tbuckley/cabot-search huggingface dataset:
The Cysteine-Rich Domain of the Macrophage Mannose Receptor Is a Multispecific Lectin That Recognizes Chondroitin Sulfates a and B and Sulfated Oligosaccharides of Blood Group Lewisa and Lewisx Types in Addition to the Sulfated <i>N</i>-Glycans of Lutropin
Authors: Christine Leteux, Wengang Chai, R. Wendy Loveless, Chun-Ting Yuen, Lars Uhlin-Hansen, Yves Combarnous, Mila Jankovic, Svetlana C. Maric, Ziva Misulovin, Michel C. Nussenzweig, Ten Feizi
Journal: The Journal of Experimental Medicine (2000)

The mannose receptor (MR) is an endocytic protein on macrophages and dendritic cells, as well as on hepatic endothelial, kidney mesangial, tracheal smooth muscle, and retinal pigment epithelial cells. The extracellular portion contains two types of carbohydrate-recognition domain (CRD): eight membrane-proximal C-type CRDs and a membrane-distal cysteine-rich domain (Cys-MR). The former bind mannose-, N-acetylglucosamine-, and fucose-terminating oligosaccharides, and may be important in innate immunity towards microbial pathogens, and in antigen trapping for processing and presentation in adaptive immunity. Cys-MR binds to the sulfated carbohydrate chains of pituitary hormones and may have a role in hormonal clearance. A second feature of Cys-MR is binding to macrophages in marginal zones of the spleen, and to B cell areas in germinal centers which may help direct MR-bearing cells toward germinal centers during the immune response. Here we describe two novel classes of carbohydrate ligand for Cys-MR: chondroitin-4 sulfate chains of the type found on proteoglycans produced by cells of the immune system, and sulfated blood group chains. We further demonstrate that Cys-MR interacts with cells in the spleen via the binding site for sulfated carbohydrates. Our data suggest that the three classes of sulfated carbohydrate ligands may variously regulate the trafficking and function of MR-bearing cells.
A novel splice variant of FcγRIIa: A risk factor for anaphylaxis in patients with hypogammaglobulinemia
Authors: Joris van der Heijden, Judy Geissler, Edwin van Mirre, Marcel van Deuren, Jos W.M. van der Meer, Abdulgabar Salama, Timo K. van den Berg, Dirk Roos, Taco W. Kuijpers
Journal: Journal of Allergy and Clinical Immunology (2013)
Lupus nephritis in the absence of renal major histocompatibility complex class I and class II molecules.
Authors: R Mukherjee, Z Zhang, R Zhong, Z Q Yin, D C Roopenian, A M Jevnikar
Journal: Journal of the American Society of Nephrology (1996)

MRL/Mp-lpr/lpr (MRL-lpr) mice develop an aggressive autoimmune disorder characterized by arthritis, vasculitis, and glomerulonephritis. Renal injury is associated with increased expression of major histocompatibility complex (MHC) molecules, as well as cytokines, adhesion molecules (intracellular adhesion molecule-1, vascular cell adhesion molecule-1), and autoantibodies. By using either MHC Class I (MRL-lpr B2m-/-) or MHC Class II deficient (MRL-lpr Ab-/-) kidneys in a transplant model, we tested the role of renal expression of these molecules in the development of autoimmune renal injury. Kidneys from MRL-lpr B2m-/- or MRL-lpr Ab-/- mice as well as control wild-type mice transplanted into MRL-lpr wt/- recipients developed nephritis, CD4+ and CD8+ T cell infiltration, and heavy glomerular deposition of immunoglobulin. Spontaneously proliferating autoreactive T cells were found in wild-type MRL-lpr and MRL-lpr B2m-/- but not MRL-lpr Ab-/- mice. These results suggest that the absence of renal expression of either Class I or Class II molecules does not provide marked protection from autoimmune lupus nephritis and supports the possibility that protection from autoimmune disease in MRL-lpr Ab-1- mice is related to the loss of autoreactive MHC Class II-dependent CD4+ T cells.
A Comparative Analysis of numt Evolution in Human and Chimpanzee
Authors: Einat Hazkani-Covo, Dan Graur
Journal: Molecular Biology and Evolution (2006)

Mitochondrial DNA sequences are frequently transferred into the nuclear genome, giving rise to numts (nuclear DNA sequences of mitochondrial origin). So far, the evolutionary history of numts has largely been studied by using single genomes. Here, we present the first attempt to study numt evolution in a comparative manner by using a pairwise genomic alignment. The total number of numts was estimated to be 452 in human and 469 in chimpanzee. numts that were found in both genomes at identical loci were deemed to be orthologous; 391 numts (>80%) were classified as such. The preponderance of orthologous numts is due to the very short divergence time between the 2 hominoids. The rest of numts were deemed to be nonorthologous. Nonorthologous numts were subdivided into 1) ancestral numts that have lost an ortholog in one species through deletion (12 in human and 11 in chimpanzee), 2) new numts acquired by the insertion of a mitochondrial sequence after the divergence of the 2 species (34 in human and 46 in chimpanzee), and 3) paralogous numts created by the tandem duplication of a preexisting numt (2 in human). This approach also enabled us to reconstruct the numt repertoire in the common ancestor of humans and chimpanzees (409 numts). Our comparative approach is also useful in identifying the exact boundaries of numts.
Active ulcerative colitis is associated with altered fatty acid precursor availability for the eicosanoid synthetic pathway
Authors: D. S. Pearl, D. Gullick, J. Bruemmer, J. Brown, J. K. Shute, G. Mills, T. M. Trebble
Journal: Gut (2011)

<h3>Introduction</h3> The polyunsaturated fatty acids (PUFA) arachidonic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are generated from dietary essential fatty acids linoleic acid (LA) and α-linolenic acid (αLNA) and direct dietary intake. AA and EPA are substrates for eicosanoid inflammatory mediators that may have critical roles in immunomodulation in Ulcerative Colitis (UC). Dietary supplementation studies alter the availability of specific PUFA (eg, EPA), but clinical studies have been disappointing leading to the hypothesis that the PUFA biosynthetic pathway in inflamed tissue may be altered. This study evaluated PUFA bioavailability in inflamed and uninflamed mucosa from UC patients and compared to matched controls. <h3>Methods</h3> Ethical approval was obtained. Patients were prospectively recruited from outpatients9 clinics. Mucosal biopsies at flexible sigmoidoscopy (FS) were taken from active UC patients within inflamed (active) and endoscopically normal proximal mucosa (internal control). Age-sex matched patients undergoing FS for IBS or similar presentations were compared (external controls). Mucosal samples were saponified, deuterated internal standards added, lipids hydrolysed and fatty acids derivatised prior to liquid-liquid extraction into heptane. PUFA were quantified by gas chromatography mass spectrometry. Data was expressed as percentage mass abundance and compared using Wilcoxon signed rank pair analysis for non-parametric data. <h3>Results</h3> 69 active UC patients (54 paired normal/inflamed mucosa) and 69 controls were compared. No biologically significant differences were noted between endoscopically normal mucosa from UC patients and external controls other than DPA (p&lt;0.0025). Inflamed mucosa compared to both control groups demonstrated highly significant reductions in the essential fatty acids LA and αLNA (p&lt;0.0001) and increased AA, DPA and DHA (p&lt;0.0001); EPA was reduced (p&lt;0.005). The ratio of AA/EPA was increased in inflamed mucosa (p&lt;0.0001) (figure 1). <h3>Conclusion</h3> PUFA bioavailability within normal mucosa in UC patients is not significantly different from matched controls; however, inflamed mucosa demonstrates significant differences in the bioavailability of PUFA with a reduction in LA and αLNA and a divergent change in AA and EPA leading to a significant increase in the AA/EPA ratio. These findings suggest alteration of the fatty acid biosynthetic pathway in inflamed tissue and may suggest that alternative therapeutic strategies are required to modify the eicosanoid profile in UC.
Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment
Authors: A.B. Kimball, G.B.E. Jemec, M. Yang, A. Kageleiry, J.E. Signorovitch, M.M. Okun, Y. Gu, K. Wang, P. Mulani, M. Sundaram
Journal: British Journal of Dermatology (2014)

