WorldWideScience

Sample records for facility b-cell quality

  1. Quality assurance program plan for 324 Building B-Cell safety cleanout project (BCCP)

    International Nuclear Information System (INIS)

    Tanke, J.M.

    1997-01-01

    This Quality Assurance Program Plan (QAPP) provides information on how the Quality Assurance Program is implemented for the 324 Building B-Cell Safety Cleanout Project (BCCP). This QAPP is responsive to the Westinghouse Hanford Company Quality Assurance Program and Implementation Plan, WHC-SP-1131, for 10 CFR 830.120, Nuclear Safety Management, Quality Assurance Requirements; and DOE Order 5700.6C, Quality Assurance. This QAPP supersedes PNNL PNL-MA-70 QAP Quality Assurance Plan No. WTC-050 Rev. 2, issue date May 3, 1996. This QAPP has been developed specifically for the BCCP. It applies to those items and tasks which affect the completion of activities identified in the work breakdown structure of the Project Management Plan (PMP). These activities include all aspects of decontaminating B-Cell and project related operations within the 324 Building as it relates to the specific activities of this project. General facility activities (i.e. 324 Building Operations) are covered in the Building 324 QAPP. In addition, this QAPP supports the related quality assurance activities addressed in CM-2-14, Hazardous Material Packaging and Shipping, and HSRCM-1, Hanford Site Radiological Control Manual, The 324 Building is currently transitioning from being a Pacific Northwest National Laboratory (PNNL) managed facility to a B and W Hanford Company (BWHC) managed facility. During this transition process existing, PNNL procedures and documents will be utilized until replaced by BWHC procedures and documents. These documents conform to the requirements found in PNL-MA-70, Quality Assurance Manual and PNL-MA-8 1, Hazardous Materials Shipping Manual. The Quality Assurance Program Index (QAPI) contained in Table 1 provides a matrix which shows how project activities relate to 10 CFR 83 0.120 and 5700.6C criteria. Quality Assurance program requirements will be addressed separate from the requirements specified in this document. Other Hanford Site organizations/companies may be

  2. Data quality objectives for the B-Cell waste stream classification sampling

    International Nuclear Information System (INIS)

    Barnett, J.M.

    1998-01-01

    This document defines the data quality objectives, (DQOS) for sampling the B-Cell racks waste stream. The sampling effort is concentrated on determining a ratio of Cs-137 to Sr-90 and Cs-137 to transuranics (TRU). Figure 1.0 shows the logic path of sampling effort. The flow chart begins with sample and data acquisition and progresses toward (a) statistical confidence and waste classification boundaries, (b) management decisions based on the input parameters and technical methods available, and (c) grout container volume/weight limits and radiation limits. The end result will be accurately classifying the B-Cell rack waste stream

  3. Air Quality Facilities

    Data.gov (United States)

    Iowa State University GIS Support and Research FacilityFacilities with operating permits for Title V of the Federal Clean Air Act, as well as facilities required to submit an air emissions inventory, and other facilities...

  4. A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production

    Science.gov (United States)

    Srour, Nivine; Chemin, Guillaume; Tinguely, Aurélien; Ashi, Mohamad Omar; Oruc, Zéliha; Péron, Sophie; Sirac, Christophe

    2016-01-01

    Aberrantly rearranged immunoglobulin (Ig) alleles are frequent. They are usually considered sterile and innocuous as a result of nonsense-mediated mRNA decay. However, alternative splicing can yield internally deleted proteins from such nonproductively V(D)J-rearranged loci. We show that nonsense codons from variable (V) Igκ exons promote exon-skipping and synthesis of V domain-less κ light chains (ΔV-κLCs). Unexpectedly, such ΔV-κLCs inhibit plasma cell (PC) differentiation. Accordingly, in wild-type mice, rearrangements encoding ΔV-κLCs are rare in PCs, but frequent in B cells. Likewise, enforcing expression of ΔV-κLCs impaired PC differentiation and antibody responses without disturbing germinal center reactions. In addition, PCs expressing ΔV-κLCs synthesize low levels of Ig and are mostly found among short-lived plasmablasts. ΔV-κLCs have intrinsic toxic effects in PCs unrelated to Ig assembly, but mediated by ER stress–associated apoptosis, making PCs producing ΔV-κLCs highly sensitive to proteasome inhibitors. Altogether, these findings demonstrate a quality control checkpoint blunting terminal PC differentiation by eliminating those cells expressing nonfunctionally rearranged Igκ alleles. This truncated Ig exclusion (TIE) checkpoint ablates PC clones with ΔV-κLCs production and exacerbated ER stress response. The TIE checkpoint thus mediates selection of long-lived PCs with limited ER stress supporting high Ig secretion, but with a cost in terms of antigen-independent narrowing of the repertoire. PMID:26666261

  5. Service quality for facilities management in hospitals

    CERN Document Server

    Sui Pheng, Low

    2016-01-01

    This book examines the Facilities Management (FM) of hospitals and healthcare facilities, which are among the most complex, costly and challenging kind of buildings to manage. It presents and evaluates the FM service quality standards in Singapore’s hospitals from the patient’s perspective, and provides recommendations on how to successfully improve FM service quality and achieve higher patient satisfaction. The book also features valuable supplementary materials, including a checklist of 32 key factors for successful facilities management and another checklist of 24 service attributes for hospitals to achieve desirable service quality in connection with facilities management. The book adopts a unique approach of combining service quality and quality theory to provide a more holistic view of how FM service quality can be achieved in hospitals. It also integrates three instruments, namely the SERVQUAL model, the Kano model and the QFD model to yield empirical results from surveys for implementation in hosp...

