tbuckley/cabot-search huggingface dataset:
The importance of endothelin-1 for vascular dysfunction in cardiovascular disease
Authors: F BOHM, J PERNOW
Journal: Cardiovascular Research (2007)

Endothelin (ET)-1 is a potent vasoconstrictor peptide originally isolated from endothelial cells. Its production is stimulated in a variety of different cell types under the influence of risk factors for cardiovascular disease and during the development of cardiovascular disease. Based on these observations and the biological effects induced by ET-1, including profound vasoconstriction, pro-inflammatory actions, mitogenic and proliferative effects, stimulation of free radical formation and platelet activation, ET-1 has been implicated as an important factor in the development of vascular dysfunction and cardiovascular disease. In the following the pathogenic role of ET-1, the mechanisms underlying the involvement of ET-1 for the development of vascular dysfunction and the potentially beneficial therapeutic effects of selective ETA and dual ETA/ETB receptor antagonists will be discussed. In particular the changes of pathophysiological importance mediated by ET-1 in clinical studies are reviewed. These changes may be of significance for the development of various cardiovascular diseases beyond pulmonary arterial hypertension which is the currently approved indication for ET receptor antagonists.
Factors That Affect Accuracy of α-Fetoprotein Test in Detection of Hepatocellular Carcinoma in Patients With Cirrhosis
Authors: Purva Gopal, Adam C. Yopp, Akbar K. Waljee, Jason Chiang, Mahendra Nehra, Pragathi Kandunoori, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2013)
Implications of Alternative Definitions of Prediabetes for Prevalence in U.S. Adults
Authors: Cherie James, Kai McKeever Bullard, Deborah B. Rolka, Linda S. Geiss, Desmond E. Williams, Catherine C. Cowie, Ann Albright, Edward W. Gregg
Journal: Diabetes Care (2011)

OBJECTIVE To compare the prevalence of prediabetes using A1C, fasting plasma glucose (FPG), and oral glucose tolerance test (OGTT) criteria, and to examine the degree of agreement between the measures. RESEARCH DESIGN AND METHODS We used the 2005–2008 National Health and Nutrition Examination Surveys to classify 3,627 adults aged ≥18 years without diabetes according to their prediabetes status using A1C, FPG, and OGTT. We compared the prevalence of prediabetes according to different measures and used conditional probabilities to examine agreement between measures. RESULTS In 2005–2008, the crude prevalence of prediabetes in adults aged ≥18 years was 14.2% for A1C 5.7–6.4% (A1C5.7), 26.2% for FPG 100–125 mg/dL (IFG100), 7.0% for FPG 110–125 mg/dL (IFG110), and 13.7% for OGTT 140–199 mg/dL (IGT). Prediabetes prevalence varied by age, sex, and race/ethnicity, and there was considerable discordance between measures of prediabetes. Among those with IGT, 58.2, 23.4, and 32.3% had IFG100, IFG110, and A1C5.7, respectively, and 67.1% had the combination of either A1C5.7 or IFG100. CONCLUSIONS The prevalence of prediabetes varied by the indicator used to measure risk; there was considerable discordance between indicators and the characteristics of individuals with prediabetes. Programs to prevent diabetes may need to consider issues of equity, resources, need, and efficiency in targeting their efforts.
Near-infrared Spectroscopic Method for Assessing the Tissue Oxygenation State of Living Lung
Authors: TOSHIO NORIYUKI, HIDEKI OHDAN, SHINKICHIRO YOSHIOKA, YOSHIHIRO MIYATA, TOSHIMASA ASAHARA, KIYOHIKO DOHI
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To quantify changes in tissue oxygenation of pathologic lungs, we applied a novel method using near-infrared spectroscopy (NIRs). In in vitro experiments, we assayed the effect of photon scattering on the absorption spectra of an in vitro system simulating structures of lung, which consists of test tube containing air in hematocrit tubes and red blood cell suspension with various predetermined hemoglobin concentrations. It was determined that photon scattering of the tissue containing air did not affect the absorption in the NIR region. In in vivo experiments, we tested the applicability of the NIRs technique in rat lungs under the following conditions: (1) hypoxic loading; (2) administration of an inhibitor (NaCN) of the mitochondrial respiratory chain; (3) hemorrhagic shock. We found that: (1) Changes in hemoglobin oxygenation state in the lung measured by NIRs depended on inspired oxygen concentrations; (2) NaCN-induced reduction of cytochrome oxidase a,a3 in the lung was observed; and (3) Total hemoglobin levels in the lung decreased after bleeding. Changes in the hemoglobin oxygenation state and cytochrome oxidase redox state in the lung were determined using the least-square-curve fitting for NIR absorption spectra. Our NIRs technique was capable of assessing the hemoglobin oxygenation and cytochrome oxidase redox state in the lung.
Raman microspectroscopy: shining a new light on reproductive medicine
Authors: Con Mallidis, Victoria Sanchez, Joachim Wistuba, Frank Wuebbeling, Martin Burger, Carsten Fallnich, Stefan Schlatt
Journal: Human Reproduction Update (2013)

