tbuckley/cabot-search huggingface dataset:
Lung Inflammation in Hyperoxia Can Be Prevented By Antichemokine Treatment in Newborn Rats
Authors: HUI DENG, S. NICHOLAS MASON, RICHARD L. AUTEN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Hyperoxia may contribute to lung disease in newborns through effects on alveolar neutrophils which predominate in respiratory distress syndrome and other acute lung injuries. Neutrophil chemokines such as interleukin-8 (IL-8) regulate chemoattraction, and are elevated in tracheal aspirates of newborns who develop bronchopulmonary dysplasia (BPD). Blockade of neutrophil chemokines may reduce hyperoxia-induced inflammatory lung injury and BPD. We therefore tested the hypothesis that hyperoxia contributes to elevations of rat neutrophil chemokines, cytokine- induced neutrophil chemoattractant-1 (CINC-1), and macrophage inflammatory protein-2 (MIP-2) in newborn rat lung. Newborn rats were exposed to air or 95% O2 for 8 d. CINC-1 and MIP-2 were measured in whole lung homogenates by ELISA. Newborn 95% O2–exposed animals were given anti-CINC-1 or anti-MIP-2, 1, 5, or 10 μ g on Days 3 and 4 of 95% O2 exposure. Bronchoalveolar lavage (BAL) was performed after perfusion on Day 6 to evaluate airway neutrophils, and myeloperoxidase (MPO) was measured in perfused whole lung. Lungs were examined histologically and immunohistochemically for effects of 95% O2 ± antichemokine. CINC-1 and MIP-2 increased nearly tenfold by Day 8 95% O2 treatment versus air control. CINC-1 and MIP-2 immunolabeling was increased in alveolar macrophages and alveolar epithelium in 95% O2. Anti-CINC-1 and anti-MIP-2 treatment at every dose reduced neutrophil number > 90% in BAL. Anti-CINC-1 10 μ g reduced tissue MPO by 50%. Antichemokine treatment on Days 3 and 4 prevented alveolar septal thickening and reduced chemokine immunolabeling on Day 6. Hyperoxia-induced neutrophil influx is mediated in part by CINC-1 and MIP-2 in newborn rats and can be partially prevented by treatment with anti-CINC-1 and anti-MIP-2.
ERRγ Suppresses Cell Proliferation and Tumor Growth of Androgen-Sensitive and Androgen-Insensitive Prostate Cancer Cells and Its Implication as a Therapeutic Target for Prostate Cancer
Authors: Shan Yu, Xianghong Wang, Chi-Fai Ng, Shiuan Chen, Franky L. Chan
Journal: Cancer Research (2007)

Abstract Estrogen receptor-related receptors (ERR) are orphan nuclear receptors, which are constitutively activated without estrogen binding. Recent evidence indicates that the ligand-independent ERRs may be involved in similar ER-mediated regulatory pathways and modulate estrogen responsiveness in certain target cells. We recently showed that an ERR subtype, ERRγ, is coexpressed with ERβ in normal human prostatic epithelial cells and exhibits reduced expression in many prostate cancer cell lines and clinical neoplastic prostate tissues. Based on this, we hypothesize that ERRγ may have growth regulatory roles in prostate and prostate cancer. We showed in this study that ERRγ was expressed in epithelial cell nuclei in fetal and pubertal human prostates, whereas its nuclear expression became reduced in advanced prostate cancer lesions. Stable ERRγ expression by retroviral transduction suppressed significantly both in vitro cell growth and in vivo tumorigenicity of two prostate cancer cell lines, LNCaP and DU145, as evidenced by a cell-cycle arrest at G1-S transition and also induction of two cyclin-dependent kinase inhibitors p21WAF1/CIP1 and p27KIP1. We further showed by reporter assay that induction of p21 and p27 by ERRγ was mediated through direct transactivation of their gene promoters. Moreover, we also showed that a selective ERRγ-agonist, DY131, could potentiate the ERRγ-induced growth inhibition in LNCaP-ERRγ and DU145-ERRγ cells in a dose-dependent manner compared with respective parental cells. Taken together, our results show that ERRγ may perform an antiproliferative or tumor-suppressing function in prostate cancer cells. More importantly, our results suggest that ERRγ could be a novel therapeutic target for prostate cancer treatment. [Cancer Res 2007;67(10):4904–14]
Ca(2+)-independent nitric oxide synthase activity in human lung after cardiopulmonary bypass.
Authors: R Delgado, A Rojas, L A Glaria, M Torres, F Duarte, R Shill, M Nafeh, E Santin, N Gonzalez, M Palacios
Journal: Thorax (1995)