  6. Quality Assurance for Operation of Nuclear Facilities

    International Nuclear Information System (INIS)

    Park, C. G.; Kwon, H. I.; Kim, K. H.; Oh, Y. W.; Lee, Y. G.; Ha, J. H.; Lim, N. J.

    2008-12-01

    This report describes QA activities performed within 'Quality Assurance for Nuclear facility project' and results thereof. Efforts were made to maintain and improve quality system of nuclear facilities. Varification activities whether quality system was implemented in compliance with requirements. QA department assisted KOLAS accredited testing and calibration laboratories, ISO 9001 quality system, establishment of QA programs for R and D, and carried out reviews and surveys for development of quality assurance technologies. Major items of this report are as follows : - Development and Improvement of QA Programs - QA Activities - Assessment of Effectiveness and Adequacy for QA Programs

  7. Quality management in nuclear facilities decommissioning

    International Nuclear Information System (INIS)

    Garonis, Omar H.

    2002-01-01

    Internationally, the decommissioning organizations of nuclear facilities carry out the decommissioning according to the safety requirements established for the regulatory bodies. Some of them perform their activities in compliance with a quality assurance system. This work establishes standardization through a Specifications Requirement Document, for the management system of the nuclear facilities decommissioning organizations. It integrates with aspects of the quality, environmental, occupational safety and health management systems, and also makes these aspects compatible with all the requirements of the nuclear industry recommended for the International Atomic Energy Agency (IAEA). (author)

  8. B-cell waste classification sampling plan

    Energy Technology Data Exchange (ETDEWEB)

    HOBART, R.L.

    1999-11-20

    This report documents the methods used to collect samples and analyze data necessary to verify and/or determine the radionuclide content of the 324 Facility B-Cell decontamination and decommissioning waste stream.

  9. Inpatient Psychiatric Facility Quality Measure Data – by State

    Data.gov (United States)

    U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

  10. Inpatient Psychiatric Facility Quality Measure Data – by Facility

    Data.gov (United States)

    U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

  11. Quality of drug prescription in primary health care facilities in ...

    African Journals Online (AJOL)

    DR Marwa

    Abstract. Background: Drug therapy can improve a patient's quality of life and health outcomes if only used properly. However, data on prescription quality at primary health care facilities in Tanzania is scanty. The objective of this study was to assess the quality of drug prescriptions in selected health care facilities in.

  12. Quality of drug prescription in primary health care facilities in ...

    African Journals Online (AJOL)

    Background: Drug therapy can improve a patient's quality of life and health outcomes if only used properly. However, data on prescription quality at primary health care facilities in Tanzania is scanty. The objective of this study was to assess the quality of drug prescriptions in selected health care facilities in two districts of ...

  13. 200 Area Liquid Effluent Facilities -- Quality assurance program plan

    International Nuclear Information System (INIS)

    Fernandez, L.

    1995-01-01

    This Quality Assurance Program Plan (QAPP) describes the quality assurance and management controls used by the 200 Area Liquid Effluent Facilities (LEF) to perform its activities in accordance with DOE Order 5700.6C. The 200 Area LEF consists of the following facilities: Effluent Treatment Facility (ETF); Treated Effluent Disposal Facility (TEDF); Liquid Effluent Retention facility (LERF); and Truck Loading Facility -- (Project W291). The intent is to ensure that all activities such as collection of effluents, treatment, concentration of secondary wastes, verification, sampling and disposal of treated effluents and solids related with the LEF operations, conform to established requirements

  14. Quality of life more impaired in younger than in older diffuse large B cell lymphoma survivors compared to a normative population : A study from the population-based PROFILES registry

    NARCIS (Netherlands)

    van der Poel, M.; Oerlemans, S.; Schouten, H.C.; Mols, F.; Pruijt, J.F.M.; Maas, H.; van de Poll-Franse, L.V.

    2014-01-01

    The objective of this study was to compare health-related quality of life (HRQOL) between diffuse large B cell lymphoma (DLBCL) survivors of different age categories (18–59/60–75/76–85 years) and to compare their HRQOL with an age- and sex-matched normative population. The population-based Eindhoven

  15. QART - the CERN facility for quality assurance

    CERN Multimedia

    Katarina Anthony

    2011-01-01

    How would your detector perform in a very high magnetic field? Or at 60°C and high humidity? Will it work for 10 or more years? Answering these questions requires specialised and thorough testing. This can be done at the Quality Assurance and Reliability Testing Laboratory (QART) - a top-notch testing facility based at CERN, providing invaluable support for CERN projects. The QART lab has become a service in 2011, and invites all projects to use its equipment and expertise.   A portable high-sensitivity infra-red thermal imaging video camera (top left) is used to observe the thermal profile of a silicon strip sensor (top right). The thermal images taken before (bottom left) and after (bottom right) applying voltage to the device clearly show a hot spot developing on the sensor, indicating a serious defect. The infra-red camera is an example of the variety of sophisticated equipment in the QART lab available to CERN projects for the analysis of problems and enviro...