BACKGROUNDThe last 20 years have seen an enormous upsurge in the number of publications reporting findings obtained by Raman spectroscopy, a non-invasive, non-destructive method which uses the inelastic scattering of light to provide a 'fingerprint' of the sample's chemical composition and constituents. Long neglected because of practical difficulties, the technique has been transformed by recent technological advances into a powerful analytical tool capable of opening avenues of investigation that were previously out of the reach of biomedical scientists. Beyond introducing the approach and describing its relative merits and weaknesses, the aim of this review is to provide a spur for discussion of what may become an invaluable tool for biomedical investigations.
Correlation analysis of the transcriptome of growing leaves with mature leaf parameters in a maize RIL population
Authors: Joke Baute, Dorota Herman, Frederik Coppens, Jolien De Block, Bram Slabbinck, Matteo Dell’Acqua, Mario Enrico Pè, Steven Maere, Hilde Nelissen, Dirk Inzé
Journal: Genome biology (2015)

To sustain the global requirements for food and renewable resources, unraveling the molecular networks underlying plant growth is becoming pivotal. Although several approaches to identify genes and networks involved in final organ size have been proven successful, our understanding remains fragmentary.Here, we assessed variation in 103 lines of the Zea mays B73xH99 RIL population for a set of final leaf size and whole shoot traits at the seedling stage, complemented with measurements capturing growth dynamics, and cellular measurements. Most traits correlated well with the size of the division zone, implying that the molecular basis of final leaf size is already defined in dividing cells of growing leaves. Therefore, we searched for association between the transcriptional variation in dividing cells of the growing leaf and final leaf size and seedling biomass, allowing us to identify genes and processes correlated with the specific traits. A number of these genes have a known function in leaf development. Additionally, we illustrated that two independent mechanisms contribute to final leaf size, maximal growth rate and the duration of growth.Untangling complex traits such as leaf size by applying in-depth phenotyping allows us to define the relative contributions of the components and their mutual associations, facilitating dissection of the biological processes and regulatory networks underneath.
Altered accessory cell function of alveolar macrophages: a possible mechanism for induction of Th2 secretory profile in idiopathic pulmonary fibrosis
Authors: H Furuie, H Yamasaki, M Suga, M Ando
Journal: European Respiratory Journal (1997)

Alveolar macrophages (AMs) are considered to play a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Recent studies have revealed a predominance of the type-2 T-helper (Th2) cytokine pattern of inflammatory response in the pulmonary interstitium in IPF. The aim of the present study was to determine whether or not the altered accessory cell function of AMs could account for the Th2 pattern of chronic inflammation in IPF. The levels of various cytokines were measured in the supernatants of soluble anti-CD3 monoclonal antibody (MoAb)-stimulated T-cells, co-cultured with autologous AMs, by enzyme-linked immunosorbent assay (ELISA). Cells from six patients with IPF and from nine normal volunteers (five nonsmokers and four smokers) were examined. The inhibitory effect of interleukin (IL)-10 on the accessory cell function of AMs and the expression of CD80 and CD86 on AMs were also investigated. IL-4 and IL-5 levels were significantly higher in the co-cultures from patients with IPF than in those from normal volunteers. IL-2, interferon-gamma (IFN-gamma), and IL-10 production in these co-cultures did not differ. IL-10 suppressed T-cell proliferation in co-cultures with AMs from healthy volunteers (smokers and nonsmokers), but not with AMs from patients with IPF. Expression of CD80 and CD86 on AMs from these groups did not differ. Thus, the altered accessory cell function of alveolar macrophages from patients with idiopathic pulmonary fibrosis may possibly relate to the pattern of type-2 T-helper cytokine production in response to inflammation.
Patterns of <i>EGFR, HER2, TP53</i>, and <i>KRAS</i> Mutations of p14arf Expression in Non–Small Cell Lung Cancers in Relation to Smoking History
Authors: Mounia Mounawar, Anush Mukeria, Florence Le Calvez, Rayjean J. Hung, Helene Renard, Alexis Cortot, Claire Bollart, David Zaridze, Paul Brennan, Paolo Boffetta, Elisabeth Brambilla, Pierre Hainaut
Journal: Cancer Research (2007)

