tbuckley/cabot-search huggingface dataset:
Lipid-laden macrophages in induced sputum are a marker of oropharyngeal reflux and possible gastric aspiration
Authors: K. Parameswaran, M. Anvari, A. Efthimiadis, D. Kamada, F.e Hargreave, C.j Allen
Journal: European Respiratory Journal (2000)

The diagnostic properties of a "lipid index" of macrophages in induced sputum as a noninvasive marker of aspiration of acidic gastric contents were evaluated. In a cross-sectional study, 33 subjects (17 with symptoms suggestive of gastrooesophageal reflux) with normal chest radiographs and no symptoms of aspiration or sinus disease, underwent dual-channel 24-h ambulatory oesophageal pH recording and sputum induction. Oropharyngeal reflux, defined as at least one episode of a fall in pH to <4 at the upper oesophageal electrode, was considered indicative of aspiration of acidic gastric contents ("gold standard"). An index for the presence of intracellular lipid in sputum macrophages, detected by oil red O stain, was obtained. The sensitivity, specificity and predictive values of this "lipid index" were calculated. The "lipid index" could be calculated in 29 of 33 samples with high interobserver repeatability (intraclass correlation coefficient 0.96). Twenty subjects showed oropharyngeal reflux and nine did not. The median "lipid index" in subjects with oropharyngeal reflux (24.5) was significantly greater than that in those without reflux (1.0) (p<0.001). A "lipid index" of 7.0 had a sensitivity of 90%, a specificity of 89%, a positive predictive value of 95% and a negative predictive value of 80%. A "lipid index" of 7.0 in the macrophages of induced sputum is a good marker of oropharyngeal reflux.
Exhaled Breath Analysis with a Colorimetric Sensor Array for the Identification and Characterization of Lung Cancer
Authors: Peter J. Mazzone, Xiao-Feng Wang, Yaomin Xu, Tarek Mekhail, Mary C. Beukemann, Jie Na, Jonathan W. Kemling, Kenneth S. Suslick, Madhu Sasidhar
Journal: Journal of Thoracic Oncology (2011)
Immunity and Antibody Formation Induced by Intraperitoneal or Subcutaneous Injection of Krebs-2 Ascites Tumor Cells Treated With Influenza Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Monroe D. Eaton, Jeana D. Levinthal, Anthony R. Scala, Marjorie L. Jewell
Journal: JNCI Journal of the National Cancer Institute (1965)

Incubation of Krebs-2 ascites tumor cells with influenza virus at high multiplicity reduced the tumor-producing capacity of cell suspensions. These virus-treated cells could then be used as an antigen to stimulate resistance to the tumor when given intraperitoneally. An attempt was made to define the optimal conditions of virus treatment for a nonlethal but effective antigen. Since less than 10 Krebs-2 cells given intraperitoneally produced lethal ascites tumors in most Swiss mice, immunization with fully viable cells by this route was virtually impossible. But some mice could be given large numbers of cells subcutaneously, with production of immunity to intraperitoneal challenge. Virus-treated cells given subcutaneously failed to immunize. Quantitation of the cell dose required for immunization indicated that a single intraperitoneal injection of 103 to 104 virus-treated cells produced some resistance, but multiple doses of 103 to 105 cells were more effective. Similar data were obtained by subcutaneous immunization with untreated cells against intraperitoneal challenge. The serum from mice hyperimmunized with Krebs-2 cells gave specific reactions by fluor-escein-antibody labeling of surface antigens. With other tumors a reaction was observed with 1 to 5 percent of cells in a suspension. When complement was present, the labeling of surface antigens of Krebs-2 cells was followed by cytolysis.
Critical Role for Monocyte Chemoattractant Protein-1 and Macrophage Inflammatory Protein-1α in Induction of Experimental Autoimmune Myocarditis and Effective Anti–Monocyte Chemoattractant Protein-1 Gene Therapy
Authors: Stefan Göser, Renate Öttl;, Alexander Brodner, Thomas J. Dengler, Jan Torzewski, Kensuke Egashira, Noel R. Rose, Hugo A. Katus, Ziya Kaya
Journal: Circulation (2005)

