tbuckley/cabot-search huggingface dataset:
The Ability of E1A to Rescue <i>ras</i>-Induced Premature Senescence and Confer Transformation Relies on Inactivation of Both p300/CBP and Rb Family Proteins
Authors: Qingdong Deng, Yilei Li, Donato Tedesco, Rong Liao, Gerhard Fuhrmann, Peiqing Sun
Journal: Cancer Research (2005)

Abstract In primary cells, oncogenic ras induces a stable growth arrest known as premature senescence. Ras-induced premature senescence is considered as a tumor-suppressing defense response that needs to be bypassed before oncogenic potential ras can be revealed. To gain insights into the mechanism of senescence bypass during oncogenic transformation, we dissected the activities of an adenoviral oncoprotein E1A, which is capable of overcoming ras-induced senescence. Our results have indicated that the senescence bypassing activity resides in the NH2 terminus and requires both Rb-binding and p300/CBP-binding functions of E1A. Although interference with the p16INK4A/Rb pathway or inactivation of p300/CBP alone did not lead to senescence bypass, these two types of genetic alterations complemented the Rb-binding defective and the p300/CBP-binding defective mutants of E1A, respectively, to rescue premature senescence. Therefore, genetic alterations disrupting the p16INK4A/Rb pathway or the p300/CBP functions both contribute to the bypass of senescence. We further showed that p300/CBP were essential for ras-induced p53 activity, providing a potential mechanism underlying the important role of p300/CBP in senescence. Furthermore, p300/CBP inactivation led to cellular transformation in cooperation with the p300/CBP-binding defective E1A mutants, MDM2 and Ha-RasV12. These results have shown that p300 and CBP are integral components of the pathway that mediates ras-induced senescence. The critical role of p300 and CBP in the senescence response that limits the oncogenic potential of ras has provided a mechanistic basis for the tumor-suppressing function of these proteins.
The Polycystic Kidney Disease Proteins, Polycystin-1, Polycystin-2, Polaris, and Cystin, Are Co-Localized in Renal Cilia
Authors: Bradley K. Yoder, Xiaoying Hou, Lisa M. Guay-Woodford
Journal: Journal of the American Society of Nephrology (2002)

Recent evidence has suggested an association between structural and/or functional defects in the primary apical cilium of vertebrate epithelia and polycystic kidney disease (PKD). In Caenorhabditis elegans, the protein orthologues of the PKD-related proteins, polycystin-1 (LOV-1), polycystin-2 (PKD2), and polaris (OSM-5), co-localize in the cilia of male-specific sensory neurons, and defects in these proteins cause abnormalities of cilia structure and/or function. This study sought to determine whether the mammalian polycystins are expressed in primary cilia of renal epithelia and whether these proteins co-localize with polaris and cystin, the newly described, cilia-associated protein that is disrupted in the cpk mouse. To begin to address this issue, the expression of the protein products encoded by the PKD1, PKD2, Tg737, and cpk genes were examined in mouse cortical collecting duct (mCCD) cells using an immunofluorescence-based approach with a series of previously well-characterized antibodies. The mCCD cells were grown on cell culture inserts to optimize cell polarization and cilia formation. The data demonstrate co-localization in cilia of polycystin-1 and polycystin-2, which are the principal proteins involved in autosomal dominant polycystic kidney disease, with polaris and cystin, which are proteins that are disrupted in the Tg737(orpk)and cpk mouse models of autosomal recessive polycystic kidney disease, respectively. These data add to a growing body of evidence that suggests that primary cilium plays a key role in normal physiologic functions of renal epithelia and that defects in ciliary function contribute to the pathogenesis of PKD.
The osteogenic differentiation of rat bone marrow stromal cells cultured with dexamethasone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles
Authors: Joaquim M. Oliveira, Rui A. Sousa, Noriko Kotobuki, Mika Tadokoro, Motohiro Hirose, João F. Mano, Rui L. Reis, Hajime Ohgushi
Journal: Biomaterials (2008)
IMPROVED TEST CRITERIA FOR PROTECTORS IN PARAGLIDING HARNESSES CONSIDERING TECHNICAL FEASIBILITY, INJURIES AND INJURY MECHANISMS
Authors: M Griesmayr
Journal: British Journal of Sports Medicine (2014)