Abstract Mutations in the tyrosine kinase domain of the epidermal growth factor receptor EGFR are common in non–small cell lung cancer (NSCLC) of never smokers, whereas HER2 mutations are rare. We have analyzed EGFR and HER2 mutations and the expression of the two products of the CDKN2A gene (p14arf and p16INK4a) in 116 NSCLC that have been previously analyzed for TP53 and KRAS mutations in relation to smoking history of patients. EGFR mutations were detected in 20 of 116 (17%) tumors, whereas five (4.3%) tumors contained HER2 mutations. No tumor contained both mutations. Of tumors with EGFR or HER2 mutation, 72% were adenocarcinomas, 68% were from never smokers, and 32% were from former smokers. EGFR but not HER2 mutations were mutually exclusive with KRAS mutation. Among never smokers, 11 of 16 tumors with EGFR mutation also had TP53 mutation, in contrast with two of 17 tumors without EGFR mutation (P = 0.0008). Expression of p14arf, but not p16ink4a, was more frequently down-regulated in never smokers (62.5%) than ever smokers (35%; P = 0.008). All tumors with EGFR or HER2 mutations and wild-type TP53 showed down-regulation of p14arf expression. These observations suggest that functional inactivation of the p14arf/p53 connection is required in tumors with EGFR or HER2 mutations, consistent with the notion that these proteins are part of a fail-safe mechanism protecting cells against untimely or excessive mitotic signals. [Cancer Res 2007;67(12):5667–72]
Identification of an Inhibitor of the EWS-FLI1 Oncogenic Transcription Factor by High-Throughput Screening
Authors: Patrick J. Grohar, Girma M. Woldemichael, Laurie B. Griffin, Arnulfo Mendoza, Qing-Rong Chen, Choh Yeung, Duane G. Currier, Sean Davis, Chand Khanna, Javed Khan, James B. McMahon, Lee J. Helman
Journal: JNCI Journal of the National Cancer Institute (2011)

Chromosomal translocations generating oncogenic transcription factors are the hallmark of a variety of tumors, including many sarcomas. Ewing sarcoma family of tumors (ESFTs) are characterized by the t(11;22)(q24;q12) translocation that generates the Ewing sarcoma breakpoint region 1 and Friend leukemia virus integration 1 (EWS-FLI1) fusion transcription factor responsible for the highly malignant phenotype of this tumor. Although continued expression of EWS-FLI1 is believed to be critical for ESFT cell survival, a clinically effective small-molecule inhibitor remains elusive likely because EWS-FLI1 is a transcription factor and therefore widely felt to be “undruggable.” We developed a high-throughput screen to evaluate more than 50 000 compounds for inhibition of EWS-FLI1 activity in TC32 ESFT cells. We used a TC32 cell–based luciferase reporter screen using the EWS-FLI1 downstream target NR0B1 promoter and a gene signature secondary screen to sort and prioritize the compounds. We characterized the lead compound, mithramycin, based on its ability to inhibit EWS-FLI1 activity in vitro using microarray expression profiling, quantitative reverse transcription–polymerase chain reaction, and immunoblot analysis, and in vivo using immunohistochemistry. We studied the impact of this inhibition on cell viability in vitro and on tumor growth in ESFT xenograft models in vivo (n = 15–20 mice per group). All statistical tests were two-sided. Mithramycin inhibited expression of EWS-FLI1 downstream targets at the mRNA and protein levels and decreased the growth of ESFT cells at half maximal inhibitory concentrations between 10 (95% confidence interval [CI] = 8 to 13 nM) and 15 nM (95% CI = 13 to 19 nM). Mithramycin suppressed the growth of two different ESFT xenograft tumors and prolonged the survival of ESFT xenograft–bearing mice by causing a decrease in mean tumor volume. For example, in the TC32 xenograft model, on day 15 of treatment, the mean tumor volume for the mithramycin-treated mice was approximately 3% of the tumor volume observed in the control mice (mithramycin vs control: 69 vs 2388 mm 3 , difference = 2319 mm 3 , 95% CI = 1766 to 2872 mm 3 , P < .001). Mithramycin inhibits EWS-FLI1 activity and demonstrates ESFT antitumor activity both in vitro and in vivo.
Strategies for automated fetal cell screening
Authors: F. A. Merchant
Journal: Human Reproduction Update (2002)

