tbuckley/cabot-search huggingface dataset:
An unappreciated role for RNA surveillance
Authors: R Tyler Hillman, Richard E Green, Steven E Brenner
Journal: Genome biology (2004)

Nonsense-mediated mRNA decay (NMD) is a eukaryotic mRNA surveillance mechanism that detects and degrades mRNAs with premature termination codons (PTC+ mRNAs). In mammals, a termination codon is recognized as premature if it lies more than about 50 nucleotides upstream of the final intron position. More than a third of reliably inferred alternative splicing events in humans have been shown to result in PTC+ mRNA isoforms. As the mechanistic details of NMD have only recently been elucidated, we hypothesized that many PTC+ isoforms may have been cloned, characterized and deposited in the public databases, even though they would be targeted for degradation in vivo.We analyzed the human alternative protein isoforms described in the SWISS-PROT database and found that 144 (5.8% of 2,483) isoform sequences amenable to analysis, from 107 (7.9% of 1,363) SWISS-PROT entries, derive from PTC+ mRNA.For several of the PTC+ isoforms we identified, existing experimental evidence can be reinterpreted and is consistent with the action of NMD to degrade the transcripts. Several genes with mRNA isoforms that we identified as PTC+--calpain-10, the CDC-like kinases (CLKs) and LARD--show how previous experimental results may be understood in light of NMD.
The influence of oxygen inflow on ventilatory parameters during manual ventilation
Authors: Pricila Oliveira, Armando Almeida-Junior, Celize Almeida, Maria Ângela Ribeiro, José Ribeiro
Journal: European Respiratory Journal (2011)

Background: Despite of self-inflating bags (SIB) widespread use, studies have confirmed that many factors may have influence on ventilation.

Aim: To evaluate and to compare ventilatory parameters during manual ventilation with 4 different oxygen flows attached to the SIB.

Method: Twenty-two physiotherapists were asked to ventilate 2 lung models (neonatal/pediatric) using 3 SIBs (Hudson®, Laerdal®, JGMoryia®) with 0, 5, 10, and 15L/min of oxygen inflow attached. A lung function monitor (CO2SMOplus®) recorded inspiratory volume (Vi), peak inspiratory pressure (PIP), peak inspiratory (PIF) and expiratory (PEF) flows, and inspiratory time (Ti). The oxygen inflows were compared using ANOVA for repeated measures and Tukey's test, with p<0.05 considered statistically significant.

Results: When we analyze all brands in neonatal and pediatric models, the oxygen inflows influenced Vi, PIP, PIF, and Ti (p<0.001). When compared 0 and 15L/min, we found a significant increase in PIP in all neonatal SIB brands. Also, there was a difference in Vi delivered by neonatal Hudson® SIB.

Conclusion: We found great variability in ventilatory parameters depending on the oxygen inflow. The Vi, PIP, PIF, and Ti showed a large variation. Professionals should be aware of those differences and the choice of the oxygen flow used should be taken with caution.
Heterozygosity for a Hereditary Hemochromatosis Gene Is Associated With Cardiovascular Death in Women
Authors: Mark Roest, Yvonne T. van der Schouw, Bart de Valk, Jo J. M. Marx, Mariëlle J. Tempelman, Philip G. de Groot, Jan J. Sixma, Jan Dirk Banga
Journal: Circulation (1999)

