tbuckley/cabot-search huggingface dataset:
Pulmonary Veins and Ligament of Marshall as Sources of Rapid Activations in a Canine Model of Sustained Atrial Fibrillation
Authors: Tsu-Juey Wu, James J. C. Ong, Che-Ming Chang, Rahul N. Doshi, Masaaki Yashima, Hsun-Lun A. Huang, Michael C. Fishbein, Chih-Tai Ting, Hrayr S. Karagueuzian, Peng-Sheng Chen
Journal: Circulation (2001)

Background —In dogs, chronic rapid pacing may result in sustained atrial fibrillation (AF). However, activation patterns in pacing-induced sustained AF are unclear. Methods and Results —We induced sustained AF (&gt;48 hours) in 6 dogs by rapid pacing for 139±84 days. We then performed computerized atrial epicardial mappings and recorded the activations in the ligament of Marshall (LOM) and the pulmonary veins (PVs). During AF, mean activation cycle length in the right atrial free wall (126±17 ms) was significantly longer than that in the left atrial free wall (96±5 ms, P =0.006). In addition, mean activation cycle length in the left atrial free wall was significantly longer than that in the LOM (84±5 ms, P &lt;0.001), the left inferior PV (81±4 ms, P =0.001), and the left superior PV (85±7 ms, P =0.003). Similarly, the dominant frequency was highest in the LOM and the PVs (range 11.2 to 13.3 Hz), followed by the left and right atria ( P &lt;0.001). In all dogs studied, rapid and complicated electrograms were consistently observed at the LOM and the PVs. During AF, both wandering wavelets and organized reentry were present. There were more wave fronts in the left atrium than in the right atrium ( P &lt;0.001). Conclusions —In chronic pacing-induced sustained AF, the LOM and the PVs are the sources of rapid activations. The mechanism by which the left atrium activates faster and has more wave fronts than the right atrium may relate to the fact that the left atrium is closer to the sources of rapid activations.
Copy Number Aberrations in Benign Serous Ovarian Tumors: A Case for Reclassification?
Authors: Sally M. Hunter, Michael S. Anglesio, Raghwa Sharma, C. Blake Gilks, Nataliya Melnyk, Yoke-Eng Chiew, Anna deFazio, Teri A. Longacre, David G. Huntsman, Kylie L. Gorringe, Ian G. Campbell
Journal: Clinical Cancer Research (2011)

Serous ovarian carcinomas are the predominant epithelial ovarian cancer subtype and it has been widely believed that some or all of these may arise from precursors derived from the ovarian surface epithelium or fimbriae, although direct molecular evidence for this is limited. This study aimed to conduct copy number (CN) analysis using a series of benign and borderline serous ovarian tumors to identify underlying genomic changes that may be indicative of early events in tumorigenesis.High resolution CN analysis was conducted on DNA from the epithelial and fibroblast components of a cohort of benign (N = 39) and borderline (N = 24) serous tumors using the Affymetrix OncoScan assay and SNP6.0 arrays.CN aberrations were detected in the epithelium of only 2.9% (1 of 35) of serous cystadenomas and cystadenofibromas. In contrast, CN aberrations were detected in the epithelium of 67% (16 of 24) of the serous borderline tumors (SBT). Unexpectedly, CN aberrations were detected in the fibroblasts of 33% (13 of 39) of the benign serous tumors and in 15% (3 of 20) of the SBTs. Of the 16 cases with CN aberrations in the fibroblasts, 12 of these carried a gain of chromosome 12.Chromosome 12 trisomy has been previously identified in pure fibromas, supporting the concept that a significant proportion of benign serous tumors are in fact primary fibromas with an associated cystic mass. This is the first high resolution genomic analysis of benign serous ovarian tumors and has shown not only that the majority of benign serous tumors have no genetic evidence of epithelial neoplasia but that a significant proportion may be more accurately classified as primary fibromas.
Multiple Nuclear Insertions of Mitochondrial Cytochrome b Sequences in Callitrichine Primates
Authors: Nicholas I. Mundy, Alcides Pissinatti, David S. Woodruff
Journal: Molecular Biology and Evolution (2000)

