tbuckley/cabot-search huggingface dataset:
Genetic variants of miRNA sequences and non–small cell lung cancer survival
Authors: Zhibin Hu, Jiaping Chen, Tian Tian, Xiaoyi Zhou, Haiyong Gu, Lin Xu, Yi Zeng, Ruifen Miao, Guangfu Jin, Hongxia Ma, Yijiang Chen, Hongbing Shen
Journal: Journal of Clinical Investigation (2008)

Recent evidence indicates that small noncoding RNA molecules known as microRNAs (miRNAs) can function as tumor suppressors and oncogenes. Mutation, misexpression, and altered mature miRNA processing are implicated in carcinogenesis and tumor progression. Because SNPs in pre-miRNAs could alter miRNA processing, expression, and/or binding to target mRNA, we conducted a systematic survey of common pre-miRNA SNPs and their surrounding regions and evaluated in detail the association of 4 of these SNPs with the survival of individuals with non–small cell lung cancer (NSCLC). When we assumed that disease susceptibility was inherited as a recessive phenotype, we found that the rs11614913 SNP in hsa-mir-196a2 was associated with survival in individuals with NSCLC. Specifically, survival was significantly decreased in individuals who were homozygous CC at SNP rs11614913. In the genotype-phenotype correlation analysis of 23 human lung cancer tissue samples, rs11614913 CC was associated with a statistically significant increase in mature hsa-mir-196a expression but not with changes in levels of the precursor, suggesting enhanced processing of the pre-miRNA to its mature form. Furthermore, binding assays revealed that the rs11614913 SNP can affect binding of mature hsa-mir-196a2-3p to its target mRNA. Therefore, the rs11614913 SNP in hsa-mir-196a2 may be a prognostic biomarker for NSCLC. Further characterization of miRNA SNPs may open new avenues for the study of cancer and therapeutic interventions.
Increased sensitivity to extracellular ATP of fibroblasts from patients affected by systemic sclerosis
Authors: A. Lo Monaco, S. Gulinelli, G. Castellino, A. Solini, D. Ferrari, R. La Corte, F. Trotta, F. Di Virgilio
Journal: Annals of the Rheumatic Diseases (2007)

Systemic sclerosis (SSc) is an autoimmune disease characterised by an excessive production of collagen and other constituents of the extracellular matrix in the skin, lung and other internal organs, by damage of the microvascular endothelium, and dysregulation of cytokine secretion.1–3 Recent studies show that extracellular nucleotides trigger cytoplasmic Ca2+ increases ([Ca2+]i), morphological changes and cytokine secretion in human fibroblasts.4 Nucleotides are released in response to traumas or inflammation, thus they may also affect fibroblast responses in scleroderma.5

We investigated intracellular second-messenger generation, cytokine secretion and morphological changes in involved, non-atrophic skin biopsies from five patients with the diffuse form of SSc.6 Fibroblasts from patients with SSc had a high rate of spontaneous interleukin (IL)-6 release, which was further enhanced by stimulation …
Preoperative Serum DNA <i>GSTP1</i> CpG Island Hypermethylation and the Risk of Early Prostate-Specific Antigen Recurrence Following Radical Prostatectomy
Authors: Patrick J. Bastian, Ganesh S. Palapattu, Xiaohui Lin, Srinivasan Yegnasubramanian, Leslie A. Mangold, Bruce Trock, Mario A. Eisenberger, Alan W. Partin, William G. Nelson
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Hypermethylation of the CpG island at the promoter region of the π-class glutathione S-transferase gene (GSTP1) is the most common somatic genome abnormality in human prostate cancer. We evaluated circulating cell-free DNA GSTP1 CpG island hypermethylation as a prognostic biomarker in the serum of men with prostate cancer. Experimental Design: Prostate cancer DNA GSTP1 CpG island hypermethylation was detected using a restriction endonuclease quantitative PCR technique. We analyzed preoperative serum from 85 men with clinically localized prostate cancer treated with radical prostatectomy and from 35 men with a negative prostate biopsy. We then assayed preoperative serum from a data set of 55 pairs of men with clinically localized prostate cancer treated with radical prostatectomy, matched for Gleason score, comprising 55 men suffering prostate-specific antigen (PSA) recurrence (median, 2 years) and 55 men who were free of disease at last follow-up (median, 3 years). The association of serum GSTP1 CpG island hypermethylation and PSA recurrence was determined. Results: Circulating cell-free DNA with GSTP1 CpG island hypermethylation was not detected in the serum of men with a negative prostate biopsy but was detected in 12% of men with clinically localized disease and 28% of men with metastatic cancer (P = 0.003). In the matched data set, eight men (15%) who developed PSA recurrence were positive for DNA with GSTP1 CpG hypermethylation, whereas no patient who was free of disease was positive for GSTP1 CpG island hypermethylation (McNemar test, χ2 = 6.1, P = 0.01). In a multivariable analysis that accounted for recognized prognostic factors, the presence of serum DNA with GTSP1 CpG island hypermethylation was the most significant predictor of PSA recurrence (hazard ratio, 4.4; 95% confidence interval, 2.2, 8.8; P &amp;lt; 0.001). Conclusion: Our study suggests that GSTP1 CpG island hypermethylation may be an important DNA-based prognostic serum biomarker for prostate cancer.
Atorvastatin Decreases Apolipoprotein C-III in Apolipoprotein B-Containing Lipoprotein and HDL in Type 2 Diabetes
Authors: Geesje M. Dallinga-Thie, Ingrid I.L. Berk-Planken, Aart H. Bootsma, Hans Jansen
Journal: Diabetes Care (2004)