Autoimmune myocarditis is a principal cause of heart failure among young adults and is often a precursor of dilated cardiomyopathy. Monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) are potent chemotactic factors for mononuclear cells. The inflammatory infiltrate observed in myocardial lesions of myocarditis consists of >70% mononuclear cells. To determine their critical role in the pathogenesis of myocarditis, we inhibited mononuclear cell activation and migration to see if it would affect disease severity and disease prevalence in experimental autoimmune myocarditis (EAM).In this report, we demonstrated that blockade of MCP-1 or MIP-1alpha with monoclonal antibodies significantly reduced severity of myocarditis in BALB/c mice immunized with cardiac myosin. Similar results were obtained when CCR2-/- and CCR5-/- mice were used. In CCR2-/- mice, not only disease severity but also disease prevalence was reduced. To further inhibit mononuclear cell activation and migration, we transfected the mice before inducing EAM with a dominant-negative inhibitor of MCP-1 gene (7ND). This transfection significantly reduced the disease severity, decreased mRNA expression levels, especially of the chemokines RANTES, MIP-2, IP-10, MCP-1, T-cell activation gene 3, and eotaxin in the myocardium, and resulted in a reduction in cardiac myosin-induced interleukin-1 and interleukin-4 and in an increase in interferon-gamma and interleukin-10 cytokine production by splenocytes.Overall, these findings suggest that the chemokines MCP-1 and MIP-1alpha, acting through their receptors CCR2 and CCR5, are important in the induction of EAM and that inhibition of MCP-1 with 7ND gene transfection significantly reduced disease severity. This strategy may be a new feasible form of gene therapy against autoimmune myocarditis.
Expression of insulin-like growth factor-1 receptor, p-AKT and p-ERK1/2 protein in extramammary Paget's disease
Authors: H. Liu, Y. Moroi, S. Yasumoto, H. Kokuba, S. Imafuku, T. Koga, T. Masuda, Y. Tu, M. Furue, K. Urabe
Journal: British Journal of Dermatology (2006)

The insulin-like growth factor-1 (IGF-1) receptor (R)-induced phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK signal transduction cascade, which have critical roles in prevention of apoptosis and regulation of cell cycle progression, plays an important role in tumorigenesis. The expression of IGF-1R, AKT and ERK1/2 has been described in some human malignancies, but not in extramammary Paget's disease (EMPD).To study the expression of IGF-1R, p-AKT and p-ERK1/2 in EMPD and to evaluate the relationships among them.Thirty-six tissue samples of 34 patients with primary EMPD were subjected to immunohistochemical staining for IGF-1R, p-AKT and p-ERK1/2.Of thirty-six EMPD tissue samples, 34, 34 and 28 were positive for IGF-IR, p-AKT and p-ERK1/2 expression, respectively; 27, 23 and 17 of the 36 specimens stained positive for IGF-IR, p-AKT and p-ERK1/2 in more than half of Paget's cells, respectively. There were significant correlations between the IGF-1R and p-AKT expression as well as between IGF-1R and p-ERK1/2 expression. Taken together, these results indicate that IGF-1R is overexpressed, and AKT and ERK1/2 are frequently phosphorylated in EMPD.Our study shows that the expression of IGF-1R and the induction of p-AKT and the p-ERK1/2 pathway may play an important role in the pathogenesis of EMPD. The IGF-IR system might be a potential therapeutic target in EMPD.
Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study
Authors: Yining Huang, Yan Cheng, Jiang Wu, Yansheng Li, En Xu, Zhen Hong, Zhengyi Li, Weiwei Zhang, Meiping Ding, Xuguang Gao, Dongsheng Fan, Jinsheng Zeng, Kasing Wong, Chuanzhen Lu, Jiangxi Xiao, Chen Yao
Journal: The Lancet Neurology (2008)
A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints
Authors: Lisa Mullen, Gill Adams, Julie Foster, Sandrine Vessillier, Mario Köster, Hansjörg Hauser, Lorna Layward, David Gould, Yuti Chernajovsky
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. <h3>Objectives</h3> To demonstrate latency and specific delivery <i>in vivo</i> and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. <h3>Methods</h3> Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised <i>in vitro</i> by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. <h3>Results</h3> Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. <h3>Conclusions</h3> Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints.
Bronchiolar disease in rheumatoid arthritis.
Authors: H Hayakawa, A Sato, S Imokawa, M Toyoshima, K Chida, M Iwata
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The pulmonary manifestations of rheumatoid arthritis (RA) include bronchiolar diseases such as follicular bronchiolitis (FB) and bronchiolitis obliterans (BO). In this study, we investigated the clinical and pathologic features of FB and BO, as well as the effect of erythromycin (EM) on these diseases. The subjects included 15 RA patients with biopsy-proven bronchiolar disease (eight with FB, seven with BO). None of the patients had Sjögren's syndrome. Eleven patients (73%) had chronic sinusitis, and 14 (93%) had a chronic cough with sputum. Bacterial culture of sputum was positive in 50% and 71% of the FB and BO patients, respectively. High-resolution computed tomography (HRCT) revealed small nodular shadows in the centrilobular regions (FB and BO), patchy areas of low attenuation (BO), and peribronchial thickening (FB and BO). Eleven patients who received EM therapy showed a significant improvement of symptoms. In addition, none of the 15 patients died of the bronchiolar disease during follow-up. In conclusion, RA patients with FB or BO basically have a chronic clinical course with main complaint of productive cough, and EM may be useful for the management of these diseases.
CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms
Authors: Sara C. Meyer, Matthew D. Keller, Sophia Chiu, Priya Koppikar, Olga A. Guryanova, Franck Rapaport, Ke Xu, Katia Manova, Dmitry Pankov, Richard J. O’Reilly, Maria Kleppe, Anna Sophia McKenney, Alan H. Shih, Kaitlyn Shank, Jihae Ahn, Eftymia Papalexi, Barbara Spitzer, Nick Socci, Agnes Viale, Emeline Mandon, Nicolas Ebel, Rita Andraos, Joëlle Rubert, Ernesta Dammassa, Vincent Romanet, Arno Dölemeyer, Michael Zender, Melanie Heinlein, Raajit Rampal, Rona Singer Weinberg, Ronald Hoffman, William R. Sellers, Francesco Hofmann, Masato Murakami, Fabienne Baffert, Christoph Gaul, Thomas Radimerski, Ross L. Levine
Journal: Cancer Cell (2015)

