tbuckley/cabot-search huggingface dataset:
THE PRODUCTION OF VESICULAR STOMATITIS VIRUS BY ANTIGEN- OR MITOGEN-STIMULATED LYMPHOCYTES AND CONTINUOUS LYMPHOBLASTOID LINES
Authors: Maja Nowakowski, Joseph D. Feldman, Shogo Kano, Barry R. Bloom
Journal: The Journal of Experimental Medicine (1973)

A variety of lymphoid cell populations were examined in terms of their ability to replicate vesicular stomatitis virus (VSV), a lytic, RNA-containing virus maturing at the cell surface. The number of cells capable of producing VSV was estimated in terms of infectious centers by the virus plaque assay (VPA), and morphologically by electron microscopy (EM). The lymphoid cells examined in this study included: (a) lymph node cells from delayed hypersensitive guinea pigs stimulated by specific antigen, (b) mouse spleen cells activated by selective bone marrow-derived (B) cell and thymus derived (T) cell mitogens, and (c) cells of human and murine continuous lymphoblastoid or lymphoma lines. In unstimulated cultures of guinea pig lymph node cells there is a background of approximately 1 in 1,000 cells which produces VSV; in purified protein derivative (PPD)-stimulated cultures the number of cells producing virus was 1.6% in the VPA and 1.9% by EM. These cells were large lymphocytes with some morphological features of transformed lymphocytes but were not typical blast cells. A few macrophages were associated with virus in both stimulated and control cultures. These observations indicate that (a) cells responsive to antigens, as detected by a marker virus, were lymphocytes; (b) cells other than lymphocytes (macrophages) were capable of replicating VSV even without antigenic stimulation; and (c) the correlation of results obtained by VPA and morphologic examination was usually quite good. Of the total number of mouse spleen cells stimulated with concanavalin (Con A), a T cell mitogen, 4.5 (EM)-5.7% (VPA) were associated with VSV. These were characteristic transformed lymphocytes, similar to phytohemagglutinin (PHA)-stimulated human lymphocytes. In contrast Escherichia coli lipopolysaccharide (LPS)-treated mouse spleen cultures contained lower numbers of virus plaque-forming cells. The majority of such cells associated with virus displayed extensive rough endoplasmic reticulum. Two cultured murine lymphomas containing lymphocytes with the theta surface marker (L5178Y and EL-4) showed a 15-100-fold higher incidence of virus-producing cells than leukemias (L1210 and C57Bl/6) which did not carry this marker. Similarly, the L2C guinea pig leukemia, a known B cell leukemia, yielded a low percent of virus plaque-forming cells (<2%). However, MOPC-104, a plasma cell tumor presumed to be of B cell origin, was found to be an efficient virus producer. There was a wide variation in the efficiency of VSV replication among human lymphoblastoid lines. One line, Wil-2, produced 80% infectious centers after 24 h of exposure to VSV, and all cells were associated with virus at the EM level. The relationship between the virus-producing cells and different lymphocyte subpopulations as well as the efficiency of the two assays for studying virus-producing lymphocytes is discussed.
Difference in the Use of Terms: Isotope-Based, Surface-Mold Brachytherapy vs Electronic Surface Brachytherapy
Authors: June K. Robinson
Journal: JAMA Dermatology (2015)

Allison L. Goddard, MD; Ruth Ann Vleugels, MD, MPH; Nicole R. LeBoeuf, MD, MPH; Desmond A. O’Farrell, MSc, DABR; Robert A. Cormack, PhD; Jorgen L. Hansen, MS; Thomas S. Kupper, MD; Phillip M. Devlin, MD
TORCH Study: How Much Longer Should We Continue to Use Erlotinib in Unselected Patients With Non–Small-Cell Lung Cancer?
Authors: Vito Lorusso, Nicola Silvestris, Ilaria Marech
Journal: Journal of Clinical Oncology (2012)

consideration in this article.Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated.
The serotonin transporter, gender, and 17 oestradiol in the development of pulmonary arterial hypertension
Authors: K. White, Y. Dempsie, M. Nilsen, A. F. Wright, L. Loughlin, M. R. MacLean
Journal: Cardiovascular Research (2010)