  16. Analysis of Student Satisfaction Toward Quality of Service Facility

    Science.gov (United States)

    Napitupulu, D.; Rahim, R.; Abdullah, D.; Setiawan, MI; Abdillah, LA; Ahmar, AS; Simarmata, J.; Hidayat, R.; Nurdiyanto, H.; Pranolo, A.

    2018-01-01

    The development of higher education is very rapid rise to the tight competition both public universities and private colleges. XYZ University realized to win the competition, required continuous quality improvement, including the quality of existing service facilities. Amenities quality services is believed to support the success of the learning activities and improve user satisfaction. This study aims to determine the extent to which the quality of the services effect on user satisfaction. The research method used is survey-based questionnaire that measure perception and expectation. The results showed a gap between perception and expectations of the respondents have a negative value for each item. This means XYZ service facility at the university is not currently meet the expectations of society members. Three service facility that has the lowest index is based on the perception of respondents is a laboratory (2.56), computer and multimedia (2.63) as well as wifi network (2.99). The magnitude of the correlation between satisfaction with the quality of service facilities is 0.725 which means a strong and positive relationship. The influence of the quality of service facilities to the satisfaction of the students is 0.525 meaning that the variable quality of the services facility can explain 52.5% of the variable satisfaction. The study provided recommendations for improvements to enhance the quality of services facility at the XYZ university facilities.

  17. Quality Assurance Project Plan for Facility Effluent Monitoring Plan activities

    International Nuclear Information System (INIS)

    Frazier, T.P.

    1994-01-01

    This Quality Assurance Project Plan addresses the quality assurance requirements for the activities associated with the Facility Effluent Monitoring Plans, which are part of the overall Hanford Site Environmental Protection Plan. This plan specifically applies to the sampling and analysis activities and continuous monitoring performed for all Facility Effluent Monitoring Plan activities conducted by Westinghouse Hanford Company. It is generic in approach and will be implemented in conjunction with the specific requirements of the individual Facility Effluent Monitoring Plans

  18. Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

    International Nuclear Information System (INIS)

    Liu, Xin; Fang, Hui; Tian, Yuan; Wang, Wei-Hu; Song, Yong-Wen; Wang, Shu-Lian; Liu, Yue-Ping; He, Xiao-Hui; Dong, Mei; Ren, Hua; Jin, Jing; Li, Ye-Xiong

    2016-01-01

    Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: The median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.

  19. Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin; Fang, Hui; Tian, Yuan; Wang, Wei-Hu; Song, Yong-Wen; Wang, Shu-Lian; Liu, Yue-Ping [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); He, Xiao-Hui; Dong, Mei [Department of Medical Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); Ren, Hua; Jin, Jing [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China); Li, Ye-Xiong, E-mail: yexiong@yahoo.com [Department of Radiation Oncology, Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing (China)

    2016-06-01

    Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: The median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.

  20. Quality Assurance Project Plan for Facility Effluent Monitoring Plan activities

    International Nuclear Information System (INIS)

    Nickels, J.M.

    1991-06-01

    This Quality Assurance Project Plan addresses the quality assurance requirements for the Facility Monitoring Plans of the overall site-wide environmental monitoring plan. This plan specifically applies to the sampling and analysis activities and continuous monitoring performed for all Facility Effluent Monitoring Plan activities conducted by Westinghouse Hanford Company. It is generic in approach and will be implemented in conjunction with the specific requirements of individual Facility Effluent Monitoring Plans. This document is intended to be a basic road map to the Facility Effluent Monitoring Plan documents (i.e., the guidance document for preparing Facility Effluent Monitoring Plans, Facility Effluent Monitoring Plan determinations, management plan, and Facility Effluent Monitoring Plans). The implementing procedures, plans, and instructions are appropriate for the control of effluent monitoring plans requiring compliance with US Department of Energy, US Environmental Protection Agency, state, and local requirements. This Quality Assurance Project Plan contains a matrix of organizational responsibilities, procedural resources from facility or site manuals used in the Facility Effluent Monitoring Plans, and a list of the analytes of interest and analytical methods for each facility preparing a Facility Effluent Monitoring Plan. 44 refs., 1 figs., 2 tabs

  1. B Cell Subsets in Atherosclerosis

    OpenAIRE

    Perry, Heather M.; Bender, Timothy P.; McNamara, Coleen A.

    2012-01-01

    Atherosclerosis, the underlying cause of heart attacks and strokes, is a chronic inflammatory disease of the artery wall. Immune cells, including lymphocytes modulate atherosclerotic lesion development through interconnected mechanisms. Elegant studies over the past decades have begun to unravel a role for B cells in atherosclerosis. Recent findings provide evidence that B cell effects on atherosclerosis may be subset-dependent. B-1a B cells have been reported to protect from atherosclerosis ...

