tbuckley/cabot-search huggingface dataset:
Isolation, partial characterization, and localization of a rat renal tubular glycoprotein antigen. Antibody-induced birth defects.
Authors: C C Leung
Journal: The Journal of Experimental Medicine (1982)

A glycoprotein with an apparent 340,000 mol wt (gp 340K) was isolated from rat kidney saline-soluble extract by ammonium sulfate precipitation, DE 52 ion-exchange cellulose chromatography, concanavalin A affinity column, Sephacryl S-300 gel filtration, and discontinuous polyacrylamide gel electrophoresis (PAGE). The relative purity of gp 340K was examined by double immunodiffusion analysis, disc PAGE, and immunoelectrophoresis. Injection of rabbit gp 340K antiserum into pregnant rats during the organogenetic period induced abnormal embryonic development, fetal growth retardation, and embryonic death. Antiserum against the immunocomplexes isolated by immobilized protein A also produced the same embryotoxic effects. The biologic effects of the antisera appeared to be dose dependent. Defects such as anophthalmia, hydrocephaly, exencephaly, cleft palate, cleft lip, and some cardiovascular anomalies were observed. The most frequently observed anomaly was anophthalmia. Immunofluorescent localization studies indicated that gp 340K antibodies localized in vivo in the visceral yolk-sac endodermal cells and the embryonic endoderm. In vitro immunofluorescent localization studies revealed that gp 340K was a component of the renal tubular cells that cross-reacted with antigen in the visceral yolk-sac endodermal cells and embryonic endoderm. The underlying mechanism whereby gp 340K antibodies induce birth defects is not known. Three hypotheses were discussed.
Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial
Authors: Gordon JS Rustin, Maria EL van der Burg, Clare L Griffin, David Guthrie, Alan Lamont, Gordon C Jayson, Gunnar Kristensen, César Mediola, Corneel Coens, Wendi Qian, Mahesh KB Parmar, Ann Marie Swart
Journal: The Lancet (2010)
Role of glycosyltransferase PomGnT1 in glioblastoma progression
Authors: J. Lan, P. Guo, Y. Lin, Q. Mao, L. Guo, J. Ge, X. Li, J. Jiang, X. Lin, Y. Qiu
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is the most aggressive and invasive brain tumor, for which novel prognostic markers and predictors of therapeutic response are urgently needed. We reported previously that levels of peptide-O-linked mannose β-1,2-N-acetylglucosaminyltransferase 1 (PomGnT1) in glioma specimens correlated with tumor grade. However, the prognostic significance of PomGnT1 in glioma patients and its function in GBM progression remain unknown.Clinical relevance of PomGnT1 in GBM patients' prognosis was analyzed both in a clinically annotated expression dataset of 446 GBM tumor specimens and in 82 GBM tumor samples collected at our institution. The function of PomGnT1 in glioma growth and invasion, and the underlying mechanisms of PomGnT1 regulation were explored in vitro and in vivo.PomGnT1 expression in GBM tissues was closely associated with poor prognosis in GBM patients. Forced overexpression of PomGnT1 in glioblastoma cells impaired cell adhesion and increased their proliferation and invasion in vitro. Subsequent in vivo experiments showed that overexpression of PomGnT1 promoted tumor growth and shortened the survival time of tumor-bearing mice in an orthotopic model. Conversely, stable short hairpin RNA-mediated knockdown of PomGnT1 expression produced opposite effects both in vitro and in vivo. Mechanistic studies revealed that activation of epidermal growth factor receptor (EGFR) resulted in EGFR/extracellular signal-regulated kinase-dependent upregulation of PomGnT1, downregulation of receptor-type protein tyrosine phosphatase β, and activation of β-catenin pathway signaling.These findings suggest that PomGnT1 promotes GBM progression via activation of β-catenin and may serve as a prognostic factor for glioma patient survival as well as a novel molecular target for anticancer therapy in malignant glioma.
HUMAN MILK GLYCANS PROTECT INFANTS AGAINST ENTERIC PATHOGENS
Authors: David S. Newburg, Guillermo M. Ruiz-Palacios, Ardythe L. Morrow
Journal: Annual Review of Nutrition (2005)