Quantification of disease severity supports the development of evidence-based treatments. Assessments to capture clinical improvement in hidradenitis suppurativa (HS) can be improved.This study aimed to validate the Hidradenitis Suppurativa Clinical Response (HiSCR), which is defined as a ≥ 50% reduction in inflammatory lesion count (sum of abscesses and inflammatory nodules, AN), and no increase in abscesses or draining fistulas in HS when compared with baseline as a meaningful clinical endpoint for HS treatment.Patients with ≥ 3 ANs at baseline in a Phase II adalimumab trial for HS were included for analysis. HiSCR achievers vs. nonachievers were assessed at week 16 and week 52. Criteria measures included physician-rated assessments [Hurley stage, modified Sartorius score (MSS), and HS Physician's Global Assessment] and patient-reported outcomes (PROs: visual analogue pain scale, Dermatology Life Quality Index, and Work Productivity and Activity Impairment questionnaire). Test-retest reliability, convergent validity, responsiveness and predictive validity of HiSCR, and its meaningfulness to patients were assessed.Among 138 eligible study participants, the majority were female (69·6%) with a mean age of 36·7 years. The mean (median) MSS was 125·2 (85·5) at baseline. Test-retest reliability of the AN count was 0·91. HiSCR was significantly correlated with improvements in all physician-rated and PRO measures (Spearman's rho between -0·61 and -0·27, all P < 0·001). Improvements of all PROs in HiSCR achievers exceeded the respective meaningful improvement thresholds.In patients with HS with ≥ 3 ANs, HiSCR achievers had significant improvements in physician-rated and patient-reported HS disease severity and impact. HiSCR is a valid and meaningful endpoint for assessing HS treatment effectiveness in controlling inflammatory manifestations in this population.
Comparative Effectiveness of Screening Strategies for Lynch Syndrome
Authors: Afsaneh Barzi, Sarmad Sadeghi, Michael W. Kattan, Neal J. Meropol
Journal: JNCI Journal of the National Cancer Institute (2015)

Colorectal cancer is the second leading cause of cancer death in the United States. Approximately 3% of colorectal cancers are associated with Lynch Syndrome. Controversy exists regarding the optimal screening strategy for Lynch Syndrome. Using an individual level microsimulation of a population affected by Lynch syndrome over several years, effectiveness and cost-effectiveness of 21 screening strategies were compared. Modeling assumptions were based upon published literature, and sensitivity analyses were performed for key assumptions. In a two-step process, the number of Lynch syndrome diagnoses (Step 1) and life-years gained as a result of foreknowledge of Lynch syndrome in otherwise healthy carriers (Step 2) were measured. The optimal strategy was sequential screening for probands starting with a predictive model, then immunohistochemistry for mismatch repair protein expression (IHC), followed by germline mutation testing (incremental cost-effectiveness ratio [ICER] of $35 143 per life-year gained). The strategies of IHC + BRAF, germline testing and universal germline testing of colon cancer probands had ICERs of $144 117 and $996 878, respectively. This analysis suggests that the initial step in screening for Lynch Syndrome should be the use of predictive models in probands. Universal tumor testing and general population screening strategies are not cost-effective. When family history is unavailable, alternate strategies are appropriate. Documentation of family history and screening for Lynch Syndrome using a predictive model may be considered a quality-of-care measure for patients with colorectal cancer.
<i>EFEMP1</i> as a Novel DNA Methylation Marker for Prostate Cancer: Array-Based DNA Methylation and Expression Profiling
Authors: Yong-June Kim, Hyung-Yoon Yoon, Seon-Kyu Kim, Young-Won Kim, Eun-Jung Kim, Isaac Yi Kim, Wun-Jae Kim
Journal: Clinical Cancer Research (2011)

Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells.Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out.Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH.Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa.
Flow-induced protein kinase A–CREB pathway acts via BMP signaling to promote HSC emergence
Authors: Peter Geon Kim, Haruko Nakano, Partha P. Das, Michael J. Chen, R. Grant Rowe, Stephanie S. Chou, Samantha J. Ross, Kathleen M. Sakamoto, Leonard I. Zon, Thorsten M. Schlaeger, Stuart H. Orkin, Atsushi Nakano, George Q. Daley
Journal: The Journal of Experimental Medicine (2015)

Fluid shear stress promotes the emergence of hematopoietic stem cells (HSCs) in the aorta–gonad–mesonephros (AGM) of the developing mouse embryo. We determined that the AGM is enriched for expression of targets of protein kinase A (PKA)–cAMP response element-binding protein (CREB), a pathway activated by fluid shear stress. By analyzing CREB genomic occupancy from chromatin-immunoprecipitation sequencing (ChIP-seq) data, we identified the bone morphogenetic protein (BMP) pathway as a potential regulator of CREB. By chemical modulation of the PKA–CREB and BMP pathways in isolated AGM VE-cadherin+ cells from mid-gestation embryos, we demonstrate that PKA–CREB regulates hematopoietic engraftment and clonogenicity of hematopoietic progenitors, and is dependent on secreted BMP ligands through the type I BMP receptor. Finally, we observed blunting of this signaling axis using Ncx1-null embryos, which lack a heartbeat and intravascular flow. Collectively, we have identified a novel PKA–CREB–BMP signaling pathway downstream of shear stress that regulates HSC emergence in the AGM via the endothelial-to-hematopoietic transition.
CD44 and OTP Are Strong Prognostic Markers for Pulmonary Carcinoids
Authors: Dorian R.A. Swarts, Mieke E.R. Henfling, Leander Van Neste, Robert-Jan van Suylen, Anne-Marie C. Dingemans, Winand N.M. Dinjens, Annick Haesevoets, Martina Rudelius, Erik Thunnissen, Marco Volante, Wim Van Criekinge, Manon van Engeland, Frans C.S. Ramaekers, Ernst-Jan M. Speel
Journal: Clinical Cancer Research (2013)

Pulmonary carcinoids are well-differentiated neuroendocrine tumors showing usually a favorable prognosis. However, there is a risk for late recurrence and/or distant metastasis. Because histologic classification in typical and atypical carcinoids is difficult and its reliability to predict disease outcome varies, we evaluated three genes as potential prognostic markers, that is, orthopedia homeobox (OTP), CD44, and rearranged during transfection (RET).These genes were analyzed in 56 frozen carcinoids by quantitative real-time PCR (qRT-PCR). RET was further studied by methylation and mutation analysis. Immunohistochemistry for CD44 and OTP protein expression was conducted on 292 carcinoids.Low mRNA expression levels of CD44 (P = 1.8e(-5)) and OTP (P = 0.00054), and high levels of RET (P = 0.025), were strongly associated with a low 20-year survival of carcinoid patients. High RET expression was not related to promoter hypomethylation or gene mutations. A direct link between gene expression and protein levels was confirmed for CD44 and OTP but not for RET. Within all carcinoids as well as atypical carcinoids, absence of CD44 protein was significantly associated with low 20-year survival (P = 0.00014 and 0.00013, respectively). The absence of nuclear OTP followed by complete loss of expression was also significantly associated with unfavorable disease outcome in all carcinoids (P = 5.2(-6)). Multivariate analyses revealed that age at diagnosis, histopathology, stage, and cytoplasmic OTP immunoreactivity were independent predictors of prognosis.Our study indicates that CD44 and OTP are strong indicators of poor outcome. We therefore argue for implementation of these markers in routine diagnostics in addition to histopathology to improve subclassification of pulmonary carcinoids into prognostically relevant categories.
Giant duodenal ulcer
Authors: K. Lumsden, J. C. MacLarnon, J. Dawson
Journal: Gut (1970)