  2. B-Cell waste classification sampling and analysis plan

    International Nuclear Information System (INIS)

    HOBART, R.L.

    1999-01-01

    This report documents the methods used to collect and analyze samples to obtain data necessary to verify and/or determine the radionuclide content of the 324 Facility B-Cell decontamination and decommissioning waste stream

  3. Project quality assurance plant: Sodium storage facility, project F-031

    International Nuclear Information System (INIS)

    Shultz, J.W.; Shank, D.R.

    1994-11-01

    The Sodium Storage Facility Project Quality Assurance Plan delineates the quality assurance requirements for construction of a new facility, modifications to the sodium storage tanks, and tie-ins to the FFTF Plant. This plan provides direction for the types of verifications necessary to satisfy the functional requirements within the project scope and applicable regulatory requirements determined in the Project Functional Design Criteria (FDC), WHC-SD-FF-FDC-009

  4. Near-facility environmental monitoring quality assurance project plan

    International Nuclear Information System (INIS)

    McKinney, S.M.

    1997-01-01

    This Quality Assurance Project Plan addresses the quality assurance requirements for the activities associated with the preoperational and near facility environmental monitoring performed by Waste Management Federal Services, Inc., Northwest Operations and supersedes WHC-EP-0538-2. This plan applies to all sampling and monitoring activities performed by waste management Federal Services, Inc., Northwest Operations in implementing facility environmental monitoring at the Hanford Site

  5. Near-Facility Environmental Monitoring Quality Assurance Project Plan

    International Nuclear Information System (INIS)

    MCKINNEY, S.M.

    2000-01-01

    This Quality Assurance Project Plan addresses the quality assurance requirements for the activities associated with the preoperational and near-facility environmental monitoring directed by Waste Management Technical Services and supersedes HNF-EP-0538-4. This plan applies to all sampling and monitoring activities performed by Waste Management Technical Services in implementing near-facility environmental monitoring at the Hanford Site. This Quality Assurance Project Plan is required by U.S. Department of Energy Order 5400.1 (DOE 1990) as a part of the Environmental Monitoring Plan (DOE-RL 1997) and is used to define: Environmental measurement and sampling locations used to monitor environmental contaminants near active and inactive facilities and waste storage and disposal sites; Procedures and equipment needed to perform the measurement and sampling; Frequency and analyses required for each measurement and sampling location; Minimum detection level and accuracy; Quality assurance components; and Investigation levels. Near-facility environmental monitoring for the Hanford Site is conducted in accordance with the requirements of U.S. Department of Energy Orders 5400.1 (DOE 1990), 5400.5 (DOE 1993), 5484.1 (DOE 1990), and 435.1 (DOE 1999), and DOE/EH-O173T (DOE 1991). It is Waste Management Technical Services' objective to manage and conduct near-facility environmental monitoring activities at the Hanford Site in a cost-effective and environmentally responsible manner that is in compliance with the letter and spirit of these regulations and other environmental regulations, statutes, and standards

  6. B Cells in Autoimmune Diseases

    OpenAIRE

    Hampe, Christiane S.

    2012-01-01

    The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell...

  7. EVALUATION OF SERVICES’ QUALITY IN UPPER SILESIA ACCOMMODATION FACILITIES

    Directory of Open Access Journals (Sweden)

    Iwona Cieślik

    2013-12-01

    Full Text Available This paper presents the results of study about impact of accommodation services’ quality, particularly quality of work and qualifications of staff, on the guests’ opinion, and thus promoting the accommodation facilities, and making a choice of a hotel in the Upper Silesia. The study involved 200 people, taking into account their gender, age, place of residence, education and occupational status. The research tool was a survey questionnaire. The results indicate close correlation between the quality of staff services (individual approach, aesthetics, discretion, understanding and the customer is satisfaction. Particular attention was paid to the quality of service by the guests with high professional status, and higher education.

  8. 233-S Plutonium Concentration Facility data quality objectives

    International Nuclear Information System (INIS)

    Encke, D.B.

    1996-08-01

    This document is a summary of the decision-making associated with the Data Quality Objective process that pertains to the characterization activities in the 233-S Plutonium Concentration Facility at the Hanford Site in Richland, Washington. The 233-S Plutonium Concentration Facility is located adjacent to, and north of, the REDOX Plant. The facility was used to concentrate the plutonium nitrate product solution from the REDOX facility. The 233-S Pipe Gallery, Control Room, SWP Change Room, Toilet, Equipment Room and the Electrical Cubicle are currently scheduled for decontamination and cleanout to support future demolition (D and D). Identification of the radiological contamination and presence of hazardous materials is needed to allow for disposal of the D and D debris

  9. Quality assessment in nursing home facilities: measuring customer satisfaction.

    Science.gov (United States)

    Mostyn, M M; Race, K E; Seibert, J H; Johnson, M

    2000-01-01

    A national study designed to assess the reliability and validity of a nursing home customer satisfaction survey is summarized. One hundred fifty-nine facilities participated, each responsible for the distribution and collection of 200 questionnaires randomly sent to the home of the resident's responsible party. A total of 9053 completed questionnaires were returned, for an average adjusted response rate of 53%. The factor analysis identified 4 scales: Comfort and Cleanliness, Nursing, Food Services, and Facility Care and Services, each with high reliability. Based on a multiple regression analysis, the scales were shown to have good criterion-related validity, accounting for 64% of the variance in overall quality ratings. Comparisons based on select characteristics indicated significantly different satisfaction ratings among facilities. The results are interpreted as providing evidence for the construct validity of a multidimensional customer satisfaction scale with measured reliability and criterion-related validity. Moreover, the scale can be used to differentiate satisfaction levels among facilities.