Although clinically tested JAK inhibitors reduce splenomegaly and systemic symptoms, molecular responses are not observed in most myeloproliferative neoplasm (MPN) patients. We previously demonstrated that MPN cells become persistent to type I JAK inhibitors that bind the active conformation of JAK2. We investigated whether CHZ868, a type II JAK inhibitor, would demonstrate activity in JAK inhibitor persistent cells, murine MPN models, and MPN patient samples. JAK2 and MPL mutant cell lines were sensitive to CHZ868, including type I JAK inhibitor persistent cells. CHZ868 showed significant activity in murine MPN models and induced reductions in mutant allele burden not observed with type I JAK inhibitors. These data demonstrate that type II JAK inhibition is a viable therapeutic approach for MPN patients.
Is high level of IgE an additional problem in smoking patients with severe and very severe chronic obstructive pulmonary disease (COPD)
Authors: Nataliia Slepchenko, Yuriy Mostovoy, Andrii Sidorov
Journal: European Respiratory Journal (2012)

Smoking is one of the greatest risk factors of COPD and it increases the risk of allergic sensibilisation.  The aim of the study was to estimate the level of IgE and its possible connection with the spirometric parameters and sensibilisation to allergens in smoking patients with severe and very severe COPD and great length of smoking.  Methods. The 30 patients with very severe COPD were enrolled. It was estimated smoking status, body mass index (BMI), spirometric parameters (forced vital capacity (FVC), forced expired volume in 1 second (FEV1)) and level of total IgE. The skin prick test with local significant allergens (home dust, pollen of ambrosia, birch, fur of cat) was performed to patients with increased level of IgE.  Results. The length of smoking was 28,5±6,8 pack-years. BMI was 26,9±2,5 kg/m². FEV1=41,5±8,9%, FVC=44,9±7,7%. The 24 patients had increased level of IgE (329,5±45,2 IU/l vs normal range is 0-87 IU/l). The 16 patients had sensibilisation to home dust and the 3 patients had sensibilisation to fur of cat. These patients also had periodically rash, itch, but they believed that symptoms are connected with COPD and did not ask for medical help to allergist. There is a strict correlative connection between the length of smoking and level of the IgE (r=0,8). There is a faint connection between the level of the IgE and FEV1 (r=0,2).  Conclusions. The smoking patients with very severe COPD has allergic constitution with increased IgE level and sensibillisation to different allergens. There is no significant connection between level of IgE and spirometric parameters. Allergic symptoms in this category of patients need for attention.
Cost-Effectiveness of Coronary Stenting and Abciximab for Patients With Acute Myocardial Infarction
Authors: Ameet Bakhai, Gregg W. Stone, Cindy L. Grines, Sabina A. Murphy, Louise Githiora, Ronna H. Berezin, David A. Cox, Thomas Stuckey, John J. Griffin, James E. Tcheng, David J. Cohen
Journal: Circulation (2003)

