tbuckley/cabot-search huggingface dataset:
Compositional Evolution of Noncoding DNA in the Human and Chimpanzee Genomes
Authors: M. T. Webster
Journal: Molecular Biology and Evolution (2003)

We have examined the compositional evolution of noncoding DNA in the primate genome by comparison of lineage-specific substitutions observed in 1.8 Mb of genomic alignments of human, chimpanzee, and baboon with 6542 human single-nucleotide polymorphisms (SNPs) rooted using chimpanzee sequence. The pattern of compositional evolution, measured in terms of the numbers of GC→AT and AT→GC changes, differs significantly between fixed and polymorphic sites, and indicates that there is a bias toward fixation of AT→GC mutations, which could result from weak directional selection or biased gene conversion in favor of high GC content. Comparison of the frequency distributions of a subset of the SNPs revealed no significant difference between GC→AT and AT→GC polymorphisms, although AT→GC polymorphisms in regions of high GC segregate at slightly higher frequencies on average than GC→AT polymorphisms, which is consistent with a fixation bias favoring high GC in these regions. However, the substitution data suggest that this fixation bias is relatively weak, because the compositional structure of the human and chimpanzee genomes is becoming homogenized, with regions of high GC decreasing in GC content and regions of low GC increasing in GC content. The rate and pattern of nucleotide substitution in 333 Alu repeats within the human-chimpanzee-baboon alignments are not significantly affected by the GC content of the region in which they are inserted, providing further evidence that, since the time of the human-chimpanzee ancestor, there has been little or no regional variation in mutation bias.
Gene Transfer of NAD(P)H Oxidase Inhibitor to the Vascular Adventitia Attenuates Medial Smooth Muscle Hypertrophy
Authors: Jianhua Liu, Adrian Ormsby, Nancy Oja-Tebbe, Patrick J. Pagano
Journal: Circulation Research (2004)

We previously showed that a systemic inhibitor of gp91(phox) (nox2)-based NAD(P)H oxidase abolishes angiotensin II (Ang II)-induced vascular hypertrophy. In the present study, we tested whether perivascular transfection with Ad-gp91ds-eGFP (an adenoviral bicistronic construct targeting NAD(P)H oxidase in fibroblasts) or controls Ad-CMV-eGFP and Ad-scrmb-eGFP would affect medial hypertrophy in response to Ang II. In C57BL/6J mice, we applied Ad-gp91ds-eGFP or controls to the left carotid adventitia, and 2 days later we implanted minipumps delivering vehicle or Ang II (750 microg/kg per day) for 7 days. None of the viral treatments affected Ang II-induced systolic blood pressure elevation. Immunohistochemical staining showed marker eGFP in adventitial fibroblasts and some macrophages, indicating expression of the gp91ds inhibitor. As expected, Ang II induced medial hypertrophy (medial cross-sectional area, 32.96+/-2.04 versus 20.57+/-1.00x10(3) microm2, Ang II versus control; P<0.001) that was significantly inhibited by Ad-gp91ds-eGFP (26.23+/-0.90x10(3) microm2; P<0.01) but not control viruses. Application of viruses alone did not change medial size under control conditions. Immunohistochemical staining and semiquantitative analysis showed a 70% increase in reactive oxygen species levels measured by the lipid peroxidation byproduct 4-hydroxynonenal (4-HNE) throughout the carotid wall in the Ang II group versus vehicle. After treatment with Ad-gp91ds-eGFP, 4-HNE generation was normalized. Thus NAD(P)H oxidases in adventitial fibroblasts and macrophages appear to modulate Ang II-induced medial hypertrophy.
Esophageal Motility Studies in the Evaluation of Hiatal Hernia.
Authors: Maurice L. Kelley
Journal: Annals of Internal Medicine (1965)

s1 May 1965Esophageal Motility Studies in the Evaluation of Hiatal Hernia.Maurice L. Kelley Jr., M.D., F.A.C.P.Maurice L. Kelley Jr., M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1079_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe purpose of this report is to describe and illustrate the three roles fulfilled by intraluminal manometric esophageal studies in the evaluation of patients with small sliding hiatal hernia. Pressures are measured under resting conditions and after swallowing at each 0.5-cm segment of the esophagus and its sphincters by a miniature balloon and two open-tip polyethylene tubes separated by 5 cm connected to pressure transducers and recorded photokymographically.The detection of small hiatal hernias is not disclosed by radiologic and endoscopic examinations. These pressure indicators include excessive length of the gastroesophageal sphincter, double (rather than a single) zones of increased... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Maurice L. KelleyJr., M.D., F.A.C.P.Affiliations: Rochester, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1079-1080KeywordsEsophagusGastroenterology and hepatologyHerniaSwallowing ePublished: 1 December 2008 Issue Published: 1 May 1965 PDF downloadLoading ...
Development of a disease specific questionnaire to measure health related quality of life in patients with chronic liver disease
Authors: Z M Younossi, G Guyatt, M Kiwi, N Boparai, D King
Journal: Gut (1999)

