tbuckley/cabot-search huggingface dataset:
Lung Function from Infancy to the Preschool Years after Clinical Diagnosis of Cystic Fibrosis
Authors: Wanda J. Kozlowska, Andrew Bush, Angela Wade, Paul Aurora, Siobhán B. Carr, Rosie A. Castle, Ah-Fong Hoo, Sooky Lum, John Price, Sarath Ranganathan, Clare Saunders, Sanja Stanojevic, John Stroobant, Colin Wallis, Janet Stocks
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

After recent standardization of forced expiratory maneuvers for both infants and preschool children, longitudinal measurements are now possible from birth.The aim of this study was to investigate the evolution of lung function during the first 6 years of life after a clinical diagnosis of cystic fibrosis (CF) in infancy in children with CF and in healthy control subjects.The raised volume technique was used during infancy and incentive spirometry during the preschool years.Forty-eight children with CF and 33 healthy control subjects had up to seven (median, 3) measurements. Over these early years, the diagnosis of CF itself accounted for a significant mean reduction of 7.5% (95% confidence interval, 0.9 - 13.6%) in FEV(0.75) and 15.1% (95% confidence interval, 3.6 - 25.3%) in FEF(25-75). Wheeze on auscultation, recent cough, and Pseudomonas aeruginosa (PsA) infection (even if apparently effectively treated) were all independently associated with further reductions in lung function. Premorbid lung function did not predict infection with PsA.This is the first study to describe physiologic measurements from infancy through the preschool years in subjects with CF and healthy control subjects, the understanding of which is critical for future intervention trials. Airflow obstruction in uncomplicated CF persists through the preschool years despite treatment, with PsA acquisition being associated with further deterioration in lung function, even when apparently eradicated. This suggests that new therapies are needed to treat the airflow obstruction of uncomplicated CF, and rigorous strategies to prevent PsA acquisition.
Translating clinical trials to clinical practice: outcomes of men with metastatic castration resistant prostate cancer treated with docetaxel and prednisone in and out of clinical trials
Authors: A.J. Templeton, F.E. Vera-Badillo, L. Wang, M. Attalla, P. De Gouveia, R. Leibowitz-Amit, J.J. Knox, M. Moore, S.S. Sridhar, A.M. Joshua, G.R. Pond, E. Amir, I.F. Tannock
Journal: Annals of Oncology (2013)
An Investigation of Airway Acidification in Asthma Using Induced Sputum
Authors: Metka Kodric, Ajay N. Shah, Leonardo M. Fabbri, Marco Confalonieri
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Acidification of the airways seems to be involved in asthma pathophysiology, but its assessment might be difficult.Objectives: The aim of our study is to assess the feasibility and validity of airway acidification measurement by induced sputum and its clinical significance in asthma.Methods: Induced-sputum samples were obtained in 57 outpatients with asthma. The between-sample repeatability after 48 hours was measured in an independent population of 14 patients with asthma. pH was measured using a pH meter. The control of asthma was established by the Asthma Control Questionnaire.Measurements and Main Results: The pH measurement was feasible in all samples and repeatable both within (intraclass correlation coefficient [ICC], 0.96) and between samples (ICC, 0.621). The mean pH was significantly different between healthy subjects and patients with asthma, including in those with controlled (mean pH: 7.54 in healthy subjects vs. 7.28 in subjects with controlled asthma; p = 0.0105) and uncontrolled disease (mean pH: 7.54 in healthy subjects vs. 7.06 in subjects with uncontrolled disease; p < 0.0001), and between patients with stable asthma and those with poorly controlled asthma (7.28 vs. 7.06, respectively; p = 0.0134). The validity of the method was assessed with the receiver operating characteristic curves and induced-sputum lower pH values (with a cutoff value of 7.3; sensitivity, 72.1%; specificity, 100%).Conclusions: Patients with asthma show lower pH than healthy subjects. Patients with poorly controlled asthma seem to have the lowest induced-sputum pH, independent of the GINA (Global Initiative for Asthma) severity level. In conclusion, induced sputum is a feasible, repeatable, noninvasive method to measure airway pH. The pH in induced sputum may reflect a different aspect of asthma from sputum eosinophils and be related to different pathophysiologic factors.
miR-29b defines the pro-/anti-proliferative effects of S100A7 in breast cancer
Authors: Helong Zhao, Tasha Wilkie, Yadwinder Deol, Amita Sneh, Akaansha Ganju, Mustafa Basree, Mohd W Nasser, Ramesh K Ganju
Journal: Molecular Cancer (2015)