<h3>ABSTRACT</h3> <h3>Purpose</h3> The Westlake BioBank for Chinese (WBBC) pilot cohort is a population-based prospective study with its major purpose to better understand the effect of genetic and environmental factors on growth and development from adolescents to adults. The dataset comprises a wide range of demographics, anthropometric measures, physical activity, sleep quality, age at menarche and bone mineral density. <h3>Participants</h3> A total of 14,726 participants (4,751 males and 9975 females) aged 14 to 25 years were recruited and the baseline survey was carried out from 2017 to 2019. The pilot cohort contains rich range of information regarding of demographics, anthropometric measurements, blood pressure and heart rate, lifestyle and sleep patterns, biological, clinical and health outcomes. <h3>Findings to date</h3> There were most of the participants were Chinese Han ethnic (97.78%), and more than 60% of them were originally from rural areas. For anthropometry measurements, the mean height and weight were 172.92 cm and 65.81 kg for men, and 160.13 cm and 52.85 kg for women; the mean waist, hip and thigh circumference were 75.51cm, 90.75cm and 51.56 cm in men, and 71.67cm, 89.75cm and 51.68 among women. Results indicated that the prevalence of underweight in female was much higher than male, but the prevalence of overweight and obesity in female was lower than male. The mean of serum 25(OH)D level in the 14,726 young participants was 22.39 ng/ml, and male had higher level of serum 25(OH)D than female, overall, 33.47% of the participants had vitamin D deficiency and even more participants suffered from vitamin D insufficiency (58.17%). The proportion of deficiency in women was much higher than that in men (41.83 vs. 16.35%). <h3>Future plans</h3> WBBC is designed as a prospective cohort study and provides a unique and rich data set analyzing health trajectories of Chinese adolescents to young adults.
Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease
Authors: Mark S. Klempner, Linden T. Hu, Janine Evans, Christopher H. Schmid, Gary M. Johnson, Richard P. Trevino, DeLona Norton, Lois Levy, Diane Wall, John McCall, Mark Kosinski, Arthur Weinstein
Journal: New England Journal of Medicine (2001)

It is controversial whether prolonged antibiotic treatment is effective for patients in whom symptoms persist after the recommended antibiotic treatment for acute Lyme disease.We conducted two randomized trials: one in 78 patients who were seropositive for IgG antibodies to Borrelia burgdorferi at the time of enrollment and the other in 51 patients who were seronegative. The patients received either intravenous ceftriaxone, 2 g daily for 30 days, followed by oral doxycycline, 200 mg daily for 60 days, or matching intravenous and oral placebos. Each patient had well-documented, previously treated Lyme disease but had persistent musculoskeletal pain, neurocognitive symptoms, or dysesthesia, often associated with fatigue. The primary outcome measures were improvement on the physical- and mental-health-component summary scales of the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36)--a scale measuring the health-related quality of life--on day 180 of the study.After a planned interim analysis, the data and safety monitoring board recommended that the studies be discontinued because data from the first 107 patients indicated that it was highly unlikely that a significant difference in treatment efficacy between the groups would be observed with the planned full enrollment of 260 patients. Base-line assessments documented severe impairment in the patients' health-related quality of life. In intention-to-treat analyses, there were no significant differences in the outcomes with prolonged antibiotic treatment as compared with placebo. Among the seropositive patients who were treated with antibiotics, there was improvement in the score on the physical-component summary scale of the SF-36, the mental-component summary scale, or both in 37 percent, no change in 29 percent, and worsening in 34 percent; among seropositive patients receiving placebo, there was improvement in 40 percent, no change in 26 percent, and worsening in 34 percent (P=0.96 for the comparison between treatment groups). The results were similar for the seronegative patients.There is considerable impairment of health-related quality of life among patients with persistent symptoms despite previous antibiotic treatment for acute Lyme disease. However, in these two trials, treatment with intravenous and oral antibiotics for 90 days did not improve symptoms more than placebo.
SDX-101, the R-enantiomer of etodolac, induces cytotoxicity, overcomes drug resistance, and enhances the activity of dexamethasone in multiple myeloma
Authors: Hiroshi Yasui, Teru Hideshima, Makoto Hamasaki, Aldo M. Roccaro, Norihiko Shiraishi, Shaji Kumar, Pierfrancesco Tassone, Kenji Ishitsuka, Noopur Raje, Yu-Tzu Tai, Klaus Podar, Dharminder Chauhan, Lorenzo M. Leoni, Sarath Kanekal, Gary Elliott, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2005)
A Randomized, Controlled Trial of Oral Propranolol in Infantile Hemangioma
Authors: Christine Léauté-Labrèze, Peter Hoeger, Juliette Mazereeuw-Hautier, Laurent Guibaud, Eulalia Baselga, Gintas Posiunas, Roderic J. Phillips, Hector Caceres, Juan Carlos Lopez Gutierrez, Rosalia Ballona, Sheila Fallon Friedlander, Julie Powell, Danuta Perek, Brandie Metz, Sebastien Barbarot, Annabel Maruani, Zsuzsanna Zsofia Szalai, Alfons Krol, Olivia Boccara, Regina Foelster-Holst, Maria Isabel Bosch, John Su, Hana Buckova, Antonio Torrelo, Frederic Cambazard, Rainer Grantzow, Orli Wargon, Dariusz Wyrzykowski, Jochen Roessler, Jose Bernabeu-Wittel, Adriana M. Valencia, Przemyslaw Przewratil, Sharon Glick, Elena Pope, Nicholas Birchall, Latanya Benjamin, Anthony J. Mancini, Pierre Vabres, Pierre Souteyrand, Ilona J. Frieden, Charles I. Berul, Cyrus R. Mehta, Sorilla Prey, Franck Boralevi, Caroline C. Morgan, Stephane Heritier, Alain Delarue, Jean-Jacques Voisard
Journal: New England Journal of Medicine (2015)

Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited.
VEGF-induced endothelial cell migration requires urokinase receptor (uPAR)-dependent integrin redistribution
Authors: Revu Ann Alexander, Gerald W. Prager, Judit Mihaly-Bison, Pavel Uhrin, Stefan Sunzenauer, Bernd R. Binder, Gerhard J. Schütz, Michael Freissmuth, Johannes M. Breuss
Journal: Cardiovascular Research (2012)

Vascular endothelial growth factor (VEGF)-initiated angiogenesis requires coordinated proteolytic degradation of extracellular matrix provided by the urokinase plasminogen activator/urokinase receptor (uPA/uPAR) system and regulation of cell migration provided by integrin-matrix interaction. In this study, we investigated the mechanisms underlying the uPAR-dependent modulation of VEGF-induced endothelial migration.We used flow cytometry to quantify integrins at the cell surface. Stimulation of human and murine endothelial cells with VEGF resulted in internalization of α5β1-integrins. Micropatterning and immunocytochemistry revealed co-clustering of uPAR and α5β1-integrins and retrieval via clathrin-coated vesicles. It was also contingent on receptors of the low-density lipoprotein receptor (LDL-R) family. VEGF-induced integrin redistribution was inhibited by elimination of uPAR from the endothelial cell surface or by inhibitory peptides that block the uPAR-integrin interaction. Under these conditions, the migratory response of endothelial cells upon VEGF stimulation was impaired both in vitro and in vivo.The observations indicate that uPAR is an essential component of the network through which VEGF controls endothelial cell migration. uPAR is a bottleneck through which the VEGF-induced signal must be funnelled for both focused proteolytic activity at the leading edge and for redistribution of integrins.
Identification of the ENT1 Antagonists Dipyridamole and Dilazep as Amplifiers of Oncolytic Herpes Simplex Virus-1 Replication
Authors: Brent J. Passer, Tooba Cheema, Bingsen Zhou, Hiroaki Wakimoto, Cecile Zaupa, Mani Razmjoo, Jason Sarte, Shulin Wu, Chin-lee Wu, James W. Noah, Qianjun Li, John K. Buolamwini, Yun Yen, Samuel D. Rabkin, Robert L. Martuza
Journal: Cancer Research (2010)

