tbuckley/cabot-search huggingface dataset:
Methylation of <i>Tip30</i> Promoter Is Associated with Poor Prognosis in Human Hepatocellular Carcinoma
Authors: Bin Lu, Yunchao Ma, Guobin Wu, Xin Tong, Huaizu Guo, Anmin Liang, Wenming Cong, Chang Liu, Hao Wang, Mengchao Wu, Jian Zhao, Yajun Guo
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To investigate Tip30 promoter methylation status in human hepatocellular carcinoma (HCC) and the correlation with clinicopathologic features and prognosis. Experimental Design: The methylation status of CpG islands in Tip30 promoter was examined in 15 HCC cell lines as well as 59 paired HCC and adjacent nontumor tissues. The associations between Tip30 methylation status and the survival of patients were analyzed. Results: Tip30 promoter was hypermethylated in 6 of 10 HCC cell lines with reduced Tip30 mRNA. DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine, greatly enhanced TIP30 expression and sensitized HCC cells to cytotoxic drug-induced cell death. The promoter region of Tip30 was identified and the main promoter activity was located in the -135 to -45 region sited within a CpG island. The minimal promoter element contained four Sp1 binding sites, which were hypermethylated in HCC cell-derived promoters. Moreover, analyses of Tip30 promoter methylation status in 59 paired HCC tissues showed that 47% of the cases were hypermethylated. Recurrence rate (95% versus 67%; P = 0.011) and mortality (82% versus 53%; P = 0.033) were significantly higher in patients with methylated Tip30. Disease-free survival was significantly higher in patients with unmethylated Tip30 (33.3% versus 4.5%; P = 0.036). Conclusions: Our results show that epigenetic silencing of Tip30 gene expression by CpG island DNA hypermethylation is associated with poor prognosis in patients with HCC.
Application of periodisation in various sports
Authors: Oleksandr Krasilshchikov
Journal: British Journal of Sports Medicine (2010)

Since various sports differ in number of competitions athletes participate in, difference would come in the periodisation patterns as well. For instance, endurance sports such as marathon and long distance running, limit participation of the athletes to few competitions within a year/season. This results in planning long macrocycles of training often equalling a year in duration. This happens when major competitions of the year are grouped together (ie, October–November) and athlete can successfully participate in them within one peaking attempt. In case major competitions are scattered over the year or the gap between them is too long (ie, April–May and October–November), we need to follow double periodisation. Power sports, like sprints, jumps, weightlifting, etc, can have their representatives participating in larger number of competitions a year and their planning pattern could be pretty different. It can well fit into double periodisation pattern, but when three to five major competitions are there to participate within the year (ie, March, July and November), triple or multiple periodisation patterns might be of use. Team games like football, basketball, hockey and others, with traditionally long competitive periods when they play league matches for 4–5 months or even longer, plan their macrocycle in completely different manner. They still follow single periodisation pattern but they change the ratio of periods within the macrocycle. Individual/group games like tennis and badminton follow more or less the multi-peaking patterns with very brief and precisely planned training periods (rather blocks). The reason being, besides participation in the four Grand Slam tournaments and year finale in the form of ATP/WTA world championships (top eight only), players need to play at least four warming up tournaments at various surfaces. Atop of it they need to play good number of ranking tournaments to ensure high ranking and good chances for better seeding in the major tournaments.
A CreER-Based Random Induction Strategy for Modeling Translocation-Associated Sarcomas in Mice
Authors: Malay Haldar, Matthew L. Hedberg, Matthew F. Hockin, Mario R. Capecchi
Journal: Cancer Research (2009)