Studies to date have demonstrated fetal sex determination and aneuploidy detection from maternal blood, but a clinical screening technique has not yet emerged. A key limiting factor is the small number of fetal cells, which makes detection specificity and reliability critical. Visual inspection of unsorted or sorted fetal cells is laborious, and cells can be easily missed. Moreover, it is impractical to examine manually all the separated cells. It is highly likely that automation may increase the number of cells inspected, resulting in higher detection sensitivities. Flow and image cytometry are two feasible approaches for automated detection of cells. This review details computerized microscopy (image cytometry) techniques for the automatic detection of fetal cells. Microscopy-based approaches used to identify fetal origin include: (i) immunocytochemical identification of fetal haemoglobin-specific cells (light or fluorescence microscopy); (ii) identification of sex chromosomes and/or aneuploidy using fluorescencein-situhybridization; and (iii) morphological identification of nucleated red blood cells using light microscopy. The relevant instrumentation, including motorized stages and filters, cameras and digitizer boards are discussed, and software algorithms, including image enhancement, autofocusing, object detection and relocation, and features for operator review and data analysis, are outlined.
Combined chemotherapy including high‐dose methotrexate in KSHV/HHV8‐associated primary effusion lymphoma
Authors: Emmanuelle Boulanger, Marie‐Thérèse Daniel, Félix Agbalika, Eric Oksenhendler
Journal: American Journal of Hematology (2003)

Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected homosexual men with severe immunosuppression and other KSHV/HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis is poor with a median survival of less than 6 months in most cohorts. The achievement of a sustained complete remission is rare. High-dose chemotherapy regimens are warranted to improve complete remission rate and survival. Seven patients with AIDS-associated PEL were treated with a combined chemotherapy including high-dose methotrexate followed by leucovorin rescue. In all cases, KSHV/HHV8 sequences were detected in the effusion samples using quantitative PCR assays. Five patients had a pre-existing KS, associated in three cases with multicentric Castleman's disease (MCD). Upon diagnosis, 6 patients received antiretroviral therapy, which was maintained during chemotherapy in 5 of them. At time of analysis, 3 out of 7 patients were in complete remission 18, 26, and 78 months after PEL diagnosis. Three patients died with a progressive PEL at 22, 67, and 153 days after diagnosis, and 1 patient died 9 months after PEL diagnosis with a MCD-associated plasmablastic NHL. Complete remission was obtained in 3 out of 7 patients treated for AIDS-associated PEL with combined chemotherapy containing high-dose methotrexate.
Measurement of effective pulmonary blood flow by soluble gas uptake in patients with chronic airflow obstruction.
Authors: R J Pierce, C F McDonald, C A Thuys, P D Rochford, C E Barter
Journal: Thorax (1987)

A study was designed to assess the accuracy and reproducibility of rebreathing and single breath soluble gas uptake measurements of effective pulmonary blood flow (Q) in patients with airways obstruction. Both rebreathing (RB) and single breath (SB) estimates of Q were compared with direct Fick and thermodilution (TD) measurements of cardiac output at rest and during exercise in eight patients with chronic, poorly reversible airflow obstruction with mean FEV1 65% predicted and mean FEV1/FVC 53%. The mean (SD) resting values obtained were QRB 3.47 (0.46), QSB 4.75 (1.15), QFick 4.77 (0.97), and QTD 5.15 (0.98). QRB was significantly lower than the other three estimates, which did not differ significantly from each other. Exercise produced significant increases in all four estimates for the group. The mean exercise values were QRB 6.23 (1.19), QSB 7.62 (1.97), QFick 8.97 (1.96), and QTD 9.09 (1.00), both QRB and QSB being significantly less than QFick and QTD. Analysis of variance of the rest, exercise, and combined data showed highly significant relationships with the TD and Fick measurements for both QRB and QSB over the range of values studied. In addition, the reproducibility of QRB and QSB was assessed in 15 other patients with chronic airflow obstruction (mean FEV1 42% predicted, FEV1/FVC 43%) and in 10 normal subjects. The coefficients of intrasubject variability for a single measurement for QRB were 8.7% in normal subjects and 10.2% in patients and for QSB were 11.7% in normal subjects and 16.1% in patients. The group differences from morning to afternoon, between days, and over a month were not significant in the normal subjects. In the patients QRB was slightly higher in the afternoon than in the morning of the same day, but the differences between days and over a month were not significant for either test. Although both tests detected the increase in pulmonary blood flow during exercise, the single breath test was more accurate at rest. Some underestimation was present for rebreathing at rest and for both tests during exercise, but this can be allowed for. In patients with mild airflow obstruction the reproducibility of the soluble gas uptake methods was similar to that of invasive catheter methods of cardiac output estimation. The single breath test in particular was, however, less reproducible in patients with more severe airflow obstruction, and the rebreathing method may be more useful for detecting increases in pulmonary blood flow in these patients.
Analog Computer Analysis of Flow Characteristics and Volume of the Pulmonary Vascular Bed
Authors: DANIEL PARRISH, DANIEL T. HAYDEN, WAYNE GARRETT, REX L. HUFF
Journal: Circulation Research (1959)