Oncolytic herpes simplex virus-1 (oHSV) vectors selectively replicate in tumor cells, where they kill through oncolysis while sparing normal cells. One of the drawbacks of oHSV vectors is their limited replication and spread to neighboring cancer cells. Here, we report the outcome of a high-throughput chemical library screen to identify small-molecule compounds that augment the replication of oHSV G47Delta. Of the 2,640-screened bioactives, 6 compounds were identified and subsequently validated for enhanced G47Delta replication. Two of these compounds, dipyridamole and dilazep, interfered with nucleotide metabolism by potently and directly inhibiting the equilibrative nucleoside transporter-1 (ENT1). Replicative amplification promoted by dipyridamole and dilazep were dependent on HSV mutations in ICP6, the large subunit of ribonucleotide reductase. Our results indicate that ENT1 antagonists augment oHSV replication in tumor cells by increasing cellular ribonucleoside activity.
Awareness and early detection of cutaneous melanoma: an analysis of factors related to delay in treatment
Authors: A. Blum, C.U. Brand, U. Ellwanger, B. Schlagenhauff, W. Stroebel, G. Rassner, C. Garbe
Journal: British Journal of Dermatology (1999)

Factors associated with the detection of cutaneous melanomas and reasons for delay in diagnosis were investigated in 429 patients with histologically proven melanoma operated on between January 1993 and June 1996. Patients were interviewed using a standardized questionnaire. In 25% of patients, treatment was delayed for more than 1 year from the time they first noticed a suspicious pigmented lesion. Melanoma was detected by the patients themselves in 67% of women and 45% of men. The three predominant clinical symptoms of melanoma were change in colour (darker), increase in size and increase in elevation of a pigmented lesion. The role of sun exposure and of naevi as risk factors for melanoma, as well as the potential benefit of early treatment, were known by 87%, 66% and 82% of the patients, respectively. However, melanoma awareness had no impact on the time period between first observation of skin changes and treatment. Among the factors associated with delay in melanoma diagnosis, an initial incorrect diagnosis as a benign lesion by the physician first visited (in 18% of all cases) had the highest significance. Patients detecting their lesions themselves were treated significantly later than patients in whom others had remarked on changes in a naevus. Furthermore, melanomas of the head and neck were treated later than melanomas at other body sites. Further efforts to educate both the public and the medical profession are essential to ensure earlier treatment for cutaneous melanomas.
Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: 52-week results of the <i>GO-FORWARD</i> study
Authors: Edward Keystone, Mark C Genovese, Lars Klareskog, Elizabeth C Hsia, Stephen Hall, Pedro C Miranda, Jacek Pazdur, Sang-Cheol Bae, William Palmer, Stephen Xu, Mahboob U Rahman
Journal: Annals of the Rheumatic Diseases (2010)

Objective To evaluate the efficacy and safety of golimumab to 52 weeks in patients with active rheumatoid arthritis despite methotrexate. Methods Patients were randomly assigned to receive placebo plus methotrexate (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus methotrexate (group 3) and golimumab 100 mg plus methotrexate (group 4). At week 16, patients in groups 1, 2 and 3 who had less than 20% improvement in tender and swollen joints entered early escape. At week 24, patients in group 1 who had not entered early escape crossed over to 50 mg golimumab plus methotrexate. Results At week 16, 31%, 27% and 17% of patients in groups 1, 2 and 3, respectively, entered early escape. At week 52, 44%, 45%, 64% and 58% of patients in groups 1, 2, 3 and 4, respectively, achieved 20% improvement in the American College of Rheumatology criteria; and 34%, 31%, 42% and 53%, respectively, achieved low disease activity (≤3.2) according to the 28-joint disease activity score. Patients in group 4 appeared to have an increased risk of serious adverse events and serious infections. Conclusion The results of various outcome measures showed that the response rates achieved by patients receiving golimumab to 24 weeks were sustained to 52 weeks. The safety profile appeared to be consistent with the known safety profile of tumour necrosis factor inhibitors.
dN/dS-Based Methods Detect Positive Selection Linked to Trade-Offs between Different Fitness Traits in the Coat Protein of Potato virus Y
Authors: B. Moury, V. Simon
Journal: Molecular Biology and Evolution (2011)