S100A7 (Psoriasin) is an inflammatory protein known to be upregulated in breast cancer. However, the role of S100A7 in breast cancer has been elusive, since both pro- and anti-proliferative roles have been reported in different types of breast cancer cells and animal models. To date, the mechanism by which S100A7 differentially regulates breast cancer cell proliferation is still not clear. We used Gene Functional Enrichment Analysis to search for the determining factor of S100A7 differential regulation. We confirmed the factor and elaborated its regulating mechanism using in vitro cell culture. We further verified the findings using xenografts of human breast cancer cells in nude mice. In the present study, we show that S100A7 significantly upregulates the expression of miR-29b in Estrogen Receptor (ER)-positive breast cancer cells (represented by MCF7), and significantly downregulates miR-29b in ER-negative cells (represented by MDA-MB-231). The differential regulation of miR-29b by S100A7 in ER-positive and ER-negative breast cancer is supported by the gene expression analysis of TCGA invasive breast cancer dataset. miR-29b transcription is inhibited by NF-κB, and NF-κB activation is differentially regulated by S100A7 in ER-positive and ER-negative breast cancer cells. This further leads to differential regulation of PI3K p85α and CDC42 expression, p53 activation and p53-associated anti-proliferative pathways. Reversing the S100A7-caused changes of miR-29b expression by transfecting exogenous miR-29b or miR-29b-Decoy can inhibit the effects of S100A7 on in vitro cell proliferation and tumor growth in nude mice. The distinct modulations of the NF-κB – miR-29b – p53 pathway make S100A7 an oncogene in ER-negative and a cancer-suppressing gene in ER-positive breast cancer cells, with miR-29b being the determining regulatory factor.
Cooperative Activation of Tissue-Specific Genes by pRB and E2F1
Authors: Stephen Flowers, Fuhua Xu, Elizabeth Moran
Journal: Cancer Research (2013)

The retinoblastoma tumor suppressor protein pRB is conventionally regarded as an inhibitor of the E2F family of transcription factors. Conversely, pRB is also recognized as an activator of tissue-specific gene expression along various lineages including osteoblastogenesis. During osteoblast differentiation, pRB directly targets Alpl and Bglap, which encode the major markers of osteogenesis alkaline phosphatase and osteocalcin. Surprisingly, p130 and repressor E2Fs were recently found to cooccupy and repress Alpl and Bglap in proliferating osteoblast precursors before differentiation. This raises the further question of whether these genes convert to E2F activation targets when differentiation begins, which would constitute a remarkable situation wherein pRB and E2F would be cotargeting genes for activation. Chromatin immunoprecipitation analysis in an osteoblast differentiation model shows that Alpl and Bglap are indeed targeted by an activator E2F, i.e., is E2F1. Promoter occupation of Alpl and Bglap by E2F1 occurs specifically during activation, and depletion of E2F1 severely impairs their induction. Mechanistically, promoter occupation by E2F1 and pRB is mutually dependent, and without this cooperative effect, activation steps previously shown to be dependent on pRB, including recruitment of RNA polymerase II, are impaired. Myocyte- and adipocyte-specific genes are also cotargeted by E2F1 and pRB during differentiation along their respective lineages. The finding that pRB and E2F1 cooperate to activate expression of tissue-specific genes is a paradigm distinct from the classical concept of pRB as an inhibitor of E2F1, but is consistent with the observed roles of these proteins in physiological models.
Localization of Sodium Channels in Intercalated Disks Modulates Cardiac Conduction
Authors: Jan P. Kucera, Stephan Rohr, Yoram Rudy
Journal: Circulation Research (2002)