BACKGROUND AND AIMS To develop and assess a disease specific instrument for measuring health related quality of life (HRQL) in patients with chronic liver disease (CLD). METHODS Based on responses from 60 patients with chronic liver disease, from 20 liver experts, and from a Medline search of the literature, items potentially affecting the HRQL of these patients were identified. A separate sample of 75 patients identified which items they found problematic and rated their importance. Results were explored using factor analysis; domains were chosen and items placed within domains. Redundant questions were eliminated and the final questionnaire was pretested in 10 patients. Using this instrument, HRQL was assessed in a further 133 patients with various types and stages of liver disease. RESULTS Patients, experts, and the literature search identified 156 items of potential importance. Of these, 35 proved important to over 50% of 75 respondents in the item reduction sample. The factor analysis suggested six domains. After eliminating redundancies, the Chronic Liver Disease Questionnaire (CLDQ) included 29 items in the following domains: fatigue, activity, emotional function, abdominal symptoms, systemic symptoms, and worry. In pretesting, patients found the CLDQ clear and easy to complete in 10 minutes. In another 133 patients, the CLDQ showed a gradient between patients without cirrhosis, Child’s A cirrhosis, and those with Child’s B or C cirrhosis. CLDQ has evidence for moderate reliability at six months and seems to be responsive. CONCLUSION The CLDQ is short, easy to administer, produces both a summary score and domain scores, and correlates with the severity of liver disease.
Atypical pulmonary tuberculosis
Authors: Wiam Elkhattabi, Abdelaziz Aichane, Zineb Berrada, Hicham Afif, Zoubida Bouayad
Journal: European Respiratory Journal (2012)

Introduction: Tuberculosis remains a common disease, but despite this, it is often diagnosed with long delay due to some atypical presentations. The aim of our work is to know unusual shapes because they may pose problems of differential diagnosis especially with malignant diseases.

Methods: We report 50 cases of pulmonary tuberculosis atypical between 2000 and 2009: 15 cases of endobronchial tuberculosis, 16 cases with basal localization and 19 cases of pseudotumoral form.

Results: The average age is 37 years. Smoking is found in 17 cases and diabetes in 12 cases. The clinical picture is dominated by bronchial syndrome. The chest rays show basal opacity in 16 cases, a pseudo-tumoral opacity in 19 cases and a retractile opacity in 15 cases. Bronchoscopy visualizes endobronchial granuloma in 6 cases, tumor buds in 5 cases andbronchial stenosis with extrinsic compression in 8 cases. CT show suspected tissular process in 19 cases, mediastinal lymphadenopathy associated in 11 cases and alveolar opacity in 5 cases. Pulmonary tuberculosis is confirmed by bacteriology in 23 cases, bronchial biopsies in 8 cases, transmural biopsy in 7 cases, by thoracotomy in 6 cases and by lymph node biopsy in 2 cases. Antibacillary treatment was prescribed in all cases with good evolution in 36 cases (72%).

Conclusions: Pulmonary tuberculosis may mimic atypical, mainly malignancy hence the interest to recognize its various unusual shapes.
Activation of Intracisternal A Particles in Mouse Liver by Diethylnitrosamine2
Authors: Hisashi Shinozuka, Larry W. Estes
Journal: JNCI Journal of the National Cancer Institute (1977)