Idiopathic and familial forms of pulmonary arterial hypertension (PAH) predominantly affect females through an unknown mechanism. Activity of the serotonin transporter (SERT) may modulate the development of PAH, and mice overexpressing SERT (SERT+ mice) develop PAH and severe hypoxia-induced PAH. In the central nervous system, oestrogens influence activity of the serotonin system. Therefore, we examined the influence of gender on the development of PAH in SERT+ mice and how this is modulated by female hormones. PAH was assessed via measurement of right ventricular systolic pressure (RVSP), pulmonary vascular remodelling (PVR), and right ventricular hypertrophy. Male SERT+ mice did not develop PAH. Female SERT+ mice demonstrated increased RVSP and PVR and this was abolished by ovariectomy. Following exposure to hypoxia, SERT+ mice exhibited severe PAH and this was also attenuated by ovariectomy. Chronic administration of 17β oestradiol re-established the PAH phenotype in ovariectomized, normoxic, and hypoxic SERT+ mice. 17β oestradiol also up-regulated tryptophan hydroxylase-1 (TPH1), 5-hydroytryptamine1B (5-HT1B) receptor, and SERT expression in human pulmonary arterial smooth muscle cells (hPASMCs). 17β oestradiol stimulated hPASMC proliferation and this was inhibited by both the TPH inhibitor para-chlorophenylalanine and the 5-HT1B receptor antagonist SB224289. 17β oestradiol is critical to the development of PAH and severe hypoxia-induced PAH in female SERT+ mice. In hPASMCs, 17β oestradiol-induced proliferation is dependant on de novo serotonin synthesis and stimulation of the 5-HT1B receptor. These interactions between the serotonin system and 17β oestradiol may contribute to the increased risk of PAH associated with female gender.
Molecular aspects on the interaction of protoberberine, benzophenanthridine, and aristolochia group of alkaloids with nucleic acid structures and biological perspectives
Authors: Motilal Maiti, Gopinatha Suresh Kumar
Journal: Medicinal Research Reviews (2006)

Abstract Alkaloids occupy an important position in chemistry and pharmacology. Among the various alkaloids, berberine and coralyne of the protoberberine group, sanguinarine of the benzophenanthridine group, and aristololactam‐β‐ d ‐glucoside of the aristolochia group have potential to form molecular complexes with nucleic acid structures and have attracted recent attention for their prospective clinical and pharmacological utility. This review highlights (i) the physicochemical properties of these alkaloids under various environmental conditions, (ii) the structure and functional aspects of various forms of deoxyribonucleic acid (DNA) (B‐form, Z‐form, H L ‐form, protonated form, and triple helical form) and ribonucleic acid (RNA) (A‐form, protonated form, and triple helical form), and (iii) the interaction of these alkaloids with various polymorphic DNA and RNA structures reported by several research groups employing various analytical techniques like absorbance, fluorescence, circular dichroism, and NMR spectroscopy; electrospray ionization mass spectrometry, thermal melting, viscosity, and DNase footprinting as well as molecular modeling and thermodynamic studies to provide detailed binding mechanism at the molecular level for structure–activity relationship. Nucleic acids binding properties of these alkaloids are interpreted in relation to their biological activity. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 649–695, 2007
CXCL13 and CCL11 Serum Levels and Lymphoma and Disease Activity in Primary Sjögren's Syndrome
Authors: G. Nocturne, R. Seror, O. Fogel, R. Belkhir, S. Boudaoud, A. Saraux, C. Larroche, V. Le Guern, J. E. Gottenberg, X. Mariette
Journal: Arthritis & Rheumatology (2015)

Non-Hodgkin's lymphoma (NHL) is a severe complication of primary Sjögren's syndrome (SS). Ectopic germinal centers (GCs) in the salivary glands are predictors of the occurrence of NHL. Given the association between CCL11 and CXCL13 and ectopic GCs, we assessed the link between these chemokines and NHL, as well as the association between these chemokines and disease activity, in patients with primary SS.Serum levels of CCL11 and CXCL13 were evaluated by multiplex assay in 385 patients included in the Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort. The association between chemokine levels, B cell biomarkers, and patient subsets was assessed using Spearman's test for continuous data and the nonparametric Mann-Whitney U test for categorical data. Multivariate analyses were performed to identify parameters associated with lymphoma and disease activity.Seventeen patients had a history of lymphoma, and 5 of them had developed NHL during followup. The median serum levels of CCL11 and CXCL13 in the total cohort were 106.48 pg/ml (interquartile range 69.33-149.85) and 108.31 pg/ml (interquartile range 58.88-200.13), respectively. Patients with lymphoma had higher levels of CXCL13 than did patients without lymphoma (P = 0.006) and a trend toward a higher level of CCL11 (P = 0.056). Low C4 and high BAFF levels were associated with NHL on multivariate analysis (P = 0.01 and P = 0.0002, respectively). CCL11 and CXCL13 levels correlated positively with the rheumatoid factor titer, the κ-to-λ free light chain ratio, and the β2 -microglubulin level. CXCL13 was the only parameter associated with disease activity on multivariate analysis.These findings demonstrate a link between CXCL13 and CCL11 and disease activity and lymphoma. This highlights the continuum between chronic B cell activation, disease activity, and lymphomagenesis in patients with primary SS.
US casino boss challenges Spain's smoking ban
Authors: A. Garcia Rada
Journal: BMJ (2013)

A US gambling magnate is challenging Spain’s laws banning smoking in enclosed public spaces by demanding that tobacco consumption be allowed in the casino that he plans to build in Madrid. It is predicted to be the largest gambling resort in Europe.

Sheldon Adelson, chairman of the Las Vegas Sands Corporation, a Nevada based casino and resort operating company, and the 12th richest American according to the Forbes list, announced his latest project earlier this year. It was promptly dubbed EuroVegas, because …
Genome sequence and global sequence variation map with 5.5 million SNPs in Chinese rhesus macaque
Authors: Xiaodong Fang, Yanfeng Zhang, Rui Zhang, Lixin Yang, Ming Li, Kaixiong Ye, Xiaosen Guo, Jun Wang, Bing Su
Journal: Genome biology (2011)

Rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate animal in biomedical research. A global map of genetic variations in rhesus macaque is valuable for both evolutionary and functional studies. Using next-generation sequencing technology, we sequenced a Chinese rhesus macaque genome with 11.56-fold coverage. In total, 96% of the reference Indian macaque genome was covered by at least one read, and we identified 2.56 million homozygous and 2.94 million heterozygous SNPs. We also detected a total of 125,150 structural variations, of which 123,610 were deletions with a median length of 184 bp (ranging from 25 bp to 10 kb); 63% of these deletions were located in intergenic regions and 35% in intronic regions. We further annotated 5,187 and 962 nonsynonymous SNPs to the macaque orthologs of human disease and drug-target genes, respectively. Finally, we set up a genome-wide genetic variation database with the use of Gbrowse. Genome sequencing and construction of a global sequence variation map in Chinese rhesus macaque with the concomitant database provide applicable resources for evolutionary and biomedical research.
Cytochrome P450 Subfamily 2J Polypeptide 2 Expression and Circulating Epoxyeicosatrienoic Metabolites in Preeclampsia
Authors: Florian Herse, Babbette LaMarca, Carl A. Hubel, Tea Kaartokallio, A. Inkeri Lokki, Eeva Ekholm, Hannele Laivuori, Martin Gauster, Berthold Huppertz, Meryam Sugulle, Michael J. Ryan, Sarah Novotny, Justin Brewer, Joon-Keun Park, Michael Kacik, Joachim Hoyer, Stefan Verlohren, Gerd Wallukat, Michael Rothe, Friedrich C. Luft, Dominik N. Muller, Wolf-Hagen Schunck, Anne C. Staff, Ralf Dechend
Journal: Circulation (2012)

Preeclampsia is a multisystem disorder of pregnancy, originating in the placenta. Cytochrome P450 (CYP)-dependent eicosanoids regulate vascular function, inflammation, and angiogenesis, which are mechanistically important in preeclampsia.We performed microarray screening of placenta and decidua (maternal placenta) from 25 preeclamptic women and 23 control subjects. The CYP subfamily 2J polypeptide 2 (CYP2J2) was upregulated in preeclamptic placenta and decidua. Reverse-transcription polymerase chain reaction confirmed the upregulation, and immunohistochemistry localized CYP2J2 in trophoblastic villi and deciduas at 12 weeks and term. The CYP2J2 metabolites, 5,6-epoxyeicosatrienoic acid (EET), 14,15-EET, and the corresponding dihydroxyeicosatrienoic acids, were elevated in preeclamptic women compared with controls in the latter two thirds of pregnancy and after delivery. Stimulating a trophoblast-derived cell line with the preeclampsia-associated cytokine tumor necrosis factor-α enhanced CYP2J2 gene and protein expression. In 2 independent rat models of preeclampsia, reduced uterine-perfusion rat and the transgenic angiotensin II rat, we observed elevated EET, dihydroxyeicosatrienoic acid, and preeclamptic features that were ameliorated by the CYP epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MsPPOH). Uterine arterial rings of these rats also dilated in response to MsPPOH. Furthermore, 5,6-EET could be metabolized to a thromboxane analog. In a bioassay, 5,6-EET increased the beating rate of neonatal cardiomyocytes. Blocking thromboxane synthesis reversed that finding and also normalized large-conductance calcium-activated potassium channel activity.Our data implicate CYP2J2 in the pathogenesis of preeclampsia and as a potential candidate for the disturbed uteroplacental remodeling, leading to hypertension and endothelial dysfunction.
Induction of Labor versus Expectant Management in Women with Preterm Prelabor Rupture of Membranes between 34 and 37 Weeks: A Randomized Controlled Trial
Authors: David P. van der Ham, Sylvia M. C. Vijgen, Jan G. Nijhuis, Johannes J. van Beek, Brent C. Opmeer, Antonius L. M. Mulder, Rob Moonen, Mariët Groenewout, Mariëlle G. van Pampus, Gerald D. Mantel, Kitty W. M. Bloemenkamp, Wim J. van Wijngaarden, Marko Sikkema, Monique C. Haak, Paula J. M. Pernet, Martina Porath, Jan F. M. Molkenboer, Simone Kuppens, Anneke Kwee, Michael E. Kars, Mallory Woiski, Martin J. N. Weinans, Hajo I. J. Wildschut, Bettina M. C. Akerboom, Ben W. J. Mol, Christine Willekes
Journal: PLoS Medicine (2012)

Background At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term. Methods and Findings We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34+0 and 37+0 wk of gestation. Participants were randomly allocated in a 1∶1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate. From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported. Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM. Conclusions In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM. Trial registration Current Controlled Trials ISRCTN29313500 Please see later in the article for the Editors' Summary
Pseudogenes Contribute to the Extreme Diversity of Nuclear Ribosomal DNA in the Hard Coral Acropora
Authors: L. M. Marquez
Journal: Molecular Biology and Evolution (2003)