Previously, we reported modeling synovial sarcomas in mice by conditionally expressing the human t(X;18) translocation-derived SYT-SSX2 fusion protein in Myf5-expressing myoblasts. Using a tamoxifen-inducible CreER system in mice, we show here that sporadic expression of SYT-SSX2 across multiple tissue types leads to exclusive formation of synovial sarcoma-like tumors, whereas its widespread expression is lethal. Certain clinical and histologic features of tumors in this new model suggest additional nonmyoblast origin for synovial sarcoma. CreER-based sporadic expression both avoids the severe early developmental phenotypes associated with widespread SYT-SSX2 expression and better models natural pathogenesis of cancers in which transformed cells usually arise within an environment of largely normal cells. Furthermore, this strategy may recapitulate multiple potential cellular origins within a single model system.
Hepatoblastoma and Familial Adenomatous Polyposis
Authors: J. E. Garber, F. P. Li, J. E. Kingston, A. J. Krush, L. C. Strong, M. J. Finegold, L. Bertario, S. BUlow, A. Filippone, T. Gedde-Dahl, H.J. Jarvinen
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Hepatoblastoma and Familial Adenomatous Polyposis Get access J. E. Garber, J. E. Garber Dana-Farber Cancer Institute, Boston, MA and Clinical Epidemiology Branch, Division of Cancer Etiology, National Cancer InstituteBethesda, MD Correspondence to: Dr. J. E. Garber, Dana Farber Cancer Institute, 44 Binney St., Boston MA 02115. Search for other works by this author on: Oxford Academic PubMed Google Scholar F. P. Li, F. P. Li Dana-Farber Cancer Institute, Boston, MA and Clinical Epidemiology Branch, Division of Cancer Etiology, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar J. E. Kingston, J. E. Kingston Childhood Cancer Research Group, St. Bartholomew's HospitalLondon, England Search for other works by this author on: Oxford Academic PubMed Google Scholar A. J. Krush, A. J. Krush The Johns Hopkins HospitalBaltimore, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar L. C. Strong, L. C. Strong University of Texas-M.D. Anderson Cancer CenterHouston, TX Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. Finegold, M. J. Finegold Baylor College of MedicineHouston, TX Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Bertario, L. Bertario Istituto Nazionale per lo Studio e la Cura dei TumoriMilan, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar S. BÜlow, S. BÜlow University of CopenhagenHvidovre, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Filippone, Jr., A. Filippone, Jr. Morristown Memorial HospitalMorristown, NJ Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Gedde-Dahl, Jr., T. Gedde-Dahl, Jr. Norwegian Radium HospitalOslo, Norway Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more H.J. Järvinen H.J. Järvinen Central HospitalHelsinki, Finland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 20, 21 December 1988, Pages 1626–1628, https://doi.org/10.1093/jnci/80.20.1626 Published: 21 December 1988 Article history Received: 30 September 1988 Accepted: 03 October 1988 Published: 21 December 1988
CHOP versus MACOP-B in aggressive lymphoma - a Nordic Lymphoma Group randomised trial
Authors: M. Jerkeman, H. Anderson, E. Cavallin-Ståhl, M. Dictor, H. Hagberg, A. Johnson, S. Kaasa, S. Kvaløy, C. Sundström, M. Åkerman
Journal: Annals of Oncology (1999)
Hormone synthesis and secretion by rat parathyroid glands in tissue culture
Authors: William Y. W. Au, Alan P. Poland, Paula H. Stern, Lawrence G. Raisz
Journal: Journal of Clinical Investigation (1970)

Rat parathyroid glands maintained in organ culture secrete biologically active parathyroid hormone (PTH) and synthesize and secrete labeled proteins from (3)H- or (14)C-labeled amino acids added to the medium. The amounts of biological activity and labeled protein in the medium are both inversely proportional to the calcium concentration. Some of the labeled low molecular weight protein was identified as PTH which had been synthesized and secreted in culture by preliminary isolation on Sephadex G-100 columns and further purification using an antibody to bovine PTH which cross-reacted with rat PTH. The cross-reacting antibody inhibited the biological effects of rat PTH and caused hypocalcemia in intact rats. The antibody bound some of the labeled low molecular weight protein of the medium at neutral pH so that it migrated as a large molecular weight complex on Sephadex. Biologically active, labeled PTH was recovered by dissociation of this complex in acid and rechromatography.
Disruption of TrkB-Mediated Signaling Induces Disassembly of Postsynaptic Receptor Clusters at Neuromuscular Junctions
Authors: Michael Gonzalez, Francis P Ruggiero, Qiang Chang, Yi-Jun Shi, Mark M Rich, Susan Kraner, Rita J Balice-Gordon
Journal: Neuron (1999)