Livers of 6- to 7-week-old male C3H/He, CBA, A, and BALB/c mice were examined by electron microscopy for the presence of intracisternal A particles (ICAP) after administration of diethylnitrosamine (DEN) in drinking water. In control mice, ICAP were extremely rare; they were found in the livers of only 2 mice (strains C3H/He and A; none in the other strains). By contrast, the treatment of mice with DEN greatly enhanced the aepearance of ICAP in the liver cells of all strains. Within 2 weeks of the treatment, ICAP were found in 8–26% of liver cells examined in all mice and the number of ICAP/cell ranged from 3 to 12. Aside from mild disorganization of the rough endoplasmic reticulum, such as segmentation and vesiculation, liver cells of carcinogentreated mice showed none of the consistent abnormalities that characterize the appearance of ICAP. The reactivation of ICAP (which are usually suppressed in adult mice) by DEN may become a useful marker for analysis of the sequential alterations of the liver that lead to the development of hepatoma during carcinogenesis.
Autologous stem-cell transplantation as consolidation therapy for diffuse large B-cell lymphoma patients with overexpression of bcl-2 protein. Results of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial LNH98-B2
Authors: P. Morel, P. Gaulard, C. Gisselbrecht, C. Ferme, G. Salles, H. Tilly, J. Brière, M.C. Copin, P. Lederlin, O. Hermine, I. Theate, C. Haioun, N. Mounier
Journal: Annals of Oncology (2007)

BackgroundOverexpression of B-cell lymphoma 2 (bcl-2) protein is a simple biological adverse prognostic factor that could delimit the poor prognosis population candidate for improvement with high-dose therapy and autologous stem-cell transplantation (ASCT) in diffuse large B-cell lymphoma (DLBCL). Therefore, we conducted a risk-adapted phase II study with ASCT as consolidation therapy in low-intermediate risk (LIR) International Prognostic Index patients aged ≤60 years with bcl-2 overexpression (bcl-2+).Patients and methodsInduction chemotherapy consisted of four courses of adriamycin, cyclophosphamide, vindesine, bleomycin, prednisone, once every 2 weeks. Responding bcl-2+ patients received ASCT as consolidation, and those without bcl-2 overexpression (bcl-2-) conventional chemotherapy. Three hundred and sixteen LIR patients with DLBCL, aged between 18 and 60 years, were included. Of these, 177 (56%) were bcl-2+ and 139 (44%) bcl-2-.ResultsComplete response rates after induction chemotherapy were similar in bcl-2+ and bcl-2- patients (74% versus 78%). Estimated 2-year event-free survival and disease-free survival for the bcl-2+ subgroup were 79% and 87%, for bcl-2- 84% and 92% and for the whole series 81% and 90%, respectively.ConclusionsThese results demonstrate that taking into account biological characteristics in prospective multicenter trials allow successful adjustment of treatment and indicate that ASCT may counteract the adverse prognostic value of bcl-2 overexpression in responding LIR patients.
A transient outward potassium current activator recapitulates the electrocardiographic manifestations of Brugada syndrome
Authors: K. Calloe, J. M. Cordeiro, J. M. Di Diego, R. S. Hansen, M. Grunnet, S. P. Olesen, C. Antzelevitch
Journal: Cardiovascular Research (2008)

Transient outward potassium current (I(to)) is thought to be central to the pathogenesis of the Brugada syndrome (BrS). However, an I((to)) activator has not been available with which to validate this hypothesis. Here, we provide a direct test of the hypothesis using a novel I(to) activator, NS5806.Isolated canine ventricular myocytes and coronary-perfused wedge preparations were used. Whole-cell patch-clamp studies showed that NS5806 (10 microM) increased peak I(to) at +40 mV by 79 +/- 4% (24.5 +/- 2.2 to 43.6 +/- 3.4 pA/pF, n = 7) and slowed the time constant of inactivation from 12.6 +/- 3.2 to 20.3 +/- 2.9 ms (n = 7). The total charge carried by I(to) increased by 186% (from 363.9 +/- 40.0 to 1042.0 +/- 103.5 pA x ms/pF, n = 7). In ventricular wedge preparations, NS5806 increased phase 1 and notch amplitude of the action potential in the epicardium, but not in the endocardium, and accentuated the ECG J-wave, leading to the development of phase 2 re-entry and polymorphic ventricular tachycardia (n = 9). Although sodium and calcium channel blockers are capable of inducing BrS only in right ventricular (RV) wedge preparations, the I(to) activator was able to induce the phenotype in wedges from both ventricles. NS5806 induced BrS in 4/6 right and 2/10 left ventricular wedge preparations.The I(to) activator NS5806 recapitulates the electrographic and arrhythmic manifestation of BrS, providing evidence in support of its pivotal role in the genesis of the disease. Our findings also suggest that a genetic defect leading to a gain of function of I(to) could explain variants of BrS, in which ST-segment elevation or J-waves are evident in both right and left ECG leads.
Nutritional content of supermarket ready meals and recipes by television chefs in the United Kingdom: cross sectional study
Authors: S. Howard, J. Adams, M. White
Journal: BMJ (2012)

<b>Objectives</b> To compare the energy and macronutrient content of main meals created by television chefs with ready meals sold by supermarkets, and to compare both with nutritional guidelines published by the World Health Organization and UK Food Standards Agency. <b>Design</b> Cross sectional study. <b>Setting</b> Three supermarkets with the largest share of the grocery market in the United Kingdom, 2010. <b>Samples</b> 100 main meal recipes from five bestselling cookery books by UK television chefs and 100 own brand ready meals from the three leading UK supermarkets. <b>Main outcome measures</b> Number of meals for which the nutritional content complied with WHO recommendations, and the proportion of nutrients classified as red, amber, or green using the UK FSA's "traffic light" system for labelling food. <b>Results</b> No recipe or ready meal fully complied with the WHO recommendations. The ready meals were more likely to comply with the recommended proportions of energy derived from carbohydrate (18% <i>v</i> 6%, P=0.01) and sugars (83% v 81%, P=0.05) and fibre density (56% <i>v</i> 14% P&lt;0.01). The recipes were more likely to comply with the recommended sodium density (36% <i>v</i> 4%, P&lt;0.01), although salt used for seasoning was not assessed. The distributions of traffic light colours under the FSA's food labelling recommendations differed: the modal traffic light was red for the recipes (47%) and green for ready meals (42%). Overall, the recipes contained significantly more energy (2530 kJ <i>v</i> 2067 kJ), protein (37.5 g <i>v</i> 27.9 g), fat (27.1 g <i>v</i> 17.2 g), and saturated fat (9.2 g <i>v</i> 6.8 g; P&lt;0.01 for all) and significantly less fibre (3.3 g <i>v </i>6.5 g, P&lt;0.01) per portion than the ready meals. <b>Conclusions</b> Neither recipes created by television chefs nor ready meals sold by three of the leading UK supermarkets complied with WHO recommendations. Recipes were less healthy than ready meals, containing significantly more energy, protein, fat, and saturated fat, and less fibre per portion than the ready meals.
The Origins of Eukaryotic Gene Structure
Authors: Michael Lynch
Journal: Molecular Biology and Evolution (2005)

Most of the phenotypic diversity that we perceive in the natural world is directly attributable to the peculiar structure of the eukaryotic gene, which harbors numerous embellishments relative to the situation in prokaryotes. The most profound changes include introns that must be spliced out of precursor mRNAs, transcribed but untranslated leader and trailer sequences (untranslated regions), modular regulatory elements that drive patterns of gene expression, and expansive intergenic regions that harbor additional diffuse control mechanisms. Explaining the origins of these features is difficult because they each impose an intrinsic disadvantage by increasing the genic mutation rate to defective alleles. To address these issues, a general hypothesis for the emergence of eukaryotic gene structure is provided here. Extensive information on absolute population sizes, recombination rates, and mutation rates strongly supports the view that eukaryotes have reduced genetic effective population sizes relative to prokaryotes, with especially extreme reductions being the rule in multicellular lineages. The resultant increase in the power of random genetic drift appears to be sufficient to overwhelm the weak mutational disadvantages associated with most novel aspects of the eukaryotic gene, supporting the idea that most such changes are simple outcomes of semi-neutral processes rather than direct products of natural selection. However, by establishing an essentially permanent change in the population-genetic environment permissive to the genome-wide repatterning of gene structure, the eukaryotic condition also promoted a reliable resource from which natural selection could secondarily build novel forms of organismal complexity. Under this hypothesis, arguments based on molecular, cellular, and/or physiological constraints are insufficient to explain the disparities in gene, genomic, and phenotypic complexity between prokaryotes and eukaryotes.
XBP1 governs late events in plasma cell differentiation and is not required for antigen-specific memory B cell development
Authors: Derrick J. Todd, Louise J. McHeyzer-Williams, Czeslawa Kowal, Ann-Hwee Lee, Bruce T. Volpe, Betty Diamond, Michael G. McHeyzer-Williams, Laurie H. Glimcher
Journal: The Journal of Experimental Medicine (2009)

