tbuckley/cabot-search huggingface dataset:
MEDI‐551 Treatment Effectively Depletes B Cells and Reduces Serum Titers of Autoantibodies in Mice Transgenic for <i>Sle1</i> and Human CD19
Authors: Sandra Gallagher, Isharat Yusuf, Tom M. McCaughtry, Sean Turman, Hong Sun, Roland Kolbeck, Ronald Herbst, Yue Wang
Journal: Arthritis & Rheumatology (2015)

To evaluate treatment with MEDI-551, a humanized anti-human CD19 monoclonal antibody, in a model of autoimmunity involving mice transgenic (Tg) for Sle1 and human CD19 (hCD19).Sle1.hCD19-Tg mice were given either a single intravenous dose of MEDI-551 or repeated doses of MEDI-551 biweekly for up to 12 weeks. The numbers of B cells in the blood, spleen, and bone marrow were determined by flow cytometry assay. In the spleen and bone marrow, the number of IgM- and IgG-specific antibody-secreting cells (ASCs) and the number of ASCs specific for anti-double-stranded DNA (anti-dsDNA) were determined by enzyme-linked immunospot assay. Serum autoantibody and total immunoglobulin levels were determined by enzyme-linked immunosorbent assay, and levels of inflammatory proteins were tested using a multianalyte profiling platform.MEDI-551 treatment of Sle1.hCD19-Tg mice resulted in effective and sustained B cell depletion throughout the duration of the experiment. The frequency of IgM and IgG ASCs in the spleen was reduced by ≥90%, whereas in the bone marrow, the total ASC frequency was not changed. Levels of autoantibodies specific for dsDNA as well as antihistone and antinuclear antibodies were each reduced by 40-80%, but total serum immunoglobulin levels were largely unchanged at the end of 12 weeks of treatment.These findings highlight the ability of MEDI-551 to deplete B cells and ASCs in autoimmune Sle1.hCD19-Tg mice. MEDI-551 treatment resulted in a robust reduction of autoantibodies but had minimal effect on total serum immunoglobulins. Thus, the novel ability of MEDI-551 to remove a broad range of B cells as well as to lower most disease-driving autoantibodies in an autoimmune disease mouse model warrants continued research. Several clinical studies to explore the safety and activity of MEDI-551 in autoantibody-associated autoimmune diseases are ongoing.
A novel treatment for ovarian cancer (OC): Anti-Müllerian inhibiting substance type II receptor (MISRII) humanized monoclonal antibody (mAb) 3C23K—Preclinical validation.
Authors: Christine Gaucher, Alexandra Jacquet, Nathalie Kersual, Veronique Garambois, Alexandre Fontayne, Nathalie Fournier, Christophe de Romeuf, Diego Tosi, Alain Sadoun, Frederique Brune, Jean-Francois Prost, Remi Urbain, Andre Pelegrin, Isabelle Teulon-Navarro
Journal: Journal of Clinical Oncology (2012)

5069 Background: Expressed on most OC subtypes while displaying a restricted expression profile in adult normal tissues, MISRII represents a potentialtarget for OC immunotherapy. We present here the preclinical assessment of a humanized anti-MISRII EMABling mAb, 3C23K. Methods: Either quantitative RT-PCR or immunohistochemistry (IHC) studies were performed to confirm MISRII expression profile in Granulosa Cell Tumor (GCT) or Epithelial OC (EOC) patient samples and to evaluate tissue cross-reactivity. For in vitro and in vivo experiments, we have generated 4 patient-derived MISRII expressing EOC cell lines. Xenograft studies were conducted in swiss nude mice on established tumors (100 mm 3 ). Mice received 2 to 3 weekly i.p. injections (10 mg/kg/inj) for 4 to 6 wks and tumor volumes were compared with control groups. Comparison of i.p. vs i.v. injections were assessed as well as combination with carboplatin (once a week for 4 weeks, 60 mg/kg/inj). In addition, 3C23K plasma level was monitored to determine half-life. Results: 1) Target validation: we confirmed by IHC the expression of MISRII in most OC tissue sections (4/4 GCT and 13/14 EOC), meanwhile, MISRII mRNA was only detected in 7/48 normal tissues. 