Neurotrophins and tyrosine receptor kinase (Trk) receptors are expressed in skeletal muscle, but it is unclear what functional role Trk-mediated signaling plays during postnatal life. Full-length TrkB (trkB.FL) as well as truncated TrkB (trkB.t1) were found to be localized primarily to the postsynaptic acetylcholine receptor– (AChR-) rich membrane at neuromuscular junctions. In vivo, dominant-negative manipulation of TrkB signaling using adenovirus to overexpress trkB.t1 in mouse sternomastoid muscle fibers resulted in the disassembly of postsynaptic AChR clusters at neuromuscular junctions, similar to that observed in mutant trkB+/− mice. When TrkB-mediated signaling was disrupted in cultured myotubes in the absence of motor nerve terminals and Schwann cells, agrin-induced AChR clusters were also disassembled. These results demonstrate a novel role for neurotrophin signaling through TrkB receptors on muscle fibers in the ongoing maintenance of postsynaptic AChR regions.
Incorporating indocyanin green clearance into the Model for End Stage Liver Disease (MELD-ICG) improves prognostic accuracy in intermediate to advanced cirrhosis
Authors: A. Zipprich, O. Kuss, S. Rogowski, G. Kleber, E. Lotterer, T. Seufferlein, W. E. Fleig, M. M. Dollinger
Journal: Gut (2010)

<h3>Background</h3> The Model for End Stage Liver Disease (MELD) predicts mortality in end stage liver disease. Incorporation of serum sodium into the MELD may improve diagnostic accuracy in decompensated patients with ascites. However, other complications of cirrhosis are not reflected. This study investigates whether quantitative liver function tests predict survival and increase prognostic accuracy of the MELD. <h3>Methods</h3> 604 patients with suspected cirrhosis were staged clinically and haemodynamically. Galactose-elimination-capacity, sorbitol clearance, lidocaine metabolism and indocyanin green (ICG) half life were determined. Survival was the primary end point of the study. Prognostic effects of individual parameters were calculated using Cox regression models and ROC curves. <h3>Results</h3> 321 patients on standard pharmacological and endoscopic treatment (PET) and 74 patients undergoing transjugular portosystemic shunting (TIPS) were studied. Of all quantitative liver function tests, ICG half life was the most accurate in predicting survival. Upon incorporation into the MELD, it modified the score in patients with PET up to 35 points. Clinically relevant changes to the score, however, occurred in patients with a MELD score between 10 and 30, allowing an objective prognostic discrimination of individual survival based on laboratory liver function and blood flow. The MELD-ICG was validated in the second cohort of patients undergoing TIPS implantation. <h3>Conclusion</h3> ICG had the highest predictive value of the examined tests. Its incorporation into the MELD adds an estimation of liver blood flow and renders the new score MELD-ICG more accurate in predicting survival in intermediate to advanced cirrhosis than the MELD and MELD-Na.
Retinoid X receptors orchestrate osteoclast differentiation and postnatal bone remodeling
Authors: María P. Menéndez-Gutiérrez, Tamás Rőszer, Lucía Fuentes, Vanessa Núñez, Amelia Escolano, Juan Miguel Redondo, Nora De Clerck, Daniel Metzger, Annabel F. Valledor, Mercedes Ricote
Journal: Journal of Clinical Investigation (2015)