Background —The genetic background of hereditary hemochromatosis ( HH ) is homozygosity for a cysteine-to-tyrosine transition at position 282 in the HFE gene. Heterozygosity for HH is associated with moderately increased iron levels and could be a risk factor for cardiovascular death. Methods and Results —We studied the relation between HH heterozygosity and cardiovascular death in a cohort study among 12 239 women 51 to 69 years of age residing in Utrecht, the Netherlands. Women were followed for 16 to 18 years (182 976 follow-up years). The allele prevalence of the HH gene in the reference group was 4.0 (95% CI 2.9 to 5.4). The mortality rate ratios for HH heterozygotes compared with wild types was 1.5 (95% CI 0.9 to 2.5) for myocardial infarction (n=242), 2.4 (95% CI 1.3 to 3.5) for cerebrovascular disease (n=118), and 1.6 (95% CI 1.1 to 2.4) for total cardiovascular disease (n=530). The population-attributable risks of HH heterozygosity for myocardial infarction and cerebrovascular and total cardiovascular death were 3.3%, 8.8%, and 4.0%, respectively. In addition, we found evidence for effect modification by hypertension and smoking. Conclusions —We found important evidence that inherited variation in iron metabolism is involved in cardiovascular death in postmenopausal women, especially in women already carrying classic risk factors.
Generation of T-helper cells in vitro. II. Analysis of supernates derived from T-helper cell cultures.
Authors: J S McDougal, D S Gordon
Journal: The Journal of Experimental Medicine (1977)

Supernates derived from in vitro generated T-helper cells have been analyzed for their capacity to substitute for T-cell carrier reactivity. T-helper cell supernates stimulate both a carrier-specific and nonspecific anti-DNP-PFC response to DNP-carrier conjugates in cultures of hapten-primed spleen cells. The carrier-specific and nonspecific activity can be distinguished by dosage optimum, antigen requirements, binding specificity for carrier, and in the requirement for additional splenic adherent accessory cell involvement. The active factors produced in this system are heat labile and sensitive to trypsin and periodate. They are removed by absorption with alloantisera directed toward the strain from which the supernate was derived but not by a variety of anti-immunoglobulin sera.
Phase I–II and pharmacokinetic study of gemcitabine combined with oxaliplatin in patients with advanced non-small-cell lung cancer and ovarian carcinoma
Authors: S. Faivre, T. Le Chevalier, C. Monnerat, F. Lokiec, S. Novello, J. Taieb, P. Pautier, C. Lhommé, P. Ruffié, L. Kayitalire, J.-P. Armand, E. Raymond
Journal: Annals of Oncology (2002)
Chondroprotective activity of N-acetylglucosamine in rabbits with experimental osteoarthritis
Authors: A R Shikhman
Journal: Annals of the Rheumatic Diseases (2004)

To examine the therapeutic efficacy of N-acetylglucosamine (GlcNAc) in rabbits with experimental osteoarthritis (OA).Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). In the first study, rabbits (six in each group) received intramuscular injections of GlcNAc or normal saline three times a week starting 1 week postoperatively. In the second study, rabbits (eight in each group) were injected intra-articularly with GlcNAc (either once or twice a week) or normal saline. In the third study, rabbits (seven in each group) were injected intra-articularly twice a week with either GlcNAc, hyaluronan, or normal saline. Animals were killed 8 weeks after ACLT for macroscopic and histological assessment of the knee joints.Intramuscular administration of GlcNAc in rabbits with experimental knee OA did not show chondroprotective effects but showed mild anti-inflammatory activity. In contrast, intra-articular administration of GlcNAc twice a week reduced cartilage degradation. Additionally, intra-articular GlcNAc also suppressed synovitis. Once a week intra-articular injections of GlcNAc did not demonstrate therapeutic efficacy. The chondroprotective efficacy of GlcNAc was better than that of viscosupplementation treatment with hyaluronan.Intra-articular GlcNAc has chondroprotective and anti-inflammatory activity in experimental OA.
Sprouty-2 regulates HIV-specific T cell polyfunctionality
Authors: Yen-Ling Chiu, Liang Shan, Hailiang Huang, Carl Haupt, Catherine Bessell, David H. Canaday, Hao Zhang, Ya-Chi Ho, Jonathan D. Powell, Mathias Oelke, Joseph B. Margolick, Joel N. Blankson, Diane E. Griffin, Jonathan P. Schneck
Journal: Journal of Clinical Investigation (2013)