Breastfed infants have lower morbidity and mortality due to diarrhea than those fed artificially. This had been attributed primarily to the secretory antibodies and prebiotic factors in human milk. Oligosaccharides are the third largest component of human milk. They were initially considered to be functionless by-products of glycoprotein and glycolipid synthesis during milk production. However, in the past few decades it has become apparent that the human milk oligosaccharides are composed of thousands of components, at least some of which protect against pathogens. Oligosaccharide protection against infectious agents may result in part from their prebiotic characteristics, but is thought to be primarily due to their inhibition of pathogen binding to host cell ligands. Most human milk oligosaccharides are fucosylated, and their production depends on enzymes encoded by the genes associated with expression of the Lewis blood group system. The expression of specific fucosylated oligosaccharides in milk thus varies in relation to maternal Lewis blood group type, and is significantly associated with the risk of infectious disease in breastfed infants. Specific fucosylated moieties of oligosaccharides and related glycoconjugates (glycans) are able to inhibit binding and disease by specific pathogens. This review presents the argument that specific glycans, especially the oligosaccharides, are the major constituent of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. The large input of energy expended by the mother in the synthesis of milk oligosaccharides is consistent with the human reproductive strategy of large parental input into rearing relatively few offspring through a prolonged period of maturation. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit diseases caused by mucosal pathogens.
Accuracy of Pulse Oximetry in Sickle Cell Disease
Authors: FELIPE O. ORTIZ, THOMAS K. ALDRICH, RONALD L. NAGEL, LENNETTE J. BENJAMIN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Pulmonary complications and hypoxemia are common in sickle cell disease (SCD) and may exacerbate microvascular occlusive phenomena. Thus, detecting hypoxemia is of particular importance in SCD. To assess the accuracy of pulse oximetry in the diagnosis of hypoxemia in SCD, we compared 22 pulse oximetric measurements of arterial oxygen saturation (SpO2 ) in adult patients with SCD and acute vasoocclusive crisis with simultaneously drawn arterial saturation (SaO2 = oxyhemoglobin divided by oxyhemoglobin plus reduced hemoglobin) measured by co-oximetry. We accepted SpO2 readings only if they were stable and characterized by strong and regular photoplethysmographic waves on the oximeter screen. To assess the position of these patients' oxyhemoglobin dissociation curves, we plotted arterial and venous oxygen saturation (SaO2 and SvO2 ) against oxygen tension. We found right-shifted oxyhemoglobin dissociation curves, with pH-corrected p50s ranging from 28 to 38 mm Hg. Pulse oximetry slightly overestimated oxyhemoglobin percentage (by an average of 3.4 percentage points), but it almost always accurately estimated SaO2 (underestimating on average by 1.1 percentage points). The error in SpO2 was never enough to classify a hypoxemic patient erroneously as normoxemic or a normoxemic patient as hypoxemic. We conclude that, as long as strong and regular photoplethysmographic waves are present, pulse oximeters can be relied upon not to misdiagnose either hypoxemia or normoxemia in SCD.
Systemic inflammation and cardiovascular risk factors predict rapid progression of atherosclerosis in rheumatoid arthritis
Authors: Inmaculada del Rincón, Joseph F Polak, Daniel H O'Leary, Daniel F Battafarano, John M Erikson, Jose F Restrepo, Emily Molina, Agustín Escalante
Journal: Annals of the Rheumatic Diseases (2014)