Osteoclasts are bone-resorbing cells that are important for maintenance of bone remodeling and mineral homeostasis. Regulation of osteoclast differentiation and activity is important for the pathogenesis and treatment of diseases associated with bone loss. Here, we demonstrate that retinoid X receptors (RXRs) are key elements of the transcriptional program of differentiating osteoclasts. Loss of RXR function in hematopoietic cells resulted in formation of giant, nonresorbing osteoclasts and increased bone mass in male mice and protected female mice from bone loss following ovariectomy, which induces osteoporosis in WT females. The increase in bone mass associated with RXR deficiency was due to lack of expression of the RXR-dependent transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MAFB) in osteoclast progenitors. Evaluation of osteoclast progenitor cells revealed that RXR homodimers directly target and bind to the Mafb promoter, and this interaction is required for proper osteoclast proliferation, differentiation, and activity. Pharmacological activation of RXRs inhibited osteoclast differentiation due to the formation of RXR/liver X receptor (LXR) heterodimers, which induced expression of sterol regulatory element binding protein-1c (SREBP-1c), resulting in indirect MAFB upregulation. Our study reveals that RXR signaling mediates bone homeostasis and suggests that RXRs have potential as targets for the treatment of bone pathologies such as osteoporosis.
Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects
Authors: S Yende
Journal: Thorax (2005)

<b>Background:</b> Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. <b>Methods:</b> The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70–79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD). <b>Results:</b> Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm <i>v</i> 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H<sub>2</sub>O <i>v</i> 74.2 cm H<sub>2</sub>O, p&lt;0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml <i>v</i> 2.2 pg/ml, p&lt;0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l <i>v</i> 2.5 mg/l, p&lt;0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV<sub>1</sub>) was associated with IL-6 (adjusted regression coefficients (β) = −5.3 (95% CI −9.1 to−1.5) and −3.1 (95% CI −4.3 to −1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (β = −6.4 (95% CI −12.8 to −0.03) and −3.4 (95% CI −5.4 to −1.3), respectively, for IL-6 and β = −10.1 (95% CI −18.7 to −1.5) and −3.8 (95% CI −7 to −0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. <b>Conclusions:</b> In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV<sub>1</sub>, quadriceps strength, and exercise capacity.
Alcohol consumption is associated with decreased risk of rheumatoid arthritis: results from two Scandinavian case–control studies
Authors: H Källberg, S Jacobsen, C Bengtsson, M Pedersen, L Padyukov, P Garred, M Frisch, E W Karlson, L Klareskog, L Alfredsson
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: To determine the association between risk of rheumatoid arthritis (RA) and alcohol consumption in combination with smoking and HLA-DRB1 shared epitope (SE). Methods: Data from two independent case–control studies of RA, the Swedish EIRA (1204 cases and 871 controls) and the Danish CACORA (444 cases and 533 controls), were used to estimate ORs of developing RA for different amounts of alcohol consumed. Results: Alcohol consumption was significantly more common in controls (p&lt;0.05) and dose-dependently associated with reduced risk of RA (p for trend &lt;0.001) in both studies. Among alcohol consumers, the quarter with the highest consumption had a decreased risk of RA of the order of 40–50% compared with the half with the lowest consumption (EIRA, OR = 0.5 (95% CI 0.4 to 0.6); CACORA, OR = 0.6 (95% CI 0.4 to 0.9)). For the subset of RA that is seropositive for antibodies to citrullinated peptide antigens, alcohol consumption reduced the risk most in smokers carrying HLA-DRB1 SE alleles. Conclusions: The observed inverse association between alcohol intake and risk of RA and the recent demonstration of a preventive effect of alcohol in experimental arthritis indicate that alcohol may protect against RA. This highlights the potential role of lifestyle in determining the risk of developing RA, and emphasises the advice to stop smoking, but not necessarily to abstain from alcohol in order to diminish risk of RA. The evidence of potential RA prevention should prompt additional studies on how this can be achieved.
Contrasting the Efficacy of Selection on the X and Autosomes in Drosophila
Authors: N. D. Singh, A. M. Larracuente, A. G. Clark
Journal: Molecular Biology and Evolution (2007)

