tbuckley/cabot-search huggingface dataset:
Cystic Fibrosis Disease–specific Centiles in 2000 and 2005
Authors: Frauke Stanke, Manfred Ballmann, Burkhard Tümmler
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

3. Kaisers U, Kuhler R, Keske U. Superimposing positive end expiratory pressure during partial liquid ventilation in experimental lung injury. Eur Respir J 1997;22:1035–1042. 4. Tutuncu AS, Faithfull NS, Lachmann B. Intratracheal perfluorocarbon administration combined with mechanical ventilation in experimental respiratory distress syndrome: dose-dependent improvement of gas exchange. Crit Care Med 1993;21:962–969. 5. Hirschl RB, Croce M, Gore D, Wiedemann H, Davis K, Zwischenberger J, Bartlett RH. Prospective, randomized controlled pilot study of partial liquid ventilation in adult acute respiratory distress syndrome. Am J Respir Crit Care Med 2002;165:781–787.
<i>N</i>‐acetylcysteine attenuates TNF‐α‐dependent reduction of IL‐4‐induced Fc<sub>ɛ</sub> RII expression in human monocytes
Authors: S. Hashimoto, Y. Gon, T. Nakayama, S. Yoshida, S. Hayashi, S. Maruoka, J. Yodoi, T. Horie, Shu Hashimoto
Journal: Allergy (1997)

We have previously shown that tumor necrosis factor‐a (TNF‐α) reduces interleukin‐4 (IL‐4)‐induced Fc e RII expression in human monocytes. It has been shown that TNF‐α activates nuclear transcriptional factors through the generation of reactive oxygen intermediates (ROIs), and antioxidant N‐acetylcysteine (NAC) inhibits TNF‐α‐induced activation of nuclear transcriptional factors. Therefore, we hypothesized that TNF‐α‐dependent reduction of IL‐4‐induced Fc e RII expression in monocytes might be mediated through the ROIs‐activated mechanism. In the present study, to test our hypothesis, we examined the effect of NAC on TNF‐α‐dependent reduction of IL‐4‐induced Fc ɛ RII expression in human monocytes. NAC attenuated TNF‐α‐dependent reduction of IL‐4‐induced Fc ɛ RII expression by attenuating TNF‐a‐dependent reduction of Fc ɛ RII mRNA expression. Similarly, the structurally unrelated antioxidant, pyrrolidine dithiocarbamate (PDTC), also effectively attenuated this reduction. These results indicate that an ROIs‐activated and antioxidant‐sensitive mechanism might be involved in TNF‐α‐dependent reduction of IL‐4‐induced Fc ɛ RII expression in monocytes.
Antibodies Neutralizing Peginterferon Alfa during Retreatment of Hepatitis C
Authors: Annemiek A. van der Eijk, Jan Maarten Vrolijk, Bart L. Haagmans
Journal: New England Journal of Medicine (2006)

To the Editor: Peginterferons are widely used to treat chronic hepatitis C virus (HCV) infection, an important cause of liver cirrhosis and hepatocellular carcinoma.1–4 We describe a patient who did not have a virologic response to peginterferon and had a virtual absence of circulating peginterferon alfa-2a but had neutralizing antibodies against interferon alfa. A 38-year-old man with liver cirrhosis (Child–Pugh class A; score, 5) was referred to our hospital for evaluation of his chronic HCV infection. He had had no response to a 16-week course of treatment with peginterferon alfa-2b and ribavirin during the previous year. We enrolled him . . .
Intrauterine Growth Retardation Is Associated With Reduced Activity and Expression of the Cationic Amino Acid Transport Systems y <sup>+</sup> /hCAT-1 and y <sup>+</sup> /hCAT-2B and Lower Activity of Nitric Oxide Synthase in Human Umbilical Vein Endothelial Cells
Authors: Paola Casanello, Luis Sobrevia
Journal: Circulation Research (2002)