2) In vitro assessment: tested in vitro 3C23K displayed both cytotoxic (ADCC) and anti-proliferative activities. 3) In vivo assessment: in the mouse xenograft models 3C23K exhibited a strong anti-tumoral activity as measured by tumor volume, with T/C ratios reaching values below 0.42 shortly after the initiation of treatment. No differences in efficacy were noticed between i.p. and i.v. injections or between thrice vs twice a week administrations. In addition, similar half lives were observed for 3C23K injected either i.v. (96.9 h) or i.p (113.5 h). Finally, the combination of 3C23K with carboplatin (CP), a standard of care in OC, exhibited an even stronger anti-tumor activity with T/C values at D22 of 0.06 (3C23K+CP), 0.18 (3C23K) and 0.69 (CP) vs vehicle. Conclusions: 3C23K represents a promising candidate for OC targeted therapy and a dose-escalation phase I study is planned in patients with OC.
AB0481 Abatacept Might not Alter Anti-Cyclic Citrullinated Peptide Levels in Established Rheumatoid Arthritis Patients -Airtight Study-
Authors: S. Anno, K. Inui, K. Mamoto, T. Okano, Y. Sugioka, M. Tada, T. Koike, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The percentage of anti-cyclic citrullinated peptide (CCP)-positive patients reported declines among early rheumatoid arthritis (RA) patients treated with abatacept (ABT). <h3>Objectives</h3> The AIRTIGHT study (UMIN:000005570) was conducted to assess the clinical and immunological impact of ABT on established RA patients. <h3>Methods</h3> The AIRTIGHT study included 32 patients (mean age, 60.7±13.6 years; mean duration of disease, 11.7±13.6 years; range, 0-35 years; MTX use, 81.9%; mean MTX dose, 6.1±4.6 mg/week) treated with ABT and 72 patients (mean age, 59.7±14.3 years; mean duration of disease, 9.5±10.9 years; range, 0-40 years; MTX use, 86.1%; mean MTX dose, 8.6±4.3 mg/week) treated with non-ABT biologics (adalimumab, n=20; etanercept, n=14; tocilizumab, n=19; infliximab, n=10; golimumab, n=9). Serum levels of anti-CCP, rheumatoid factor (RF), and autoantibody to galactose-deficient immunoglobulin (Ig)G (CA-RF) were measured at baseline and 48 weeks after treatment. Paired t-tests were used to compare changes in anti-CCP, RF, and CA-RF between each time point. <h3>Results</h3> Mean DAS28 score decreased from 4.5±1.3 to 3.5±1.3 after 48 weeks on ABT. Titers of anti-CCP were 143.4±176.0 U/ml at baseline and 151.1±176.1 after 48 weeks of treatment, values for RF were 150.4±233.7 IU/ml at baseline and 137.0±191.0 IU/ml after 48 weeks of treatment, and values of CA-RF were 163.0±301.4 AU/ml at baseline and 152.8±249.3 after 48 weeks of treatment on ABT. Titers of anti-CCP (p=0.64), RF (p=0.63) and CA-RF (p=0.57) were unchanged during ABT treatment. Seven patients who achieved improvement (good DAS28 response) on ABT also did not show the decraese of those titers. Titers of anti-CCP (p=0.47), RF (p=0.12) and CA-RF (p=0.12) did not correlate significantly with changes in DAS28. Mean DAS28 decreased from 4.5±1.3 to 2.8±1.1 at 48 weeks on non-ABT. Titers of anti-CCP were 147.1±145.9 U/ml at baseline and 109.7±138.8 IU/ml after 48 weeks of treatment, levels of RF were 145.5±201.3 IU/ml at baseline and 75.4±106.0 IU/ml after 48 weeks of treatment, and levels of CA-RF were 170.1±280.7 AU/ml at baseline and 95.3±130.1 AU/ml after 48 weeks of treatment with non-ABT. Titers of anti-CCP (p&lt;0.001), RF (p&lt;0.001) and CA-RF (p=0.002) were reduced significantly during non-ABT treatment. <h3>Conclusions</h3> These findings suggest that the titer of autoimmunity did not decrease during ABT treatment in established RA, regardless of disease activity. Although the titer of autoimmunity decreases during non-ABT treatment in established RA, percentage of MTX use might be involved (ABT: 71.9%, non-ABT: 86.1%; p=0.05). <h3>Disclosure of Interest</h3> None declared