It is well known that the sodium current ( I Na ) and the degree of gap-junctional electrical coupling are the key determinants of action potential (AP) conduction in cardiac tissue. Immunohistochemical studies have shown that sodium channels (NaChs) are preferentially located in intercalated disks (IDs). Using dual immunocytochemical staining, we confirmed the colocalization of NaChs with connexin43 in cultures of neonatal rat ventricular myocytes. In mathematical simulations of conduction using the Luo-Rudy dynamic model of the ventricular AP, we assessed the hypothesis that conduction could be modulated by the preferential localization of NaChs in IDs. Localization of I Na at the ID caused a large negative potential in the intercellular cleft, which influenced conduction in two opposing ways, depending on the degree of electrical coupling: (1) for normal and moderately reduced coupling, the negative cleft potential led to a large overshoot of the transmembrane potential resulting in a decreased driving force for I Na itself (self-attenuation), which slowed conduction; (2) for greatly reduced coupling (&lt;10%), the negative cleft potential induced by I Na in the prejunctional membrane led to suprathreshold depolarization of the postjunctional membrane, which facilitated and accelerated conduction. When cleft potential effects were not incorporated, conduction was not significantly affected by the ID localization of I Na . By enhancing conduction through the establishment of cleft potentials, the localization of NaChs in IDs might protect the myocardium from conduction block, very slow conduction, and microreentry under conditions of greatly reduced coupling. Conversely, by supporting moderately slow conduction, this mechanism could also promote arrhythmias.
A38: Twelve Years' Experience with Etanercept in the Treatment of Juvenile Idiopathic Arthritis: How It Has Changed Practice-The German Biologics JIA Registry (BiKeR)
Authors: Heinrike Schmeling, Kirsten Minden, Ivan Foeldvari, Johannes-Peter Haas, Anton Hospach, Gerd Horneff
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

The outcome of children with JIA refractory to disease-modifying antirheumatic drugs (DMARDs) has improved significantly since Etanercept became available. The objectives were to analyse data from the German Biologics JIA Registry (BiKeR) and to report on practice changes of the last twelve years.



Methods:

Baseline demographics, pre-treatment, concomitant treatment, clinical characteristics and disease activity parameters and outcome have been prospectively documented in BiKeR since 2000. Efficacy was determined using the PedACR response criteria, the JADAS-10 and the proposed criteria for inactive disease on medication.



Results:

From 2000 to 2012 1678 children with JIA on Etanercept with a total of 11,474 visits have been enrolled in BiKer (3424.2 total patient-years). The median disease duration at treatment start decreased from 4.5 to 2 years. While initially children have been pre-treated with numerous antirheumatic agents, including cytotoxic agents, pre–treatment markedly decreased by a mean 6.3 (median 4.3) to 0.99 (median 1.0) DMARDssol;patient. Concomitant treatment initially consisted of corticosteroids in 83%, Methotrexate in 95% and other DMARDs in 45% of children compared to 40%, 74% and 6.7% respectively in 2012. At Registry start, 26% of newly enrolled children belonged to the systemic JIA category compared to only 1% in 2012. In contrast, the rate of children with enthesitis related arthritis increased from 2% to 16%. The median JADAS-10 in 2000 compared to 2012 was significantly higher at treatment start (24.4+/−6.8 vs. 13.3+/−6.2) and remained higher after 6 months on treatment (7.5+/−7.2 vs. 4.5+/−5.2). The number of patients that have reached a PedACR 70 after 12 months on treatment increased from 41% starting in 2000 to 51% of patients starting in 2012. Inactive disease within one year was documented initially in 20% of children and increased to 43% in 2012.



Conclusion:

In recent years, children with JIA have been treated earlier, received less pre- and concomitant treatment with corticosteroids as well as with DMARDs. Patients have shown a markedly better outcome reflected in the higher PedACR response, lower JADAS-10 and higher rate of patients with inactive disease after one year on treatment. These data suggest that early disease control and better pre–selection of patients who need biologics are important to improve outcome in children with JIA.
Host discrimination of Mycoplasma pneumoniae proteinaceous immunogens.
Authors: D K Leith, L B Trevino, J G Tully, L B Senterfit, J B Baseman
Journal: The Journal of Experimental Medicine (1983)