Intrauterine growth retardation (IUGR) is associated with vascular complications leading to hypoxia and abnormal fetal development. The effect of IUGR on l -arginine transport and nitric oxide (NO) synthesis was investigated in cultures of human umbilical vein endothelial cells (HUVECs). IUGR was associated with membrane depolarization and reduced l -arginine transport ( V max = 5.8±0.2 versus 3.3±0.1 pmol/μg protein per minute), with no significant changes in transport affinity ( K m =159±15 versus 137±14 μmol/L). l -Arginine transport was trans -stimulated (8- to 9-fold) in cells from normal and IUGR pregnancies. IUGR was associated with reduced production of l -[ 3 H]citrulline from l -[ 3 H] arginine, lower nitrite and intracellular l -arginine, l -citrulline, and cGMP. IUGR decreased hCAT-1 and hCAT-2B mRNA, and increased eNOS mRNA and protein levels. IUGR-associated inhibition of l -arginine transport and NO synthesis, and membrane depolarization were reversed by the NO donor S -nitroso- N -acetyl- l , d -penicillamine. In summary, endothelium from fetuses with IUGR exhibit altered l -arginine transport and NO synthesis ( l -arginine/NO pathway), reduced expression and activity of hCAT-1 and hCAT-2B and reduced eNOS activity. Alterations in l -arginine/NO pathway could be critical for the physiological processes involved in the etiology of IUGR in human pregnancies.
The ABCA5 Protein: A Urine Diagnostic Marker for Prostatic Intraepithelial Neoplasia
Authors: Youji Hu, Min Wang, Karen Veverka, Fernando U. Garcia, Mark E. Stearns
Journal: Clinical Cancer Research (2007)

To develop a urine diagnostic test for preneoplastic intraepithelial neoplasia of the prostate.We have used a DNA-binding assay and electrophoretic mobility shift assays (EMSA) to screen for novel duplexed DNA-binding sequences, which bind protein(s) overexpressed in crude protein extracts from high-grade prostatic intraepithelial neoplasia (HGPIN). EMSAs, immunohistochemistry, and ELISAs were used to measure expression of the ABCA5 protein identified as a specific marker in prostate tissue and patient urine.Following screening of 4,096 sequences, an 8-bp dsDNA sequence (i.e., TCCAGCGA) was identified, which binds the ABCA5 protein, a member of the ATP-binding cassette multidrug resistant family. EMSAs showed that ABCA5 was overexpressed in HGPIN tissue (n=11/11) and in the urine of patients with HGPIN (n=18/18) but was not expressed in prostate cancer, benign prostatic hyperplasia, or stroma. Immunohistochemistry indicated that ABCA5 was overexpressed in foci of intermediate basal cells in normal glands and in HGPIN. ABCA5 was faintly expressed in prostate cancer glands. ELISAs showed in 'blinded studies' that ABCA5 was a highly sensitive (>98% sensitivity) urine diagnostic marker for HGPIN in biopsy-positive patients (n=107) at a 'cutoff' of 25 ng/mL. ABCA5 was present at very low levels (i.e., <25 ng/mL) in the urine of patients diagnosed with benign prostatic hyperplasia (n=79) or prostatitis or kidney and bladder cancer (>86% specificity).The data indicate that ABCA5 might be a specific urine marker for diagnosis of patients with HGPIN.
Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment
Authors: A W R van Kuijk, P Reinders-Blankert, T J M Smeets, B A C Dijkmans, P P Tak
Journal: Annals of the Rheumatic Diseases (2006)

The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis (PsA). Identification of proinflammatory molecules in the synovium may help to identify potentially therapeutic targets.To investigate extensively the features of cell infiltration and expression of mediators of inflammation and joint destruction in the synovium of patients with PsA compared with patients with rheumatoid arthritis matched for disease duration and use of drugs.Multiple synovial tissue biopsy specimens were obtained by arthroscopy from an inflamed joint in 19 patients with PsA (eight oligoarthritis, 11 polyarthritis) and 24 patients with rheumatoid arthritis. Biopsy specimens were analysed by immunohistochemistry to detect T cells, plasma cells, fibroblast-like synoviocytes, macrophages, proinflammatory cytokines, matrix metalloproteinases and tissue inhibitor metalloproteinase-1, adhesion molecules and vascular markers. Stained sections were evaluated by digital image analysis.The synovial infiltrate of patients with PsA and rheumatoid arthritis was comparable with regard to numbers of fibroblast-like synoviocytes and macrophages. T cell numbers were considerably lower in the synovium of patients with PsA. The number of plasma cells also tended to be lower in PsA. The expression of tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, IL6 and IL18 was as high in PsA as in rheumatoid arthritis. The expression of matrix metalloproteinases, adhesion molecules and vascular markers was comparable for PsA and rheumatoid arthritis.These data show increased proinflammatory cytokine expression in PsA synovium, comparable to results obtained for rheumatoid arthritis, and support the notion that, in addition to TNFalpha blockade, there may be a rationale for treatments directed at IL1beta, IL6 and IL18.
CALCIUM AND IRON INCRUSTATION AND OTHER LESIONS OF THE ELASTIC TISSUE OF THE SPLEEN AND LIVER
Authors: Thomas P. Sprunt
Journal: The Journal of Experimental Medicine (1911)