Attributable mortality of noscomial candidemia caused by Candida non-albicans spp in critically ill patients
Authors: Stijn Blot, Jan De Waele, Koenraad Vandewoude, Dirk De Bacquer, Eric Hoste, J Deschuijmer, Johan Decruyenaere, Francis Colardyn
Journal: Clinical Microbiology and Infection (2004)
PTU-297 Experience of early morning emergency endoscopy at princess alexandra harlow (pah)
Authors: D Tai, K Bryce, D Cruz, M Bose
Journal: Gut (2015)

<h3>Introduction</h3> Endoscopy within 24 h of admission with acute upper GI bleeding (AUGIB) is associated with improved outcomes.<sup>1</sup>NICE guidance<sup>2</sup>recommends endoscopy to be available 24/7 but such standards are difficult to meet. A dedicated 8 until 9 am list has been suggested to minimise out-of-hours endoscopy.<sup>3</sup>An audit at PAH of AUGIB related massive transfusion protocol activations in 2011 and 2013 showed a reduction in mortality (from 10/19 to 0/3 mortality per activations) after implementing a dedicated list. This descriptive study analyses how this list has evolved and identifies areas for improvement. <h3>Method</h3> We audited endoscopic procedures between 8–9 am on weekdays between the 22/12/2014 and 27/01/2015. Patient demographic, referral dates, indications and findings were analysed. <h3>Results</h3> Fifty patients (mean age 73.5 range 20.7– 93.5, 60% male) were audited (86% OGD, 24% flexible sigmoidoscopy, FS). Twelve percent of procedures (4 OGD 2 FS) were cancelled because of haemodynamic instability (2/6), low SpO2 (1/6), inappropriate palliative patient (1/6), non-consent (1/6) and no MCA2 declaration (1/6). Mean time between referral and procedure was 2.5 days (range 1–13). Procedures were done within 24 and 48 h after referral in 48% and 80% of the time, respectively, while 50% suspected UGI bleeds had an OGD within 24 h. OGD referrals were for assessment of suspected UGIB (72%), dysphagia (12%), varices screening (7%) and dyspepsia (6%). Endotherapy was performed in 23%. A probable cause for UGIB was found in 44%, blood in upper GI tract in 11% and haemostatic endotherapy was delivered in 22%. In those with dysphagia, oesophageal stricturing (3/5, 2 requiring dilatation), post-oesophagectomy (1/5) and oesophagitis (1/5) were seen. <h3>Conclusion</h3> This list allows an average of 2 extra procedures to be performed daily, without interrupting elective work. Since over 10% of patients are sent back to wards we propose optimising use of list capacity. We report similar waiting times for suspected UGIB to other UK endoscopy units, although still not in line with NICE recommendations. Around 1 in 5 patients required endotherapy. We suggest that our current endoscopy referral triage to an early morning endoscopy list effectively manages AUGIB locally but could be optimised by improving time to endoscopy in suspected AUGIB and decreasing non ultilisation rates. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Chak A, <i>et al</i>. Effectiveness of endoscopy in patients admitted to the intensive care unit with upper GI hemorrhage. Gastrointest Endosc. 2001;53:6–13 NICE Guideline:Acute upper gastrointestinal bleeding:management, CG141, June 2012 Provision of Endoscopy Related Services in District General Hospitals. BSG Working Party Report 2001 Acute Upper Gastrointestinal Bleeding:An overview of out of hours service provision and equity of access. NHS Improving Quality/BSG, January 2014
Reply
Authors: Maria B. Lauvsnes, Ole J. Greve, Ingeborg Kvivik, Erna Harboe, Anne B. Tjensvoll, Mona K. Beyer, Jan T. Kvaløy, Lasse G. Gøransson, Simone Appenzeller, Roald Omdal
Journal: Arthritis & Rheumatology (2015)
Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target