Objective To estimate atherosclerosis progression and identify influencing factors in rheumatoid arthritis (RA). Methods We used carotid ultrasound to measure intima-media thickness (IMT) in RA patients, and ascertained cardiovascular (CV) risk factors, inflammation markers and medications. A second ultrasound was performed approximately 3 years later. We calculated the progression rate by subtracting the baseline from the follow-up IMT, divided by the time between the two scans. We used logistic regression to identify baseline factors predictive of rapid progression. We tested for interactions of erythrocyte sedimentation rate (ESR) with CV risk factors and medication use. Results Results were available for 487 RA patients. The mean (SD) common carotid IMT at baseline was 0.571 mm (0.151). After a mean of 2.8 years, the IMT increased by 0.050 mm (0.055), p≤0.001, a progression rate of 0.018 mm/year (95% CI 0.016 to 0.020). Baseline factors associated with rapid progression included the number of CV risk factors (OR 1.27 per risk factor, 95% CI 1.01 to 1.61), and the ESR (OR 1.12 per 10 mm/h, 95% CI 1.02 to 1.23). The ESR×CV risk factor and ESR×medication product terms were significant, suggesting these variables modify the association between the ESR and IMT progression. Conclusions Systemic inflammation and CV risk factors were associated with rapid IMT progression. CV risk factors may modify the role of systemic inflammation in determining IMT progression over time. Methotrexate and antitumour necrosis factor agents may influence IMT progression by reducing the effect of the systemic inflammation on the IMT.
Splenic sequestration associated with sickle cell trait and hereditary spherocytosis
Authors: Yih‐Ming Yang, Cynthia Donnell, Walter Wilborn, Steven R. Goodman, Bea Files, R. Blaine Moore, Narla Mohandas, Vipul N. Mankad
Journal: American Journal of Hematology (1992)

Abstract Coexistence of sickle cell trait and hereditary spherocytosis (HS) is unusual, and only 16 cases have been reported in the literature. These patients have the same clinical and hematological features as individuals having HS alone. We report a serious complication, acute splenic sequestration crisis (ASSC), occurring in two patients with sickle cell trait and HS. One patient experienced four episodes of ASSC during an 11‐year span, while the other had two episodes of this complication during a 4‐year period. Red blood cell studies and membrane protein analysis confirmed the diagnosis of HS as a consequence of spectrin deficiency. Splenectomy resulted in marked clinical and hematological improvement in both patients. Histological examination of spleens following splenectomy confirmed that significant erythrostasis and sickling had indeed occurred. ASSC can occur in patients with coexistence of sickle cell trait and HS, and this potentially life‐threatening complication should be considered in this condition. © 1992 Wiley‐Liss, Inc.
NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8+ T cells
Authors: Andreas Kupz, Greta Guarda, Thomas Gebhardt, Leif E Sander, Kirsty R Short, Dimitri A Diavatopoulos, Odilia L C Wijburg, Hanwei Cao, Jason C Waithman, Weisan Chen, Daniel Fernandez-Ruiz, Paul G Whitney, William R Heath, Roy Curtiss, Jürg Tschopp, Richard A Strugnell, Sammy Bedoui
Journal: Nature Immunology (2012)
Exercise in Maintenance Hemodialysis Patients Induces Transcriptional Changes in Genes Favoring Anabolic Muscle
Authors: Joel D. Kopple, Huiyuan Wang, Richard Casaburi, Mario Fournier, Michael I. Lewis, Wayne Taylor, Thomas W. Storer
Journal: Journal of the American Society of Nephrology (2007)