Background The German hang-glider association reports that approximately 60% of serious injuries resulting from hang-glider accidents are to the spine. The market-approval of back protectors encompasses an impact test. Objective When the impact test was introduced, information concerning accident situations was scarce. The objective of this study is to investigate how the impact test can be improved. Design Relevant load cases were derived from a survey among 61 pilots which have sustained a spinal injury in a paragliding accident. Paragliding accident videos were analysed in terms of impact velocities and angles. Based on the gathered information an enhanced test procedure was proposed. A Finite Element model of a harness was created and validated against impact tests. The baseline model's performance was evaluated according to the enhanced impact test procedure. Risk factor assessment The performance was rated using the Dynamic Response-model (DR) and the maximum acceleration. Results The current impact test covers approximately 50% of impact scenarios. In terms of impact velocity far less than 25% of impacts are covered by the current test procedure. Conclusions An enhanced test procedure with a vertical impact velocity of 8m/s and an impactor mass of 80 kg is suggested, considering impacts to the side, to the front, to the rear and to the bottom of the protector. The enhanced test procedure covers 80% of impact scenarios, 50% of impact velocities and about 50% of occupants in terms of weight. For the evaluation of injury risk the DR was suggested, as it is sensitive to the load direction. It is shown that current protectors will likely fail in the enhanced test procedure. However, the FE study also shows that room for improvement still exists with regards to the shape of protectors and materials used.
BIOMECHANICAL AND MOLECULAR REGULATION OF BONE REMODELING
Authors: Alexander G. Robling, Alesha B. Castillo, Charles H. Turner
Journal: Annual Review of Biomedical Engineering (2006)

Bone is a dynamic tissue that is constantly renewed. The cell populations that participate in this process--the osteoblasts and osteoclasts--are derived from different progenitor pools that are under distinct molecular control mechanisms. Together, these cells form temporary anatomical structures, called basic multicellular units, that execute bone remodeling. A number of stimuli affect bone turnover, including hormones, cytokines, and mechanical stimuli. All of these factors affect the amount and quality of the tissue produced. Mechanical loading is a particularly potent stimulus for bone cells, which improves bone strength and inhibits bone loss with age. Like other materials, bone accumulates damage from loading, but, unlike engineering materials, bone is capable of self-repair. The molecular mechanisms by which bone adapts to loading and repairs damage are starting to become clear. Many of these processes have implications for bone health, disease, and the feasibility of living in weightless environments (e.g., spaceflight).
Long-term outcomes of laparoscopic adrenalectomy for Cushing disease
Authors: Giovanni Conzo, Daniela Pasquali, Claudio Gambardella, Cristina Della Pietra, Daniela Esposito, Salvatore Napolitano, Ernesto Tartaglia, Claudio Mauriello, Guglielmo Thomas, Angela Pezzolla, Annamaria De Bellis, Luigi Santini, Antonio Agostino Sinisi
Journal: International Journal of Surgery (2014)
Effects of High-Density Lipoprotein Elevation With Cholesteryl Ester Transfer Protein Inhibition on Insulin Secretion
Authors: Andrew L. Siebel, Alaina K. Natoli, Felicia Y. T. Yap, Andrew L. Carey, Medini Reddy-Luthmoodoo, Dmitri Sviridov, Chek Ing Kiu Weber, Georgina Meneses-Lorente, Cyrille Maugeais, Josephine M. Forbes, Bronwyn A. Kingwell
Journal: Circulation Research (2013)

High-density lipoprotein cholesterol elevation via cholesteryl ester transfer protein (CETP) inhibition represents a novel therapy for atherosclerosis, which also may have relevance for type 2 diabetes mellitus.The current study assessed the effects of a CETP inhibitor on postprandial insulin, ex vivo insulin secretion, and cholesterol efflux from pancreatic β-cells.Healthy participants received a daily dose of CETP inhibitor (n=10) or placebo (n=15) for 14 days in a randomized double-blind study. Insulin secretion and cholesterol efflux from MIN6N8 β-cells were determined after incubation with treated plasma. CETP inhibition increased plasma high-density lipoprotein cholesterol, apolipoprotein AI, and postprandial insulin. MIN6N8 β-cells incubated with plasma from CETP inhibitor-treated individuals (compared with placebo) exhibited an increase in both glucose-stimulated insulin secretion and cholesterol efflux over the 14-day treatment period.CETP inhibition increased postprandial insulin and promoted ex vivo β-cell glucose-stimulated insulin secretion, potentially via enhanced β-cell cholesterol efflux.
Interstitial Fluid Pressure
Authors: ARTHUR C. GUYTON, JOHN PRATHER, KONRAD SCHEEL, JAMES MCGEHEE
Journal: Circulation Research (1966)