Authors: Marina Bolzoni, Martina Chiu, Fabrizio Accardi, Rosanna Vescovini, Irma Airoldi, Paola Storti, Katia Todoerti, Luca Agnelli, Gabriele Missale, Roberta Andreoli, Massimiliano G. Bianchi, Manfredi Allegri, Amelia Barilli, Francesco Nicolini, Albertina Cavalli, Federica Costa, Valentina Marchica, Denise Toscani, Cristina Mancini, Eugenia Martella, Valeria Dall’Asta, Gaetano Donofrio, Franco Aversa, Ovidio Bussolati, Nicola Giuliani
Journal: Blood (2016)
Syndromic surveillance of epidemic-prone diseases in response to an influx of migrants from North Africa to Italy, May to October 2011
Authors: F Riccardo, C Napoli, A Bella, C Rizzo, M C Rota, M G Dente, S De Santis, S Declich
Journal: Eurosurveillance (2011)

Following civil unrest in North Africa early in 2011, there was a large influx of migrants in Italy. A syndromic surveillance system was set up in April to monitor the health of this migrant population and respond rapidly to any health emergency. In the first six months, the system produced 67 alerts across all syndromes monitored and four alarms. There were no health emergencies, however, indicating that this migration flow was not associated with an increased risk of communicable disease transmission in Italy.
AB0565 Routine Investigations for Circulating Igg4 and/or Igg4+ Salivary Gland Histopathology Fail to Reveal Undiagnosed Cases of Igg4 Related Disease in Sicca Patients not Fulfilling the Diagnosis of Sjogren's Syndrome
Authors: E. Astorri, C. Croia, G. Picarelli, N. Sutcliffe, A. Tappuni, M. Bombardieri, R. Priori
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition characterized by dense IgG4+ plasmacytic infiltration of diverse organs, fibrosis, tumefactive lesions and eosinophilia. Salivary and lacrimal glands are frequent targets that can present with enlargement and severe hypofunction. The diagnosis of IgG4-RD is challenging because of its serological and histopathological overlaps with other diseases, in particular, a differential diagnosis with Sjogren9s syndrome (SS) can sometimes be achieved only on the basis of a labial salivary gland biopsy. <h3>Objectives</h3> In this study we evaluated whether some of the patients with sicca symptoms not fulfilling SS classification criteria, were in fact affected by IgG4-RD. <h3>Methods</h3> A total of 81 Sicca and 50 SS patients were retrospectively evaluated for IgG4-RD-associated signs and symptoms. Additionally, IgG4 and total-IgG staining was performed on lip gland biopsies from all patients while IgG4 serum levels were evaluated on the Italian cohort. <h3>Results</h3> Only 2 of the Sicca patients had positive IgG4 staining but did not fulfil the diagnostic criteria. The serum analysis found 3 sicca patients with raised IgG4 (≥1.35 g/L) but none had a concomitant positive histology nor IgG4-RD related symptoms. <h3>Conclusions</h3> In our cohort of patients with sicca symptoms not fulfilling SS criteria no case could be accounted as an undiagnosed IgG4-RD based upon IgG4 staining on labial salivary gland biopsies. This study also suggests that in the absence of a clear clinical suspicious of an IgG4-RD, a routine IgG4 staining on labial salivary gland biopsies is not of clinical utility. <h3>References</h3> Yamamoto M, Harada S, Ohara M, Suzuki C, Naishiro Y, Yamamoto H, et al. Clinical and pathological differences between Mikulicz9s disease and Sjogren9s syndrome. Rheumatology (Oxford). 2005 Feb;44(2):227-34. PubMed PMID: 15509627. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21-30. PubMed PMID: 22218969. <h3>Disclosure of Interest</h3> None declared
Crohn Disease
Authors: Adam Cheifetz
Journal: JAMA (2014)

People with Crohn disease have inflamed tissues in their digestive tract.Crohn disease is one type of inflammatory bowel disease (IBD).It is a chronic (long-lasting) condition.Crohn disease can develop at any age, but it most commonly develops between ages 20 and 30 years.What Are the Symptoms of Crohn Disease?