Both stenting and the glycoprotein IIb/IIIa inhibitor abciximab improve outcomes for patients undergoing primary angioplasty for acute myocardial infarction (AMI). However, the cost-effectiveness of these strategies is unknown.We performed a prospective cost-utility analysis among US participants in the CADILLAC trial. Patients with AMI (n=1703) were randomized to stenting versus balloon angioplasty (PTCA) and abciximab versus no abciximab according to a 2-by-2 factorial design. Total 1-year costs and lifetime incremental cost-effectiveness ratios, measured as cost per quality-adjusted year of life (QALY) gained, were calculated. Compared with PTCA, stenting increased procedural costs by 1148 dollars and initial hospital costs by 1384 dollars (both P<0.001). By 1-year, stenting led to fewer repeat revascularization procedures and reduced follow-up medical care costs by 1215 dollars, such that aggregate costs were similar for the PTCA and stent groups (18 690 dollars versus 18 859 dollars, P=0.75). The cost-effectiveness ratio for stenting versus PTCA was favorable at 11 237 dollars/QALY gained and remained <20 000 dollars/QALY in sensitivity analyses. Compared with standard anticoagulation, abciximab increased initial procedural costs by 1122 dollars (P<0.001). By facilitating accelerated hospital discharge, abciximab reduced length of stay by approximately 0.6 days, offsetting most of the drug costs. These cost offsets were not maintained, however; aggregate 1-year costs for the abciximab group were 1244 dollars greater than for standard therapy (19 389 dollars versus 18 145 dollars , P=0.02). Abciximab was reasonably cost-effective (cost-effectiveness ratio 21 305 dollars/QALY) only if nonsignificant differences in 1-year mortality (3.7% versus 4.3%, P=0.62) were incorporated in the analysis.Primary stenting is a highly cost-effective treatment for AMI. The cost-effectiveness of abciximab in this setting is uncertain and depends primarily on whether long-term survival is enhanced.
Early Age at Menarche, Lung Function, and Adult Asthma
Authors: Ferenc Macsali, Francisco Gómez Real, Estel Plana, Jordi Sunyer, Josep Anto, Julia Dratva, Christer Janson, Deborah Jarvis, Ernst Reidar Omenaas, Elisabeth Zemp, Matthias Wjst, Benedicte Leynaert, Cecilie Svanes
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

hormonal and metabolic status appears to influence lung health in women, and there are findings suggesting that early menarche may be related to asthma, cardiovascular disease, diabetes, and breast cancer.this study investigates whether age at menarche is related to adult lung function and asthma.among participants in the European Community Respiratory Health Survey II, 3,354 women aged 27-57 years from random population samples in 21 centers responded to a questionnaire concerning women's health (1998-2002). Of these women, 2,873 had lung function measurements, 2,136 had measurements of bronchial hyperreactivity, and 2,743 had IgE measurements. Logistic, linear, and negative binomial regression analyses included adjustment for age, height, body mass index, education, smoking, family size, and center.FEV(1) and FVC were lower and asthma was more common in women with early menarche. Women reporting menarche at age 10 years or less, as compared with women with menarche at age 13 years (reference category), had lower FEV(1) (adjusted difference, -113 ml; 95% confidence interval [CI], -196 to -33 ml) and FVC (-126 ml; 95% CI, -223 to -28 ml); also lower FEV(1) expressed as a percentage of the predicted value (-3.28%; 95% CI, -6.25 to -0.30%) and FVC expressed as a percentage of the predicted value (-3.63%; 95% CI, -6.64 to -0.62%). Women with early menarche more often had asthma symptoms (odds ratio, 1.80; 95% CI, 1.09-2.97), asthma with bronchial hyperreactivity (odds ratio, 2.79; 95% CI, 1.06-7.34), and higher asthma symptom score (mean ratio, 1.58; 95% CI, 1.12-2.21).women with early menarche had lower lung function and more asthma in adulthood. This supports a role for metabolic and hormonal factors in women's respiratory health.
Multiplex Identification of Gram-Positive Bacteria and Resistance Determinants Directly from Positive Blood Culture Broths: Evaluation of an Automated Microarray-Based Nucleic Acid Test
Authors: Blake W. Buchan, Christine C. Ginocchio, Ryhana Manii, Robert Cavagnolo, Preeti Pancholi, Lettie Swyers, Richard B. Thomson, Christopher Anderson, Karen Kaul, Nathan A. Ledeboer
Journal: PLoS Medicine (2013)