In conclusion, it may be said that the lesion described consists of a selective impregnation of the elastic tissue in the splenic trabeculae and vessels with the phosphates-and perhaps other salts-of calcium and iron. There is a further chemical change in the elastic fibers which may be expressed by the term "elacin." Degenerated and, especially, calcified elastic tissue-even more than calcification in general-seems to possess an affinity for iron salts. The iron incrustations occur principally in congested or hemorrhagic tissues. The etiological agent in this case is obscure. The only other example of this lesion in the spleen was in a case of Banti's disease. Many features of this case suggest a primary splenomegaly, but the evidence in its favor is not conclusive. Calcified elastic fibers, without the iron and elacin reactions, were also present in the liver, which was the seat of a recent, apparently biliary or infectious, cirrhosis. The elastic tissue of other organs showed nothing remarkable except in the skin, where the fibers were undergoing the usual senile changes.
Centralised multidisciplinary re-evaluation of diagnostic procedures in patients with newly diagnosed Hodgkin lymphoma
Authors: W.B.C. Stevens, J.H. van Krieken, R.D.M. Mus, A.I.J. Arens, V. Mattijssen, M. Oosterveld, E.J.F.M. de Kruijf, F. de Vries, A. Koster, R. van der Maazen, J. Raemaekers
Journal: Annals of Oncology (2012)
Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats
Authors: D GOLTZ, J SCHULTZ, C STUCKE, M WAGNER, P BASSALAY, A SCHWOERER, H EHMKE, T VOLK
Journal: Cardiovascular Research (2007)

A reduction of the Ca(2+)-independent transient outward potassium current (I(to)) in epicardial but not in endocardial myocytes of the left ventricle has been observed in cardiac hypertrophy and is thought to contribute to the electrical vulnerability associated with this pathology.In the present study we investigated the molecular mechanisms underlying regional alterations in I(to) in hypertrophied hearts of spontaneously hypertensive rats (SHR) using the whole-cell patch-clamp technique, quantitative RT-PCR and heterologous expression of underlying ion channel subunits.I(to) was significantly smaller in epicardial myocytes of SHR than in Wistar-Kyoto (WKY) controls (11.1+/-0.9 pA/pF, n=20 vs. 16.8+/-1.7 pA/pF, n=20, p<0.01), but not different in endocardial myocytes from both groups. Quantitative RT-PCR analysis of the genes encoding I(to) revealed significantly lower levels of Kv4.2 and Kv4.3 mRNA in the epicardial region of SHR rats compared to WKY rats. In contrast, mRNA expression levels of all three splice variants of the beta-subunit KChIP2 were significantly higher in both endo- and epicardial myocytes from SHR than from WKY rats. In parallel, inactivation of I(to), which is negatively modulated by KChIP2, was slowed down in SHR while recovery from inactivation remained unchanged. Heterologous co-expression of increasing amounts of KChIP2b together with a fixed amount of Kv4.2 in Xenopus laevis oocytes revealed a hyperbolic relation of recovery from inactivation and inactivation time constant, demonstrating that KChIP2 preferentially affects inactivation, if its expression level is high.These results suggest that downregulation of I(to) in the left ventricle of SHR is mediated by a reduced expression of Kv4.2 and Kv4.3 (but not of KChIP2), whereas the slower inactivation of I(to) can be explained by increased expression levels of KChIP2 in SHR.
Depressed Myocardial Creatine Phosphokinase Activity Following Experimental Myocardial Infarction in Rabbit
Authors: JOHN K. KJEKSHUS, BURTON E. SOBEL
Journal: Circulation Research (1970)

Since creatine phosphokinase (CPK) is found predominantly in myocardial and skeletal muscle cells, in contrast to cells participating in the inflammatory response, it was considered likely that measurement of activity of this enzyme in the heart would provide a sensitive and relatively specific index of the extent of ischemic injury following acute coronary artery occlusion. Accordingly, CPK activity was measured serially following coronary artery occlusion in extracts from rabbit myocardium with gross infarction and from normal rabbit left ventricle. In addition, myocardial CPK activity was assayed in extracts from various portions of dog hearts 24 hours after ligation of the coronary artery. CPK activity of rabbit myocardium with infarction was uniformly depressed within 6 hours following coronary occlusion. After 24 hours, activity declined from 15.5±0.9 (mean±SE) to 3.4±0.3. CPK activity in whole left ventricular extracts was depressed and in general, the extent of depression was proportional to the size of the gross infarct. CPK depression in various regions of the dog heart 24 hours after coronary occlusion correlated with the extent of reduction of blood flow determined with the use of radioactively labeled microspheres. Results suggest that depression of myocardial CPK activity may be useful in estimating the extent of tissue damage following experimental coronary artery occlusion and the effect of prophylactic and therapeutic measures on the survival of myocardium in this setting.
RNA recognition by human TLR8 can lead to autoimmune inflammation
Authors: Cristiana Guiducci, Mei Gong, Alma-Martina Cepika, Zhaohui Xu, Claudio Tripodo, Lynda Bennett, Chad Crain, Pierre Quartier, John J. Cush, Virginia Pascual, Robert L. Coffman, Franck J. Barrat
Journal: The Journal of Experimental Medicine (2013)