Randomized phase IIb study of nivolumab (anti-PD-1; BMS-936558, ONO-4538) alone or in combination with ipilimumab versus bevacizumab in patients (pts) with recurrent glioblastoma (GBM).
Authors: John Howard Sampson, Gordana Vlahovic, Annick Desjardins, Henry S. Friedman, Joachim M. Baehring, David Hafler, Linda Rollin, Vlad Coric, Susan N. Perez, David A. Reardon
Journal: Journal of Clinical Oncology (2014)

TPS2101 Background: GBM, the most common primary brain tumor in adults, has an aggressive clinical course and a median survival of 12–15 months post first-line therapy with maximal surgical resection, radiation, and temozolomide. Bevacizumab is approved in the US for pts with progressive disease following therapy; no data has shown durable improvement of disease-related symptoms or overall survival (OS). With limited efficacy of current therapy, more effective treatments to extend survival and preserve quality of life are needed. Ipilimumab, a cytotoxic T-lymphocyte antigen-4 receptor blocking antibody, has shown clinical activity in advanced melanoma pts with brain metastases; preclinical studies demonstrate a benefit from combining a programmed death-1 (PD-1) pathway inhibitor with radiation in a mouse glioma model. We present a phase IIb, randomized, open-label study to evaluate the efficacy and safety of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, alone or with ipilimumab, vs bevacizumab in pts with recurrent GBM. Methods: Pts with Karnofsky performance status ≥70, grade IV malignant glioma treated with radiotherapy and temozolomide, and documented first GBM recurrence within 28 days of randomization are eligible. Pts with >1 recurrence of GBM, extracranial disease, autoimmune conditions, or previous VEGF inhibitor or anti-angiogenic treatment are ineligible. Safety cohort 1; nivolumab 3 mg/kg [n=10; Q2W x 4] and nivolumab 1 mg/kg + ipilimumab 3 mg/kg [n=10; Q3W x 4 followed by nivolumab 3 mg/kg Q2W]) will establish safety and tolerability in GBM pts. Upon successful completion of cohort 1, efficacy cohort 2 will enroll up to 240 pts with recurrent GBM, randomized 1:1:1 to receive nivolumab, nivolumab + ipilimumab (dosed as cohort 1), or bevacizumab (10 mg/kg Q2W). The primary objectives are to evaluate safety in cohort 1 and OS in cohort 2, vs bevacizumab, with secondary objectives of PFS and ORR. Responses will be assessed (Response Assessment Neuro-Oncology criteria) at the end of wks 6 and 12, and Q8W until progression or treatment discontinuation. Clinical trial information: NCT02017717.
Antigenic Cross-Reactivity Between Benign and Malignant Neoplasms of the Human Breast 2
Authors: Frederick Avis, Ingalill Mosonov, Geoffrey Haughton
Journal: JNCI Journal of the National Cancer Institute (1974)

Lymphocytes from patients who had fibroadenoma alone or combined with fibrocystic disease of the breast were specifically cytotoxic to breast adenocarcinoma cells, as measured in vitro by the microcytotoxicity test. The cell-mediated immunity was specific for breast tumor cells and there was no unexpected cross-reactivity with other types of tumor cells or with normal fibroblasts. In some cases, criss-cross type experiments were used between fibroadenoma patients and those with unrelated types of cancer. These results implied the existence of a common antigen on the cell surface of fibroadenomas and adenocarcinomas of the breast.
Influence of Pre-Existing Immunity Upon Effect of Sabin Vaccine
Authors: M HIRAYAMA, K SAWADA
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Staphylococcal Sepsis in Children
Authors: Ricardo G Branco, Robert C Tasker
Journal: New England Journal of Medicine (2005)

n engl j med 353;26 www.nejm.org december 29, 2005 2820 analyses, however, identified no selection bias, and they also indicated that treatment with CMV hyperimmune globulin was an independent predictor of fetal outcome. Furthermore, all relevant biologic data are consistent with our observations, which included the following findings: the CMV hyperimmune globulin contained high levels of neutralizing antibody; the rates of CMV transmission and disease that we observed were in line with those previously reported by others; preexisting maternal immunity is protective against CMV infection and disease; and in experiments in animals going back 25 years, passive immunization is effective.1 We encourage Dr. Revello and her colleagues to conduct confirmatory trials.
AB1203 Targeted-Ultrasound Initiative in Brazil: Access and Barriers to Ultrasound Dissemination in Clinical Practice
Authors: R. Chakr, J.A. Mendonça, K. Bonfiglioli, I. Moss, K. Luz, I. Laurindo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Although consistent divulgation and training US initiatives have been underway nationwide, the number of ultrasound (US) machines and experienced examiners in Brazil is inadequate for covering the country demand. There are 36 machines used by rheumatologists, mostly in the southeast, for a population of approximately 800,000 rheumatoid arthritis (RA) patients. Clearly there are barriers to US dissemination that could be related to the acceptance of the method or practical barriers such as machine cost and reimbursement. <h3>Objectives</h3> To get insights on the barriers and unmet needs in Brazil in order to define Targeted-Ultrasound Initiative (TUI -educational program aimed to promote greater use of ultrasound in the management of rheumatoid arthritis) strategies. <h3>Methods</h3> A web-based questionnaire about US practice and basic concepts was developed and distributed to members of the Brazilian Society of Rheumatology (BSR). <h3>Results</h3> Among 2.206 BSR active members, 249 rheumatologists from all over the country answered the questionnaire, roughly following the allocation pattern of the rheumatologists in the country. Interestingly, 37,8% of the responders graduated after 2000 and 45,8% between 1981 and 2000. About half of them had never participated in an US course (51%), but only 8.8% reported no interest in learning. Access to US was prevalent but mostly through a radiologist (72.3%), with no specific training in rheumatology. Most rheumatologists supported US value in diagnosis (90.4%) and treatment follow up (78.7%) as well as in treatment guidance (87.9%), contributing to indicate treatment changes in inflammatory arthropathies. On the other hand, US was recognized as useful tool for erosion assessment by only 59% of the rheumatologists. Regarding barriers, the limited access to machines and reimbursement issues were mentioned respectively by 52.7 and 32% of the rheumatologists but surprisingly the lack of continuous and supervised practice necessary to the learning process and proper qualification was considered an important barrier by 66%. <h3>Conclusions</h3> Most rheumatologists understand the importance of US and its value in improving patient outcomes. This recognition of US usefulness could be interpreted a result of the divulgation and training initiatives. The significant barriers were not only related to cost (machine vs. reimbursement) but to the practical aspects of the learning process and adequate qualification; the most pressing unmet needs hence identified. <h3>References</h3> Ann Rheum Dis 2012;71:6799-803. <h3>Disclosure of Interest</h3> None declared