We report the presence of four nuclear paralogs of a 380-bp segment of cytochrome b in callitrichine primates (marmosets and tamarins). The mitochondrial cytochrome b sequence and each nuclear paralog were obtained from several species, allowing multiple comparisons of rates and patterns of substitution both between mitochondrial and nuclear sequences and among nuclear sequences. The mitochondrial DNA had high overall rates of molecular evolution and a strong bias toward substitutions at third codon positions. Rates of molecular evolution among the nuclear sequences were low and constant, and there were small differences in substitution patterns among the nuclear clades which were probably attributable to the small number of sites involved. A novel method of phylogenetic reconstruction based on the large difference in rates of evolution at different codon positions among mitochondrial and nuclear clades was used to determine whether different nuclear paralogs represent independent transposition events or duplications following a single insertion. This method is generally applicable in cases where differences in pattern of molecular evolution are known, and it showed that at least three of the four nuclear clades represent independent transposition events. The insertion events giving rise to two of the nuclear clades predate the divergence of the callitrichines, whereas those leading to the other two nuclear clades may have occurred in the common ancestor of marmosets.
Murine Cytotoxic T Lymphocytes Recognize an Epitope in an EBNA-1 Fragment, but Fail to Lyse EBNA-1–expressing Mouse Cells
Authors: Siddhartha Mukherjee, Pankaj Trivedi, David M. Dorfman, George Klein, Alain Townsend
Journal: The Journal of Experimental Medicine (1998)

Major histocompatibility complex class I–restricted cytotoxic T lymphocytes (CTLs) specific for epitopes within eight of the nine Epstein Barr Virus (EBV)-encoded latency-associated proteins have been recovered from EBV-infected human subjects by restimulation of lymphocytes in vitro. However, human class I–restricted CTL responses capable of recognizing EBNA-1 expressing cells were not detected in these studies. We have raised a murine CTL line that recognizes an epitope within EBNA-1 by immunizing mice with a vaccinia virus encoding a COOH-terminal EBNA-1 fragment. This novel CTL line was used to investigate whether the epitope (positions 509–517 in EBNA-1, presented through Kd) was presented to CTL by mouse cells expressing full-length EBNA-1 or a deletion mutant of EBNA-1, lacking the Glycine-Alanine (Gly-Ala)–rich region. Cells expressing full-length EBNA-1 are not lysed by the CTL line, whereas cells expressing the Gly-Ala deletion mutant are recognized. These results suggest that epitopes from full-length EBNA-1 are poorly presented, and that the Gly-Ala–rich region is responsible for this phenomenon. The inefficient presentation of EBNA-1–derived epitopes may explain the absence or rarity of EBNA-1–specific CTLs in vivo, a strategy that may allow EBV to maintain persistence within the immunocompetent host without being eliminated by CTLs.
The impact of dermoscopy on the management of pigmented lesions in everyday clinical practice of general dermatologists: a prospective study
Authors: J.I. Van Der Rhee, W. Bergman, N.A. Kukutsch
Journal: British Journal of Dermatology (2009)

Journal Article The impact of dermoscopy on the management of pigmented lesions in everyday clinical practice of general dermatologists: a prospective study Get access J.I. Van Der Rhee, J.I. Van Der Rhee Department of Dermatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands Jasper van der Rhee. E‐mail: j.i.van_der_rhee@lumc.nl Search for other works by this author on: Oxford Academic Google Scholar W. Bergman, W. Bergman Department of Dermatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar N.A. Kukutsch N.A. Kukutsch Department of Dermatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 3, 1 March 2010, Pages 563–567, https://doi.org/10.1111/j.1365-2133.2009.09551.x Published: 01 March 2010
nalyot, a Mutation of the Drosophila Myb-Related Adf1 Transcription Factor, Disrupts Synapse Formation and Olfactory Memory
Authors: James DeZazzo, David Sandstrom, Steve de Belle, Klara Velinzon, Patrick Smith, Lori Grady, Maria DelVecchio, Mani Ramaswami, Tim Tully
Journal: Neuron (2000)
Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure
Authors: Jason Moore, Amy Jayne McKnight, Bernd Döhler, Matthew J. Simmonds, Aisling E. Courtney, Oliver J. Brand, David Briggs, Simon Ball, Paul Cockwell, Christopher C. Patterson, Alexander P. Maxwell, Stephen C.L. Gough, Gerhard Opelz, Richard Borrows
Journal: Journal of the American Society of Nephrology (2012)