The immune response of experimentally infected hamsters and human patients to Mycoplasma pneumoniae was examined by radioimmunoprecipation in conjunction with gel electrophoresis and fluorography. Both intrinsically and extrinsically labeled mycoplasma proteins were coincubated with acute and convalescent sera in a radioimmunoprecipitation assay. Two M. pneumoniae proteins were selectively precipitated by convalescent sera. These predominant immunogens were trypsin-sensitive, antibody-accessible surface proteins that co-migrate on polyacrylamide gels with proteins P1 and P2, which were previously implicated by us as mediators of cytadsorption. Anti-M. pneumoniae antiserum did not precipitate radiolabeled antigens derived from Mycoplasma orale or Mycoplasma salivarium. These data indicate that M. pneumoniae infection stimulates a specific and highly targeted host antibody response to key proteinaceous immunogens.
Angiotensin II-induced changes in smooth muscle calcium in rat renal arterioles.
Authors: J D Conger, S A Falk, J B Robinette
Journal: Journal of the American Society of Nephrology (1993)

The isolated rat renal arteriole technique was adapted for use in a fluorescence ratio imaging system in which angiotensin II (AII)-induced changes in lumen diameter and smooth muscle cell (SMC) cytosolic calcium [(Ca2+]i were serially determined for 4 min with Fura-2. Selective fluorescence acquisition from SMC was guided by direct image visualization of the vessel walls. A maximal constricting concentration of AII (10(-8) M) caused similar abrupt and sustained increases in SMC [Ca2+]i in afferent arterioles (AA) at 80 mm Hg and efferent arterioles (EA) at 30 mm Hg. When lumen pressure was reduced to 0 mm Hg, 10(-8) M AII caused abrupt peak increases in SMC [Ca2+]i in 15 s in both AA and EA, which declined rapidly thereafter--patterns distinctly different from pressurized vessels (P < 0.02). With diltiazem (10(-5) M) in the bathing media, 10(-8) M AII caused an abrupt rise and decline in SMC [Ca2+]i in AA, but a sustained elevation in EA (P < 0.02). In low-Ca(2+)-EGTA media, there was an abrupt peak and rapid decline in SMC [Ca2+]i to 10(-8) M AII in AA and EA; the abrupt peaks were attenuated by the prior addition of dantrolene (5 x 10(-5) M) to the low-Ca(2+)-EGTA media. When half-maximal constricting (EC50) AII for AA (4 x 10(-11) M) was added, there was a slow, progressive increase in SMC [Ca2+]i that was distinctly different from the abrupt peak and decline with EC50 AII (5 x 10(-12) M) in EA. Collectively, these findings indicate that maximal AII stimulates both Ca2+ entry and storage mobilization in AA and EA; EC50 AII stimulates primarily Ca2+ entry in AA, but storage mobilization in EA. Lumen pressure modifies the AII SMC [Ca2+]i response profiles.
Percutaneous transluminal coronary angioplasty versus medical treatment for non-acute coronary heart disease: meta-analysis of randomised controlled trials
Authors: H. C Bucher
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To determine whether percutaneous transluminal coronary angioplasty (angioplasty) is superior to medical treatment in non-acute coronary artery disease. <b>Design:</b> Meta-analysis of randomised controlled trials. <b>Setting:</b> Randomised controlled trials conducted worldwide and published between 1979 and 1998. <b>Participants:</b> 953 patients treated with angioplasty and 951 with medical treatment from six randomised controlled trials, three of which included patients with multivessel disease and pre-existing myocardial infarction. <b>Main outcome measures:</b> Angina, fatal and non-fatal myocardial infarction, death, repeated angioplasty, and coronary artery bypass grafting. <b>Results:</b> In patients treated with angioplasty compared with medical treatment the risk ratios were 0.70 (95% confidence interval 0.50 to 0.98; heterogeneity P&lt;0.001) for angina; 1.42 (0.90 to 2.25) for fatal and non-fatal myocardial infarction, 1.32 (0.65 to 2.70) for death, 1.59 (1.09 to 2.32) for coronary artery bypass graft, and 1.29 (0.71 to 3.36; heterogeneity P&lt;0.001) for repeated angioplasty. Differences in the methodological quality of the trials, in follow up, or in single versus multivessel disease did not explain the variability in study results in any analysis. <b>Conclusions:</b> Percutaneous transluminal coronary angioplasty may lead to a greater reduction in angina in patients with coronary heart disease than medical treatment but at the cost of more coronary artery bypass grafting. Trials have not included enough patients for informative estimates of the effect of angioplasty on myocardial infarction, death, or subsequent revascularisation, though trends so far do not favour angioplasty.
Comparative Evolution of the Mitochondrial Cytochrome b Gene and Nuclear β-Fibrinogen Intron 7 in Woodpeckers
Authors: Thomas M. Prychitko, William S. Moore
Journal: Molecular Biology and Evolution (2000)

