tbuckley/cabot-search huggingface dataset:
Abstract 2166: Identification of novel epigenetically silenced genes by a global reactivation screen of prostate cancer
Authors: Ilsiya Ibragimova, Inmaculada Ibáñez de Cáceres, Amanda M. Hoffman, Tahseen Al-Saleem, Gary R. Hudes, Michael F. Ochs, Paul Cairns
Journal: Cancer Research (2010)

Abstract The epigenetic alteration of aberrant DNA methylation of CpG island in the promoter region is a common mechanism of inactivation of tumor suppressor genes in cancer cells and a number of other cancer genes have been identified as hypermethylated with associated loss of expression in prostate cancer. By definition, a candidate gene approach has resulted in the examination of only a limited number of genes for epigenetic alteration. Many other tumor suppressor and cancer genes important in prostate tumorigenesis likely remain to be identified. A global approach to the identification of epigenetically silenced genes in prostate tumor cells could provide methylation signatures for early detection and for prognostic and predictive classification studies, identify novel targets for therapy, and lead to further elucidation of the biology of this disease. One global approach to the identification of epigenetically silenced genes in tumor cells is based on the reversal of epigenetic silencing by drugs such as 5-aza-2 deoxycytidine resulting in re-expression analyzed by well-annotated gene expression arrays. This approach can preferentially identify re-expression of epigenetically silenced genes over methylated CpG islands that do not affect transcription. A proportion of the reexpressed genes will have been silenced by promoter hypermethylation in the untreated tumor cell lines. In this study we performed a demethylating drug-based global epigenetic reactivation screen with an expression microarray on 4 well-established prostate cancer cell lines (LNCaP, DU-145, PC-3 and MDA2b) to identify new methylated genes in prostate cancer. A total of 2998 genes were found to have at least 2-fold upregulation of expression after drug treatment in one or more of four prostate tumor cell lines. Using qMSP and bisulfite sequencing, we studied the first 45 upregulated genes that were prioritized by examination of expression status in the normal cell counterpart compared to the tumor cell and the presence and location of a CpG island in the promoter region. Validation studies revealed several novel genes hypermethylated in primary prostate tumors compared to normal prostate that may have utility in methylation-based detection of prostate cancer tests. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2166.
In vitro activation of low-grade non-Hodgkin’s lymphoma by murine fibroblasts, IL-4, anti-CD40 antibodies and the soluble CD40 ligand
Authors: C Buske, A Twiling, G Gogowski, K Schreiber, M Feuring-Buske, GG Wulf, W Hiddemann, B Wörmann
Journal: Leukemia (1997)
A Quantitative Method for Assessing the Degree of Axial Proptosis in Relation to Orbital Tissue Involvement in Graves' Orbitopathy
Authors: Irene Campi, Guia M. Vannucchi, Andrea M. Minetti, Davide Dazzi, Sabrina Avignone, Danila Covelli, Nicola Currò, Roberto Ratiglia, Claudio Guastella, Lorenzo Pignataro, Paolo Beck-Peccoz, Mario Salvi
Journal: Ophthalmology (2013)
Enhanced noradrenaline response in cardiomyopathic hamsters: possible relation to changes in adrenoceptors studied by radioligand binding
Authors: J. S KARLINER, C. ALABASTER, H. STEPHENS, P. BARNES, C. DOLLERY
Journal: Cardiovascular Research (1981)