Radioisotope dilution data were obtained from the pulmonary artery and pulmonary vein of catheterized dogs and an analysis for pulmonary transfer characteristics was performed with an electronic analog computer. The analog for these studies consisted of a cascade of linear delay units arranged so that both transport delay and dispersion could be independently varied. This technic makes it possible to characterize the pulmonary vascular bed without making any assumptions as to its nature. The results indicate that the dominant response of the lung is not that of a single mixing pool as suggested by Newman and others, but rather is more analogous to a laminar flow system. In addition it has been shown that an exponential extrapolation of the downslopes of the indicator dilution curves to calculate pulmonary blood volume results in a measurable error.
Tailored thrombolytic therapy. A perspective.
Authors: M L Simoons, A E Arnold
Journal: Circulation (1993)

BACKGROUND In contrast with current standard regimens, it seems more appropriate to tailor thrombolytic therapy to individual patient characteristics. A proposed model for such tailored therapy is based on individual assessment of benefits and risks of thrombolytic therapy, taking into account the response of individual patients to the therapy given. METHODS AND RESULTS Potential benefits of thrombolysis in individual patients can be predicted by use of demographic patient characteristics (age, sex, history of previous infarction) together with indicators of the ischemic area at risk (total ST segment deviation) and treatment delay. Using these parameters, the number of "lives saved" by thrombolytic therapy for specific patient characteristics can be estimated. Similarly, the risk of intracranial hemorrhage during thrombolytic therapy can be estimated from the patient's age, blood pressure at admission, and body weight. Depending on benefit/risk estimates, a choice can be made between regimens with high, medium, or modest thrombolytic efficacy. Continuous multilead ECG ischemia monitoring and rapid assays of myocardial proteins in serum can be used to assess the occurrence or absence of reperfusion and to detect signs of reocclusion. Such data help to decide whether thrombolytic therapy should be continued or intensified or might be discontinued in individual patients before the total standard dose has been administered. Such tailored reduction of the total thrombolytic dose will reduce the risk for bleeding complications in some of the patients. CONCLUSIONS The concept of tailoring thrombolytic therapy and the models presented for benefit/risk assessment should be tested in clinical studies and may subsequently help the physician to select the optimal approach in individual patients.
Ultrasound detected synovial change and pain response following intra-articular injection of corticosteroid and a placebo in symptomatic osteoarthritic knees: a pilot study
Authors: Michelle Hall, Sally Doherty, Philip Courtney, Khalid Latief, Weiya Zhang, Michael Doherty
Journal: Annals of the Rheumatic Diseases (2014)

Intra-articular injection (IAI) of steroid is a safe and effective treatment for painful knee osteoarthritis (OA).1 The mechanism of action is thought to be partly mediated by an anti-inflammatory effect on the synovium which may be detected by changes observed on ultrasound (US) examination.2 Placebo IAI of saline can also significantly reduce pain though the mechanisms are not generally thought to associate with a peripheral effect.3–5 This pilot study aimed to investigate whether improved knee pain correlated with improved US measures following IAI of a corticosteroid or a placebo in OA knees.

Twenty-five participants with painful knee OA (Kellgren and Lawrence grade ≥2) were randomised to one of two treatment sequences (IAI of methylprednisolone (40 mg in 1 mL) followed by IAI of saline placebo (1 mL, 0.9%), or vice versa) to their most painful knee. Synovial fluid equal to volume injected …