tbuckley/cabot-search huggingface dataset:
MicroRNA-24 Regulates Vascularity After Myocardial Infarction
Authors: Jan Fiedler, Virginija Jazbutyte, Bettina C. Kirchmaier, Shashi K. Gupta, Johan Lorenzen, Dorothee Hartmann, Paolo Galuppo, Susanne Kneitz, John T.G. Pena, Cherin Sohn-Lee, Xavier Loyer, Juergen Soutschek, Thomas Brand, Thomas Tuschl, Joerg Heineke, Ulrich Martin, Stefan Schulte-Merker, Georg Ertl, Stefan Engelhardt, Johann Bauersachs, Thomas Thum
Journal: Circulation (2011)

Background— Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood. Methods and Results— Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2–associated death promoter) and Sirtuin1 were identified by transcriptome, protein arrays, and chromatin immunoprecipitation analyses. Overexpression of miR-24 or silencing of its targets significantly impaired angiogenesis in zebrafish embryos. Blocking of endothelial miR-24 limited myocardial infarct size of mice via prevention of endothelial apoptosis and enhancement of vascularity, which led to preserved cardiac function and survival. Conclusions— Our findings indicate that miR-24 acts as a critical regulator of endothelial cell apoptosis and angiogenesis and is suitable for therapeutic intervention in the setting of ischemic heart disease.
T-B cell interaction inhibits spontaneous apoptosis of mature lymphocytes in Bcl-2-deficient mice.
Authors: K Nakayama, K Nakayama, L B Dustin, D Y Loh
Journal: The Journal of Experimental Medicine (1995)

Bcl-2 expression is tightly regulated during lymphocyte development. Mature lymphocytes in Bcl-2-deficient mice show accelerated spontaneous apoptosis in vivo and in vitro. Stimulation of Bcl-2-deficient lymphocytes by anti-CD3 antibody inhibited the spontaneous apoptosis not only in T cells but also in B cells. The rescue of B cells was dependent on the presence of T cells, mainly through CD40L and interleukin (IL)-4. Furthermore, we generated Bcl-2-deficient mice transgenic for a T cell receptor or an immunoglobulin, both specific for chicken ovalbumin, to test for antigen-specific T-B cell interaction in the inhibition of the spontaneous apoptosis. The initial T cell activation by antigenic peptides presented by B cells suppressed apoptosis in T cells. Subsequently, T cells expressed CD40L and released ILs, leading to the protection of B cells from spontaneous apoptosis. These results suggest that the antiapoptotic signaling via CD40 or IL-4 may be largely independent of Bcl-2. Engagement of the Ig alone was not sufficient for the inhibition of B cell apoptosis. Thus, the physiological role of Bcl-2 in mature lymphocytes may be to protect cells from spontaneous apoptosis and to extend their lifespans to increase the opportunity for T cells and B cells to interact with each other and specific antigens in secondary lymphoid tissues. Bcl-2, however, appears to be dispensable for survival once mature lymphocytes are activated by antigen-specific T-B cell collaboration.
General considerations for lung function testing
Authors: M. R. Miller, R. Crapo, J. Hankinson, V. Brusasco, F. Burgos, R. Casaburi, A. Coates, P. Enright, C. P. M van der Grinten, P. Gustafsson, R. Jensen, D. C. Johnson, N. MacIntyre, R. McKay, D. Navajas, O. F. Pedersen, R. Pellegrino, G. Viegi, J. Wanger
Journal: European Respiratory Journal (2005)

SERIES “ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING”

Edited by V. Brusasco, R. Crapo and G. Viegi

Number 1 in this Series

⇓In preparing the joint statements on lung function testing for the American Thoracic Society (ATS) and the European Respiratory Society (ERS), it was agreed by the working party that the format of the statements should be modified so that they were easier to use by both technical and clinical staff. This statement contains details about procedures that are common for many methods of lung function testing and, hence, are presented on their own. A list of abbreviations used in all the documents is also included as part of this statement.