The ability of individual T cells to perform multiple effector functions is crucial for protective immunity against viruses and cancer. This polyfunctionality is frequently lost during chronic infections; however, the molecular mechanisms driving T cell polyfunctionality are poorly understood. We found that human T cells stimulated by a high concentration of antigen lacked polyfunctionality and expressed a transcription profile similar to that of exhausted T cells. One specific pathway implicated by the transcription profile in control of T cell polyfunctionality was the MAPK/ERK pathway. This pathway was altered in response to different antigen concentrations, and polyfunctionality correlated with upregulation of phosphorylated ERK. T cells that were stimulated with a high concentration of antigen upregulated sprouty-2 (SPRY2), a negative regulator of the MAPK/ERK pathway. The clinical relevance of SPRY2 was confirmed by examining SPRY2 expression in HIV-specific T cells, where high levels of SPRY2 were seen in HIV-specific T cells and inhibition of SPRY2 expression enhanced the HIV-specific polyfunctional response independently of the PD-1 pathway. Our findings indicate that increased SPRY2 expression during chronic viral infection reduces T cell polyfunctionality and identify SPRY2 as a potential target for immunotherapy.
Chondroitinase ABC I–Mediated Enhancement of Oncolytic Virus Spread and Antitumor Efficacy
Authors: Nina Dmitrieva, Lianbo Yu, Mariano Viapiano, Timothy P. Cripe, E. Antonio Chiocca, Joseph C. Glorioso, Balveen Kaur
Journal: Clinical Cancer Research (2010)

The inhibitory role of secreted chondroitin sulfate proteoglycans on oncolytic viral (OV) therapy was examined. Chondroitinase ABC (Chase-ABC) is a bacterial enzyme that can remove chondroitin sulfate glycosaminoglycans from proteoglycans without any deleterious effects in vivo. We examined the effect of Chase-ABC on OV spread and efficacy.Three-dimensional glioma spheroids placed on cultured brain slices were utilized to evaluate OV spread. Replication-conditional OV-expressing Chase-ABC (OV-Chase) was engineered using HSQuik technology and tested for spread and efficacy in glioma spheroids. Subcutaneous and intracranial glioma xenografts were utilized to compare antitumor efficacy of OV-Chase, rHsvQ (control), and PBS. Titration of viral particles was performed from OV-treated subcutaneous tumors. Glioma invasion was assessed in collagen-embedded glioma spheroids in vitro and in intracranial tumors. All statistical tests were two sided.Treatment with Chase-ABC in cultured glioma cells significantly enhanced OV spread in glioma spheroids grown on brain slices (P < 0.0001). Inoculation of subcutaneous glioma xenografts with Chase-expressing OV significantly increased viral titer (>10 times, P = 0.0008), inhibited tumor growth, and significantly increased overall animal survival (P < 0.006) compared with treatment with parental rHsvQ virus. Single OV-Chase administration in intracranial xenografts also resulted in longer median survival of animals than rHsvQ treatment (32 vs. 21 days, P < 0.018). Glioma cell migration and invasion were not increased by OV-Chase treatment.We conclude that degradation of glioma extracellular matrix with OV-expressing bacterial Chase-ABC enhanced OV spread and antitumor efficacy.
Population Pharmacokinetic Analysis of Topotecan in Pediatric Cancer Patients
Authors: Paula Schaiquevich, John C. Panetta, Lisa C. Iacono, Burgess B. Freeman, Victor M. Santana, Amar Gajjar, Clinton F. Stewart
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To characterize the population pharmacokinetics of topotecan lactone in children with cancer and identify covariates related to topotecan disposition. Patients and Methods: The study population consisted of 162 children in seven clinical trials receiving single agent topotecan as a 30-min infusion. A population approach via nonlinear mixed effects modeling was used to conduct the analysis. Results: A two-compartment model was fit to topotecan lactone plasma concentrations (n = 1874), and large pharmacokinetic variability was observed among studies, among individuals, and within individuals. We conducted a covariate analysis using demographics, biochemical data, trial effects, and concomitant drugs. The most significant covariate was body surface area, which explained 54% of the interindividual variability for topotecan systemic clearance. Interoccasion variability was considerable in both clearance and volume (20% and 22%, respectively), but was less than interindividual variability in both variables. Other covariates related to clearance were concomitant phenytoin, calculated glomerular filtration rate, and age (&amp;lt;0.5 years). Including them in the model reduced the interindividual variability for topotecan clearance by an additional 48% relative to the body surface area–normalized model. The full covariate model explained 76% and 50% of interindividual variability in topotecan clearance and volume, respectively. Conclusions: We developed a descriptive and robust population pharmacokinetic model which identified patient covariates that account for topotecan disposition in pediatric patients. Additionally, dosing topotecan based on the covariate model led to a more accurate and precise estimation topotecan systemic exposure compared with a fixed dosing approach, and could be a tool to assist clinicians to individualize topotecan dosing.
<i>S</i> -Nitroso Human Serum Albumin Treatment Reduces Ischemia/Reperfusion Injury in Skeletal Muscle via Nitric Oxide Release
Authors: Seth Hallström, Harald Gasser, Christoph Neumayer, Alexander Fügl, Joseph Nanobashvili, Andrzej Jakubowski, Ihor Huk, Günther Schlag, Tadeusz Malinski
Journal: Circulation (2002)