Most molecular phylogenetic studies of vertebrates have been based on DNA sequences of mitochondrial-encoded genes. MtDNA evolves rapidly and is thus particularly useful for resolving relationships among recently evolved groups. However, it has the disadvantage that all of the mitochondrial genes are inherited as a single linkage group so that only one independent gene tree can be inferred regardless of the number of genes sequenced. Introns of nuclear genes are attractive candidates for independent sources of rapidly evolving DNA: they are pervasive, most of their nucleotides appear to be unconstrained by selection, and PCR primers can be designed for sequences in adjacent exons where nucleotide sequences are conserved. We sequenced intron 7 of the β-fibrinogen gene (β-fibint7) for a diversity of woodpeckers and compared the phylogenetic signal and nucleotide substitution properties of this DNA sequence with that of mitochondrial-encoded cytochrome b (cyt b) from a previous study. A few indels (insertions and deletions) were found in the β-fibint7 sequences, but alignment was not difficult, and the indels were phylogentically informative. The β-fibint7 and cyt b gene trees were nearly identical to each other but differed in significant ways from the traditional woodpecker classification. Cyt b evolves 2.8 times as fast as β-fibint7 (14.0 times as fast at third codon positions). Despite its relatively slow substitution rate, the phylogenetic signal in β-fibint7 is comparable to that in cyt b for woodpeckers, because β-fibint7 has less base composition bias and more uniform nucleotide substitution probabilities. As a consequence, compared with cyt b, β-fibint7 nucleotide sites are expected to enter more distinct character states over the course of evolution and have fewer multiple substitutions and lower levels of homoplasy. Moreover, in contrast to cyt b, in which nearly two thirds of nucleotide sites rarely vary among closely related taxa, virtually all β-fibint7 nucleotide sites appear free of selective constraints, which increases informative sites per unit sequenced. However, the estimated gamma distribution used to model rate variation among sites suggests constraints on some β-fibint7 sites. This study suggests that introns will be useful for phylogenetic studies of recently evolved groups.
Examination of patients whose eosinophilic ratio in sputum was more than 3% with wheezing or cough symptoms
Authors: Naoto Watanabe, Sohei Makino
Journal: European Respiratory Journal (2014)

Background: Bronchial asthma (BA) is defined as a chronic allergic airway inflammatory disease. Sputum eosinophilia is an important indicator of allergic inflammation of the respiratory tract.  Aim: This study determined the eosinophilic ratio of sputum for patients with wheeze or cough symptoms and distinguished patients showing sputum eosinophilia.  Methods: Subjects comprised 96 outpatients (47 men, 49 women; mean age, 44 years) with sputum eosinophilic ratio more than 3% among outpatients who had complained of wheeze or cough symptoms excluded pneumonia.  Diagnoses of subjects were made based on various examinations (particularly blood data, sputum culture, chest X-ray, pulmonary function test and broncho-hypersensitivity challenge, etc.). In addition, we examined cell fractionation as same as eosinophil in sputum.  Results: Sixty-one patients were diagnosed with BA(or CVA). In the remaining patients, there were 2 atopic coughs, 2 chronic sinusitis, a chronic bronchitis, 29 atypical infections (virus, mycoplasma, chlamydia, or pertussis) and a bacterial bronchitis. Increased lymphocytes with eosinophils were observed in sputum of many patients with atypical infection.  Conclusion: Confirmation of eosinophilia in sputum is very useful for early diagnosis of BA. However, eosinophils are also increased in sputum with other pathologies. Therefore, checking other cell ratios (neutrophils and lymphocytes) is very important. Various diseases with wheeze or cough symptoms should be distinguished by cell fractionation in sputum. Use of inhaled corticosteroids as a first-line treatment based solely on an observation of eosinophilia in sputum may not recommend.