Fluid movement through the capillary membrane has been measured in the lower legs of dogs by using implanted, perforated capsules as internal plethysmographs. Utilizing this procedure it was possible to compare the effects of changes in interstitial fluid pressure with the effects of changes in venous pressure and arterial pressure on movement of fluid through the capillary membrane. A decrease in interstitial fluid pressure of 1 mm Hg increased the filtration of fluid out of the capillaries 1.20 as much as did 1 mm Hg increase in venous pressure. The filtration coefficient for fluid movement through the capillary wall per unit change in interstitial fluid pressure was 0.058 µliter/min per mm Hg per g of tissue. This value is in the same range as filtration coefficients that others have determined following changes in capillary pressure .
Identical peptides recognized by MHC class I- and II-restricted T cells.
Authors: D L Perkins, M Z Lai, J A Smith, M L Gefter
Journal: The Journal of Experimental Medicine (1989)

Previous data from many groups show that both class I and class II-restricted T cells recognize short synthetic peptides in the context of their respective MHC molecules (9-18), all of the peptides described to date are restricted to only a single class of MHC molecules; however, structural homology between the class I and II MHC molecules and the use of similar TCRs by class I and II-restricted T cells suggest that antigen recognition mechanisms are similar in both systems. To directly compare antigen recognition in the two systems, we analyzed peptides for the ability to function in both a class I and II-restricted system and found that seven of seven individual peptides tested stimulate both class I and II-restricted T cell responses. In addition, two of the peptides can function in different species stimulating both human class I and murine class II T cell responses. Thus, the process of T cell recognition of antigen in the context of MHC molecules was highly conserved in evolution not only between the class I and class II MHC systems, but also between the murine and human species.
Early Growth Response 1 Acts as a Tumor Suppressor<i>In vivo</i>and<i>In vitro</i>via Regulation of p53
Authors: Anja Krones-Herzig, Shalu Mittal, Kelly Yule, Hongyan Liang, Chris English, Rafael Urcis, Tarun Soni, Eileen D. Adamson, Dan Mercola
Journal: Cancer Research (2005)

Abstract The early growth response 1 (Egr1) gene is a transcription factor that acts as both a tumor suppressor and a tumor promoter. Egr1-null mouse embryo fibroblasts bypass replicative senescence and exhibit a loss of DNA damage response and an apparent immortal growth, suggesting loss of p53 functions. Stringent expression analysis revealed 266 transcripts with &amp;gt;2-fold differential expression in Egr1-null mouse embryo fibroblasts, including 143 known genes. Of the 143 genes, program-assisted searching revealed 66 informative genes linked to Egr1. All 66 genes could be placed on a single regulatory network consisting of three branch points of known Egr1 target genes: TGFβ1, IL6, and IGFI. Moreover, 19 additional genes that are known targets of p53 were identified, indicating that p53 is a fourth branch point. Electrophoretic mobility shift assay as well as chromatin immunoprecipitation confirmed that p53 is a direct target of Egr1. Because deficient p53 expression causes tumors in mice, we tested the role of Egr1 in a two-step skin carcinogenesis study (144 mice) that revealed a uniformly accelerated development of skin tumors in Egr1-null mice (P &amp;lt; 0.005). These studies reveal a new role for Egr1 as an in vivo tumor suppressor.
Effect of melatonin on sleep quality of chronic obstructive pulmonary disease (COPD) patients
Authors: Abolhasan Halvani, Fatemeh Mohsenpour, Elham Eshaghieh Firouz Abadi
Journal: European Respiratory Journal (2012)

Introduction: One of the clinical complaints of COPD is disordered sleep quality. Studies have shown that melatonin increases the sleep quality in certain COPD patients, but its effectiveness is not yet clear.

Methods: This randomized, double-blind, placebo-controlled trial included 52 moderate to severe COPD patients with poor sleep quality. The subjects received oral 3 mg melatonin (N = 27) or placebo (N = 27) in one dose 1 hours before sleep for a period of 30 days. The sleep quality was measured by Pittsburg Sleep Quality Index (PSQI) and daytime sleepiness was measured by Epworth Sleepiness Scale. Lung function and oxygenation was measured by spirometry and pulse oximeter.