Background — Peroxynitrite generated from nitric oxide (NO) and superoxide (O 2 − ) contributes to ischemia/reperfusion (I/R) injury. Feedback inhibition of endothelial NO synthase by NO may inhibit O 2 − production generated also by endothelial NO synthase at diminished local l -arginine concentrations accompanying I/R. Methods and Results — During hindlimb I/R (2.5 hours/2 hours), in vivo NO was monitored continuously (porphyrinic sensor), and high-energy phosphates, reduced and oxidized glutathione (chromatography), and I/R injury were measured intermittently. Rabbits receiving human serum albumin (HSA) (controls) were compared with those receiving S -nitroso human serum albumin (S-NO-HSA) beginning 30 minutes before reperfusion for 1 hour or 30 minutes before ischemia for 3.5 hours (0.1 μmol · kg −1 · h − 1 ). The onset of ischemia led to a rapid increase of NO from its basal level (50±12 nmol/L) to 120±20 and 220±15 nmol/L in the control and S-NO-HSA–treated groups, respectively. In control animals, NO dropped below basal levels at the end of ischemia and to undetectable levels (&lt;1 nmol/L) during reperfusion. In S-NO-HSA–treated animals, maximal NO levels never decreased below basal concentration and on reperfusion were 100±15 nmol/L (S-NO-HSA preischemia group, 175±15 nmol/L). NO supplementation by S-NO-HSA led to partial and in the preischemia group to total preservation of high-energy phosphates and glutathione status in reperfused muscle (eg, preischemia groups: ATP, 30.23±5.02 μmol/g versus control, 15.75±4.33 μmol/g, P &lt;0.0005; % oxidized glutathione, 4.49± 1.87% versus control, 22.84±6.39%, P &lt;0.0001). S-NO-HSA treatment in all groups led to protection from vasoconstriction and reduced edema formation after reperfusion (eg, preischemia groups: interfiber area, 12.94±1.36% versus control, 27.83±1.95%, P &lt; 0.00001). Conclusions — Long-lasting release of NO by S-NO-HSA provides significant protection of skeletal muscle from I/R injury.
XPO1/CRM1 Inhibition Causes Antitumor Effects by Mitochondrial Accumulation of eIF5A
Authors: Takahito Miyake, Sunila Pradeep, Sherry Y. Wu, Rajesha Rupaimoole, Behrouz Zand, Yunfei Wen, Kshipra M. Gharpure, Archana S. Nagaraja, Wei Hu, Min Soon Cho, Heather J. Dalton, Rebecca A. Previs, Morgan L. Taylor, Takeshi Hisamatsu, Yu Kang, Tao Liu, Sharon Shacham, Dilara McCauley, David H. Hawke, John E. Wiktorowicz, Robert L. Coleman, Anil K. Sood
Journal: Clinical Cancer Research (2015)

