively) was higher with motesanib treatment.Motesanib plus carboplatin/paclitaxel did not significantly improve OS over carboplatin/paclitaxel alone in patients with advanced nonsquamous NSCLC or in the adenocarcinoma subset.
Macrosomia and Hyperinsulinaemic Hypoglycaemia in Patients with Heterozygous Mutations in the HNF4A Gene
Authors: Ewan R Pearson, Sylvia F Boj, Anna M Steele, Timothy Barrett, Karen Stals, Julian P Shield, Sian Ellard, Jorge Ferrer, Andrew T Hattersley
Journal: PLoS Medicine (2007)

Background Macrosomia is associated with considerable neonatal and maternal morbidity. Factors that predict macrosomia are poorly understood. The increased rate of macrosomia in the offspring of pregnant women with diabetes and in congenital hyperinsulinaemia is mediated by increased foetal insulin secretion. We assessed the in utero and neonatal role of two key regulators of pancreatic insulin secretion by studying birthweight and the incidence of neonatal hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY) genes HNF4A (encoding HNF-4α) and HNF1A/TCF1 (encoding HNF-1α), and the effect of pancreatic deletion of Hnf4a on foetal and neonatal insulin secretion in mice. Methods and Findings We examined birthweight and hypoglycaemia in 108 patients from families with diabetes due to HNF4A mutations, and 134 patients from families with HNF1A mutations. Birthweight was increased by a median of 790 g in HNF4A-mutation carriers compared to non-mutation family members (p < 0.001); 56% (30/54) of HNF4A-mutation carriers were macrosomic compared with 13% (7/54) of non-mutation family members (p < 0.001). Transient hypoglycaemia was reported in 8/54 infants with heterozygous HNF4A mutations, but was reported in none of 54 non-mutation carriers (p = 0.003). There was documented hyperinsulinaemia in three cases. Birthweight and prevalence of neonatal hypoglycaemia were not increased in HNF1A-mutation carriers. Mice with pancreatic β-cell deletion of Hnf4a had hyperinsulinaemia in utero and hyperinsulinaemic hypoglycaemia at birth. Conclusions HNF4A mutations are associated with a considerable increase in birthweight and macrosomia, and are a novel cause of neonatal hypoglycaemia. This study establishes a key role for HNF4A in determining foetal birthweight, and uncovers an unanticipated feature of the natural history of HNF4A-deficient diabetes, with hyperinsulinaemia at birth evolving to decreased insulin secretion and diabetes later in life.
Comparison of inhaled and intravenous terbutaline in acute severe asthma.
Authors: S J Williams, S J Winner, T J Clark
Journal: Thorax (1981)

<h3>Objective:</h3> We aimed to quantify the effects of white matter hyperintensities (WMHs) on specific cognitive functions with particular attention to WMH progression and localization. <h3>Methods:</h3> PubMed (January 1990–July 2013) and bibliographies from included articles were used. Studies that were included (1) used MRI; (2) had a population-based or case-control design with a healthy control group that could be used for analysis; (3) matched/adjusted for age, sex, and education; and (4) addressed ≥1 predefined cognitive domains with ≥1 validated neuropsychological tests. Data were independently extracted by 2 investigators. Pearson <i>r</i> was extracted/calculated and used as the common metric for the effect size across studies. <h3>Results:</h3> Twenty-three cross-sectional and 14 longitudinal studies were included with a total of 8,685 and 7,731 participants. Presence of WMHs was significantly associated with concurrent cognitive deficits in all examined domains: general intelligence (Fisher <i>z</i> −0.10, 95% confidence interval [CI] −0.19 to −0.04), memory (−0.08, −0.13 to −0.06), processing speed (−0.11, −0.17 to −0.07), attention and executive functions (−0.11, −0.16 to −0.07), and perception/construction (−0.15, −0.21 to −0.07). Similar effect sizes were observed for cognitive decline over time. WMH progression was associated with greater cognitive decline, particularly for general intelligence (Fisher <i>z</i> −0.31, 95% CI −0.5 to −0.02) and attention and executive functions (−0.32, −0.34 to −0.28). <h3>Conclusions:</h3> The small but robust and consistent effects of WMHs on all cognitive domains suggest a more global effect on cognition than previously thought. Progression of WMHs was associated with even worse cognitive functioning, most pronounced in attention and executive functioning.
Effects of Bay k 8644, a dihydropyridine analog, on [3H]nitrendipine binding to canine cardiac sarcolemma and the relationship to a positive inotropic effect.
Authors: P L Vaghy, I L Grupp, G Grupp, A Schwartz
Journal: Circulation Research (1984)