All terms and abbreviations used here are based on a report of the American College of Chest Physicians/ATS Joint Committee on Pulmonary Nomenclature 1. The metrology definitions agreed by the International Standards Organization (ISO) are recommended 2 and some important terms are defined as follows.

Accuracy is the closeness of agreement between the result of a measurement and the conventional true value.

Repeatability is the closeness of agreement between the results of successive measurements of the same item carried out, subject to all of the following conditions: same method, same observer, same instrument, same location, same condition of use, and repeated over a short space of time. In previous documents, the term reproducibility was used in this context, and this represents a change towards bringing this document in line with the ISO.

Reproducibility is the closeness of agreement of the results of successive measurements of the same item where the individual measurements are carried out with changed conditions, such as: method of measurement, observer, instrument, location, conditions of use, and time. Thus, if a technician tests a subject several times, this is looking at the …
High-Density Lipoprotein Particle Size and Concentration and Coronary Risk
Authors: Karim El Harchaoui, Benoit J Arsenault, Remco Franssen, Jean-Pierre Després, G Kees Hovingh, Erik S G Stroes, James D Otvos, Nicholas J Wareham, John J P Kastelein, Kay-Tee Khaw, S Matthijs Boekholdt
Journal: Annals of Internal Medicine (2009)

High-density lipoprotein (HDL) cholesterol levels are inversely related to risk for coronary artery disease (CAD). Because HDL particles are heterogeneous in size and composition, they may be differentially associated with other cardiovascular risk factors and with cardiovascular risk.To study the independent relationships of HDL size and particle concentration to risk for future CAD.Nested case-control study within the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk cohort; baseline survey between 1993 and 1997, follow-up until November 2003.Norfolk, United Kingdom.Case patients were 822 apparently healthy men and women who developed CAD during follow-up. Control participants were 1401 participants who remained without CAD and were matched to case patients by sex, age, and enrollment time.First CAD event leading to either hospitalization or death.Nuclear magnetic resonance spectroscopy-measured HDL particle concentration (mean, 33.9 micromol/L [SD, 5] vs. 32.9 micromol/L [SD, 6]; P < 0.001) and HDL size (mean, 8.9 nm [SD, 0.5] vs. 8.8 nm [SD, 0.5]; P < 0.001), as well as gradient gel electrophoresis-measured HDL size (mean, 8.9 nm [SD, 0.4] vs. 8.8 nm [SD, 0.4]; P = 0.005) were lower in case patients than in control participants. High-density lipoprotein size and HDL particle concentration were only weakly correlated (r = 0.08, for those measured with nuclear magnetic resonance spectroscopy; r = 0.10, for those measured with gradient gel electrophoresis). High-density lipoprotein size was strongly associated with risk factors characteristic of the metabolic syndrome, including waist-to-hip ratio, triglyceride level, and apolipoprotein B level, whereas HDL particle concentration was not. Both HDL size and HDL particle concentration were independently associated with CAD risk. The association between HDL size and CAD risk was abolished on adjustment for apolipoprotein B and triglyceride levels (adjusted odds ratio, 1.00 [95% CI, 0.71 to 1.39] for top vs. bottom quartile), whereas HDL particle concentration remained independently associated with CAD risk (adjusted odds ratio, 0.50 [CI, 0.37 to 0.66]).Measurements were performed in nonfasting blood samples, and residual confounding cannot be excluded.Both HDL size and HDL particle concentration were independently associated with other cardiovascular risk factors and with the risk for CAD. The relationship between HDL size and CAD risk was explained by markers associated with the metabolic syndrome, indicating that part of the relationship between HDL cholesterol and CAD risk is merely a reflection of this metabolic risk.
Validation of TPX2 as a Potential Therapeutic Target in Pancreatic Cancer Cells
Authors: Steven L. Warner, Bret J. Stephens, Stanley Nwokenkwo, Galen Hostetter, Anastasia Sugeng, Manuel Hidalgo, Jeffery M. Trent, Haiyong Han, Daniel D. Von Hoff
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The targeting protein for Xklp2 (TPX2) has recently gained attention as a putative oncogene possibly amplified in several human malignancies, including pancreatic adenocarcinoma. In this work, we sought to evaluate the copy number and expression of TPX2 in pancreatic cancer cell lines and tumor tissues and to further explore the potential of TPX2 as a therapeutic target. Experimental Design: The DNA copy number and expression of the TPX2 gene were surveyed in pancreatic cancer cell lines and tumor tissues and compared with those of immortalized normal pancreatic ductal cells and normal pancreatic tissues. The cellular effects of TPX2 knockdown using small interfering RNA oligonucleotides in pancreatic cancer cells, such as growth in tissue culture, in soft agar, and in nude mice; apoptosis; and sensitivity to paclitaxel, were also investigated using various assays. Results: Low-copy-number TPX2 amplification was found in pancreatic cancer cell lines and low-passage pancreatic cancer tumor xenografts. TPX2 expression was upregulated in pancreatic cancer cell lines at both the mRNA and protein levels relative to the immortalized pancreatic ductal epithelial cell line HPDE6. Immunohistochemical staining of a tissue microarray showed that TPX2 expression was higher in pancreatic tumors compared with their normal counterparts. Treatment with TPX2 targeting small interfering RNAs effectively reduced pancreatic cancer cell growth in tissue culture, induced apoptosis, and inhibited growth in soft agar and in nude mice. Knockdown of TPX2 also sensitized pancreatic cancer cells to paclitaxel treatment. Conclusions: Our results suggest that TPX2 might be an attractive target for pancreatic cancer therapy. (Clin Cancer Res 2009;15(21):6519–28)
Notes of Abdominal Surgical Cases
Authors: J. C. Renton
Journal: BMJ (1894)