  10. The medical director and quality requirements in the dialysis facility.

    Science.gov (United States)

    Schiller, Brigitte

    2015-03-06

    Four decades after the successful implementation of the ESRD program currently providing life-saving dialysis therapy to >430,000 patients, the definitions of and demands for a high-quality program have evolved and increased at the same time. Through substantial technological advances ESRD care improved, with a predominant focus on the technical aspects of care and the introduction of medications such as erythropoiesis-stimulating agents and active vitamin D for anemia and bone disease management. Despite many advances, the size of the program and the increasingly older and multimorbid patient population have contributed to continuing challenges for providing consistently high-quality care. Medicare's Final Rule of the Conditions for Coverage (April 2008) define the medical director of the dialysis center as the leader of the interdisciplinary team and the person ultimately accountable for quality, safety, and care provided in the center. Knowledge and active leadership with a hands-on approach in the quality assessment and performance improvement process (QAPI) is essential for the achievement of high-quality outcomes in dialysis centers. A collaborative approach between the dialysis provider and medical director is required to optimize outcomes and deliver evidence-based quality care. In 2011 the Centers for Medicare & Medicaid Services introduced a pay-for-performance program-the ESRD quality incentive program (QIP)- with yearly varying quality metrics that result in payment reductions in subsequent years when targets are not achieved during the performance period. Success with the QIP requires a clear understanding of the structure, metrics, and scoring methods. Information on achievement and nonachievement is publicly available, both in facilities (through the facility performance score card) and on public websites (including Medicare's Dialysis Facility Compare). By assuming the leadership role in the quality program of dialysis facilities, the medical

  11. Inpatient Psychiatric Facility Follow-Up After Hospitalization for Mental Illness (FUH) Quality Measure Data – by Facility

    Data.gov (United States)

    U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

  12. B cells in operational tolerance.

    Science.gov (United States)

    Chesneau, M; Danger, R; Soulillou, J-P; Brouard, S

    2018-02-16

    Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunosuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal. This review summarizes studies that suggest a role for B cells as biomarkers of operational tolerance and discusses the use of B cells as a predictive tool for immunologic risk. Copyright © 2018. Published by Elsevier Inc.

  13. Quality Assurance of ARM Program Climate Research Facility Data

    Energy Technology Data Exchange (ETDEWEB)

    Peppler, RA; Kehoe, KE; Sonntag, KL; Bahrmann, CP; Richardson, SJ; Christensen, SW; McCord, RA; Doty, DJ; Wagener, Richard [BNL; Eagan, RC; Lijegren, JC; Orr, BW; Sisterson, DL; Halter, TD; Keck, NN; Long, CN; Macduff, MC; Mather, JH; Perez, RC; Voyles, JW; Ivey, MD; Moore, ST; Nitschke, DL; Perkins, BD; Turner, DD

    2008-03-01

    This report documents key aspects of the Atmospheric Radiation Measurement (ARM) Climate Research Facility (ACRF) data quality assurance program as it existed in 2008. The performance of ACRF instruments, sites, and data systems is measured in terms of the availability, usability, and accessibility of the data to a user. First, the data must be available to users; that is, the data must be collected by instrument systems, processed, and delivered to a central repository in a timely manner. Second, the data must be usable; that is, the data must be inspected and deemed of sufficient quality for scientific research purposes, and data users must be able to readily tell where there are known problems in the data. Finally, the data must be accessible; that is, data users must be able to easily find, obtain, and work with the data from the central repository. The processes described in this report include instrument deployment and calibration; instrument and facility maintenance; data collection and processing infrastructure; data stream inspection and assessment; the roles of value-added data processing and field campaigns in specifying data quality and haracterizing the basic measurement; data archival, display, and distribution; data stream reprocessing; and engineering and operations management processes and procedures. Future directions in ACRF data quality assurance also are presented.

  14. Quality Assurance of ARM Program Climate Research Facility Data

    International Nuclear Information System (INIS)

    Peppler, R.A.; Kehoe, K.E.; Sonntag, K.L.; Bahramann, C.P.; Richardson, S.J.; Christensen, S.W.; McCord, R.A.; Doty, D.J.; Wagener, R.; Eagan, R.C.; Lijegren, J.C.; Orr, B.W.; Sisterson, D.L.; Halter, T.D.; Keck, N.N.; Long, C.N.; Macduff, M.C.; Mather, J.H.; Perez, R.C.; Voyles, J.W.; Ivey, M.D.; Moore, S.T.; Nitschke, D.L.; Perkins, B.D.; Turner, D.D.