The dN/dS ratio between nonsynonymous and synonymous substitution rates has been used extensively to identify codon positions involved in adaptive processes. However, the accuracy of this approach has been questioned, and very few studies have attempted to validate experimentally its predictions. Using the coat protein (CP) of Potato virus Y (PVY; genus Potyvirus, family Potyviridae) as a case study, we identified several candidate positively selected codon positions that differed between clades. In the CP of the N clade of PVY, positive selection was detected at codon positions 25 and 68 by both the softwares PAML and HyPhy. We introduced nonsynonymous substitutions at these positions in an infectious cDNA clone of PVY and measured the effect of these mutations on virus accumulation in its two major cultivated hosts, tobacco and potato, and on its efficiency of transmission from plant to plant by aphid vectors. The mutation at codon position 25 significantly modified the virus accumulation in the two hosts, whereas the mutation at codon position 68 significantly modified the virus accumulation in one of its hosts and its transmissibility by aphids. Both mutations were involved in adaptive trade-offs. We suggest that our study was particularly favorable to the detection of adaptive mutations using dN/dS estimates because, as obligate parasites, viruses undergo a continuous and dynamic interaction with their hosts that favors the recurrent selection of adaptive mutations and because trade-offs between different fitness traits impede (or at least slow down) the fixation of these mutations and maintain polymorphism within populations.
A Novel Anti-Human HB-EGF Monoclonal Antibody with Multiple Antitumor Mechanisms against Ovarian Cancer Cells
Authors: Shingo Miyamoto, Ryo Iwamoto, Akiko Furuya, Kumiko Takahashi, Yuka Sasaki, Hiroshi Ando, Fusanori Yotsumoto, Tomoko Yoneda, Miki Hamaoka, Hiroshi Yagi, Takuya Murakami, Sayaka Hori, Kenya Shitara, Eisuke Mekada
Journal: Clinical Cancer Research (2011)

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family and plays a pivotal role in tumor progression in ovarian cancer. We developed an anti-HB-EGF monoclonal antibody (mAb) and investigated its antitumor activities in vitro and in vivo to evaluate its potential as a therapeutic antibody against ovarian cancer.We prepared mAbs from HB-EGF null mice immunized with recombinant human soluble HB-EGF and evaluated their binding and neutralizing activity against HB-EGF. Next, we generated a mouse-human chimeric antibody and examined its in vitro and in vivo antitumor activities.Two murine anti-HB-EGF mAbs were developed, and one of them, KM3566, was revealed to have a high binding reactivity for membrane-anchored HB-EGF (pro-HB-EGF) expressed on the cell surface, as well as neutralizing activity against growth promoting activity of soluble HB-EGF. The mouse-human chimeric counterpart for KM3566 (cKM3566) induced dose-dependent antibody-dependent cellular cytotoxicity (ADCC) against cancer cells expressing HB-EGF in vitro, and significantly inhibited tumor growth in severe combined immunodeficient mice inoculated with MCAS or ES-2 human ovarian cancer cells.A novel anti-HB-EGF chimeric antibody, cKM3566, with two antitumor mechanisms, neutralization and ADCC, exhibits potent in vivo antitumor activity. These results indicate that cKM3566 is a promising antiovarian cancer therapeutic antibody.
Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling
Authors: Wangsen Cao, Clare Bao, Elizaveta Padalko, Charles J. Lowenstein
Journal: The Journal of Experimental Medicine (2008)

The mitogen-activated protein kinase (MAPK) pathway plays a critical role in Toll-like receptor (TLR) signaling. MAPK phosphatase-1 (MKP-1) inhibits the MAPK pathway and decreases TLR signaling, but the regulation of MKP-1 is not completely understood. We now show that MKP-1 is acetylated, and that acetylation regulates its ability to interact with its substrates and deactivate inflammatory signaling. We found that LPS activates acetylation of MKP-1. MKP-1 is acetylated by p300 on lysine residue K57 within its substrate-binding domain. Acetylation of MKP-1 enhances its interaction with p38, thereby increasing its phosphatase activity and interrupting MAPK signaling. Inhibition of deacetylases increases MKP-1 acetylation and blocks MAPK signaling in wild-type (WT) cells; however, deacetylase inhibitors have no effect in cells lacking MKP-1. Furthermore, histone deacetylase inhibitors reduce inflammation and mortality in WT mice treated with LPS, but fail to protect MKP-1 knockout mice. Our data suggest that acetylation of MKP-1 inhibits innate immune signaling. This pathway may be an important therapeutic target in the treatment of inflammatory diseases.
Effect of coal tar on cutaneous aryl hydrocarbon hydroxylase induction and anthralin irritancy
Authors: C.M. LAWRENCE, M.J. FINNEN, SAM SHUSTER
Journal: British Journal of Dermatology (1984)

The inflammatory dose-response to topical anthralin and whole skin aryl hydrocarbon hydroxylase (AHH) activity were measured before and 24 h after application of coal tar solution to the uninvolved skin of patients with psoriasis. The inflammatory response to anthralin decreased and total AHH activity increased after the tar treatment. A possible explanation is that anthralin or an irritant product is metabolized by AHH activity in the skin. Induction of AHH by coal tar increases its removal and reduces anthralin irritancy.