To assess the possible relation between catecholamine responses and adrenoceptor affinity and density, we compared the effect of noradrenaline, isoprenaline and ouabain on right ventricular muscle strips from normal and cardiomyopathic hamsters with α1− and β-adrenoceptor characteristics assessed by radioligand binding methods. At concentrations of 1.28, 2.56, 5.0 and 10 × 10−6 mol·litre−1 noradrenaline raised isometric tension by 27 ± 4, 39 ± 5, 52 ± 5 and 61 = 6% in normal animals (n = 6). Corresponding increases of 65 ± 8, 92 ± 8, 109 ± 9 and 115 ± 10% occurred in cardiomyopathic hamsters (n = 11, all P < 0.02). The responses to isoprenaline (EmaK = 82%) and ouabain did not differ between the two groups of hamsters. [3H]-prazosin, a new radioligand, and [−3H]-dihydroalprenolol were used to assess α1− and β-adrenoceptors in cardiac membranes. By Scatchard analysis, the KD values for both ligands did not differ between normal and cardiomyopathic hamsters, but the maximum number of binding sites was higher in the myopathic group: 5.5 vs 3.9 fmol·mg−1 protein for [3H]-prazosin and 27 vs 20 fmol·mg−1 protein for [−3H]-dihydroal-prenolol (both P < 0.05). Histochemically, oxidative and glycolytic activity were normal but lyso-zosomal acid phosphatase was high. Possible explanations for the raised response to noradrenaline in cardiomyopathic hamsters include an increased concentration of noradrenaline in the synaptic cleft due to defective neuronal uptake and / or stimulation of an augmented population of α1-(postsynaptic) adrenoceptors.
Neutrophil-Dependent and Neutrophil-Independent Alterations in the Nasal Epithelium of Ozone-Exposed Rats
Authors: HYE Y. CHO, JON A. HOTCHKISS, CATHERINE B. BENNETT, JACK R. HARKEMA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Ozone induces epithelial hyperplasia and mucous cell metaplasia (MCM) in nasal transitional epithelium (NTE) of rats. A transient neutrophil influx accompanies upregulation of mucin messenger RNA (mRNA) before the onset of MCM. The present study was designed to examine the role of neutrophils in ozone-induced epithelial changes in the NTE of rats. Fourteen hours before inhalation exposure, male F344/N rats were injected intraperitoneally with antirat neutrophil antiserum to deplete circulating neutrophils, or were injected with normal (control) serum. Rats were then exposed to 0 ppm (filtered air) or 0.5 ppm ozone (8 h/d) for 1 or 3 d. Maxilloturbinates lined with NTE were analyzed to determine the epithelial labeling index; numeric densities of neutrophils, total epithelial cells, and mucous secretory cells; amount of stored intraepithelial mucosubstances; and steady-state ratMUC-5AC (mucin) mRNA levels. At 2 h after 3 d of exposure, rats treated with antiserum had 90% fewer circulating neutrophils than did rats treated with control serum. Antiserum-treated, ozone-exposed rats had 87% fewer infiltrating neutrophils than did control serum-treated, ozone-exposed rats. At 4 d after 3 d of exposure, antiserum-treated, ozone-exposed rats had 66% less stored intraepithelial mucosubstances and 58% fewer mucous cells in their NTE than did control serum-treated, ozone-exposed rats. Antiserum treatment had no effects on ozone-induced epithelial cell proliferation or mucin mRNA upregulation. The results of this study indicated that ozone-induced MCM was neutrophil-dependent, whereas ozone-induced epithelial cell proliferation and mucin gene upregulation were neutrophil-independent.
Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line
Authors: Haizhen Zhu, Hongshan Zhao, Christin D. Collins, Sarah E. Eckenrode, Qingguo Run, Richard A. McIndoe, James M. Crawford, David R. Nelson, Jin-Xiong She, Chen Liu
Journal: Hepatology (2003)

Interferon alfa (IFN–α)–based treatment is the only therapeutic option for chronic hepatitis C viral infection. However, the molecular mechanisms of IFN–α antiviral activity are not completely understood. The recent development of an HCV replicon cell culture system provides a feasible experimental model to investigate the molecular details of IFN–induced direct antiviral activity in hepatocytes. In this report, we show that IFN–α can effectively inhibit HCV subgenomic RNA replication and suppress viral nonstructural protein synthesis. Using cDNA microarray analysis, we also show that the replicon cells have different gene expression profile compared with the parental hepatoma cells (Huh7). IFN–α can induce a number of responsive genes in the replicon cells. One of the genes, 6–16 (G1P3), can enhance IFN–α antiviral efficacy. In addition, we demonstrate that IFN–α can significantly activate STAT3 in hepatoma cells, suggesting that this pathway plays a role in IFN–α signaling. In conclusion, our results indicate that IFN–α antiviral activity is associated with activation of STAT3–signaling pathway and intracellular gene activation. Our results also suggest that IFN–α–induced target genes may play an important role in IFN–α anti–HCV activity.
Distinct immunologic changes in vivo following combination versus individual PD-1 or CTLA-4 checkpoint blockade in human cancer
Authors: Kavita Dhodapkar, Rakesh Verma, Mario Sznol, Chandra Sekhar Boddupalli, Scott Gettinger, Harriet Kluger, Madhav Dhodapkar, Rituparna Das
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Therapies targeting T cell immune checkpoints such as CTLA4 and PD1/PDL1 axis have shown considerable promise in the therapy of human cancer. Combination therapy with dual immune checkpoint blockade (ICB) was recently shown to be highly active in melanoma. While signaling via both
Role of the occupational health service in screening and increasing the uptake of rubella immunisation.
Authors: S J Jachuck, C L Bound, C E Jones
Journal: BMJ (1985)

An occupational health department in a district general hospital in Newcastle upon Tyne screened 487 women of childbearing age for rubella immunity who were prospective employees and whose immunity state was unknown. Ninety per cent of these women were immune. Of the 51 who were found to be susceptible, 29 accepted vaccination.
Endothelial injury of arteries following catheterisation with polyethylene tubes: experimental studies on rabbit aorta using the Seldinger technique
Authors: J. K. MADSEN, C. GARBARSCH, P. E. NIELSEN
Journal: Cardiovascular Research (1979)

The effect of catheterisation on the rabbit aortic wall is investigated employing a technique identical to that used for continuous monitoring of blood pressure in humans. The catheters were introduced into the aorta through the right femoral artery of the rabbit using the Seldinger technique, except that the catheters were introduced directly into the femoral artery and not percutaneously. It was found that catheterisation for 24 h was followed by intimal and medial injuries. 3 to 60% (mean 20.4%) de-endothelialisation of the aortic surfaces was observed. The present experiments appear to explain some of the complications observed after continuous registration of blood pressure in humans. Case histories are referred to in which the brachial artery was catheterised.
A quantitative genetic analysis of intermediate asthma phenotypes
Authors: S. F. Thomsen, M. A. R. Ferreira, K. O. Kyvik, M. Fenger, V. Backer
Journal: Allergy (2009)

Aim: To study the relative contribution of genetic and environmental factors to the correlation between exhaled nitric oxide (FeNO), airway responsiveness, airway obstruction, and serum total immunoglobulin E (IgE). Methods: Within a sampling frame of 21 162 twin subjects, 20–49 years of age, from the Danish Twin Registry, a total of 575 subjects (256 intact pairs and 63 single twins) who either themselves and/or their co‐twins reported a history of asthma at a nationwide questionnaire survey, were clinically examined. Traits were measured using standard techniques. Latent factor models were fitted to the observed data using maximum likelihood methods. Results: Additive genetic factors explained 67% of the variation in FeNO, 43% in airway responsiveness, 22% in airway obstruction, and 81% in serum total IgE. In general, traits had genetically and environmentally distinct variance structures. The most substantial genetic similarity was observed between FeNO and serum total IgE, genetic correlation (ρ A ) = 0.37, whereas the strongest environmental resemblance was observed between airway responsiveness and airway obstruction, specific environmental correlation (ρ E ) = −0.46, and between FeNO and airway responsiveness, ρ E = 0.34. Conclusions: Asthma is a complex disease characterized by a set of etiologically heterogeneous biomarkers, which likely constitute diverse targets of intervention.
The Pattern of Nucleotide Difference at Individual Codons Among Mouse, Rat, and Human
Authors: R. Friedman
Journal: Molecular Biology and Evolution (2005)

The patterns of nucleotide difference were compared at 3,473,111 codons from 9,390 aligned orthologous genes of mouse (Mus musculus), rat (Rattus norvegicus), and human (Homo sapiens). The results showed evidence of a higher frequency of both synonymous and nonsynonymous differences from human in the rat than in the mouse. However, contrary to a previous report, there was no evidence of a greater frequency of codons with multiple nonsynonymous substitutions between the two rodent species than expected under random substitution.
The mechanism of action of decay-accelerating factor (DAF). DAF inhibits the assembly of C3 convertases by dissociating C2a and Bb.
Authors: T Fujita, T Inoue, K Ogawa, K Iida, N Tamura
Journal: The Journal of Experimental Medicine (1987)

DAF is a 70,000-Mr membrane protein that inhibits the amplification of the complement cascade on the cell surface, and protects cells from damage by complement. The precise mechanism of action of DAF is not entirely clear. Purified DAF was incorporated into the membrane of EAC4b cells. EAC4b2 and EDAF AC4b2 cells were prepared with radiolabeled C2. The same amount of labeled C2 bound to both cells, showing that DAF does not prevent the binding of C2 zymogen to C4b. After adding Cl, the radioactivity of bound C2 dissociated more rapidly from EDAF AC4b cells than from EAC4b cells. In EAC4b cells, bound C2 was converted to C2a, which gradually dissociated into the supernatants. In the DAF-treated cells, on the other hand, a large amount of C2a rapidly appeared in the supernatants and only a small amount of C2a remained on the cells. In a similar experiment using EhuAC4b, DAF on human erythrocyte membrane also dissociated the C2a from the cells. These results were confirmed by hemolytic assay and the accelerated decay of C2a caused the rapid depletion of C2 from the fluid phase. In addition, we found that DAF functions on the alternative pathway C3 convertase, C3bBb in the same manner. Thus, DAF, which associates with C4b and C3b in the membrane, acts on C2a and Bb, but not on intact C2 and B, and dissociates them rapidly from the binding sites, thereby preventing the assembly of the classical and alternative pathways C3 convertases.
Hippocampal Memory Traces Are Differentially Modulated by Experience, Time, and Adult Neurogenesis
Authors: Christine A. Denny, Mazen A. Kheirbek, Eva L. Alba, Kenji F. Tanaka, Rebecca A. Brachman, Kimberly B. Laughman, Nicole K. Tomm, Gergely F. Turi, Attila Losonczy, René Hen
Journal: Neuron (2014)
Papaverine inhibits transcytotic vesicle transport and lipid excretion into bile in isolated perfused rat liver
Authors: Tomihiro Hayakawa, Kenji Katagiri, Makoto Hoshino, Tomio Nakai, Takayuki Ohiwa, Tomoyuki Kumai, Makoto Miyaji, Toshihiko Takeuchi, James Corasanti, James L. Boyer
Journal: Hepatology (1992)

Papaverine is a nonspecific smooth muscle relaxant and a phosphodiesterase inhibitor. Its effects on biliary excretion of lipids and horseradish peroxidase were investigated in a single-pass isolated perfused rat liver model. A constant infusion of papaverine (1.6 μmol/min; 40 μmol/L) significantly increased bile flow (microliters per minute per gram of liver) before (2.03 ± 0.09 vs. 1.0 ± 0.06) and after sodium taurocholate infusion (2.77 ± 0.10 vs. 1.88 ± 0.11). However, papaverine significantly and reversibly reduced biliary excretion of phospholipids and cholesterol (nanomoles per minute per gram of liver) after a 1.0 μmol/min sodium taurocholate infusion, from 7.45 ± 0.83 and 1.42 ± 0.15 to 1.75 ± 0.18 and 0.39 ± 0.06, respectively (p < 0.01), whereas secretion of bile acids was unaffected. When a 1-min pulse of horseradish peroxidase (25 mg) was infused in isolated perfused rat liver after a continuous infusion of N6, O-2′-dibutyryladenosine 3′,5′-cyclic monophosphate (0.25 μmol/min; 6.25 μmol/L), horseradish peroxidase appeared in bile in an early (4 to 6 min) and late (20 to 25 min) peak. Papaverine significantly reduced the late peak, from 1.211 ± 0.264 to 0.498 ± 0.107 (p < 0.01). Papaverine had no significant effects on either cyclic AMP or cyclic GMP in the liver and bile, although it has been reported that papaverine is a phosphodiesterase inhibitor. These findings indicate that papaverine inhibits biliary excretion of lipids but not bile acids, and they suggest that papaverine has an inhibitory effect on transcytotic vesicle transport independent of an increase of cyclic nucleotides in hepatocytes. (HEPATOLOGY 1992;16:1036–1042.)
Book: Textbook of Rehabilitation Medicine
Authors: L. Turner-Stokes
Journal: BMJ (2000)

Michael Barnes, Anthony B Ward Oxford University Press, £32.98, pp 391 ISBN 0 19 262805 4 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Rehabilitation medicine—now there's a subject for a textbook. Already the reader's eyes glaze over and scan to the next section. But hold on a minute, come back! Just what exactly do you know about rehab medicine? How well do you manage the disability problems of your patients? … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
BIRTH OF QUADRUPLETS.
Authors: S. V. WILKING
Journal: JAMA (1907)

The birth of quadruplets is sufficiently rare (1 in 371,126) to make of interest the following data regarding a case of this kind: <h3>History.</h3> —The mother, aged 36, Irish, weighed 125 pounds and was one of three children born singly. She had been married 14 years and this was her eleventh pregnancy. In all of her previous pregnancies she had gone to term with the exception of two, in which she aborted. Three of her children had been stillborn, one of these being a breech presentation. The father, aged 40, American, was one of seventeen children, all born singly. Labor was rapid and the delivery, which was exceptionally easy, occurred May 30, 1907. The weight and sex of each child was as follows: First, 2 pounds 15% ounces, female; second, 2 pounds 12 ounces, female; third, 2 pounds 15½ ounces, male; fourth, 2 pounds 15 ounces, female. None of the
Polymorphisms of the interleukin 10 gene promoter in patients from brazil with epidermodysplasia verruciformis
Authors: Walmar Roncalli P de Oliveira, Peter L Rady, James Grady, Thomas K Hughes, Cyro Festa Neto, Evandro A Rivitti, Stephen K Tyring
Journal: Journal of the American Academy of Dermatology (2003)
JCVI processes are at least as robust as those of scientific journals
Authors: A. J. Hall
Journal: BMJ (2012)

Hawkes proposes that the evidence on which the Joint Committee on Vaccination and Immunisation (JCVI) bases its decisions should be placed on a website.1 He also suggests that not to do so can only be due to academic vanity. However, academics are now judged and rewarded on the basis of their …
Androstenedione and Its Conversion to Plasma Testosterone in Congenital Adrenal Hyperplasia*
Authors: R. Horton, S. D. Frasier
Journal: Journal of Clinical Investigation (1967)

The plasma concentration, production rate, and conversion ratio of androstenedione and testosterone were studied in seven children with congenital adrenal hyperplasia (CAH) of the 21-hydroxylase type. Plasma androstenedione and testosterone measured by double isotope derivative assay and estimated blood production rates were manyfold increased in the untreated state, markedly suppressed with glucocorticoid, and increased after the administration of ACTH. The metabolic clearance rate when corrected for body size and the conversion ratio of androstenedione to testosterone were similar to previously determined values in normal adults. Consideration of the androgen concentrations and conversion ratios indicates that in children with CAH, 76% of the plasma testosterone in prepubertal females and 36% in males are derived from peripheral conversion of blood androstenedione. The calculated amount of testosterone unaccounted for by peripheral conversion is similar to normal prepubertal values. This approach indicates that virilization in these children results from increased levels of testosterone but that the major source in CAH of this potent androgen is androstenedione secreted by the adrenal cortex.
Shin Lesions From Ladder Rungs
Authors: GEORGE E. Ehrlich
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Electricians are not the only ones to experience the development of soft-tissue lesions of the pretibial area.<sup>1</sup>I had drawn attention to these lesions, which, as a matter of fact, can involve the subjacent bone as well, in a house painter, who not only recognized the cause of the lesions but reported that all others who used ladders, as he did, had the same lesions. At the time, I called them "painter's bosses."<sup>2</sup>However, within the month of publication of my article, I saw a cartoon in a controlled-circulation medical journal, showing a painter with lumps on his shins, over a caption that called them "step-ladder bumps." As the cartoonist could not possibly have seen my article before drawing his cartoon and as the publication of the cartoon was too close after mine to have been derived from mine, I have to assume that the
Comparing the Prevalence of Smoking in Pregnant and Nonpregnant Women, 1985 to 1986
Authors: David F. Williamson
Journal: JAMA (1989)

The 1990 health objectives for the nation state that pregnant women should be only half as likely to smoke as nonpregnant women. To assess progress toward meeting this objective, we used cross-sectional data from the 26 states in the Behavioral Risk Factor Surveillance System in 1985 and 1986. We compared the prevalence of self-reported smoking among pregnant (N = 836) and nonpregnant (N = 18,025) women aged 18 to 45 years. Overall, pregnant women were 70% as likely to be current smokers as nonpregnant women (prevalence ratio, 0.7; 95% confidence interval, 0.6 to 0.8), while blacks showed the largest pregnancy-associated reduction in the prevalence of smoking (prevalence ratio, 0.5; 95% confidence interval, 0.3 to 0.9). Most of the difference in smoking prevalence occurred not because pregnant women were less likely to have ever smoked, but because pregnant women were more likely to have quit smoking than nonpregnant women. However, unmarried pregnant white women were 40% more likely to smoke than their nonpregnant counterparts (prevalence ratio, 1.4; 95% confidence interval, 1.1 to 1.7). We conclude from this analysis that the 1990 health objective for smoking among pregnant women is unlikely to be achieved. Clinicians providing care to pregnant women need to pay increased attention to smoking cessation.
Follow-up of anti HCV +VE chronic liver disease (CLD) after IFN treatment. Response to retreatement
Authors: R. Pérez, R. Pravia, A. Linares, M. Rodríguez, J.L.S. Lombrana, A. Suárez, S. Riostra, C.A. Navascués, N.G. Sotorrío, L. Rodrigo
Journal: Journal of Hepatology (1991)