    2008-01-01

    This report documents key aspects of the Atmospheric Radiation Measurement (ARM) Climate Research Facility (ACRF) data quality assurance program as it existed in 2008. The performance of ACRF instruments, sites, and data systems is measured in terms of the availability, usability, and accessibility of the data to a user. First, the data must be available to users; that is, the data must be collected by instrument systems, processed, and delivered to a central repository in a timely manner. Second, the data must be usable; that is, the data must be inspected and deemed of sufficient quality for scientific research purposes, and data users must be able to readily tell where there are known problems in the data. Finally, the data must be accessible; that is, data users must be able to easily find, obtain, and work with the data from the central repository. The processes described in this report include instrument deployment and calibration; instrument and facility maintenance; data collection and processing infrastructure; data stream inspection and assessment; the roles of value-added data processing and field campaigns in specifying data quality and characterizing the basic measurement; data archival, display, and distribution; data stream reprocessing; and engineering and operations management processes and procedures. Future directions in ACRF data quality assurance also are presented

  15. Development of a quality system for a contract irradiation facility

    International Nuclear Information System (INIS)

    Siyakus, G.

    2002-01-01

    . Even, some conditions required by the primary producer may be impossible to apply because of the design parameters of the facility or economical reasons. The worst situation is, transforming the commodity to be processed into garbage, because of the any misapprehension among the customer and the organization running the facility, or any level of misleading among the internal communication chain of the organization. Therefore, every step of the process from delivery of the product by the principal manufacturer up to the release of the commodity after irradiation should be firmly defined, organized, documented, validated and certified. The purpose of the irradiation may be at variance from decontamination of a food commodity to the sterilization of a medical supply. To make things easier, the case study which will be presented in the scope of this paper is limited with the radiation sterilization of medical supplies at the Food Irradiation and Sterilization Department (FISD) of Ankara Nuclear Research Center of Agriculture and Animal Science (ANRCAAS). To meet the requirements stated by the contract, an appropriate quality management system should be implemented. Basic activities for implementing a quality management system should be: A policy for quality management, An appropriate work flow, Contract model to make certain the demand of the primary producer, Straightforward documentation of the management responsibilities, Suitable premises, equipment and materials, Well defined and documented procedures, processes to be applied on the product, Traceable batch, product and dosimetry records, Definitely the radiation, chemical and biological safety issues related to the personnel working in the quality control laboratories and irradiation facility are more essential issues than the above mentioned topics and should be included into the quality system

  16. Air quality impacts due to construction of LWR waste management facilities

    International Nuclear Information System (INIS)

    1977-06-01

    Air quality impacts of construction activities and induced housing growth as a result of construction activities were evaluated for four possible facilities in the LWR fuel cycle: a fuel reprocessing facility, fuel storage facility, fuel fabrication plant, and a nuclear power plant. Since the fuel reprocessing facility would require the largest labor force, the impacts of construction of that facility were evaluated in detail

  17. Impacts of iron and steelmaking facilities on soil quality.

    Science.gov (United States)

    Strezov, Vladimir; Chaudhary, Chandrakant

    2017-12-01

    Iron and steel are highly important materials used in a wide range of products with important contribution to the economic development. The processes for making iron and steel are energy intensive and known to contribute to local pollution. Deposition of the metals may also have adverse impacts on soil quality, which requires detailed assessment. The aim of this study was to investigate the impacts of iron and steelmaking facilities on the local soil quality. Soil samples were collected in the vicinity of two steelmaking sites in Australia, one based on blast furnace steelmaking operation, while the second site was based on electric arc furnace steel recycling. The soil samples were compared to a background site where no industrial impact is expected. The soil collected near industrial facilities contained larger toxic metal contents, however this concentration for all priority metals was within the Australian National Environmental Protection Measure guidelines for the acceptable recreational soil quality. When compared to the international soil quality guidelines, some of the soils collected near the industrial sites, particularly near the blast furnace operated steelmaking, exceeded the arsenic, iron and manganese (according to United States Environmental Protection Agency guidelines) and chromium, copper and nickel concentrations (according to the Canadian guidelines). The work further provided a novel environmental assessment model taking into consideration the environmental and health impacts of each element. The environmental assessment revealed most significant contribution of manganese, followed by titanium, zinc, chromium and lead. Titanium was the second most important contributor to the soil quality, however this metal is currently not included in any of the international soil quality guidelines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. B cell activating factor (BAFF) selects IL-10-B cells over IL-10+B cells during inflammatory responses.

    Science.gov (United States)

    Ma, Ning; Zhang, Yu; Liu, Qilin; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Yu, Dandan; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Ma, Yuanfang; Shen, Beifen; Li, Yan; Xiao, He; Wang, Renxi

    2017-05-01

    B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10 - B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10 + Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10 + B cells over IL-10 - B cells under noninflammatory conditions in vitro, whereas it expanded IL-10 - B cells over IL-10 + B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10 - B cells over IL-10 + B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10 - B cells over IL-10 + regulatory B cells via BAFF receptors in inflammatory responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. B-cell leukemia/lymphoma panel

    Science.gov (United States)

    ... ency/article/003518.htm B-cell leukemia/lymphoma panel To use the sharing features on this page, please enable JavaScript. B-cell leukemia/lymphoma panel is a blood test that looks for certain ...