Results: Finally 48 patients completed the protocol and entered the final phase. Melatonin significantly resulted in improved global PSQI scores, especially sleep quality (P = 0.001), sleep latency (P = 0.001), sleep duration (P = 0.024) and sleep efficacy (P = 0.003). There was no significant difference in daytime sleepiness, lung function and oxygenation.

View this table:

Table 1: sleep quality, daytime sleepiness before and after treatment with melatonin or placebo





Conclusion: Melatonin results in improved sleep quality of moderate to severe COPD patients with sleep quality disorders.
Zebrafish promoter microarrays identify actively transcribed embryonic genes.
Authors: Fiona C Wardle, Duncan T Odom, George W Bell, Bingbing Yuan, Timothy W Danford, Elizabeth L Wiellette, Elizabeth Herbolsheimer, Hazel L Sive, Richard A Young, James C Smith
Journal: Genome biology (2006)

Abstract We have designed a zebrafish genomic microarray to identify DNA-protein interactions in the proximal promoter regions of over 11,000 zebrafish genes. Using these microarrays, together with chromatin immunoprecipitation with an antibody directed against tri-methylated lysine 4 of Histone H3, we demonstrate the feasibility of this method in zebrafish. This approach will allow investigators to determine the genomic binding locations of DNA interacting proteins during development and expedite the assembly of the genetic networks that regulate embryogenesis.
Psychosis in the Community and in Prisons: A Report From the British National Survey of Psychiatric Morbidity
Authors: Traolach Brugha, Nicola Singleton, Howard Meltzer, Paul Bebbington, Michael Farrell, Rachel Jenkins, Jeremy Coid, Tom Fryers, David Melzer, Glyn Lewis
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Reports of increased rates of psychosis in prisons could be due to sampling and ascertainment differences. The authors compared two samples of subjects 16–64 years of age: those from the general population of residents in Great Britain and prisoners in England and Wales. METHOD: A random sample of remanded and sentenced male and female prisoners (N=3,142) and a two-phase, cross-sectional random sample of household residents (N=10,108) were assessed with structured questionnaires and the semistructured Schedules for Clinical Assessment in Neuropsychiatry. RESULTS: The weighted prevalence of probable functional psychosis in the past year was 4.5 per thousand (95% CI=3.1 to 5.8) in the household survey. In the prison survey, the weighted prevalence was over 10 times greater: 52 per thousand (95% CI=45 to 60). One in four prisoners with a psychotic disorder had psychotic symptoms attributed to toxic or withdrawal effects of psychoactive substances. The proportion of subjects with specific types of hallucinations or delusions did not differ between prison and household psychosis cases. CONCLUSIONS: This large study using standardized comparisons showed that the prevalence of psychosis in prisons is substantially higher than in the community and is deserving of greater attention to treatment and prevention. Apart from a minority of prisoners with symptoms attributable to psychoactive substances, the clinical symptom profile of psychosis is the same in both settings. Longitudinal research is needed to better understand these prevalence differences.
Integrative Genomic Analysis of Phosphatidylinositol 3′-Kinase Family Identifies <i>PIK3R3</i> as a Potential Therapeutic Target in Epithelial Ovarian Cancer
Authors: Lin Zhang, Jia Huang, Nuo Yang, Joel Greshock, Shun Liang, Kosei Hasegawa, Antonis Giannakakis, Nikolaos Poulos, Ann O'Brien-Jenkins, Dionyssios Katsaros, Ralf Butzow, Barbara L. Weber, George Coukos
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The phosphatidylinositol 3′-kinase (PI3K) family plays a key regulatory role in various cancer-associated signal transduction pathways. Here, we investigated the genomic alterations and gene expression of most known PI3K family members in human epithelial ovarian cancer. Experimental Design: The DNA copy number of PI3K family genes was screened by a high-resolution array comparative genomic hybridization in 89 human ovarian cancer specimens. The mRNA expression level of PI3K genes was analyzed by microarray retrieval approach, and further validated by real-time reverse transcription-PCR. The expression of p55γ protein in ovarian cancer was analyzed on tissue arrays. Small interfering RNA was used to study the function of PIK3R3 in ovarian cancer. Results: In ovarian cancer, 6 of 12 PI3K genes exhibited significant DNA copy number gains (&amp;gt;20%), including PIK3CA (23.6%), PIK3CB (27.0%), PIK3CG (25.8%), PIK3R2 (29.2%), PIK3R3 (21.3%), and PIK3C2B (40.4%). Among those, only PIK3R3 had significantly up-regulated mRNA expression level in ovarian cancer compared with normal ovary. Up-regulated PIK3R3 mRNA expression was also observed in liver, prostate, and breast cancers. The PIK3R3 mRNA expression level was significantly higher in ovarian cancer cell lines (n = 18) than in human ovarian surface epithelial cells (n = 6, P = 0.002). Overexpression of p55γ protein in ovarian cancer was confirmed by tissue array analysis. In addition, we found that knockdown of PIK3R3 expression by small interfering RNA significantly increased the apoptosis in cultured ovarian cancer cell lines. Conclusion: We propose that PIK3R3 may serve as a potential therapeutic target in human ovarian cancer.
Multiple Cytokine and Growth Factor Serum Biomarkers Predict Therapeutic Response and Survival in Advanced-Stage Head and Neck Cancer Patients
Authors: William L. Bigbee, Jennifer R. Grandis, Jill M. Siegfried
Journal: Clinical Cancer Research (2007)