a traee of peritonitis was found, but an intense swelling and inijmtioup of tlhe milucous membranie of tlle stomach and upper part of the snmall intestine, witlh miniute hiemoirllages into tie mucous inembrane.The coniverse was seen in a patient of my own from whom a, steiosed vermiform appendix was removed from an abscess
STUDIES IN CIRRHOSIS OF THE LIVER. I. RELATIONSHIP BETWEEN PLASMA VOLUME, PLASMA PROTEIN CONCENTRATIONS AND TOTAL CIRCULATING PROTEINS
Authors: Glenn I. Hiller, Elston R. Huffman, Stanley Levey
Journal: Journal of Clinical Investigation (1949)

Predicted normal weight and plasma volume for each patient.t Accepted minimum normal values for total protein, albumin and globulin concentrations.t Minimum normal quantity of total circulating protein, albumin, globulin and fibrinogen for each patient.
Effect of Longitudinal Changes in Visceral Fat Area and Other Anthropometric Indices to the Changes in Metabolic Risk Factors in Japanese Men
Authors: Yumi Matsushita, Toru Nakagawa, Shuichiro Yamamoto, Yoshihiko Takahashi, Tetsuji Yokoyama, Tetsuya Mizoue, Mitsuhiko Noda
Journal: Diabetes Care (2012)

The effects of longitudinal changes in the visceral fat area (VFA), and other anthropometric indices, on the risk factors of metabolic syndrome were not studied. We calculated the changes in metabolic risk factors in relation to changes in certain anthropometric indices in a large-scale study of Japanese men.The subjects were 1,106 men participating in the Hitachi Health Study who received a computed tomography examination in both 2004 and 2007. VFA, subcutaneous fat area (SFA), and waist circumference were measured using the computed tomography. We examined how longitudinal changes in each anthropometric index over a 3-year period influenced the value of each metabolic risk factor.Changes (Δ) over a 3-year period in body weight, SFA, and waist circumference strongly correlated, while the changes in body weight and VFA were weakly correlated. Changes in the VFA were associated with changes in metabolic risk factors, especially changes in triglyceride and HDL; we found these changes to be independent of the body weight and waist circumference.Change in body weight is not a precise surrogate marker of VFA, and repeated VFA measurements over time are useful. Adopting a lifestyle that does not increase the VFA is important in preventing metabolic syndrome.
Relationship between FEV<sub>1</sub>reduction and respiratory symptoms in the general population
Authors: N. Jakeways, T. McKeever, S.A. Lewis, S.T. Weiss, J. Britton
Journal: European Respiratory Journal (2003)