Equilibrium dissociation constants of Bay k 8644, a calcium agonist, and nitrendipine, a calcium antagonist, were determined in canine cardiac sarcolemma. The equilibrium dissociation constant for Bay k 8644 was compared to the concentration that produced a fifty percent increase, and the equilibrium dissociation constant for nitrendipine was compared to the concentration that produced a fifty percent decrease, in contractile force in canine heart trabecular muscle. Both saturation and inhibition binding data suggest that Bay k 8644 and nitrendipine bind to and compete for a high affinity dihydropyridine-binding site present in isolated cardiac sarcolemma preparations. The equilibrium dissociation constant (7-10 nM) and concentration that produced a fifty percent increase in contractile force in the canine trabecular muscle (30 +/- 8 nM) of Bay k 8644 were in a similar concentration range, but the equilibrium dissociation constant (0.29 +/- 0.025 nM) of nitrendipine binding was more than a thousand-fold lower than the concentration that produced a fifty percent decrease in contractile force in canine trabecular muscle (613 +/- 109 nM). These data suggest that binding of Bay k 8644 to high affinity binding sites is pharmacologically relevant, and is related to a positive inotropic effect.
Hormones and the immune response.
Authors: A K Bhalla
Journal: Annals of the Rheumatic Diseases (1989)

Hormones and the immune responseRecent advances suggest that the immune system does not function in isolation but is influenced by other physiological systems such as the endocrine and neuroendocrine systems.This review discusses aspects of immune function altered by neuroendo- crine peptides, sex hormones, and vitamin D metabolites. Neuroendocrine effectsA system of bidirectional communication between the immune and neuroendocrine system exists, in which the two systems share a common set of hormones and receptors.' 2 Not only do immune cells possess receptors for neuroendocrine peptides, they are also capable of synthesising them and of responding to them.Products of immune cells affect the central nervous system, which possesses recep- tors for cytokines and can also synthesise them (Fig. 1).Receptors for neuroendocrine peptides, such as adrenocorticotrophic hormone (ACTH), ,3-endorphin, thyroid stimulating hormone, and growth hormone are present on immune cells.High and low affinity ACTH receptors, similar to those on adrenal hormones 1 copyright.
Radiation Damage to the Heart Enhances Early Radiation-Induced Lung Function Loss
Authors: Peter van Luijk, Alena Novakova-Jiresova, Hette Faber, Jacobus M. Schippers, Harm H. Kampinga, Harm Meertens, Rob P. Coppes
Journal: Cancer Research (2005)

In many thoracic cancers, the radiation dose that can safely be delivered to the target volume is limited by the tolerance dose of the surrounding lung tissue. It has been hypothesized that irradiation of the heart may be an additional risk factor for the development of early radiation-induced lung morbidity. In the current study, the dependence of lung tolerance dose on heart irradiation is determined. Fifty percent of the rat lungs were irradiated either including or excluding the heart. Proton beams were used to allow very accurate and conformal dose delivery. Lung function toxicity was scored using a breathing rate assay. We confirmed that the tolerance dose for early lung function damage depends not only on the lung region that is irradiated but also that concomitant irradiation of the heart severely reduces the tolerance of the lung. This study for the first time shows that the response of an organ to irradiation does not necessarily depend on the dose distribution in that organ alone.
Lymphoma and other malignancies in primary Sjogren's syndrome: a cohort study on cancer incidence and lymphoma predictors
Authors: E Theander
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To assess the risk of lymphoproliferative disease or other malignancy (standardised incidence ratios (SIRs)), in patients with primary Sjögren's syndrome according to the American-European Consensus Criteria (AECC), compared with patients with sicca syndrome (non-AECC) and the background population. To identify predictors of malignancy and describe lymphoma types and survival probabilities<i>.</i> <b>Methods:</b> A linked register study using information from the Malmö Primary SS Register, Swedish Cancer Register, and Cause-of-Death Register for calculation of SIRs was carried out. Detected lymphomas were reclassified according to the WHO classification. Cox regression analysis was used to study the predictive value of clinical, laboratory, and histological findings at the time of diagnosis. <b>Results:</b> 507 patients with a median follow up of 8 years (range 1 month to 19 years) were included. SIRs (95% confidence interval (CI)) for malignancies in total and for non-Hodgkin's lymphomas (NHL) were 1.42 (0.98 to 2.00) and 15.57 (7.77 to 27.85), respectively, in those fulfilling the AECC (n = 286). In non-AECC sicca patients (n = 221) SIR for malignancy of any kind was 0.77 (0.41 to 1.32); no lymphoproliferative neoplasms were detected. Significant predictors of lymphoproliferative disease were purpura/skin vasculitis (hazard ratio (HR) = 4.64, 95% CI 1.13 to 16.45), low complement factor C3 (HR = 6.18, 95% CI 1.57 to 24.22), low C4 (HR = 9.49, 95% CI 1.94 to 46.54), CD4+ T lymphocytopenia (HR = 8.14, 95% CI 2.10 to 31.53), and a low CD4+/CD8+ T cell ratio ⩽0.8 (HR = 10.92, 95% CI 2.80 to 41.83). 7/12 (58%) NHLs were diffuse large B cell lymphomas. <b>Conclusion:</b> A 16-fold increased risk for development of NHL was found. CD4+ T lymphocytopenia is an additional strong risk factor for developing lymphoma.
A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities
Authors: Yuta Kochi, Ryo Yamada, Akari Suzuki, John B Harley, Senji Shirasawa, Tetsuji Sawada, Sang-Cheol Bae, Shinya Tokuhiro, Xiaotian Chang, Akihiro Sekine, Atsushi Takahashi, Tatsuhiko Tsunoda, Yozo Ohnishi, Kenneth M Kaufman, Changsoo Paul Kang, Changwon Kang, Shigeru Otsubo, Wako Yumura, Akio Mimori, Takao Koike, Yusuke Nakamura, Takehiko Sasazuki, Kazuhiko Yamamoto
Journal: Nature Genetics (2005)
High resolution computed tomography of the lung in lifelong non-smoking patients with rheumatoid arthritis.
Authors: W U Hassan, N P Keaney, C D Holland, C A Kelly
Journal: Annals of the Rheumatic Diseases (1995)