Studies on the role of the RNA receptor TLR8 in inflammation have been limited by its different function in human versus rodents. We have generated multiple lines of transgenic mice expressing different levels of human TLR8. The high copy number chimeras were unable to pass germline; developed severe inflammation targeting the pancreas, salivary glands, and joints; and the severity of the specific phenotypes closely correlated with the huTLR8 expression levels. Mice with relatively low expression levels survived and bred successfully but had increased susceptibility to collagen-induced arthritis, and the levels of huTLR8 correlated with proinflammatory cytokines in the joints of the animals. At the cellular level, huTLR8 signaling exerted a DC-intrinsic effect leading to up-regulation of co-stimulatory molecules and subsequent T cell activation. A pathogenic role for TLR8 in human diseases was suggested by its increased expression in patients with systemic arthritis and the correlation of TLR8 expression with the elevation of IL-1β levels and disease status. We found that the consequence of self-recognition via TLR8 results in a constellation of diseases, strikingly distinct from those related to TLR7 signaling, and points to specific inflammatory diseases that may benefit from inhibition of TLR8 in humans.
Identification of Novel Mammalian Caspases Reveals an Important Role of Gene Loss in Shaping the Human Caspase Repertoire
Authors: L. Eckhart, C. Ballaun, M. Hermann, J. L. VandeBerg, W. Sipos, A. Uthman, H. Fischer, E. Tschachler
Journal: Molecular Biology and Evolution (2008)