  20. Primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    Martelli, Maurizio; Ferreri, Andrés; Di Rocco, Alice; Ansuinelli, Michela; Johnson, Peter W M

    2017-05-01

    Primary mediastinal large B-cell lymphoma (PMLBCL) is a distinct clinical and biological disease from other types of DLBCL. It is more frequent in young female and constitutes 6%-10% of all DLBCL. PMLBCL is characterized by a diffuse proliferation of medium to large B-cells associated with sclerosis. Molecular analysis shows it to be a distinct entity from other DLBCL. Rituximab CHOP/MACOP-B-like regimens followed by mediastinal radiotherapy (RT) were associated with a 5-years PFS of 75%-85%. More intensive regimens, as DA-EPOCH-R without mediastinal RT, have shown very promising results, but this therapeutic advance needs to be confirmed in further prospective trials. The role of consolidative mediastinal RT should be still better assess in prospective comparative studies. PET-CT scan is a powerful tool to define the real quality of response and it is hoped that future prospective trials may allow its role in the de-escalation of mediastinal RT. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Environmental Monitoring, Water Quality - Water Pollution Control Facilities

    Data.gov (United States)

    NSGIC Education | GIS Inventory — A Water Pollution Control Facility is a DEP primary facility type related to the Water Pollution Control Program. The sub-facility types related to Water Pollution...

  2. HCV Infection and B-Cell Lymphomagenesis

    Directory of Open Access Journals (Sweden)

    Masahiko Ito

    2011-01-01

    Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

  3. The BNCT facility at the HFR Petten: Quality assurance for reactor facilities in clinical trials

    International Nuclear Information System (INIS)

    Moss, R.; Watkins, P.; Vroegindeweij, C.; Stecher-Rasmussen, F.; Huiskamp, R.; Ravensberg, K.; Appelman, K.; Sauerwein, W.; Hideghety, K.; Gabel, D.

    2001-01-01

    The first clinical trial in Europe of Boron Neutron Capture Therapy (BNCT) for the treatment of glioblastoma was opened in July 1997. The trial is a Phase I study with the principal aim to establish the maximum tolerated radiation dose and the dose limiting toxicity under defined conditions. It is the first time that a clinical application could be realised on a completely multi-national scale. The treatment takes place at the High Flux Reactor (HFR) in Petten, the Netherlands, is operated by an international team of experts under the leadership of a German radiotherapist, and treats patients coming from different European countries. It has therefore been necessary to create a very specialised organisation and contractual structure with the support of administrations from different countries, who had to find and adapt solutions within existing laws that had never foreseen such a situation. Furthermore, the treatment does not take place in an hospital environment and even more so, the facility is at a nuclear research reactor. Hence, special efforts were made on quality assurance, in order that the set-up at the facility and the personnel involved complied, as closely as possible, with similar practices in conventional radiotherapy departments. (author)

  4. Inpatient Psychiatric Facility Quality Measure Data – National

    Data.gov (United States)

    U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

  5. Water quality facility investigation report : final summary of project and evaluation of monitoring plan implementation.

    Science.gov (United States)

    2005-07-05

    The Oregon Department of Transportation (ODOT) has installed several stormwater : treatment facilities throughout the State to improve the quality of runoff discharged from : highways. These facilities include a variety of both above ground and below...

  6. Health-related quality of life and persistent symptoms in relation to (R-)CHOP14, (R-)CHOP21, and other therapies among patients with diffuse large B-cell lymphoma : Results of the population-based PHAROS-registry

    NARCIS (Netherlands)

    Oerlemans, Simone; Issa, Djamila E; van den Broek, Esther C; Nijziel, Marten R; Coebergh, Jan Willem W; Huijgens, Peter C; Mols, Floortje; van de Poll-Franse, L.

    2014-01-01

    The increasing number of longer-living patients with diffuse large B-cell lymphoma (DLBCL) and serious side effects of treatment urged us to study the health-related quality of life (HRQoL) and persistent (treatment-related) symptoms in unselected patients after different treatment modalities and

  7. B-Cell Hematologic Malignancy Vaccination Registry

    Science.gov (United States)

    2017-12-29

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  8. Quality of the delivery services in health facilities in Northern Ethiopia.