Obstructive airways diseases typically present with dyspnoea, cough and wheeze, and are defined by a reduced forced expiratory volume in one second (FEV 1 )/forced vital capacity (FVC) ratio. Traditionally, however, the severity of chronic obstructive pulmonary disease is graded by the FEV 1 % predicted rather than the FEV 1 /FVC ratio, whilst other potentially valid measures of FEV 1 impairment, such as the absolute difference of FEV 1 from predicted or the absolute level of FEV 1 , tend not to be used. The authors have therefore explored the relationship between these different measures of FEV 1 impairment and chronic respiratory symptoms in a general population sample. FEV 1 and FVC were measured and questionnaire data were obtained on cough, wheeze, shortness of breath and general self-reported breathing trouble in a cross-sectional survey of 2,633 adults aged 18–70 yrs from a district of Nottingham, UK. Odds ratios for each symptom were calculated for declining levels of absolute FEV 1 , FEV 1 % pred, absolute difference of FEV 1 from predicted, and FEV 1 /FVC ratio. They were plotted to display the shape and strength of these relationships before and after adjustment for each other measure. The odds of symptoms increased with declining levels of all FEV 1 measures, particularly for wheeze and general breathing trouble. Although this study was not sufficiently powerful to detect significant differences between measures, these relationships were consistently strongest, before and after adjustment, for FEV 1 % pred, particularly below a threshold of ∼75%. The authors conclude that forced expiratory volume in one second % predicted appears to be the measure of airflow impairment most closely associated with chronic respiratory symptoms in the general population.
Ongoing Myocardial Injury in Stable Severe Heart Failure
Authors: Eduardo R. Perna, Stella M. Macin, Juan P. Cimbaro Canella, Natalia Augier, Jorge L. Riera Stival, Jorge R. Cialzeta, Ariel E. Pitzus, Edgar H. Garcia, Ricardo Obregón, Mónica Brizuela, Alejandro Barbagelata
Journal: Circulation (2004)

Background— The progression of chronic heart failure (CHF) is related to ongoing myocyte loss, which can be detected by cardiac troponin T (cTnT). We examined the prevalence and prognostic value of increased cTnT concentrations in serial blood specimens from patients with severe CHF. Methods and Results— Clinical, echocardiographic, and 6-minute walk test data were collected prospectively at baseline and at 1 year in 115 outpatients (mean age, 61±11 years; 75% men; 62% coronary heart disease) with CHF and a left ventricular ejection fraction &lt;40%. Blood samples were collected at baseline and at 3, 6, and 12 months of follow-up. cTnT concentrations ≥0.02 ng/mL were considered abnormal, and a Tn index (highest cTnT measurement/0.02 ng/mL) was calculated. In 62 patients (54%), cTnT was consistently &lt;0.02 ng/mL (group 1); 28 (24%) had a single abnormal cTnT result (group 2); and 25 (22%) had ≥2 abnormal cTnT results (group 3). At 18 months, CHF hospitalization-free survival was 63%, 46%, and 17%, respectively ( P =0.0001). In a Cox proportional-hazards model, hospitalization for worsening CHF in the previous year (HR=2.1; 95% CI, 1.1 to 4.1), functional class III–IV (HR=2.3; 95% CI, 1.1 to 4.6), and number of abnormal cTnT samples (HR=1.6; 95% CI, 1.1 to 2.4) were independently associated with prognosis. A cTnT rise of 0.020 ng/mL in any sample was associated with an excess of 9% (95% CI, 1% to 18%) in the incidence of combined end point. Conclusions— Abnormal cTnT concentrations were detected in &gt;50% of outpatients with advanced CHF. This ongoing myocardial necrosis was a strong predictor of worsening CHF, suggesting a role of cTnT-based monitoring to identify high-risk patients.
Serum levels of CC16, SP-A and SP-B reflect tobacco-smoke exposure in asymptomatic subjects
Authors: M. Robin, P. Dong, C. Hermans, A. Bernard, A.D. Bersten, I.R. Doyle
Journal: European Respiratory Journal (2002)