To investigate the relative efficacy of both positive and purifying natural selection on the X chromosome and the autosomes in Drosophila, we compared rates and patterns of molecular evolution between these chromosome sets using the newly available alignments of orthologous genes from 12 species. Parameters that may influence the relative X versus autosomal substitution rates include the relative effective population sizes, the male and female germline mutation rates, the distribution of allelic effects on fitness, and the degree of dominance of novel mutations. Our analysis reveals that codon usage bias is consistently greater for X-linked genes, suggesting that purifying selection consistently has greater efficacy on the X chromosome than on the autosomes across the Drosophila phylogeny. However, our results are less consistent with respect to the efficacy of positive selection, with only some lineages showing a higher substitution rate on the X chromosome. This suggests that either the distribution of selective effects of mutations or other relevant parameters are sufficiently variable across species to tip the balance in different ways in individual lineages. These data suggest that rates of substitution are not solely governed by adaptive evolution. This genome-wide analysis provides a clear picture that the efficacy of selection varies intragenomically and that this effect is markedly more consistent across the phylogeny in the case of purifying selection. Our results also suggest that simple models that predict systematic differences in rates of evolution between the X and the autosomes can only be made to be compatible with these Drosophila data if the relevant population genetic parameters that drive substitution rates differ among species and chromosomal contexts.
The ursodeoxycholic acid story in primary biliary cirrhosis.
Authors: A G Lim, R P Jazrawi, T C Northfield
Journal: Gut (1995)

The ursodeoxycholic acid story in primary biliary cirrhosisThe name ursodeoxycholic acid (UDCA) is derived from 'ursocholeinische saure' used by Hammarsten in 1902 to describe a bile acid discovered in polar bears.The bile acid he identified was actually chenodeoxycholic acid.1 UDCA on July 9, 2023 by guest.
Using genetically isolated populations to understand the genomic basis of disease
Authors: Eleftheria Zeggini
Journal: Genome Medicine (2014)

Rare variation has a key role in the genetic etiology of complex traits. Genetically isolated populations have been established as a powerful resource for novel locus discovery and they combine advantageous characteristics that can be leveraged to expedite discovery. Genome-wide genotyping approaches coupled with sequencing efforts have transformed the landscape of disease genomics and highlight the potentially significant contribution of studies in founder populations.
S1 HIV-1 infection of macrophages modulates host responses to Mycobacterium tuberculosis to contribute to immunopathogenesis and viral propagation
Authors: G. S. Tomlinson, P. T. G. Elkington, M. Noursadeghi
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> Human immunodeficiency virus (HIV)-1 infection increases the risk of active tuberculosis (TB) by 50-fold. The concurrent HIV and TB pandemics therefore represent a major threat to global health. We study the immunopathogenesis of co-infection with a focus on the role of macrophages. These are sentinel cells of the immune system that orchestrate innate and adaptive immune responses, and within the lung, in particular, can host both <i>Mycobacterium tuberculosis</i> (MTb) and productive HIV infection. We tested the hypothesis that HIV infection of macrophages modulates host responses to MTb, and contributes to the pathogenesis of co-infection. <h3>Methods</h3> Innate immune responses to MTb were assessed in human macrophages with and without productive HIV-1 infection using genome-wide transcriptional profiling. Array data were validated by quantitative PCR of selected genes and Luminex analysis of cell culture supernatants. ELISA and ELIspot assays were used to assess the effects of co-infection on HIV replication and anti-mycobacterial T cell responses. <h3>Results</h3> Major gene expression changes assessed by principle component analysis showed that HIV-infected macrophages exhibited attenuated primary transcriptional responses to MTb, but augmented responses at later time points. In keeping with this assessment, we found that MTb stimulation of macrophages induced early IL10 expression, which was attenuated in HIV co-infected cells, and associated with sustained increased expression of pro-inflammatory mediators at later time points. We confirmed the functional relationship between the IL10 response and consequent homeostatic control of inflammatory responses, by complementing deficient IL10 responses in HIV-infected cells to reverse the pro-inflammatory phenotype. We established that exaggerated inflammatory responses in HIV-infected cells were sustained at 72 h, and likely to affect both HIV replication and consequent anti-mycobacterial immune responses. We show that sustained inflammatory responses to MTb are associated with increased HIV replication and have the capacity to alter T cell responses by increasing Th17 polarisation. <h3>Conclusion</h3> HIV-1 infection of macrophages attenuates IL10 responses to MTb, and leads to sustained pro-inflammatory responses that support viral propagation and immunopathogenesis of TB.