Apolipoprotein (apo)C-III is a constituent of HDL (HDL apoC-III) and of apoB-containing lipoproteins (LpB:C-III). It slows the clearance of triglyceride-rich lipoproteins (TRLs) by inhibition of the activity of the enzyme lipoprotein lipase (LPL) and by interference with lipoprotein binding to cell-surface receptors. Elevated plasma LpB:C-III is an independent risk factor for cardiovascular disease. We studied the effect of atorvastatin on plasma LpB:C-III and HDL apoC-III.We studied the effect of 30 weeks' treatment with 10 and 80 mg atorvastatin on plasma apoC-III levels in a randomized, double-blind, placebo-controlled trial involving 217 patients with type 2 diabetes and fasting plasma triglycerides between 1.5 and 6.0 mmol/l.Baseline levels of total plasma apoC-III, HDL apoC-III, and LpB:C-III were 41.5 +/- 10.0, 17.7 +/- 5.5, and 23.8 +/- 7.7 mg/l, respectively. Plasma apoC-III was strongly correlated with plasma triglycerides (r = 0.74, P < 0.001). Atorvastatin 10- and 80-mg treatment significantly decreased plasma apoC-III (atorvastatin 10 mg, 21%, and 80 mg, 27%), HDL apoC-III (atorvastatin 10 mg, 22%, and 80 mg, 28%) and LpB:C-III (atorvastatin 10 mg, 23%, and 80 mg, 28%; all P < 0.001). The decrease in plasma apoC-III, mainly in LpB:C-III, strongly correlated with a decrease in triglycerides (atorvastatin 10 mg, r = 0.70, and 80 mg, r = 0.78; P < 0.001). Atorvastatin treatment also leads to a reduction in the HDL apoC-III-to-HDL cholesterol and HDL apoC-III-to-apoA-I ratios, indicating a change in the number of apoC-III per HDL particle (atorvastatin 10 mg, -21%, and 80 mg, -31%; P < 0.001).Atorvastatin treatment resulted in a significant dose-dependent reduction in plasma apoC-III, HDL apoC-III, and LpB:C-III levels in patients with type 2 diabetes. These data indicate a potentially important antiatherogenic effect of statin treatment and may explain (part of) the triglyceride-lowering effect of atorvastatin.
A computerised dichromatic earpiece densitometer for the measurement of cardiac output
Authors: P. S. ROBINSON, A. CROWTHER, B. S. JENKINS, M. M. WEBB-PEPLOE, D. J. COLTART
Journal: Cardiovascular Research (1979)