Proteases of the caspase family play central roles in apoptosis and inflammation. Recently, we have described a new gene encoding caspase-15 that has been inactivated independently in different mammalian lineages. To determine the dynamics of gene duplication and loss in the entire caspase gene family, we performed a comprehensive evolutionary analysis of mammalian caspases. By comparative genomics and reverse transcriptase–polymerase chain reaction analyses, we identified 3 novel mammalian caspase genes, which we tentatively named caspases-16 through -18. Caspase-16, which is most similar in sequence to caspase-14, has been conserved in marsupials and placental mammals, including humans. Caspase-17, which is most similar to caspase-3, has been conserved among fish, frog, chicken, lizard, and the platypus but is absent from marsupials and placental mammals. Caspase-18, which is most similar to caspase-8, has been conserved among chicken, platypus, and opossum but is absent from placental mammals. These gene distribution patterns suggest that, in the evolutionary lineage leading to humans, caspase-17 was lost after the split of protherian and therian mammals and caspase-18 was lost after the split of marsupials and placental mammals. In the canine genome, the number of caspases has been reduced by the fusion of the neighboring genes caspases-1 and -4, resulting in a single coding region. Further lineage-specific gene inactivations were found for caspase-10 in murine rodents and caspase-12 in humans, rabbit, and cow. Lineage-specific gene duplications were found for caspases-1, -3, and -12 in opossum and caspase-4 in primates. Other caspases were generally conserved in all mammalian species investigated. Using the positions of introns as stable characters during recent vertebrate evolution, we define 3 phylogenetic clades of caspase genes: caspases-1/-2/-4/-5/-9/-12/-14/-15/-16 (clade I), caspases-3/-6/-7/-17 (clade II), and caspases-8/-10/-18/CFLAR (clade III). We conclude that gene inactivations have occurred in each of the 3 caspase clades and that gene loss has been as critical as gene duplication in the evolution of the human repertoire of caspases.
Pretreatment Transcriptional Profiling for Predicting Response to Neoadjuvant Chemoradiotherapy in Rectal Adenocarcinoma
Authors: Kate H. Brettingham-Moore, Cuong P. Duong, Danielle M. Greenawalt, Alexander G. Heriot, Jason Ellul, Christopher A. Dow, William K. Murray, Rodney J. Hicks, Joe Tjandra, Michael Chao, Andrew Bui, Daryl Lim Joon, Robert J. S. Thomas, Wayne A. Phillips
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Patients presenting with locally advanced rectal cancer currently receive preoperative radiotherapy with or without chemotherapy. Although pathologic complete response is achieved for approximately 10% to 30% of patients, a proportion of patients derive no benefit from this therapy while being exposed to toxic side effects of treatment. Therefore, there is a strong need to identify patients who are unlikely to benefit from neoadjuvant therapy to help direct them toward alternate and ultimately more successful treatment options. Experimental Design: In this study, we obtained expression profiles from pretreatment biopsies for 51 rectal cancer patients. All patients underwent preoperative chemoradiotherapy, followed by resection of the tumor 6 to 8 weeks posttreatment. Gene expression and response to treatment were correlated, and a supervised learning algorithm was used to generate an original predictive classifier and validate previously published classifiers. Results: Novel predictive classifiers based on Mandard's tumor regression grade, metabolic response, TNM (tumor node metastasis) downstaging, and normal tissue expression profiles were generated. Because there were only 7 patients who had minimal treatment response (&amp;gt;80% residual tumor), expression profiles were used to predict good tumor response and outcome. These classifiers peaked at 82% sensitivity and 89% specificity; however, classifiers with the highest sensitivity had poor specificity, and vice versa. Validation of predictive classifiers from previously published reports was attempted using this cohort; however, sensitivity and specificity ranged from 21% to 70%. Conclusions: These results show that the clinical utility of microarrays in predictive medicine is not yet within reach for rectal cancer and alternatives to microarrays should be considered for predictive studies in rectal adenocarcinoma. Clin Cancer Res; 17(9); 3039–47. ©2011 AACR.
Effects of the Selective MPS1 Inhibitor MPS1-IN-3 on Glioblastoma Sensitivity to Antimitotic Drugs
Authors: Bakhos A. Tannous, Mariam Kerami, Petra M. Van der Stoop, Nicholas Kwiatkowski, Jinhua Wang, Wenjun Zhou, Almuth F. Kessler, Grant Lewandrowski, Lotte Hiddingh, Nik Sol, Tonny Lagerweij, Laurine Wedekind, Johanna M. Niers, Marco Barazas, R. Jonas A. Nilsson, Dirk Geerts, Philip C. De Witt Hamer, Carsten Hagemann, W. Peter Vandertop, Olaf Van Tellingen, David P. Noske, Nathanael S. Gray, Thomas Würdinger
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundGlioblastomas exhibit a high level of chemotherapeutic resistance, including to the antimitotic agents vincristine and taxol. During the mitotic agent-induced arrest, glioblastoma cells are able to perform damage-control and self-repair to continue proliferation. Monopolar spindle 1 (MPS1/TTK) is a checkpoint kinase and a gatekeeper of the mitotic arrest.
Letter by Farmakis and Aessopos Regarding Article, “Echocardiographic Markers of Elevated Pulmonary Pressure and Left Ventricular Diastolic Dysfunction Are Associated With Exercise Intolerance in Adults and Adolescents With Homozygous Sickle Cell Anemia in the United States and United Kingdom”
Authors: Dimitrios Farmakis, Athanasios Aessopos
Journal: Circulation (2012)
A Public Health Emergency of International Concern? Response to a Proposal to Apply the International Health Regulations to Antimicrobial Resistance
Authors: Adam Kamradt-Scott
Journal: PLoS Medicine (2011)

There is little question that the international spread of antimicrobial resistance (AMR) is an alarming development that the global public health community must confront as a matter of some priority.Reducing the incidence of new cases will take the concerted effort and participation of all community sectors, and will require strong political leadership.The World Health Organization (WHO) is best placed to lead the international community's efforts to tackle this phenomenon, and as evidenced by the release of a new fact sheet on 21 February 2011 [1], the WHO Secretariat is acutely aware of the dangers microbial resistance presents.In the paper ''A Call for Action: The Application of the International Health Regulations to the Global Threat of Antimicrobial Resistance'' published this week in PLoS Medicine [2], Stephen Harbarth and colleagues make the case to utilize the revised International Health Regulations (2005) (IHR 2005) to encourage Member States to report all cases of AMR as they fulfil ''at least two'' of the criteria for a public health emergency of international concern (PHEIC).While I commend the authors for seeking to further the field of understanding relating to the interpretation, application, and implementation of the IHR, I disagree with their proposal.For reasons of brevity, I will outline just three reasons here.The Perspective section is for experts to discuss the clinical practice or public health implications of a published study that is freely available online.