Nathan Ledeboer and colleagues assess the performance of a diagnostic platform for detecting Gram-positive bacteria in blood cultures, an important step in the diagnosis and treatment of patients with sepsis. Please see later in the article for the Editors' Summary
Phase III Randomized Multicenter Study of a Humanized Anti-CD33 Monoclonal Antibody, Lintuzumab, in Combination With Chemotherapy, Versus Chemotherapy Alone in Patients With Refractory or First-Relapsed Acute Myeloid Leukemia
Authors: Eric J. Feldman, Joseph Brandwein, Richard Stone, Matt Kalaycio, Joseph Moore, Julie O'Connor, Nancy Wedel, Gail J. Roboz, Carole Miller, Raj Chopra, Joseph C. Jurcic, Randy Brown, W. Christopher Ehmann, Philip Schulman, Stanley R. Frankel, Daniel De Angelo, David Scheinberg
Journal: Journal of Clinical Oncology (2005)

Lintuzumab (HuM195) is an unconjugated humanized murine monoclonal antibody directed against the cell surface myelomonocytic differentiation antigen CD33. In this study, the efficacy of lintuzumab in combination with induction chemotherapy was compared with chemotherapy alone in adults with first relapsed or primary refractory acute myeloid leukemia (AML).Patients with relapsed or primary resistant AML (duration of first response, zero to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m(2), etoposide 80 mg/m(2), and cytarabine 1 g/m(2) daily for 6 days (MEC) in combination with lintuzumab 12 mg/m(2), or MEC alone. Overall response, defined as the rate of complete remission (CR) and CR with incomplete platelet recovery (CRp), was the primary end point of the study, with additional analyses of survival time and toxicity.A total of 191 patients were randomly assigned from November 1999 to April 2001. The percent CR plus CRp with MEC plus lintuzumab was 36% v 28% in patients treated with MEC alone (P = .28). The overall median survival was 156 days and was not different in the two arms of the study. Apart from mild antibody infusion-related toxicities (fever, chills, and hypotension), no differences in chemotherapy-related adverse effects, including hepatic and cardiac dysfunction, were observed with the addition of lintuzumab to induction chemotherapy.The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/relapsed AML.
Sam68 expression and cytoplasmic localization is correlated with lymph node metastasis as well as prognosis in patients with early-stage cervical cancer
Authors: Z. Li, C.-P. Yu, Y. Zhong, T.-J. Liu, Q.-D. Huang, X.-H. Zhao, H. Huang, H. Tu, S. Jiang, Y. Zhang, J.-H. Liu, L.-B. Song
Journal: Annals of Oncology (2011)
Approximate methods for estimating the pattern of nucleotide substitution and the variation of substitution rates among sites
Authors: Z. Yang, S. Kumar
Journal: Molecular Biology and Evolution (1996)

We propose two approximate methods (one based on parsimony and one on pairwise sequence comparison) for estimating the pattern of nucleotide substitution and a parsimony-based method for estimating the gamma parameter for variable substitution rates among sites. The matrix of substitution rates that represents the substitution pattern can be recovered through its relationship with the observable matrix of site pattern frequences in pairwise sequence comparisons. In the parsimony approach, the ancestral sequences reconstructed by the parsimony algorithm were used, and the two sequences compared are those at the ends of a branch in the phylogenetic tree. The method for estimating the gamma parameter was based on a reinterpretation of the numbers of changes at sites inferred by parsimony. Three data sets were analyzed to examine the utility of the approximate methods compared with the more reliable likelihood methods. The new methods for estimating the substitution pattern were found to produce estimates quite similar to those obtained from the likelihood analyses. The new method for estimating the gamma parameter was effective in reducing the bias in conventional parsimony estimates, although it also overestimated the parameter. The approximate methods are computationally very fast and appear useful for analyzing large data sets, for which use of the likelihood method requires excessive computation.