To define pulmonary involvement on high resolution computed tomography (HRCT) of the thorax in lifelong non-smoking rheumatoid arthritis patients and to relate the results to pulmonary function, bronchial reactivity, and a variety of clinical and serological factors.Twenty lifelong non-smoking RA patients (mean age 59 years (range 44-72; 18 females) were studied. Detailed medical and drug histories were taken. Protease inhibitor phenotype (Pi) and HLA-DR4 status were assessed. Schirmer's tear tests were performed to detect keratoconjunctivitis sicca (KCS). Spirometry, flow volume loops, and gas transfer factor measurement were recorded. The degree of bronchial reactivity (PC20 FEV1) was measured by a methacholine inhalation test. Chest and hand radiographs and HRCT of the lung were performed in all patients.Thirteen patients were HLA-DR4 positive. Eighteen had the Pi MM and two the Pi MS phenotype. Eight patients had evidence of KCS on Schirmer's tear testing. Ten patients achieved PC20 FEV1 in the methacholine inhalation test. All the patients had normal chest radiographs and all showed evidence of erosive arthropathy on hand radiographs. Five patients (25%) showed basal bronchiectasis and one mild interstitial lung disease on HRCT. All five patients with bronchiectasis had the Pi MM phenotype, four had HLA-DR4, four had KCS and three achieved PC20 FEV1; these values were not significantly different (p > 0.05) from those in patients without bronchiectasis.Using the highly sensitive technique of HRCT, we found evidence to suggest that the incidence of bronchiectasis in lifelong non-smoking RA patients may be much higher than previously reported.
Patterns of Clinical Recurrence of Node-positive Prostate Cancer and Impact on Long-term Survival
Authors: Alessandro Nini, Giorgio Gandaglia, Nicola Fossati, Nazareno Suardi, Vito Cucchiara, Paolo Dell’Oglio, Walter Cazzaniga, Stefano Luzzago, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2015)
Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention (SORT OUT V): a randomised non-inferiority trial
Authors: Evald Høj Christiansen, Lisette Okkels Jensen, Per Thayssen, Hans-Henrik Tilsted, Lars Romer Krusell, Knud Nørregaard Hansen, Anne Kaltoft, Michael Maeng, Steen Dalby Kristensen, Hans Erik Bøtker, Christian Juhl Terkelsen, Anton Boel Villadsen, Jan Ravkilde, Jens Aarøe, Morten Madsen, Leif Thuesen, Jens Flensted Lassen
Journal: The Lancet (2013)
Nitric oxide (NO), a new test gas for study of alveolar-capillary diffusion
Authors: M Meyer, J Piiper
Journal: European Respiratory Journal (1989)