Since the 16-kDa bronchiolar Clara cell protein (CC16) and the alveolar surfactant-associated proteins (SP)-A and -B leak into the circulation when parenchymal health is disturbed, the aim of this study was to determine whether their serum levels could serve as early peripheral markers of tobacco smoke-induced epithelial injury. Sixty-nine (51 yrs (32–54) median (25–75th percentile)) nonsmokers and 54 (42 yrs (31–53)) asymptomatic smokers were enrolled in the study. Serum levels of SP-A did not differ between subjects (270 (208–389) versus 259 (168–392) µg·L −1 ), however, CC16 levels decreased (10.6 (8.7–14.6) versus 7.6 (6.0–11.2) µg·L −1 ) and SP-B levels increased (2,529 (2,091–2,943) versus 3,053 (2,613–4,188) µg·L −1 ) in the smokers. When tobacco smoke exposure, serum creatinine (renal index), age and sex were used as independent variables, CC16 was negatively influenced by cumulative smoking and positively influenced by age. SP-A and -B were negatively influenced by creatinine and positively influenced by cumulative smoking. Serum SP-B was inversely correlated with forced expiratory volume in one second/vital capacity, suggesting an association between obstructive disease and parenchymal lung health. The authors suggest that serum surfactant-associated proteins-A and -B reflect increased alveolocapillary leakage whereas Clara cell secretory protein 16 reflects tobacco smoke-induced Clara cell toxicity. Their evaluation may allow the effects of tobacco smoke on different levels of the respiratory tract, cellular toxicity and epithelial leakage to be distinguished.
Do simple models lead to generality in ecology?
Authors: Matthew R. Evans, Volker Grimm, Karin Johst, Tarja Knuuttila, Rogier de Langhe, Catherine M. Lessells, Martina Merz, Maureen A. O’Malley, Steve H. Orzack, Michael Weisberg, Darren J. Wilkinson, Olaf Wolkenhauer, Tim G. Benton
Journal: Trends in Ecology & Evolution (2013)
Quantitative Detection of Micrometastases in Pelvic Lymph Nodes in Patients with Clinically Localized Prostate Cancer by Real-time Reverse Transcriptase-PCR
Authors: Hideaki Miyake, Isao Hara, Toshifumi Kurahashi, Taka-aki Inoue, Hiroshi Eto, Masato Fujisawa
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Routine pathologic examination can miss micrometastatic tumor foci in the lymph nodes of patients with prostate cancer, resulting in confusion during tumor staging and clinical decision-making. The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical prostatectomy for prostate cancer. Experimental Design: The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 2,215 lymph nodes isolated from 120 patients with clinically localized prostate cancer was assessed by a fully quantitative real-time reverse transcriptase-PCR. We regarded specimens in which either PSA or PSMA mRNAs were positive as proof of the “presence of micrometastasis.” Immunohistochemical staining of lymph node specimens with an antibody against PSA was also done. Results: Pathologic examinations detected tumor cells in 29 lymph nodes from 11 patients, and real-time reverse transcriptase-PCR further identified micrometastasis in 143 lymph nodes from 32 patients with no pathologic evidence of lymph node involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 61 lymph nodes from 17 patients with pathologically negative lymph nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including serum PSA value, pathologic stage, Gleason score, and tumor volume. Biochemical recurrence was detected in 32 patients, 17 of whom were negative for lymph node metastasis by pathologic examination (including 4 patients with pathologically organ-confined disease), but were diagnosed as having micrometastasis. Biochemical recurrence–free survival rate in patients without micrometastasis was significantly higher than in those with micrometastasis irrespective of the presence of pathologically positive nodes. Furthermore, only the presence of micrometastasis was independently associated with biochemical recurrence regardless of other factors examined. Conclusions: These findings suggest that ∼30% of clinically localized prostate cancers shed cancer cells to the pelvic lymph nodes, and that biochemical recurrence after radical prostatectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.