In this issue of Clinical Cancer Research , Allen et al. ([1][1]) report that serum levels and temporal velocities of multiple cytokine and growth factors interleukin IL-6, IL-8, growth regulated oncogene 1 (GRO-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF),
Homozygous A polymorphism of the complement C1qA 276 correlates with prolonged overall survival in patients with diffuse large B cell lymphoma treated with R-CHOP
Authors: Xuan Jin, Huirong Ding, Ning Ding, Zhiying Fu, Yuqin Song, Jun Zhu
Journal: Journal of Hematology & Oncology (2012)

Abstract Background The precise mechanism of action for rituximab (R) is not fully elucidated. Besides antibody-dependent cellular cytotoxicity (ADCC), complements may also play an important role in the clinical response to rituximab-based therapy in diffuse large B cell lymphoma (DLBCL). The purpose of this study was to explore the relationship between C1qA [276] polymorphism and the clinical response to standard frontline treatment with R-CHOP in DLBCL patients. Methods Genotyping for C1qA [276A/G] was done in 164 patients with DLBCL. 129 patients treated with R-CHOP as frontline therapy (R ≥ 4 cycles) were assessable for the efficacy. Results Patients with homozygous A were found to have a higher overall response rate than those with heterozygous or homozygous G alleles (97.3% vs. 83.7%, P = 0.068). The complete response rate in patients with homozygous A was statistically higher than that in AG and GG allele carriers (89.2% vs. 51.1%, P = 0.0001). The overall survival of patients with homozygous A was longer than that of the G allele carriers (676 days vs. 497 days, P = 0.023). Multivariate Cox regression analysis showed that C1qA A/A allele was an independent favorable prognostic factor for DLBCL patients treated with R-CHOP as first-line therapy. Conclusion These results suggest that C1qA polymorphism may be a biomarker to predict response to R-CHOP as frontline therapy for DLBCL patients.
PD-L1 on Tumor Cells Is Induced in Ascites and Promotes Peritoneal Dissemination of Ovarian Cancer through CTL Dysfunction
Authors: Kaoru Abiko, Masaki Mandai, Junzo Hamanishi, Yumiko Yoshioka, Noriomi Matsumura, Tsukasa Baba, Ken Yamaguchi, Ryusuke Murakami, Ayaka Yamamoto, Budiman Kharma, Kenzo Kosaka, Ikuo Konishi
Journal: Clinical Cancer Research (2013)

Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be expressed in cancer cells. The purpose of this study is to elucidate the function of PD-L1 in peritoneal dissemination.Ovarian cancer cases were studied by microarray and immunohistochemistry. PD-L1 expression in mouse ovarian cancer cell line in various conditions was assessed by flow cytometry. PD-L1-overexpression cell line and PD-L1-depleted cell line were generated, and cytolysis by CTLs was analyzed, and alterations in CTLs were studied by means of timelapse and microarray. These cell lines were injected intraperitoneally to syngeneic immunocompetent mice.Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and peritoneal positive cytology. PD-L1 expression in mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and coculture with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression inhibited gathering and degranulation of CTLs. Gene expression profile of CTLs caused by PD-L1-overexpressing ovarian cancer was associated with CTLs exhaustion. In mouse models, PD-L1 depletion resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival.PD-L1 expression in tumor cell promotes peritoneal dissemination by repressing CTL function. PD-L1-targeted therapy is a promising strategy for preventing and treating peritoneal dissemination.