In a previous issue a paper by BoRLAND and HlGENBOTIAM [1) explores the potential of a new test gas for assessment of alveolar-capillary diffusion, nitric oxide (NO).This editorial is intended to provide a background and a discussion of this remarkable new development.
Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells
Authors: Wei-Lun Huang, Hsuan-Heng Yeh, Chien-Chung Lin, Wu-Wei Lai, Jang-Yang Chang, Wen-Tsan Chang, Wu-Chou Su
Journal: Molecular Cancer (2010)

Abstract Background Spontaneous interleukin-6 (IL-6) production has been observed in various tumors and implicated in the pathogenesis, progression and drug resistance in cancer. However, the regulation of IL-6 autocrine production in cancer cells is not fully understood. IL-6 is auto-regulated in many types of cell. Two of the three major downstream pathways of IL-6, MEK/extracellular signal-related kinase (Erk) pathway and phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, have been shown to regulate IL-6 expression through the activation of AP-1 and NF-κB. However, it is not clear what the role of Janus kinase (Jak) 2/signal transducer and activator of transcription (Stat) 3 pathway. This study was designed to determine the role of Jak2/Stat3 pathway in the regulation of IL-6 autocrine production in cancer cells. Results Inhibitors of Jak2/Stat3, MEK/Erk and PI3-K/Akt pathways down-regulated IL-6 secretion in the lung adenocarcinoma PC14PE6/AS2 (AS2) cells, which spontaneously secreted IL-6 and possessed constitutively activated Stat3. Transfection with dominant-negative Stat3, Stat3 siRNA, or Stat3 shRNA decreased IL-6 expression in AS2 cells. Conversely, transfection with constitutively-activated Stat3 increased the production of IL-6. In AS2 derived cells, resistance to paclitaxel was positively correlated with Stat3 activation status and the expression of IL-6, which is commonly secreted in drug resistant cancer cells. The pharmacological inhibition of NF-κB, PI3-K/Akt and MEK/Erk and the pharmacological inhibition and genetic inhibition (Stat3 siRNA) of Jak2/Stat3 pathway decreased IL-6 autocrine production in various drug resistant cancer cell lines and similarly decreased IL-6 autocrine production in clinically isolated lung cancer cells. Conclusions This study is the first to directly address the role Stat3 plays on the autocrine production of IL-6, which occurs through a positive-feedback loop. Our biochemical and genetic studies clearly demonstrated that Jak2/Stat3, in combination with other IL-6 downstream pathways, contributed frequently and substantially to IL-6 autocrine production in a broad spectrum of cancer cell lines as well as in clinical cancer samples. Our findings suggest that Stat3 could potentially be regulated to suppress IL-6 autocrine production in cancer cells to inhibit the progression of cancer and reduce drug resistance.
Faster femoral artery blood velocity kinetics at the onset of exercise following short-term training
Authors: J.K. Shoemaker, S.M. Phillips, H.J. Green, R.L. Hughson
Journal: Cardiovascular Research (1996)

Objective: The hypothesis that the adaptation to endurance exercise training included a faster increase in blood flow at the onset of exercise was tested in 12 healthy young men who endurance-trained (ET) 2 h/day, for 10 days at 65% V̇O2 peak on a cycl and in 11 non-training control (C) subjects. Methods: Blood flow was estimated from changes in femoral artery mean blood velocity (MBV) by pulsed Doppler. Beat-by-beat changes in cardiac output (CO) and mean arterial pressure (MAP) were obtained by impedance cardiography and a Finapres finger cuff, respectively. MBV, MAP and CO were measured at rest and during 5 min of dynamic knee extension exercise. Both legs worked alternately with 2 s raising and lowering a weight (15% maximal voluntary contraction) followed by 2 s rest while the other leg raised and lowered the weight. Results: In the ET group the time to 63% (T63%) of the approximately exponential increase in MBV following 10 days of training (8.6 ± 1.2 s, mean ± s.e.) was significantly faster than the Day 0 response (14.2 ± 2.1 s, P < 0.05). The T63% of femoral artery vascular conductance (VCfa) was also faster following 10 days of ET (9.4 ± 0.9 s) versus Day 0 (16.0 ± 2.5 s) (0.05). There was no change in the T63% of both MBV and VCfa for the C group. The kinetics of CO were not significantly affected by ET, but the amplitude of CO in the adaptive phase, and at steady state, were significantly greater (P < 0.05) at Day 10 compared to Day 0 for the ET group with no change in the C group. Conclusions: These data supported the hypothesis that endurance training resulted in faster adaptation of blood flow to exercising muscle, and further showed that this response occurred early in the training program.