Exercise training increases exercise capacity of maintenance hemodialysis patients, but the cellular mechanisms responsible for this effect are unclear. We studied the effects of different forms of exercise training (endurance, strength, or a combination where patients underwent about one-half each
Lymphocytic Lymphoma of Intermediate Differentiation: Morphologic, Immunophenotypic, and Prognostic Factors
Authors: M. A. Bookman, P. Lardelli, E. S. Jaffe, P. L. Duffey, D. L. Longo
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Lymphocytic Lymphoma of Intermediate Differentiation: Morphologic, Immunophenotypic, and Prognostic Factors Get access Michael A. Bookman, Michael A. Bookman Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Pilar Lardelli, Pilar Lardelli Laboratory of Pathology, Division of Cancer Treatment, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Elaine S. Jaffe, Elaine S. Jaffe Laboratory of Pathology, Division of Cancer Treatment, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia L. Duffey, Patricia L. Duffey Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan L. Longo Dan L. Longo * Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer InstituteBethesda, MD * Correpondence to: Dan L. Longo, M.D., Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research Facility, Bldg. 567, Rm. 135, Frederick, MD 21701. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 9, 2 May 1990, Pages 742–748, https://doi.org/10.1093/jnci/82.9.742 Published: 02 May 1990
Evolution of Mutation Rates: Phylogenomic Analysis of the Photolyase/Cryptochrome Family
Authors: J. I. Lucas-Lledo, M. Lynch
Journal: Molecular Biology and Evolution (2009)

Photoreactivation, one of the first DNA repair pathways to evolve, is the direct reversal of premutagenic lesions caused by ultraviolet (UV) irradiation, catalyzed by photolyases in a light-dependent, single-enzyme reaction. It has been experimentally shown that photoreactivation prevents UV mutagenesis in a broad range of species. In the absence of photoreactivation, UV-induced photolesions are repaired by the more complex and much less efficient nucleotide excision repair pathway. Despite their obvious beneficial effects, several lineages, including placental mammals, lost photolyase genes during evolution. In this study, we ask why photolyase genes have been lost in those lineages and discuss the significance of these losses in the context of the evolution of the genomic mutation rates. We first perform an extensive phylogenomic analysis of the photolyase/cryptochrome family, to assess what species lack each kind of photolyase gene. Then, we estimate the ratio of nonsynonymous to synonymous substitution rates in several groups of photolyase genes, as a proxy of the strength of purifying natural selection, and we ask whether less evolutionarily constrained photolyase genes are more likely lost. We also review functional data and compare the efficiency of different kinds of photolyases. We find that eukaryotic photolyases are, on average, less evolutionarily constrained than eubacterial ones and that the strength of natural selection is correlated with the affinity of photolyases for their substrates. We propose that the loss of photolyase genes in eukaryotic species may be due to weak natural selection and may result in a deleterious increase of their genomic mutation rates. In contrast, the loss of photolyase genes in prokaryotes may not cause an increase in the mutation rate and be neutral in most cases.
Differential Gene Expression in Ovarian Tumors Reveals <i>Dusp 4</i> and <i>Serpina 5</i> As Key Regulators for Benign Behavior of Serous Borderline Tumors
Authors: Nathalie L.G. Sieben, Jan Oosting, Adrienne M. Flanagan, Jaime Prat, Guido M.J.M. Roemen, Sandra M. Kolkman-Uljee, Ronald van Eijk, Cees J. Cornelisse, Gert Jan Fleuren, Manon van Engeland
Journal: Journal of Clinical Oncology (2005)

Purpose Ovarian serous borderline tumors (SBT) are characterized by arborizing papillae lined by stratified epithelial cells, varying atypia, and absence of stromal invasion. Originally, these tumors have been classified as borderline because they behaved in a remarkably indolent manner, even with widespread tumor deposits called implants and the presence of lymph node involvement. The molecular biology of these lesions has just begun to be explored. High prevalence of B-RAF/K-RAS mutations in SBTs in contrast to serous carcinomas (SCAs) indicates that the mitogenic RAS-RAF-MEK-ERK-MAP kinase pathway is crucial for the pathogenesis of SBTs. The purpose of this study was to further unravel the genetic pathways through which SBTs develop, with a special focus on explaining the generally benign SBT behavior. Materials and Methods We generated RNA expression profiles of 38 ovarian serous neoplasms. Global Test pathway analysis and significance analysis of microarrays (SAM) of the expression profiles was performed. Results SAM and Global Testing showed that although the mitogenic pathway is activated in SBTs, activation of downstream genes involved in extracellular matrix (ECM) degradation is absent, suggesting an uncoupling of both events. In addition, we show that two genes involved in regulating this uncoupling, ERK-inhibitor Dusp 4 and uPA-inhibitor Serpina 5, are downregulated in SCAs in contrast to SBTs. In SCAs, this was associated with downstream MMP-9 activation at both mRNA and protein level. Conclusion We propose that the putative tumor suppressor genes Dusp 4 and Serpina 5 provide a major clue to the indolent behavior of SBTs.
CREB/ATF-dependent T cell receptor–induced <i>FoxP3</i> gene expression: a role for DNA methylation
Authors: Hyoung-Pyo Kim, Warren J. Leonard
Journal: The Journal of Experimental Medicine (2007)