The unfolded protein response (UPR) is a stress response pathway that is driven by the increased load of unfolded proteins in the endoplasmic reticulum of highly secretory cells such as plasma cells (PCs). X box binding protein 1 (XBP1) is a transcription factor that mediates one branch of the UPR and is crucial for the development of antibody-secreting PCs. PCs represent only one class of terminally differentiated B cells, however, and little is known about the role for XBP1 in the other class: memory B cells. We have developed an XBP1fl/fl CD19+/cre conditional knockout (XBP1CD19) mouse to build upon our current understanding of the function of XBP1 in PC differentiation as well as to explore the role of XBP1 in memory cell development. Using this model, we show that XBP1CD19 mice are protected from disease in an autoantibody-mediated mouse lupus model. We also identify a novel developmental stage at which B cells express the traditional PC marker CD138 (syndecan-1) but have yet to undergo XBP1-dependent functional and morphological differentiation into antibody-secreting cells. Finally, we show that memory B cells develop normally in XBP1CD19 mice, demonstrating that XBP1-mediated functions occur independently of any memory cell lineage commitment.
Endogenous Vascular Endothelial Growth Factor-C Expression Is Associated with Decreased Drug Responsiveness in Childhood Acute Myeloid Leukemia
Authors: Hendrik J.M. de Jonge, Alida C. Weidenaar, Arja ter Elst, H. Marike Boezen, Frank J.G. Scherpen, Jessica C.A. Bouma-ter Steege, Gertjan J.L. Kaspers, Bianca F. Goemans, Ursula Creutzig, Martin Zimmermann, Willem A. Kamps, Eveline S.J.M. de Bont
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We hypothesized that downstream effects of endogenous vascular endothelial growth factor (VEGF)/VEGF receptor signaling on acute myelogenous leukemia (AML) cell survival resulted in increased in vitro cellular drug resistance and a longer time to kill most leukemic cells in vivo upon drug exposure. Experimental Design: In primary AML cells from pediatric patients, VEGFA and VEGFC mRNA expression and in vitro cellular resistance to nine cytotoxic drugs were studied. As in vivo equivalents for in vitro drug resistance, in vivo AML blast reduction upon drug exposure, measured as blast cell reduction on day 15 in the bone marrow and as time in days from diagnosis to complete remission (CR) were used. Results: Increased endogenous VEGFC levels significantly correlated with increased in vitro resistance for six typical AML drugs in primary AML cells from pediatric patients. Patients with &amp;gt;5% blasts on day 15 showed a 12.9-fold increase in the median VEGFC level compared with patients with ≤5% blasts (P = 0.002). Time to reach CR was studied using linear regression analysis with VEGFC, age at diagnosis, sex, treatment protocol, FAB type, cytogenetic risk profile, and WBC counts as variables. There was a significant positive independent association between VEGFC levels and time to CR (b = 6.02, SE = 1.58, P ≤ 0.0001, n = 72). Conclusions: These results suggest for the first time that higher endogenous VEGFC levels of AML cells are related to decreased in vitro and in vivo drug responsiveness.
Low Microsatellite Instability Is Associated With Poor Prognosis in Stage C Colon Cancer
Authors: Maija R.J. Kohonen-Corish, Joseph J. Daniel, Charles Chan, Betty P.C. Lin, Sun Young Kwun, Owen F. Dent, Varinderpal S. Dhillon, Ronald J.A. Trent, Pierre H. Chapuis, E. Leslie Bokey
Journal: Journal of Clinical Oncology (2005)

The significance of low microsatellite instability (MSI-L) in colorectal cancer is poorly understood. No clear biologic distinction has been found between MSI-L and microsatellite stable (MSS) colorectal cancer, and these two phenotypes are usually combined when analyzed against the well-defined high MSI (MSI-H) phenotype. Evidence is emerging that an O(6)-methylguanine DNA methyltransferase (MGMT) gene defect is associated with MSI-L. Therefore, to further define this phenotype, we undertook a detailed analysis of the prognostic significance of MSI-L and loss of MGMT expression in colon cancer.The study cohort was 183 patients with clinicopathologic stage C colon cancer who had not received adjuvant therapy. We analyzed MSI status, MGMT, and mismatch repair protein expression, as well as MGMT and p16 promoter hypermethylation.We showed that MSI-L defines a group of patients with poorer survival (P = .026) than MSS patients, and that MSI-L was an independent prognostic indicator (P = .005) in stage C colon cancer. Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival.MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.