This study assesses a precalibrated dichromatic earpiece densitometer and microprocessor for the measurement of cardiac output by indocyanine green dye dilution. The measured cardiac output is compared with values of cardiac output simultaneously determined using a cuvette densitometer. The microprocessor computation of cardiac output agreed very closely with the cardiac output determined by manual calculation from the same dye dilution curves (standard deviation ±1.47%). The reproducibility of the earpiece densitometer (standard deviation ±5.2%) was virtually identical to that of the cuvette densitometer (±5.3%). In a comparison of earpiece and cuvette densitometers for 60 measurements of cardiac output following pulmonary arterial injection of dye and for 50 measurements following femoral venous injection of dye, correlation coefficients were 0.83 and 0.78 and the standard deviations of the differences of simultaneous measurements were 7.2% and 8.3% respectively. The instrument offers an accurate reproducible and relatively noninvasive technique for measuring cardiac output.
Combination of a Poxvirus-Based Vaccine with a Cyclooxygenase-2 Inhibitor (Celecoxib) Elicits Antitumor Immunity and Long-Term Survival in CEA.Tg/MIN Mice
Authors: Hasan E. Zeytin, Arti C. Patel, Connie J. Rogers, Daniel Canter, Stephen D. Hursting, Jeffrey Schlom, John W. Greiner
Journal: Cancer Research (2004)

Abstract The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with lowered plasma prostaglandin E2 levels and reduced COX-2 mRNA expression levels in their splenic T cells. Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-γ production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib. When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the ApcΔ850 gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning at 30 days of age, the administration of a diversified prime/boost recombinant CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet reduced the number of intestinal neoplasms by 54% and 65%, respectively. Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced tumor burden by 95% and significantly improved overall long-term survival. Both tumor reduction and improved overall survival were achieved without any evidence of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is prescribed for the treatment of familial adenomatous polyposis in humans, and the CEA-based vaccines have been well tolerated and capable of eliciting anti-CEA host immune responses in early clinical studies. The results suggest that the administration of a recombinant poxvirus-based vaccine is compatible with celecoxib, and this combined chemoimmuno-based approach might lead to an additive therapeutic antitumor benefit not only in patients diagnosed with familial adenomatous polyposis but, perhaps, in other preventive settings in which COX-2 overexpression is associated with progression from premalignancy to neoplasia.
Regulating Chemicals: Law, Science, and the Unbearable Burdens of Regulation
Authors: Ellen K. Silbergeld, Daniele Mandrioli, Carl F. Cranor
Journal: Annual Review of Public Health (2015)

The challenges of regulating industrial chemicals remain unresolved in the United States. The Toxic Substances Control Act (TSCA) of 1976 was the first legislation to extend coverage to the regulation of industrial chemicals, both existing and newly registered. However, decisions related to both law and science that were made in passing this law inevitably rendered it ineffectual. Attempts to fix these shortcomings have not been successful. In light of the European Union's passage of innovative principles and requirements for chemical regulation, it is no longer possible to deny the opportunity and need for reform in US law and practice.
Infliximab treatment for rheumatoid arthritis, with dose titration based on the Disease Activity Score: dose adjustments are common but not always sufficient to assure sustained benefit
Authors: P Sidiropoulos
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Randomised controlled trials have shown that treatment with anti-tumour necrosis factor (anti-TNF) agents is effective in refractory rheumatoid arthritis (RA). <b>Objective:</b> To determine the effectiveness of anti-TNF in a general unselected group of patients with refractory RA. <b>Methods:</b> 68 patients with active RA despite treatment with disease modifying antirheumatic drugs were studied during 12 infliximab infusions. Infliximab (3 mg/kg/infusion) was given every 8 or 6 weeks. Clinical efficacy was assessed by the Disease Activity Score (DAS) index (44 joints). Dose adjustments were based on residual disease activity (DAS score &gt;2.4). The primary end points were the percentage of patients achieving good or moderate response by the EULAR response criteria and the proportion of patients requiring dose adjustment. <b>Results:</b> 20 (29%) patients discontinued treatment owing to side effects, early inefficacy, or other considerations. Among the patients who continued treatment, 27 (56%) and 32 (67%) were responders on the 6th and 12th infliximab infusion, respectively. In the same patients, disease activity gradually improved without modifications in the initial dosing in 10 (21%), whereas in 38 (79%) the dose of infliximab and/or methotrexate was increased. Intensification of treatment led to a significant decrease in the mean DAS score in this group (from 5.27 just before dose modification to 4.54 before the 12th infusion, p&lt;0.002). The EULAR response category improved in only 10/38 (26%), however. <b>Conclusions:</b> In this initial observational study of patients with RA treated with recommended doses of infliximab, adjustments in treatment were common but not always sufficient to maintain adequate disease control. Longitudinal controlled trials are needed to define the optimal dose escalation in patients with suboptimal response.
Actinomycin-eluting stent for coronary revascularization
Authors: Patrick W. Serruys, John A. Ormiston, Georgios Sianos, J. Eduardo Sousa, Eberhard Grube, Peter den Heijer, Pim de Feyter, Pawel Buszman, Albert Schömig, Jean Marco, Lech Polonski, Leif Thuesen, Andreas M. Zeiher, J.H. Nicholas Bett, Maarten J. Suttorp, Helmut D. Glogar, Mark Pitney, Gerard T. Wilkins, Robert Whitbourn, Susan Veldhof, Karine Miquel, Rachel Johnson, Leslie Coleman, Renu Virmani
Journal: Journal of the American College of Cardiology (2004)
A Computerized Self-Assessment Examination for Residents
Authors: SHERWYN M. WOODS
Journal: American Journal of Psychiatry (1974)