Regulatory T cells (T reg cells) are a population of CD4+ T cells that limit immune responses. FoxP3 is a master control transcription factor for development and function of these cells, but its regulation is poorly understood. We have identified a T cell receptor–responsive enhancer in the FoxP3 first intron that is dependent on a cyclic-AMP response element binding protein (CREB)/activating transcription factor (ATF) site overlapping a CpG island. Methylation of this island inversely correlates with CREB binding and FoxP3 expression. Interestingly, transforming growth factor-β, which induces T reg cell formation, decreases methylation of the CpG island and increases FoxP3 expression. Similarly, inhibiting methylation with 5-azacytidine or knocking down the DNA methyltransferase Dnmt1 also induces FoxP3 expression. Conversely, methylation of the CpG island, which decreases CREB binding or expression of dominant-negative CREB, decreases FoxP3 gene expression. Thus, T cell receptor–induced FoxP3 expression in T reg cells is controlled both by sequence-specific binding of CREB/ATF and by DNA methylation of a CpG island.
Ankylosing spondylitis monocytes show upregulation of proteins involved in inflammation and the ubiquitin proteasome pathway
Authors: C Wright, M Edelmann, K diGleria, S Kollnberger, H Kramer, S McGowan, K McHugh, S Taylor, B Kessler, P Bowness
Journal: Annals of the Rheumatic Diseases (2008)

To determine if peripheral blood monocytes from patients with ankylosing spondylitis (AS) differed in protein expression compared to rheumatoid arthritis (RA) and healthy controls (HC).Monocyte protein expression was characterised by 2D gel electrophoresis and by label-free quantitative expression profiling, using nano-ultra performance liquid chromatography coupled to electrospray ionisation mass spectrometry (ESI-MS(E), where (E) refers to low/high collision energy switching). Data sets were analysed using the Waters expression profiling system and Ingenuity pathway analysis (IPA).Two-dimensional gel electrophoresis showed upregulation of proteasomal constituents in AS monocytes, including the beta subunit of proteasome activator (PA)28. Monocyte expression profiling and IPA showed that significant changes in protein expression within the ubiquitin proteasome pathway (UPP) were restricted to AS monocytes. Statistically significant differences in protein expression involving the leucocyte extravasation, vascular endothelial growth factor, integrin and Toll-like receptor signalling pathways were seen in AS and RA monocytes compared to healthy controls. No evidence of upregulation of proteins involved in the endoplasmic reticulum stress response pathway was found in either AS or RA monocytes. Finally, the PA28 complex was shown to increase the generation of human leucocyte antigen (HLA)-B27 antigenic epitopes by the proteasome in vitro.Our proteomic analyses support the hypothesis that monocytes play an important role in the pathogenesis of AS and RA, and further suggest a specific role in AS for the UPP. Quantitative proteomic expression profiling constitutes a powerful new tool for rheumatology research.
Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System
Authors: Jaewon Lee, Dong-Gyu Jo, Daeui Park, Hae Young Chung, Mark P. Mattson
Journal: Pharmacological Reviews (2014)

During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phytochemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examplesof such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-<i>κ</i>B, hypoxia-inducible factor 1<i>α</i>, peroxisome proliferator-activated receptor <i>γ</i>, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Translational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied.