tbuckley/cabot-search huggingface dataset:
FRI0004 Modulating FC-linked glycosylation patterns of human IGG1
Authors: J. Wang, C.I. Balog, K. Stavenhagen, C.A. Koeleman, M.H. Selman, A.M. Deelder, T.W. Huizinga, R.E. Toes, M. Wuhrer, H.U. Scherer
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Glycosylation of the Fc tail of human IgG strongly influences Fc-mediated effector functions. Recently, we have shown that anti-citrullinated protein antibodies (ACPA) isolated from serum and synovial fluid of patients with rheumatoid arthritis (RA) exhibit a specific, pro-inflammatory Fc-linked glycosylation profile. This glycan pattern is distinct from the glycan residues attached to the Fc tail of non-specific total IgG. As these data indicate a potential role of Fc-linked glycans for the biological effects that ACPA exert within the pathogenesis of RA, it is of interest to understand the mechanisms that regulate the Fc-glycosylation machinery of B cells. <h3>Objectives</h3> To study the effect of various mediators (cytokines, vitamins, microbial products) with relevance to adaptive and innate immune responses on Fc-linked glycan residues of human IgG. <h3>Methods</h3> Peripheral blood mononuclear cells were obtained from healthy human donors. CD19 expressing B cells were isolated by magnetic bead-based positive selection and cultured in the presence of anti-IgM, IL-2 and IL-10 on a layer of irradiated, CD40L transfected fibroblasts to induce IgG production. In addition, mediators described to have immunomodulatory activity on B cells (IL-4/6/17/21, IFN-γ, TNF-α, LT-α, TGF-β, CpG, all-trans retinoic acid (ATRA)) were added to the cultures. After 7-9 days of culture, IgG molecules (IgG1, 2 and 4) were isolated from culture supernatants by protein A affinity chromatography and subjected to tryptic digest. IgG1-linked Fc-glycopeptides were analyzed by mass-spectrometry. <h3>Results</h3> Whereas IL-21 and CpG significantly and consistently increased the degree of galactosylation and sialylation of the Fc-linked glycan, ATRA strongly decreased the frequency of these glycoforms. No significant effects were observed for the other mediators tested. Of interest, IL-21 additionally decreased the frequency of bisecting N-acteylglucosamine (GlcNAc), whereas ATRA left this sugar moiety unchanged. Once induced, the Fc-linked glycan profiles of secreted IgG1 remained stable, even after the added mediators were withdrawn after 5 days of culture. <h3>Conclusions</h3> Our data indicate that several factors, present in the microenvironment of B cells during activation and differentiation, are capable of differentially regulating the Fc-glycosylation of IgG1. Once B cells differentiate into antibody secreting cells, the IgG1 Fc-linked glycan profile remained stable. These data further our understanding of the mechanisms underlying IgG1 Fc-glycosylation in the human and may open up novel approaches for therapeutic intervention. <h3>Disclosure of Interest</h3> None Declared
Plasma Insulin in Normal Late Pregnancy
Authors: William N. Spellacy, Frederick C. Goetz
Journal: New England Journal of Medicine (1963)

DESPITE a voluminous amount of research directed at elucidating the mechanisms of human carbohydrate metabolism many unexplored areas remain, especially in the pregnant state. Many studies have made reference to the altered carbohydrate metabolism in pregnancy based upon changes in the oral glucose tolerance tests. Studies using intravenous glucose tolerance tests have shown normal curves during pregnancy and in fact suggest that more insulin may be released by the pancreas during the pregnant state.1 This is supported by pathological study of the pancreases of pregnant women that shows an increase in the size and number of the islands of Langerhans. . . .
Clinical Management of Ebola Virus Disease in the United States and Europe
Authors: Timothy M. Uyeki, Aneesh K. Mehta, Richard T. Davey, Allison M. Liddell, Timo Wolf, Pauline Vetter, Stefan Schmiedel, Thomas Grünewald, Michael Jacobs, Jose R. Arribas, Laura Evans, Angela L. Hewlett, Arne B. Brantsaeter, Giuseppe Ippolito, Christophe Rapp, Andy I.M. Hoepelman, Julie Gutman
Journal: New England Journal of Medicine (2016)

Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited.We reviewed available clinical, laboratory, and virologic data from all patients with laboratory-confirmed Ebola virus infection who received care in U.S. and European hospitals from August 2014 through December 2015.A total of 27 patients (median age, 36 years [range, 25 to 75]) with EVD received care; 19 patients (70%) were male, 9 of 26 patients (35%) had coexisting conditions, and 22 (81%) were health care personnel. Of the 27 patients, 24 (89%) were medically evacuated from West Africa or were exposed to and infected with Ebola virus in West Africa and had onset of illness and laboratory confirmation of Ebola virus infection in Europe or the United States, and 3 (11%) acquired EVD in the United States or Europe. At the onset of illness, the most common signs and symptoms were fatigue (20 patients [80%]) and fever or feverishness (17 patients [68%]). During the clinical course, the predominant findings included diarrhea, hypoalbuminemia, hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia; 14 patients (52%) had hypoxemia, and 9 (33%) had oliguria, of whom 5 had anuria. Aminotransferase levels peaked at a median of 9 days after the onset of illness. Nearly all the patients received intravenous fluids and electrolyte supplementation; 9 (33%) received noninvasive or invasive mechanical ventilation; 5 (19%) received continuous renal-replacement therapy; 22 (81%) received empirical antibiotics; and 23 (85%) received investigational therapies (19 [70%] received at least two experimental interventions). Ebola viral RNA levels in blood peaked at a median of 7 days after the onset of illness, and the median time from the onset of symptoms to clearance of viremia was 17.5 days. A total of 5 patients died, including 3 who had respiratory and renal failure, for a mortality of 18.5%.Among the patients with EVD who were cared for in the United States or Europe, close monitoring and aggressive supportive care that included intravenous fluid hydration, correction of electrolyte abnormalities, nutritional support, and critical care management for respiratory and renal failure were needed; 81.5% of these patients who received this care survived.
Abstract 576: Gadd45a sensitizes medulloblastoma cells to irradiation and modulates the cellular switch from migratory to stationary cell phase by downregulating MMP-9
Authors: Swapna Asuthkar, Arun Kumar Nalla, Dzung H. Dinh, Meena Gujrati, Sanjeeva Mohanam, Jasti S. Rao
Journal: Cancer Research (2011)

Abstract Gadd45a protein is induced in medulloblastoma cell lines by treatment with ionizing radiation (IR), which requires p53 stabilization. The role of Gadd45a in IR-induced G2-M arrest of medulloblastoma cells is demonstrated by its increased binding to Cdc2, thereby inactivating Cdc2 kinase activity. Knockdown of Gadd45a alleviates G2-M blockage and results in decreased binding of Gadd45a to Cdc2. Further, the anti-tumorigenic role of Gadd45a is mediated by the negative regulation of β-catenin and its nuclear translocation, which might decrease the β-catenin/LEF-1-mediated transactivation of cell invasion proteins, such as MMP-9, examined in the present study. Overexpression of Gadd45a protein with IR treatment resulted in decreased nuclear levels of β-catenin, increased cytoplasmic levels of p-β-catenin, and increased distribution of β-catenin on membrane E and N-cadherins. The IR-treated control cells showed contrary results with demonstrated loss of E-cadherin, gain of N-cadherin, and inhibition of β-catenin binding to membrane cadherins as well as increased nuclear translocation of β-catenin. Zymography studies demonstrate the negative regulation of IR-induced MMP-9 activity by Gadd45a overexpression. Wound healing and Matrigel invasion assays confirmed the anti-tumorigenic and anti-metastatic role of Gadd45a in medulloblastoma cell lines. Furthermore, siRNA-mediated knockdown of MMP-9 results in prominent expression levels of Gadd45a protein in animal tumors. Thus, we confirm that overexpression of Gadd45a in combination with ionizing radiation has therapeutic implications by preventing recurrence of MMP-9-mediated cancer cell invasion and effectively containing cells in a static phase by maintaining CCA/CCI. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 576. doi:10.1158/1538-7445.AM2011-576
RADIOIMMUNOTHERAPY WITH Y-90 LABELED MONOCLONAL ANTIBODIES: PRACTICAL CONSIDERATIONS FOR THE TECHNOLOGIST
Authors: P. F. Cutrera, A. M. Zimmer, M. W. Groch, W. G. Spies, S. M. Spies
Journal: Clinical Nuclear Medicine (1997)

Scientific Abstracts: Central Chapter, Society Of Nuclear Medicine Meeting, April 11-13, 1997, Grand Geneva Resort, Lake Geneva, Wi
Abstract 831: uPAR Expression is Up-regulated in Cervical Cancer
Authors: Toru Sasaki, Hirotaka Nishi, Fumitoshi Terauchi, Chinatsu Higuma, Takeshi Nagai, Toshitaka Nagao, Keiichi Isaka
Journal: Cancer Research (2010)

Abstract Hypoxia occurs during development of cervical cancer and is considered to correlate with its invasion. Hypoxia induces cancer cells to have more invasive property through the urokinase plasminogen activator receptor (uPAR) expression. Also, poor prognosis of uterine cervical cancer is correlated with hypoxic condition. Thus, we examined the relationship among the uPAR mRNA level and clinical prognostic factors, such as clinical and pathological stage, hemoglobin level, histologic type, tumor marker level and the effect on clinical outcome, using 66 cases of cervical cancer and 10 normal cervical tissues. These factors were evaluated by t test and Spearman's rank correlation coefficient. Survival analysis was performed using Kaplan-Meier curves. The uPAR mRNA level is significantly up-regulated in cervical cancers, compared with that in normal cervixes. The level of hemoglobin was significantly correlated with uPAR mRNA expression. Whereas, no other clinical prognostic factor had correlation with uPAR mRNA expression. Also, the uPAR mRNA level was not correlated with survival. According to the invasion assays, cervical cancer cell lines, CA and CaSki, under hypoxic condition (1% O2) showed more invasive property than those under normoxia. Hypoxia enhanced the endogenous uPAR mRNA level and protein expression by realtime RT-PCR and western blot analysis, respectively. Although we hypothesized that uPAR expression was correlated with tumor invasion and poor prognosis, the results revealed that uPAR mRNA expression was not correlated with survival nor most clinical factors except for the hemoglobin level. Although uPAR seems to be critical for the invasiveness in cervical cancer cell lines, uPAR may not be involved in cervical cancer invasion in vivo. Only real hypoxia may regulate the uPAR mRNA expression in cervical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 831.
Case 29-2009
Authors: Valerie E. Stone, Brenna C. Bounds, Victorine V. Muse, Judith A. Ferry
Journal: New England Journal of Medicine (2009)

An 81-year-old man was admitted to this hospital because of cough and weight loss for 15 months and recent onset of odynophagia and failure to thrive. He had a history of asbestos exposure. Chest imaging showed pleural plaques and bilateral pulmonary opacities. A barium swallow showed an abnormal esophageal mucosal pattern, with a cobblestone appearance, and an abdominal CT scan showed multiple low-attenuation lesions throughout the liver. Additional diagnostic tests were performed.
RESULTS OF THE INTERNATIONAL INTERLABORATORY COMPARISON OF MGMT PROMOTER METHYLATION ANALYSIS INVOLVING TWENTY-THREE ACADEMIC CENTERS IN GERMANY, AUSTRIA AND THE NETHERLANDS
Authors: G. Reifenberger, B. Malzkorn, T. Acker, M. Bettstetter, R. Buslei, A. von Deimling, W. Dietmaier, H. J. Dubbink, S. Eigenbrod, B. K. Garvalov, U. Gerstenmaier, A. Giese, D. Haase, M. Hasselblatt, E. Kirches, A. Koch, R. Marienfeld, M. Mittelbronn, M. Montesinos-Rongen, A. Pagenstecher, M. J. Riemenschneider, M. Prinz, B. Romeike, A. Roos, S. Spiegl-Kreinecker, J. Schittenhelm, J. Schlegel, D. R. Thal, B. B. J. Tops, J. Weis, G. Westphal, K. Worm, J. Felsberg
Journal: Neuro-Oncology (2014)

BACKGROUND: Molecular testing for MGMT promoter methylation has become of clinical importance in the diagnostic assessment of malignant gliomas since test results may guide therapeutic decision making, in particular in elderly patients with glioblastoma. However, the patterns and extent of MGMT promoter methylation may vary from tumor to tumor, and standardized approaches for its routine diagnostic assessment are lacking. Thus, external quality assessment (EQA) measures are required to ensure accuracy and reproducibility of results across different laboratories. METHODS: We performed an interlaboratory comparison of MGMT promoter methylation analysis involving twenty-three academic institutions in Germany, Austria and the Netherlands. Two different test rounds were carried out, the first one using high molecular weight DNA extracted from frozen tissue samples of 20 tumors and the second one using formalin-fixed paraffin-embedded tissue sections of 16 tumors. All samples were centrally retrieved from the CNS tumor tissue bank at Heinrich Heine University Düsseldorf. Each participating center evaluated the same set of samples using the locally established methods. Results were centrally collected, together with information on the individual assays and the number of tests carried out per year. RESULTS: Methylation specific-PCR was the most commonly used method at the participating centers. Other less common techniques included pyrosequencing of bisulfite-modified DNA, MethyQESD (methylation-quantification of endonuclease-resistant DNA), MLPA (Multiplex Ligation-dependent Probe Amplification), and PCR-based fragment analysis. MGMT testing results showed a good overall concordance across the participating laboratories for those tumors that either had strongly methylated or clearly unmethylated MGMT promoter sequences. However, poor concordance was obtained for cases with only weak or partial MGMT promoter methylation. CONCLUSIONS: Our study provides an overview of the current practice of MGMT testing in glioma diagnostics in a large number of different institutions. The results underscore the importance of EQA measures to assure optimal quality and interlaboratory reproducibility of test results in order to avoid wrong treatment decisions. The assessment of tumors with only partialy or weakly methylated MGMT promoter sequences is problematic and may need to be improved by testing algorithms involving more than a single technique. SECONDARY CATEGORY: Clinical Neuro-Oncology.
AB0343 Description of Pulmonary Dysfunction in Early Rheumatoid Arthritis
Authors: M. Blettery, M.-E. Truchetet, T. Barnetche, C. Vessier, J. Foret, P. Germain, C. Richez, F. Laurent, T. Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2014)

Background Several environmental factors were found to be associated with rheumatoid arthritis (RA), such as tobacco, silica, or atmospheric pollutants. These factors are characterized by a first contact with the respiratory tract, suggesting that the lung could be a candidate site of RA initiation or preclinical phase of RA. Most studies on lung disorders during RA have been performed with long evolution affected RA patients. Objectives The aim of this study was to describe the pulmonary manifestations associated with early RA. Methods Inclusion criteria were as follow: patients presenting RA according to ACR/EULAR 2010 criteria and with less than 2 years of evolution. Patients presenting a respiratory disorder already identified or another autoimmune disease were excluded. The respiratory check-up included a non-contrast high resolution computed tomography-scan (HRCT), lung function tests with carbon monoxide diffusion and capillary gases values. Results Twenty-four patients were included, with a mean age of 54,2±11,1 years old, a 58% female proportion (n=14/24), and 76% (n=18/24) were active or past smokers. 67% (n=11/15) of active or past smokers were ACPA-positive vs. 60% (n=3/5) for the non-smokers group. The mean DAS28-VS were about 3,15±1,61 at inclusion with 58% of patients (n=14/24) with a low disease activity, and a mean duration of disease about 10±8 months. 35% of patients (n=7/20) presented pulmonary symptoms: cough, dyspnea, or sputums. The pulmonary examination was found abnormal for 10% of patients (n=2/20). Lung function tests identified a bronchial obstruction for 19% (n=4/21) and a restrictive ventilatory disorder for 10% of patients (n=2/21), and an abnormal level of DLCO for 7 patients (33%). HRCT-scan identified 13 elementary lesions for 10 patients: nodules (n=5), reticulations (n=2), thickening of the bronchial walls (n=3), condensations (n=1), bronchiectasis (n=1) and ground glass opacities (n=1). Description of HRCT-scan results allowed finding 2 cases of interstitial lung disease (with restrictive ventilatory disorder), a bronchodilation for 2 patients and emphysema for 4 patients. 50% (n=8/16) of seropositive patients (ACPA and/or RF) were found to have pulmonary lesions, vs. 33% (n=2/6) for the seronegatives ones (p=0,646). Finally, abnormalities in lung function tests were highlighted for 31% (n=5/16) of seropositive patients vs. 14% (n=1/7) for seronegative patients (p=0,621). Conclusions This pilot study allowed the identification of early respiratory disorders in early RA affected patients, suggesting the putative role of lung in RA physiopathology. Further inclusions are needed to confirm the aetiology of several autoimmune and environmental factors in pulmonary lesions for RA patients. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3537
GPR56 contributes to the development of acute myeloid leukemia in mice
Authors: D Daria, N Kirsten, A Muranyi, M Mulaw, S Ihme, A Kechter, M Hollnagel, L Bullinger, K Döhner, H Döhner, M Feuring-Buske, C Buske
Journal: Leukemia (2016)
Experts call for younger men to be offered PSA test for prostate cancer
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Clinicians should consider offering men in their 40s the prostate specific antigen (PSA) test if the men have concerns about prostate cancer or are at higher than average risk of getting the disease, new guidance recommends. And GPs have been given an improved Public Health England prostate cancer pack to help them discuss the PSA test with their male patients.1