The author administered 194 randomly selected multiple-choice questions from the APA Psychiatric Knowledge and Skills Self-Assessment Program to 65 residents via a computerized response apparatus. The system provides immediate feedback on each question and on the test as a whole. Upon completion of the test, a computer printout indicates each resident's percent correct, score, and rank in the group being tested. Analysis of question-by-question group performance data can benefit teaching programs by revealing areas of insufficient instruction.
Transcription Factor KLF11 Integrates Progesterone Receptor Signaling and Proliferation in Uterine Leiomyoma Cells
Authors: Ping Yin, Zhihong Lin, Scott Reierstad, Ju Wu, Hiroshi Ishikawa, Erica E. Marsh, Joy Innes, Youhong Cheng, Kerry Pearson, John Sayler Coon, J. Julie Kim, Debabrata Chakravarti, Serdar E. Bulun
Journal: Cancer Research (2010)

Uterine leiomyoma is the most common tumor of the female genital tract and the leading cause of hysterectomy. Although progesterone stimulates the proliferation of uterine leiomyoma cells, the mechanism of progesterone action is not well understood. We used chromatin immunoprecipitation (ChIP)-cloning approach to identify progesterone receptor (PR) target genes in primary uterine leiomyoma smooth muscle cells. We identified 18 novel PR-binding sites, one of which was located 20.5 kb upstream of the transcriptional start site of the Krüppel-like transcription factor 11 (KLF11) gene. KLF11 mRNA levels were minimally downregulated by progesterone but robustly upregulated by the progesterone antagonist RU486. Luciferase reporter assays showed significant baseline and RU486-inducible promoter activity in the KLF11 basal promoter or distal PR-binding region, both of which contained multiple Sp1-binding sequences but lacked classic progesterone response elements. RU486 stimulated recruitment of Sp1, RNA polymerase II, PR, and the coactivators SRC-1 and SRC-2 to the distal region and basal promoter. siRNA knockdown of PR increased KLF11 expression, whereas knockdown of KLF11 increased leiomyoma cell proliferation and abolished the antiproliferative effect of RU486. In vivo, KLF11 expression was significantly lower in leiomyoma tissues compared with adjacent myometrial tissues. Taken together, using a ChIP-cloning approach, we uncovered KLF11 as an integrator of PR signaling and proliferation in uterine leiomyoma cells.
Prognostic Significance of Papilledema in Course of Respiratory Insufficiency
Authors: Paul M. Stevens
Journal: JAMA (1963)

Three patients with papilledema, asterixis, and impairment of consciousness secondary to hypoxemia, hypercapnia, and right- and left-sided heart failure were observed for 6 yr after the first appearance of these signs. Although two of the patients required rehospitalization because of recurrence of papilledema and cardiopulmonary failure, each is still living and enjoying varying degrees of activity. The results of pulmonary function studies made recently did not differ appreciably from those carried out 6 yr previously. Papilledema occurring in the course of cardiopulmonary failure did not appear to alter the prognosis in the cases observed, and it seems likely that the outcome is largely dependent on the course of the underlying pulmonary disease. Vigorous treatment of episodic acute cardiopulmonary failure has made possible a considerably improved prognosis.
A Comprehensive View of Nuclear Receptor Cancer Cistromes
Authors: Qianzi Tang, Yiwen Chen, Clifford Meyer, Tim Geistlinger, Mathieu Lupien, Qian Wang, Tao Liu, Yong Zhang, Myles Brown, Xiaole Shirley Liu
Journal: Cancer Research (2011)

Nuclear receptors comprise a superfamily of ligand-activated transcription factors that play important roles in both physiology and diseases including cancer. The technologies of chromatin immunoprecipitation followed by array hybridization (ChIP-chip) or massively parallel sequencing (ChIP-seq) has been used to map, at an unprecedented rate, the in vivo genome-wide binding (cistrome) of nuclear receptors in both normal and cancer cells. We developed a curated database of 88 nuclear receptor cistrome data sets and other associated high-throughput data sets including 121 collaborating factor cistromes, 94 epigenomes, and 319 transcriptomes. Through integrative analysis of the curated nuclear receptor ChIP-chip/seq data sets, we discovered novel factor-specific noncanonical motifs that may have important regulatory roles. We also revealed a common feature of nuclear receptor pioneering factors to recognize relatively short and AT-rich motifs. Most nuclear receptors bind predominantly to introns and distal intergenetic regions, and binding sites closer to transcription start sites were found to be neither stronger nor more evolutionarily conserved. Interestingly, while most nuclear receptors appear to be predominantly transcriptional activators, our analysis suggests that the binding of ESR1, RARA, and RARG has both activating and repressive effects. Through meta-analysis of different omic data of the same cancer cell line model from multiple studies, we generated consensus cistrome and expression profiles. We further made probabilistic predictions of the nuclear receptor target genes by integrating cistrome and transcriptome data and validated the predictions using expression data from tumor samples. The final database, with comprehensive cistrome, epigenome, and transcriptome data sets and downstream analysis results, constitutes a valuable resource for the nuclear receptor and cancer community.
Induction of Early Atherosclerosis in LDL-Receptor–Deficient Mice Immunized With β <sub>2</sub> -Glycoprotein I
Authors: Jacob George, Arnon Afek, Boris Gilburd, Miri Blank, Yair Levy, Anabel Aron-Maor, Hana Levkovitz, Aviv Shaish, Iris Goldberg, Juri Kopolovic, Dror Harats, Yehuda Shoenfeld
Journal: Circulation (1998)

Background —Immunization with β 2 -glycoprotein I (β2GPI), the probable target of autoimmune anticardiolipin antibodies, results in experimental antiphospholipid syndrome in different mouse strains. The present study was undertaken to evaluate the effect of β2GPI immunization on the progression of atherosclerosis. Methods and Results —In the first experiment, 3 groups of LDL receptor–deficient (LDL-RD) mice (n=15 per group) were immunized with either β2GPI or ovalbumin or were not immunized and were fed a chow diet for 12 weeks. In a second experiment, 3 groups of LDL-RD mice (n=10 per group) were immunized similarly and fed an atherogenic diet for 6 weeks. All β2GPI-immunized mice developed high titers of anti-β2GPI antibodies as well as a specific lymph node proliferation to β2GPI. The average cholesterol levels did not differ between the mice fed similar diets, regardless of the immunization protocol. Atherosclerosis was enhanced in the β2GPI-immunized mice (mean aortic lesion, 26 000±5700 μm 2 ) in comparison with their ovalbumin-immunized (mean, 3000±1099 μm 2 ; P &lt;0.01) and nonimmunized (mean, 2250±700 μm 2 ; P &lt;0.01) littermates. The average lesion size in the β2GPI-immunized mice fed an atherogenic diet (mean, 98 000±8305 μm 2 ) was larger than the ovalbumin-immunized mice (mean, 81 250±12 933 μm 2 ; P =NS) or the nonimmunized controls (mean, 75 625±7281 μm 2 ; P =NS). The atherosclerotic plaques in the β2GPI-immunized mice appeared to be more mature, and denser infiltration of CD4 lymphocytes was present in the subendothelium of the aortic sinuses from this group of mice. Conclusions —The results of the present study provide the first direct evidence for the proatherogenic effect of β2GPI immunization and establish a new model for immune-mediated atherosclerosis.