Twenty-five cases of benign giant duodenal ulcer have been studied. In every case a barium meal examination showed an ulcer crater with a radiographic diameter of at least 2 centimetres. Abdominal pain was the commonest symptom but less than half of the patients had had pain characteristic of chronic peptic ulcer. Haemorrhage from the ulcer occurred in a large majority of them. The radiological appearances are described, and it has been shown that the giant ulcer may be missed through being mistaken for the duodenal cap or else misdiagnosed.It appears that the death rate in this condition has been falling but it is still high. The management of patients with giant ulcers is discussed.
Purification and partial biochemical characterization of normal human interleukin 1.
Authors: J A Schmidt
Journal: The Journal of Experimental Medicine (1984)

A protocol for the rapid, efficient purification of the major charged species of human interleukin 1 (IL-1) has been developed using high performance anion exchange and size exclusion chromatography. The isolated material is pure as determined by sodium dodecyl sulfate (SDS) gradient polyacrylamide gel electrophoresis (PAGE) and analytical isoelectric focusing (IEF). The molecular weight of the purified material is 15,000 and the isoelectric point (pI) is 6.8, values that are in good agreement with those previously reported for human IL-1. 10(-10) M concentrations of the purified material give half-maximal stimulation in the thymocyte proliferation assay. Amounts of IL-1 sufficient for receptor studies and detailed biochemical analysis can now be produced on a regular basis.
Effects of simvastatin on the development of the atrial fibrillation substrate in dogs with congestive heart failure☆
Authors: A SHIROSHITATAKESHITA, B BRUNDEL, B BURSTEIN, T LEUNG, H MITAMURA, S OGAWA, S NATTEL
Journal: Cardiovascular Research (2007)

Background: Congestive heart failure (CHF) is a common cause of atrial fibrillation (AF). Oxidative stress and inflammation (profibrotic) and peroxisome proliferator-activated receptor-α (PPAR-α, antifibrotic) factors may be involved in CHF-related remodeling. We evaluated the effects of simvastatin (antioxidant, anti-inflammatory) and fenofibrate (PPAR-α activator) on CHF-related atrial remodeling.
Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study
Authors: Sameek Roychowdhury, Matthew K. Iyer, Dan R. Robinson, Robert J. Lonigro, Yi-Mi Wu, Xuhong Cao, Shanker Kalyana-Sundaram, Lee Sam, O. Alejandro Balbin, Michael J. Quist, Terrence Barrette, Jessica Everett, Javed Siddiqui, Lakshmi P. Kunju, Nora Navone, John C. Araujo, Patricia Troncoso, Christopher J. Logothetis, Jeffrey W. Innis, David C. Smith, Christopher D. Lao, Scott Y. Kim, J. Scott Roberts, Stephen B. Gruber, Kenneth J. Pienta, Moshe Talpaz, Arul M. Chinnaiyan
Journal: Science Translational Medicine (2011)

The mutations present in advanced cancers can be identified by integrative high-throughput sequencing to enable biomarker-driven clinical trials and, ultimately, treatment.
Vascular and Neoplastic Risk in a Large Cohort of Patients With Polycythemia Vera
Authors: Roberto Marchioli, Guido Finazzi, Raffaele Landolfi, Jack Kutti, Heinz Gisslinger, Carlo Patrono, Raphael Marilus, Ana Villegas, Gianni Tognoni, Tiziano Barbui
Journal: Journal of Clinical Oncology (2005)

Purpose The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. Patients and Methods Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. Results The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. Conclusion The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemiologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease.