tbuckley/cabot-search huggingface dataset:
Post-resuscitation central venous pressure and serum lactate associated with survival in severe sepsis and septic shock
Authors: Kuei-Pin Chung, Hou-Tai Chang, Jih-Shuin Cheng, Chong-Jen Yu
Journal: European Respiratory Journal (2012)

Background 

The survival in severe sepsis and septic shock is improved by quantitative resuscitation, with goals as mean arterial pressure (MAP), central venous pressure (CVP), oxygen saturation of central venous blood (ScvO2), and lactate clearance.

Objectives 

To investigate whether post-resuscitation MAP, CVP, ScvO2, and lactate level predict the survival in severe sepsis and septic shock.

Methods 

This prospective study was conducted in two tertiary medical centers in Taiwan. Adult patients admitted for severe sepsis or septic shock would be enrolled. Patients with cirrhosis or advanced malignancies were excluded. All patients received initial hemodynamic resuscitation before ICU admission. We evaluated the association between 28-day survival and post-resuscitation MAP, CVP, ScvO2, and lactate level.

Results 

A total of 124 patients were enrolled from Aug 2009 to Dec 2011. The APACHE II and SOFA scores were 25.3±0.7 and 9.9±0.3, respectively. The 28-day mortality was 26.6%. Multi-variate logistic regression analyses showed that CVP ( P =0.010) and serum lactate ( P =0.011) were associated with 28-day mortality. Post-resuscitation hemodynamic scores were established with two subscores: CVP (1 if ≥ 13.5 mmHg) and serum lactate level (1 if ≥ 5.3 mmol/L). Higher post-resuscitation hemodynamic scores were associated with higher APACHE II and SOFA scores ( P < 0.001 and < 0.001 by Kruskal-Wallis test, respectively), and higher risk of 28-day mortality (hazard ratio 3.14, P <0.001 by logistic regression).

Conclusions 

In our patients with severe sepsis and septic shock, high post-resuscitation CVP and serum lactate were associated with organ dysfunction and high mortality.
Noninvasive Imaging of Apoptosis and Its Application in Cancer Therapeutics
Authors: Julia M. Coppola, Brian D. Ross, Alnawaz Rehemtulla
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Activation of the apoptotic cascade plays an important role in the response of tumors to therapy. Noninvasive imaging of apoptosis facilitates optimization of therapeutic protocols regarding dosing and schedule and enables identification of efficacious combination therapies. Experimental Design: We describe a hybrid polypeptide that reports on caspase-3 activity in living cells and animals in a noninvasive manner. This reporter, ANLucBCLuc, constitutes a fusion of small interacting peptides, peptide A and peptide B, with the NLuc and CLuc fragments of luciferase with a caspase-3 cleavage site (DEVD) between pepANLuc (ANLuc) and pepBCLuc (BCLuc). During apoptosis, caspase-3 cleaves the reporter, enabling separation of ANLuc from BCLuc. A high-affinity interaction between peptide A and peptide B restores luciferase activity by NLuc and CLuc complementation. Using a D54 glioma model, we show the utility of the reporter in imaging of apoptosis in living subjects in response to various chemotherapy and radiotherapy regimens. Results: Treatment of live cells and mice carrying D54 tumor xenografts with chemotherapeutic agents such as temozolomide and perifosine resulted in induction of bioluminescence activity, which correlated with activation of caspase-3. Treatment of mice with combination therapy of temozolomide and radiation resulted in increased bioluminescence activity over individual treatments and increased therapeutic response due to enhanced apoptosis. Conclusion: The data provided show the utility of the ANLucBCLuc reporter in dynamic, noninvasive imaging of apoptosis and provides a rationale for use of this technology to optimize dose and schedule of novel therapies or to develop novel combination therapies using existing drugs.
Glycoprotein 90K, downregulated in advanced colorectal cancer tissues, interacts with CD9/CD82 and suppresses the Wnt/ -catenin signal via ISGylation of -catenin
Authors: J. H. Lee, J. A. Bae, J. H. Lee, Y.-W. Seo, D. H. Kho, E. G. Sun, S. E. Lee, S. H. Cho, Y. E. Joo, K. Y. Ahn, I. J. Chung, K. K. Kim
Journal: Gut (2010)

<h3>Background and aims</h3> 90K, a tumour-associated glycoprotein, interacts with galectins and has roles in host defence by augmenting the immune response, but the serum 90K level was suggested to indicate poor prognosis in several cancers. The cellular mechanisms of 90K action on colorectal cancer (CRC) cell motility and its effect on CRC progression were investigated. <h3>Methods</h3> The impact of 90K was analysed by combining cell cultures, in vitro assays, and immunohistochemistry. <h3>Results</h3> Secreted 90K suppresses CRC cell invasion, but this action of 90K is masked through binding with extracellular galectins. A novel pathway is identified comprising a secretory 90K and a CD9/CD82 tetraspanin web; in this pathway, 90K interacts with CD9/CD82, suppresses the Wnt/β-catenin signal via a novel proteasomal-ubiquitination mechanism of β-catenin that is dependent on ISG15 (interferon-stimulated gene-15) modification (ISGylation) but not on glycogen synthase kinase 3β (GSK-3β) and Siah/Adenomatous polyposis coli (APC). In a syngeneic mouse colon tumour model, tumour growth and lung metastasis were increased with 90K knockdown. In colon tissues from stage IV human CRC and invading cancer cells of corresponding metastatic liver tissues, in which β-catenin and galectin expression was higher, immunostained 90K and CD9/CD82 were lower than in adjacent hepatic tissues or colon tissues from stage I. <h3>Conclusions</h3> 90K itself has antitumour activity in CRC cells via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin when it interacts with CD9/CD82, but is downregulated in advanced CRC tissues. The data suggest a strategy of strengthening this novel pathway with concomitant knockdown of galectins as a potential therapeutic approach to CRC progression.
Age and Sex Differences in the Clustering of Metabolic Syndrome Factors
Authors: Jennifer L. Kuk, Chris I. Ardern
Journal: Diabetes Care (2010)

OBJECTIVE The metabolic syndrome is a general term given to a clustering of cardiometabolic risk factors that may consist of different phenotype combinations. The purpose of this study was to determine the prevalence of the different combinations of factors that make up the metabolic syndrome as defined by the National Cholesterol Education Program and to examine their association with all-cause mortality in younger and older men and women. RESEARCH DESIGN AND METHODS A total of 2,784 men and 3,240 women from the Third National Health and Nutrition Examination Survey with public-access mortality data linkage (follow-up = 14.2 ± 0.2 years) were studied. RESULTS Metabolic syndrome was present in 26% of younger (aged ≤65 years) and 55.0% of older (aged &amp;gt;65 years) participants. The most prevalent metabolic syndrome combination was the clustering of high triglycerides, low HDL cholesterol, and elevated blood pressure in younger men (4.8%) and triglycerides, HDL cholesterol, and elevated waist circumference in younger women (4.2%). The presence of all five metabolic syndrome factors was the most common metabolic syndrome combination in both older men (8.0%) and women (9.2%). Variation existed in how metabolic syndrome combinations were associated with mortality. In younger adults, having all five metabolic syndrome factors was most strongly associated with mortality risk, whereas in older men, none of metabolic syndrome combinations were associated with mortality. In older women, having elevated glucose or low HDL as one of the metabolic syndrome components was most strongly associated with mortality risk. CONCLUSIONS Metabolic syndrome is a heterogeneous entity with age and sex variation in component clusters that may have important implications for interpreting the association between metabolic syndrome and mortality risk. Thus, metabolic syndrome used as a whole may mask important differences in assessing health and mortality risk.
Taxanes Alone or in Combination With Anthracyclines As First-Line Therapy of Patients With Metastatic Breast Cancer
Authors: Martine J. Piccart-Gebhart, Tomasz Burzykowski, Marc Buyse, George Sledge, James Carmichael, Hans-Joachim Lück, John R. Mackey, Jean-Marc Nabholtz, Robert Paridaens, Laura Biganzoli, Jacek Jassem, Marijke Bontenbal, Jacques Bonneterre, Stephen Chan, Gul Atalay Basaran, Patrick Therasse
Journal: Journal of Clinical Oncology (2008)

Purpose Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. Patients and Methods Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. Results Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P &lt; .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. Conclusion Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.
Reconsidering the arm span-height relationship in patients referred for spirometry
Authors: A. Capderou, M. Berkani, M-H. Becquemin, M. Zelter
Journal: European Respiratory Journal (2010)

The interpretation of pulmonary function tests relies on reference values corrected for age, sex and height. Height may be difficult to measure in patients with deformities of the thoracic cage or those unable to stand up properly. Current practice is to substitute arm span to height, once corrected either by a fixed factor or by an age- and sex-dependent regression equation. However arm span may be difficult to measure in some patients. This study evaluated the relationship between arm span, measured height, height as mentioned on an identity document (ID), sex and age in a population of 2,452 Caucasian subjects with no chest or spine deformities. The present study demonstrates that age and sex have to be taken into account to best predict height from arm span or ID height values. The equations predicting height from ID height give the best diagnosis concordance compared to reference in males and females. Age correction does not improve concordance below 70 yrs. The estimation of height from ID height can be substituted to that from arm span when clinically relevant, providing ID height has been measured before the occurrence of stature problems.
EXTRAORDINARY ASSOCIATION BETWEEN HLA-DR2 AND NARCOLEPSY
Authors: Michel Billiard, Jean Seignalet, Takeo Juji, Kazumasa Matsuki, Tohru Naohara, Masahiro Satake, Yutaka Honda, Nicola Langdon, MiekeVan Dam, KenI. Walsh, RobertW. Vaughan, David Parkes
Journal: The Lancet (1985)
Microfluidic Cell Sorter (<i>μ</i>FCS) for On‐chip Capture and Analysis of Single Cells
Authors: Jaehoon Chung, Huilin Shao, Thomas Reiner, David Issadore, Ralph Weissleder, Hakho Lee
Journal: Advanced Healthcare Materials (2012)

A low-cost and rapid microfluidic cell sorter (μFCS) for circulating tumor cell (CTC) detection, culture and analyses is developed. Based on size separation and molecular characterization, μFCS efficiently enriches CTCs from unprocessed whole blood, allows on-chip culture and molecular profiling, and provides cell retrieval for subsequent analyses. The potential clinical application of the technology is demonstrated by capturing and genetically analyzing CTCs in tumor-bearing mice. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The combination of autofluorescence endoscopy and molecular biomarkers is a novel diagnostic tool for dysplasia in Barrett's oesophagus
Authors: Massimiliano di Pietro, David F Boerwinkel, Mohammed Kareem Shariff, Xinxue Liu, Emmanouil Telakis, Pierre Lao-Sirieix, Elaine Walker, George Couch, Leanne Mills, Tara Nuckcheddy-Grant, Susan Slininger, Maria O'Donovan, Mike Visser, Sybren L Meijer, Philip V Kaye, Lorenz Wernisch, Krish Ragunath, Jacques J G H M Bergman, Rebecca C Fitzgerald
Journal: Gut (2014)

<h3>Objective</h3> Endoscopic surveillance for Barrett9s oesophagus (BO) is limited by sampling error and the subjectivity of diagnosing dysplasia. We aimed to compare a biomarker panel on minimal biopsies directed by autofluorescence imaging (AFI) with the standard surveillance protocol to derive an objective tool for dysplasia assessment. <h3>Design</h3> We performed a cross-sectional prospective study in three tertiary referral centres. Patients with BO underwent high-resolution endoscopy followed by AFI-targeted biopsies. 157 patients completed the biopsy protocol. Aneuploidy/tetraploidy; 9p and 17p loss of heterozygosity; <i>RUNX3</i>, <i>HPP1</i> and <i>p16</i> methylation; p53 and cyclin A immunohistochemistry were assessed. Bootstrap resampling was used to select the best diagnostic biomarker panel for high-grade dysplasia (HGD) and early cancer (EC). This panel was validated in an independent cohort of 46 patients. <h3>Results</h3> Aneuploidy, p53 immunohistochemistry and cyclin A had the strongest association with dysplasia in the per-biopsy analysis and, as a panel, had an area under the receiver operating characteristic curve of 0.97 (95% CI 0.95 to 0.99) for diagnosing HGD/EC. The diagnostic accuracy for HGD/EC of the three-biomarker panel from AFI+ areas was superior to AFI− areas (p&lt;0.001). Compared with the standard protocol, this panel had equal sensitivity for HGD/EC, with a 4.5-fold reduction in the number of biopsies. In an independent cohort of patients, the panel had a sensitivity and specificity for HGD/EC of 100% and 85%, respectively. <h3>Conclusions</h3> A three-biomarker panel on a small number of AFI-targeted biopsies provides an accurate and objective diagnosis of dysplasia in BO. The clinical implications have to be studied further.
Automated Structural Comparisons Clarify the Phylogeny of the Right-Hand-Shaped Polymerases
Authors: Heli A. M. Mönttinen, Janne J. Ravantti, David I. Stuart, Minna M. Poranen
Journal: Molecular Biology and Evolution (2014)

Polymerases are essential for life, being responsible for replication, transcription, and the repair of nucleic acid molecules. Those that share a right-hand-shaped fold and catalytic site structurally similar to the DNA polymerase I of Escherichia coli may catalyze RNA- or DNA-dependent RNA polymerization, reverse transcription, or DNA replication in eukarya, archaea, bacteria, and their viruses. We have applied novel computational methods for structure-based clustering and phylogenetic analyses of this functionally diverse polymerase superfamily, which currently comprises six families. We identified a structural core common to all right-handed polymerases, composed of 57 amino acid residues, harboring two positionally and chemically conserved residues, the catalytic aspartates. The structural conservation within each of the six families is considerable, for example, the structural core shared by family Y DNA polymerases covers over 90% of the polymerase domain of the Sulfolobus solfataricus Dpo4. Our phylogenetic analyses propose an early separation of RNA-dependent polymerases that use primers from those that are primer-independent. Furthermore, the exchange of polymerase genes between viruses and their hosts is evident. Because of this horizontal gene transfer, the phylogeny of polymerases does not always reflect the evolutionary history of the corresponding organisms.
Continuous positive airway pressure titration for obstructive sleep apnoea: automatic versus manual titration
Authors: N. McArdle, B. Singh, M. Murphy, K. R. Gain, C. Maguire, S. Mutch, D. R. Hillman
Journal: Thorax (2010)

<h3>Background and aims</h3> Manual laboratory continuous positive airway pressure (CPAP) titration for obstructive sleep apnoea (OSA) is costly, time intensive and delays access to treatment. Automatic positive airway pressure (APAP) titration has the potential to reduce cost and improve access to treatment. The aim of this study was to assess the clinical efficacy and costs of APAP titration compared with manual titration in moderate–severe OSA. <h3>Methods</h3> Patients with moderate–severe OSA (apnoea/hypopnoea index &gt;15 and Epworth Sleepiness Score ≥8) who were free of co-morbidities that could impair APAP titration were eligible. 249 participants were randomised to manual titration, home APAP or laboratory APAP titration to determine a fixed pressure for CPAP. Clinical and direct cost outcomes were assessed after 4 weeks of treatment. <h3>Results</h3> Average nightly CPAP use, subjective sleepiness, SF36 quality of life, Trails A and B cognitive function and polysomnographic outcomes were similar among the per-protocol groups. Non-hypertensive patients had a lower resting heart rate (and greater reduction in heart rate) at 4 weeks after laboratory APAP titration compared with home APAP titration. Costs per patient were highest in manual (AU$817.84), followed by laboratory (AU$647.56) and home (AU$132.09) APAP titration. An intention-to-treat analysis confirmed the effectiveness of APAP titration compared with manual titration in the standard clinical setting. <h3>Conclusions</h3> Among patients with moderate–severe OSA without serious co-morbidities, outcomes at 1 month indicate that APAP titration is more cost-effective than manual laboratory titration to determine an appropriate pressure for CPAP for long-term use; with the largest savings occurring in the home APAP patients. <h3>Australian New Zealand Clinical Trials Registry Number</h3> ACTRN12608000054314.
Impact of physical training on the ultrastructure of midthigh muscle in normal subjects and in patients treated with glucocorticoids.
Authors: F F Horber, H Hoopeler, J R Scheidegger, B E Grünig, H Howald, F J Frey
Journal: Journal of Clinical Investigation (1987)

Exercise-training might be a logical method to reverse muscle atrophy and weakness in patients treated with glucocorticoids. The purpose of the present investigation was to establish whether a treatment with low dose prednisone (10 +/- 2.9 mg/d) modulates the effect of a moderate strength type isokinetic training during 7 wk (21 sessions of 20 min) on "muscle efficiency" (power output/muscle mass) and on concomitant changes in ultrastructure of the thigh muscle measured by quantitative electron-microscopic morphometry. Training caused a similar increase in "muscle efficiency" in patients on prednisone (n = 9) as in normal volunteers (n = 9). In normal subjects the increase in muscle efficiency was associated with an increase in sarcoplasm, whereas in patients on prednisone the functional improvement was associated with an increase in sarcoplasm, capillaries, and mitochondria content. Thus, a therapy with low dose prednisone does not abrogate training-induced improvement of muscle efficiency but modulates the ultrastructural response of the muscle to the training.
Gastrointestinal involvement in Behcet's syndrome: a controlled study.
Authors: S Yurdakul, N Tuzuner, I Yurdakul, V Hamuryudan, H Yazici
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To make a retrospective and prospective analysis of the frequency of symptomatic inflammatory bowel disease in patients with Behçet9s syndrome (BS). METHODS: The medical records of the first 1000 patients with BS were reviewed retrospectively for past or present history of diarrhoea. The past and present history of diarrhoea was also elicited prospectively among 147 consecutive patients with BS and 78 diseased controls (42 with rheumatoid arthritis, 17 with systemic lupus erythematosus, seven with seronegative spondylarthropathy, and 12 with miscellaneous rheumatic diseases). Inflammatory mucosal changes were sought in rectal biopsy specimens from 75 patients with BS, 47 diseased controls (29 with nephrotic syndrome, eight with rheumatoid arthritis, six with familial Mediterranean fever, and four with ankylosing spondylitis), and 14 patients with ulcerative colitis. RESULTS: In chart review there were only seven Behçet9s patients with diarrhoea; none of them had inflammatory bowel disease. In the prospective survey there were no significant differences between the BS and control groups in the past and present history of diarrhoea. There were no significant differences in the rectal mucosal histology between patients with BS and controls, while patients with ulcerative colitis showed pronounced differences. CONCLUSION: Symptomatic inflammatory bowel disease is not common in BS patients from Turkey.
Lysophosphatidylcholine Enhances Cytokine-Induced Interferon Gamma Expression in Human T Lymphocytes
Authors: Eiichiro Nishi, Noriaki Kume, Yasushi Ueno, Hiroshi Ochi, Hideaki Moriwaki, Toru Kita
Journal: Circulation Research (1998)

Abstract —Accumulation of substantial numbers of activated T lymphocytes, as well as monocyte/macrophages, in focal areas of arterial intima appears to be a hallmark of atherogenesis. Our previous report demonstrated that lysophosphatidylcholine (lyso-PC), a polar phospholipid component that is increased in atherogenic lipoproteins and atherosclerotic lesions, can upregulate the expression of heparin-binding epidermal growth factor–like growth factor and the interleukin (IL)-2 receptor in cultured human peripheral T lymphocytes. In this study, we show that lyso-PC can also enhance interferon gamma (IFN-γ) secretion and gene expression in human T lymphocytes. Lyso-PC–induced upregulation of IFN-γ depended on the presence of IL-2, IL-12, or phytohemagglutinin in culture media and was similarly observed in both CD4 + and CD8 + subsets. Actinomycin D chase by Northern blotting showed that lyso-PC significantly prolonged IFN-γ mRNA half-lives in human T cells. Transient transfection of IFN-γ promoter-reporter gene construct in the human T-cell line Jurkat cells demonstrated that lyso-PC stimulated the transcription of IFN-γ promoter-driven luciferase gene. Analyses of serial deletion mutations of IFN-γ promoter revealed that the lyso-PC–responsive element is located between base pairs −102 and −78 of the transcription initiation site of the IFN-γ gene. Enhanced expression of IFN-γ in T lymphocytes by lyso-PC may play a crucial role in atherogenesis.