Currently around 47 000 men have a diagnosis of prostate cancer in the United Kingdom, and about 11 000 die from the disease every year. Men are at higher …
AB1047 Evidence that a systemic predisposition to chondrocalcinosis exists, and is mediated by osteoarthritis at most but not all joints
Authors: A. Abhishek, S. Doherty, R. Maciewicz, K. Muir, W. Zhang, M. Doherty
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is not known whether radiographic chondrocalcinosis (CC) results from a systemic predisposition or whether the association between CC and osteoarthritis (OA) is joint specific or generalized. <h3>Objectives</h3> To ascertain if there is a systemic predisposition to CC, and to examine if the association between CC and OA is joint specific or systemic. <h3>Methods</h3> A cross-sectional study embedded in GOAL – the Genetics of Osteoarthritis and Lifestyle study (n=3,170). All participants in GOAL have radiographs of knees, hands, and pelvis, and these have been scored for changes of osteoarthritis (OA), and for the presence of CC. The risk of CC at each joint was estimated and compared according to CC in the distant joint, as well as OA at the same and distant joints. Odds ratio (OR) and 95% confidence interval (CI) was used to measure the association. The OR was adjusted for age, gender, body mass index (BMI), and OA at the distant joints (aOR). OA was defined if the Kellgren and Lawrence score was ≥2 at either hips, ≥3 at either knees, and there was definite joint space narrowing at either wrist. <h3>Results</h3> CC at one joint is associated with CC at other joints. This association was observed in knees, hips, wrists, metacarpophalangeal joints (MCPJs), and symphysis pubis (Table 1). CC was associated with OA at the same knee, wrist and MCPJ. The aOR (95%CI) ranged from 2.20 (1.62-2.99) to 5.58 (2.72-11.47). However, there was no association between CC and OA at the same hip (aOR 1.05, 95%CI 0.72-1.55 right, and 0.68, 0.41-1.13 left hip). While knee OA associated with CC at all distant joints, hip OA did not associate with CC at any of the distant joints. <h3>Conclusions</h3> CC occurs at least in part due to a systemic predisposition, some of which is mediated by OA. While there is evidence to suggest that OA associates with CC due to a generalised predisposition, this varies according to the joint affected by OA – the predisposition being present for knee OA and not for hip OA. <h3>Disclosure of Interest</h3> None Declared.
Prediction of the Risk of Hereditary Retinoblastoma, Using DNA Polymorphisms within the Retinoblastoma Gene
Authors: J Wiggs, M Nordenskjöld, D Yandell, J Rapaport, V Grondin, M Janson, B Werelius, R Petersen, A Craft, K Riedel
Journal: New England Journal of Medicine (1988)

Using molecular cloning, we earlier isolated the "retinoblastoma gene"; mutations or deletions at this locus are associated with the hereditary predisposition to some human cancers, especially retinoblastoma and osteosarcoma. To develop diagnostic tests for such a predisposition, we identified restriction-fragment-length polymorphisms (RFLPs) within the retinoblastoma gene and tested their usefulness in predicting the risk of cancer in 20 families with members who had hereditary retinoblastoma. We were able to make predictions in 19 of the 20 kindreds. In 18 kindreds, we demonstrated a consistent association of marker RFLPs with the mutation predisposing to retinoblastoma. In the 19th kindred, there may be a lack of cosegregation of the DNA polymorphisms within the gene and the site of the mutation predisposing to retinoblastoma. However, there is uncertainty about the clinical diagnosis of the retinal lesion in a key member of this kindred; if the lesion is not a retinoblastoma, there is no discrepancy between the DNA polymorphisms and the retinoblastoma trait. We conclude that it is feasible and clinically useful to use these DNA polymorphisms to determine the risk of cancer.
Presurgical Lateralization of Seizure Focus in Temporal Lobe Epilepsy With Noninvasive Imaging
Authors: Jay J Pillai, Hadyn T Williams, Scott E Forseen, Yong D Park
Journal: Clinical Nuclear Medicine (2012)

We retrospectively compared the seizure focus-localizing capability of interictal PET/CT to that of interictal magnetic resonance diffusion-weighted imaging and ictal SPECT in 21 patient candidate for neurosurgery with temporal lobe epilepsy (TLE) by assessing overall lateralizing ability of these modalities and concordance of findings on these studies with results of electroencephalography (EEG). PET/CT demonstrated the greatest lateralizing ability of any of the imaging modalities and had the highest concordance rate for lateralization with EEG, highlighting its increasing diagnostic utility in the preoperative imaging workup of patients with medically intractable TLE.