One characteristic of Indo-Pacific Acropora spp. is extremely high diversity in rDNA sequences at both the species and individual levels. In order to test the hypothesis that pseudogenes may contribute to this diversity, three kinds of analyses were conducted. First, for A. millepora (the species containing the most diverse suite of rDNA types), RT-PCR was used to determine which 5.8S rDNA types are expressed. Second, as previous studies have indicated that interspecific hybridization has occurred in the genus Acropora and silencing of rDNA loci via nucleolar dominance has been shown in some cases to involve methylation, patterns of variation were examined at methylation-susceptible sites. Third, patterns of substitution at conserved sites (including those that are likely to contribute to secondary structure in rRNA) in the 5.8S rDNA were examined. These analyses consistently indicated that one rDNA sequence type present in a broad range of Indo-Pacific Acropora species is likely to consist predominantly of pseudogenes. Patterns of variation also suggest that species may differ with respect to which rDNA sequence types have been silenced and which are active. These pseudogenes are likely to have arisen as a consequence of the introduction of highly divergent rDNA types into single genomes by interspecific hybridization events, and we attribute the extreme rDNA diversity characteristic of many Acropora species to both the independent evolution of these silenced rDNA types and to the suppressive effects of high sequence diversity on homogenization processes acting on functional loci.
Splice Variant Specific Modulation of Ca <sub>V</sub> 1.2 Calcium Channel by Galectin-1 Regulates Arterial Constriction
Authors: Juejin Wang, Sharon S.C. Thio, Sophia S.H. Yang, Dejie Yu, Chye Yun Yu, Yuk Peng Wong, Ping Liao, Shengnan Li, Tuck Wah Soong
Journal: Circulation Research (2011)

Ca(V)1.2 channels are essential for excitation-contraction coupling in the cardiovascular system, and alternative splicing optimizes its role. Galectin-1 (Gal-1) has been reported to regulate vascular smooth muscle cell (VSMC) function and play a role in pulmonary hypertension. We have identified Gal-1 multiple times in yeast 2-hybrid assays using the Ca(V)1.2 I-II loop as bait.Our hypothesis is that Gal-1 interacts directly with Ca(V)1.2 channel at the I-II loop to affect arterial constriction.Unexpectedly, Gal-1 was found to selectively bind to the I-II loop only in the absence of alternatively spliced exon 9*. We found that the current densities of Ca(V)1.2(Δ9*) channels were significantly inhibited as a result of decreased functional surface expression due to the binding of Gal-1 at the export signal located on the C-terminus of exon 9. Moreover, the suppression of Gal-1 expression by siRNA in rat A7r5 and isolated VSMCs produced the opposite effect of increased I(Ca,L). The physiological significance of Gal-1 mediated splice variant-specific inhibition of Ca(V)1.2 channels was demonstrated in organ bath culture where rat MAs were reversibly permeabilized with Gal-1 siRNA and the arterial wall exhibited increased K(+)-induced constriction.The above data indicated that Gal-1 regulates I(Ca,L) via decreasing the functional surface expression of Ca(V)1.2 channels in a splice variant selective manner and such a mechanism may play a role in modulating vascular constriction.
Effect of Tumor Promoters on Cell Kinetics in Mouse Epidermis
Authors: O. S. Frankfurt, Eugenia Raitcheva
Journal: JNCI Journal of the National Cancer Institute (1972)

Tumor promoters (Tween-60 and croton oil) were applied on normal mouse skin and skin initiated by 7,12-dimethylbenz[a]anthracene a month previously. The proliferative response in treated epidermis was estimated by the use of autoradiography with 3H-thymidine. The number of cells synthesizing DNA in the basal layer increased 12 hours after application of tumor promoters and was highly elevated for 72 hours. DNA-synthesizing cells also appeared among mature cells. The labeling index for basal cells in initiated epidermis was significantly higher than in normal epidermis 12–16 hours after application of tumor promoters. During the period of active proliferation, the mitotic cycle, as estimated by the method of labeled mitoses, was 10 hours, both in normal and initiated epidermis, i.e., 8 times shorter than in normal, unstimulated epidermis. Cell maturation, as measured by transition of labeled cells from the basal layer into the layer of spinous cells, was accelerated in the epidermis stimulated by tumor promoters. Cell number/1 mm of epidermis did not change significantly during the first hours after application of tumor promoters, but rose thereafter because of elevation in the number of mature cells. This el evation tended to be more pronounced in initiated skin. It is hypothesized that the action of tumor promoters on initiated epidermis leads to the selection of cells with shortened G1 phase, which may be associated with weakened response to the factors regulating cell proliferation.