The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20–2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21–2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08–3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.
Tumoral Calcinosis in England
Authors: G. Slavin, L. Klenerman, A. Darby, S. Bansal
Journal: BMJ (1973)

Two cases of tumoral calcinosis are presented in patients living in England. The clinical and pathological features are described and attention is drawn to the need to consider exotic diseases in patients who have originated from or lived in the tropics.The cause of tumoral calcinosis is not known. It may be a metabolic disease of obscure aetiology but local trauma often appears to be a factor in its development.
A Novel Test for Selection on cis-Regulatory Elements Reveals Positive and Negative Selection Acting on Mammalian Transcriptional Enhancers
Authors: Justin D. Smith, Kimberly F. McManus, Hunter B. Fraser
Journal: Molecular Biology and Evolution (2013)

Measuring natural selection on genomic elements involved in the cis-regulation of gene expression—such as transcriptional enhancers and promoters—is critical for understanding the evolution of genomes, yet it remains a major challenge. Many studies have attempted to detect positive or negative selection in these noncoding elements by searching for those with the fastest or slowest rates of evolution, but this can be problematic. Here, we introduce a new approach to this issue, and demonstrate its utility on three mammalian transcriptional enhancers. Using results from saturation mutagenesis studies of these enhancers, we classified all possible point mutations as upregulating, downregulating, or silent, and determined which of these mutations have occurred on each branch of a phylogeny. Applying a framework analogous to Ka/Ks in protein-coding genes, we measured the strength of selection on upregulating and downregulating mutations, in specific branches as well as entire phylogenies. We discovered distinct modes of selection acting on different enhancers: although all three have experienced negative selection against downregulating mutations, the selection pressures on upregulating mutations vary. In one case, we detected positive selection for upregulation, whereas the other two had no detectable selection on upregulating mutations. Our methodology is applicable to the growing number of saturation mutagenesis data sets, and provides a detailed picture of the mode and strength of natural selection acting on cis-regulatory elements.
Histamine and DNA Synthesis as Age-Related and Strain-Related Factors During Rat Mammary Carcinogenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: P. Jackson Schad, Douglas H. Janss
Journal: JNCI Journal of the National Cancer Institute (1980)

The incorporation of [3H]thymidine into DNA in mammary glands of inbred virgin SD and LEJ rats was studied to evaluate proliferative changes of the mammary parenchyma in the rats at reported ages of varying sensitivity to 7,12-dimethylbenz[a]anthracene (DMBA) carcinogenesis. Animals were monitored at 50, 57, 65, 80, 95, and 120 days of age during either estrus or diestrus and on days 25 and 35 before estrous cycles began. In SD rats, DNA synthesis increased at day 50 (estrus) and day 80 (diestrus). Elevated DNA synthesis on day 50 correlated with the reported age of maximal sensitivity to DMBA. In contrast, LEJ rats exhibited only one growth period, day 80 (diestrus). Low levels of DNA synthesis in 50-day-old LEJ rats agreed with the age of minimal sensitivity to DMBA known for this strain. Furthermore, mammary gland concentrations of histamine, a diamine that reportedly facilitates estradiol-stimulated growth of the rat uterus, were measured. Whereas LEJ rat mammary glands exhibited low histamine amounts at all ages, SD rat mammary glands had increases in histamine on day 50, an observation that correlated with elevated DNA synthesis and the age of maximal DMBA sensitivity. As a test of whether histamine influenced DNA synthesis, 50-day-old SD rats received a single ip injection of either diphenhydramine or burimamide (7 mg/kg body wt), antihistamine drugs acting, respectively, on histamine H1 or H2 receptors. Diphenhydramine elicited declines in both histamine amounts and the rate of DNA synthesis 24 hours later, whereas burimamide exerted no observable effect. These findings suggested that 1) the mammary epithelium of the 50-day-old SD rat exhibited H1 receptor histamine activity and 2) histamine participated in the SD rat mammary gland as an intermediate in the regulation of cell proliferation on day 50, the age of maximal susceptibility of this strain to DMBA.
Enzymatic function of nitric oxide synthases
Authors: P Andrew
Journal: Cardiovascular Research (1999)

Nitric oxide (NO) is synthesised from l-arginine by the enzyme NO synthase (NOS). The complex reaction involves the transfer of electrons from NADPH, via the flavins FAD and FMN in the carboxy-terminal reductase domain, to the haem in the amino-terminal oxygenase domain, where the substrate l-arginine is oxidised to l-citrulline and NO. The haem is essential for dimerisation as well as NO production. The pteridine tetrahydrobiopterin (BH4) is a key feature of NOS, affecting dimerisation and electron transfer, although its full role in catalysis remains to be determined. NOS can also catalyse superoxide anion production, depending on substrate and cofactor availability. There are three main isoforms of the enzyme, named neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS), which differ in their dependence on Ca2+, as well as in their expression and activities. These unique features give rise to the distinct subcellular localisations and mechanistic features which are responsible for the physiological and pathophysiological roles of each isoform.
Study of Etanercept, a Tumor Necrosis Factor-Alpha Inhibitor, in Recurrent Ovarian Cancer
Authors: Srinivasan Madhusudan, Sethupathi R. Muthuramalingam, Jeremy P. Braybrooke, Susan Wilner, Kulwinder Kaur, Cheng Han, Susan Hoare, Frances Balkwill, Trivadi S. Ganesan
Journal: Journal of Clinical Oncology (2005)

Convincing data support the link between inflammation and ovarian cancer. Tumor necrosis factor-alpha (TNF-alpha), a major mediator of inflammation, is chronically produced in the ovarian tumor microenvironment and may enhance tumor growth and invasion by inducing the secretion of cytokines, proangiogenic factors, and metalloproteinases. Etanercept is a recombinant human soluble p75 TNF receptor that binds to TNF-alpha and renders it biologically unavailable. In the current study, we sought to determine the toxicity, biologic activity, and therapeutic efficacy of etanercept in recurrent ovarian cancer.We initiated a phase I-B, nonrandomized, open-label study in patients with recurrent ovarian cancer. Etanercept was administered subcutaneously at a dose of 25 mg twice weekly (cohort one) and 25 mg thrice weekly (cohort two) until disease progression.Thirty patients were recruited (cohort one, 17 patients; cohort two, 13 patients). Eighteen of the 30 patients (cohort one, 11 patients; cohort two, seven patients) completed > or = 12 weeks of treatment. Six patients achieved prolonged disease stabilization (cohort one, two patients [40 and 25 weeks]; cohort two, four patients [34, 24, 22, and 24 weeks]). A significant rise in immunoreactive TNF was seen in all patients (pretreatment compared with end of treatment). A phytohemagglutinin-stimulated whole-blood cytokine assay showed a significant fall in interleukin-6 (cohort one [11 of 17]) and CCL2 (cohort one [13 of 17]) levels. Common adverse effects were injection-site reactions and fatigue.We provide evidence for the biologic activity and safety of etanercept in recurrent ovarian cancer. Our data suggest possible clinical activity that must be confirmed in future studies.
Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus.
Authors: M Hogan, A Cerami, R Bucala
Journal: Journal of Clinical Investigation (1992)

Advanced glycosylation endproducts (AGEs) accumulate on long-lived tissue proteins such as basement membrane collagen and have been implicated in many of the long-term complications of diabetes mellitus. These products originate from glucose-derived Schiff base and Amadori products but undergo a series of complex rearrangement reactions to form ultimately protein-bound, fluorescent heterocycles. AGEs can react with and chemically inactivate nitric oxide (NO), a potent endothelial cell-derived vasodilator and antiproliferative factor. Since mesenchymal cell proliferation is an early and characteristic lesion of diabetic vasculopathy and glomerulopathy, we investigated the possibility that collagen-bound AGEs functionally inactivate the antiproliferative effect of NO. In model cell culture systems, AGEs were found to block the cytostatic effect of NO on aortic smooth muscle and renal mesangial cells. The inactivation of endothelial cell-derived NO by basement membrane AGEs may represent a common pathway in the development of the accelerated vascular and renal disease that accompany long-term diabetes mellitus.
Neurophysiological dysfunction in young women with intractable constipation.
Authors: J S Varma, A N Smith
Journal: Gut (1988)

Fifteen women with intractable chronic idiopathic constipation dating from adolescence were investigated by anorectal manometry, neurophysiological evaluation of the conus medullaris and external anal sphincter. Comparison was made with 25 asymptomatic female control subjects. Urological disturbances were common amongst the constipated, in five of whom incidental lumbosacral spinal dysraphism was found. No differences in sphincter pressures or the rectosphincteric reflex were demonstrable between the two groups. Rectal defecatory sensation was blunted and the compliance was increased in the constipated group. The latency of the pudendo-anal reflex was significantly prolonged in idiopathic constipation, two women having an absent reflex (greater than 100 ms). Mean motor unit potential duration of the external anal sphincter was not significantly prolonged in the eight constipated women tested. A central neurogenic deficit is postulated in some women with this disorder.
Tandem autotransplant as first-line consolidative treatment in poor-risk aggressive lymphoma: A pilot study of 36 patients
Authors: C. Haioun, N. Mounier, B. Quesnel, P. Morel, C. Rieux, F. Beaujean, J.-P. Marolleau, K. Belhadj, D. Simon, Ph. Gaulard, E. Lepage, Ch. Gisselbrecht, F. Reyes
Journal: Annals of Oncology (2001)
Catalytic Subunit of Human Telomerase Reverse Transcriptase Is an Independent Predictor of Survival in Patients Undergoing Curative Resection of Hepatic Colorectal Metastases: A Multicenter Analysis
Authors: Julien Dômont, Timothy M. Pawlik, Valérie Boige, Mathieu Rose, Jean-Christophe Weber, Paulo M. Hoff, Thomas D. Brown, Daria Zorzi, Luc Morat, Jean-Pierre Pignon, Asif Rashid, Daniel Jaeck, Laure Sabatier, Dominique Elias, Thomas Tursz, Jean-Charles Soria, Jean-Nicolas Vauthey
Journal: Journal of Clinical Oncology (2005)

Purpose To determine the role of the catalytic subunit of human telomerase reverse transcriptase (hTERT) in predicting survival after resection of hepatic colorectal metastases (CRM). Patients and Methods Two hundred one patients who underwent curative resection of hepatic CRM between 1990 and 2000 were identified from a multicenter database. The CRM were analyzed for hTERT nucleolar expression by standard immunohistochemical techniques. hTERT expression and known clinicopathologic factors of survival were examined. Results With a median follow-up of 80 months, 152 patients (75.6%) had died; the 5-year overall survival was 30.7%. On univariate analysis, number of metastases greater than two (P = .0005), extrahepatic disease (P = .0054), disease-free interval less than 12 months (P = .006), carcinoembryonic antigen level greater than 200 ng/mL (P = .0071), and positive hTERT nucleolar staining (P &lt; .0001) were associated with decreased survival. On multivariate analysis, three factors independently predicted survival: number of metastases (relative risk [RR] = 1.74; P = .0011); disease-free interval (RR = 1.70; P = .0035); and positive hTERT nucleolar staining (RR = 2.03; P &lt; .0001). Patients with none or one of these factors had a 5-year survival rate of 48%, whereas those with two or three of these factors had a 5-year survival of 15% (P &lt; .0001). Conclusion hTERT nucleolar expression is associated with worse survival after resection of hepatic CRM. hTERT expression in conjunction with number of hepatic metastases and disease-free interval may permit more accurate prediction of survival after resection of hepatic CRM.