XPO1 inhibitors have shown promise for cancer treatment, and yet the underlying mechanisms for the antitumor effects are not well understood. In this study, we explored the usefulness of selective inhibitors of nuclear export (SINE) compounds that are specific inhibitors of XPO1.We used proteomic analysis in XPO1 inhibitor-treated ovarian cancer cell lines and examined antitumor effects in ovarian and breast cancer mouse models. We also studied the effects of XPO1 inhibitor in combination with chemotherapeutic agents.XPO1 inhibitor treatment substantially increased the percentage of apoptotic cells (60%) after 72 hours of incubation. XPO1 inhibitor promoted the accumulation of eIF5A in mitochondria, leading to cancer cell death. Topotecan showed the greatest synergistic effect with XPO1 inhibitor. XPO1 inhibitors prevented the translocation of IGF2BP1 from the nucleus to the cytoplasm, thereby permitting the localization of eIF5A in the mitochondria. This process was p53, RB, and FOXO independent. Significant antitumor effects were observed with XPO1 inhibitor monotherapy in orthotopic ovarian (P < 0.001) and breast (P < 0.001) cancer mouse models, with a further decrease in tumor burden observed in combination with topotecan or paclitaxel (P < 0.05). This mitochondrial accumulation of eIF5A was highly dependent on the cytoplasmic IGF2BP1 levels.We have unveiled a new understanding of the role of eIF5A and IGF2BP1 in XPO1 inhibitor-mediated cell death and support their clinical development for the treatment of ovarian and other cancers. Our data also ascertain the combinations of XPO1 inhibitors with specific chemotherapy drugs for therapeutic trials.
INFUSION OF LIN-/SCA-1&amp;plus; AND ENDOTHELIAL PROGENITOR CELLS IMPROVES PROINFLAMMATORY AND OXIDATIVE STRESS MARKERS IN ATHEROSCLEROTIC MICE
Authors: Alexandros Briasoulis, Dimitris Tousoulis, Georgia Vogiatzi, Aggeliki Valatsou, Kostas Toutouzas, Charalambos Antoniades, Costas Tentolouris, Despoina Perrea
Journal: Journal of the American College of Cardiology (2012)
Short Form of the Chinese Version Diabetes Quality of Life for Youth Scale
Authors: Ruey-Hsia Wang, Fu-Sung Lo, Bai-Hsiun Chen, Hsiu-Yueh Hsu, Yann-Jinn Lee
Journal: Diabetes Care (2011)

OBJECTIVE To test the psychometric properties of the short form of the Chinese version Diabetes Quality of Life for Youth scale (C-DQOLY-SF). RESEARCH DESIGN AND METHODS A 30-item C-DQOLY-SF was administered to 371 adolescents with type 1 diabetes. Exploratory and confirmatory factor analysis, correlation with HbA1c, internal consistency, and test-retest reliability were used to examine the psychometric characteristics of C-DQOLY-SF. RESULTS A 25-item questionnaire with three correlated second-order factor structures best fitted data. Scores on the 25-item C-DQOLY-SF significantly correlated with HbA1c values. Cronbach’s α and ICCs of each scale and subscale ranged from 0.77 to 0.90 and from 0.70 to 0.92, respectively. CONCLUSIONS The C-DQOLY-SF has satisfactory reliability and validity. The C-DQOLY-SF can be conveniently used in clinical settings to assess the quality of life of adolescents with type 1 diabetes.
Effects of Physical Activity on Health Status in Older Adults I: Observational Studies
Authors: E H Wagner, A Z LaCroix, D M Buchner, E B Larson
Journal: Annual Review of Public Health (1992)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Epstein-Barr Virus-Associated and Other Antiviral Antibodies During Intense BCG Administration to Patients With Burkitt's Lymphoma in Remission 2
Authors: Peter Gunvén, George Klein, John L. Ziegler, Ian T. Magrath, Charles L. Olweny, Werner Henle, Gertrude Henle, Arne Svedmyr, Aberra Demissie
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Epstein-Barr Virus-Associated and Other Antiviral Antibodies During Intense BCG Administration to Patients With Burkitt's Lymphoma in Remission Get access Peter Gunvén, Peter Gunvén 3Department of Tumor Biology, Karolinska Institutet, S-104 01 Stockholm, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar George Klein, George Klein 3Department of Tumor Biology, Karolinska Institutet, S-104 01 Stockholm, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar John L. Ziegler, John L. Ziegler 4Division of Cancer Treatment, NCI, National Institutes of Health, PHS, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ian T. Magrath, Ian T. Magrath 4Division of Cancer Treatment, NCI, National Institutes of Health, PHS, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles L. Olweny, Charles L. Olweny 5Lymphoma Treatment Center, Uganda Cancer Institute, P.O. Box 3935, Kampala, Uganda. Search for other works by this author on: Oxford Academic PubMed Google Scholar Werner Henle, Werner Henle 6The Joseph Stokes, Jr., Research Institute of the Children's Hospital of Philadelphia and School of Medicine, University of Pennsylvania, Philadelphia, Pa. 19104. 7Recipient of PHS career award 5-K6-AI-22683 from the National Institute of Allergy and Infectious Diseases. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gertrude Henle, Gertrude Henle 6The Joseph Stokes, Jr., Research Institute of the Children's Hospital of Philadelphia and School of Medicine, University of Pennsylvania, Philadelphia, Pa. 19104. Search for other works by this author on: Oxford Academic PubMed Google Scholar Arne Svedmyr, Arne Svedmyr 8Virus Department, Central Microbiological Laboratory of the Stockholm County Council, P.O. Box 177, S-101 22 Stockholm, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar Aberra Demissie Aberra Demissie 8Virus Department, Central Microbiological Laboratory of the Stockholm County Council, P.O. Box 177, S-101 22 Stockholm, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 1, January 1978, Pages 31–37, https://doi.org/10.1093/jnci/60.1.31 Published: 01 January 1978 Article history Received: 24 February 1977 Accepted: 03 August 1977 Published: 01 January 1978
The evolution of the psoriatic lesion
Authors: P.C.M. van de Kerkhof
Journal: British Journal of Dermatology (2007)

Psoriasis comprises a host of abnormalities, and various aspects of the pathogenesis of psoriasis have been suggested to be of primary relevance. The aim of this review is to identity driving factors in the pathogenesis of psoriasis and to explore the dynamics of processes eventually resulting in a psoriatic lesion. In this review observations on the evolution from the symptomless skin to lesional skin in patients with psoriasis will be integrated with observations in various animal models of psoriasis.
Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials
Authors: James Chih-Hsin Yang, Yi-Long Wu, Martin Schuler, Martin Sebastian, Sanjay Popat, Nobuyuki Yamamoto, Caicun Zhou, Cheng-Ping Hu, Kenneth O'Byrne, Jifeng Feng, Shun Lu, Yunchao Huang, Sarayut L Geater, Kye Young Lee, Chun-Ming Tsai, Vera Gorbunova, Vera Hirsh, Jaafar Bennouna, Sergey Orlov, Tony Mok, Michael Boyer, Wu-Chou Su, Ki Hyeong Lee, Terufumi Kato, Dan Massey, Mehdi Shahidi, Victoria Zazulina, Lecia V Sequist
Journal: The Lancet Oncology (2015)