    Science.gov (United States)

    Fisseha, Girmatsion; Berhane, Yemane; Worku, Alemayehu; Terefe, Wondwossen

    2017-03-09

    Substantial improvements have been observed in the coverage of and access to maternal health service, especially in skilled birth attendants, in Ethiopia. However, the quality of care has been lagging behind. Therefore, this study investigated the status of the quality of delivery services in Northern Ethiopia. A facility based survey was conducted from December 2014 to February 2015 in Northern Ethiopia. The quality of delivery service was assessed in 32 health facilities using a facility audit checklist, by reviewing delivery, by conducting in-depth interview and observation, and by conducting exit interviews with eligible mothers. Facilities were considered as 'good quality' if they scored positively on 75% of the quality indicators set in the national guidelines for all the three components; input (materials, infrastructure, and human resource), process (adherence to standard care procedures during intrapartum and immediate postpartum periods) and output (the mothers' satisfaction and utilization of lifesaving procedures). Overall 2 of 32 (6.3%) of the study facilities fulfilled all the three quality components; input, process and output. Two of the three components were assessed as good in 11 of the 32 (34.4%) health facilities. The input quality was the better of the other quality components; which was good in 21 out of the 32 (65.6%) health facilities. The process and output quality was good in only 10 of the 32 (31.3%) facilities. Only 6.3% of the studied health facilities had good quality in all three dimensions of quality measures that was done in accordance to the national delivery service guidelines. The most compromised quality component was the process. Systematic and sustained efforts need to be strengthened to improve all dimensions of quality in order to achieve the desired quality of delivery services and increase the proportion of births occurring in health facilities.

  9. Quality along the continuum: a health facility assessment of intrapartum and postnatal care in Ghana.

    Science.gov (United States)

    Nesbitt, Robin C; Lohela, Terhi J; Manu, Alexander; Vesel, Linda; Okyere, Eunice; Edmond, Karen; Owusu-Agyei, Seth; Kirkwood, Betty R; Gabrysch, Sabine

    2013-01-01

    To evaluate quality of routine and emergency intrapartum and postnatal care using a health facility assessment, and to estimate "effective coverage" of skilled attendance in Brong Ahafo, Ghana. We conducted an assessment of all 86 health facilities in seven districts in Brong Ahafo. Using performance of key signal functions and the availability of relevant drugs, equipment and trained health professionals, we created composite quality categories in four dimensions: routine delivery care, emergency obstetric care (EmOC), emergency newborn care (EmNC) and non-medical quality. Linking the health facility assessment to surveillance data we estimated "effective coverage" of skilled attendance as the proportion of births in facilities of high quality. Delivery care was offered in 64/86 facilities; only 3-13% fulfilled our requirements for the highest quality category in any dimension. Quality was lowest in the emergency care dimensions, with 63% and 58% of facilities categorized as "low" or "substandard" for EmOC and EmNC, respectively. This implies performing less than four EmOC or three EmNC signal functions, and/or employing less than two skilled health professionals, and/or that no health professionals were present during our visit. Routine delivery care was "low" or "substandard" in 39% of facilities, meaning 25/64 facilities performed less than six routine signal functions and/or had less than two skilled health professionals and/or less than one midwife. While 68% of births were in health facilities, only 18% were in facilities with "high" or "highest" quality in all dimensions. Our comprehensive facility assessment showed that quality of routine and emergency intrapartum and postnatal care was generally low in the study region. While coverage with facility delivery was 68%, we estimated "effective coverage" of skilled attendance at 18%, thus revealing a large "quality gap." Effective coverage could be a meaningful indicator of progress towards reducing maternal

  10. Quality along the continuum: a health facility assessment of intrapartum and postnatal care in Ghana.

    Directory of Open Access Journals (Sweden)

    Robin C Nesbitt

    Full Text Available To evaluate quality of routine and emergency intrapartum and postnatal care using a health facility assessment, and to estimate "effective coverage" of skilled attendance in Brong Ahafo, Ghana.We conducted an assessment of all 86 health facilities in seven districts in Brong Ahafo. Using performance of key signal functions and the availability of relevant drugs, equipment and trained health professionals, we created composite quality categories in four dimensions: routine delivery care, emergency obstetric care (EmOC, emergency newborn care (EmNC and non-medical quality. Linking the health facility assessment to surveillance data we estimated "effective coverage" of skilled attendance as the proportion of births in facilities of high quality.Delivery care was offered in 64/86 facilities; only 3-13% fulfilled our requirements for the highest quality category in any dimension. Quality was lowest in the emergency care dimensions, with 63% and 58% of facilities categorized as "low" or "substandard" for EmOC and EmNC, respectively. This implies performing less than four EmOC or three EmNC signal functions, and/or employing less than two skilled health professionals, and/or that no health professionals were present during our visit. Routine delivery care was "low" or "substandard" in 39% of facilities, meaning 25/64 facilities performed less than six routine signal functions and/or had less than two skilled health professionals and/or less than one midwife. While 68% of births were in health facilities, only 18% were in facilities with "high" or "highest" quality in all dimensions.Our comprehensive facility assessment showed that quality of routine and emergency intrapartum and postnatal care was generally low in the study region. While coverage with facility delivery was 68%, we estimated "effective coverage" of skilled attendance at 18%, thus revealing a large "quality gap." Effective coverage could be a meaningful indicator of progress towards

  11. Recommendations for quality assurance programs in nuclear medicine facilities. Radiation recommendations series

    International Nuclear Information System (INIS)

    Segal, P.; Hamilton, D.R.

    1984-10-01

    The publication provides the elements that should be considered by nuclear medicine facilities to improve their existing programs or develop new quality assurance programs. The important administrative aspects of quality assurance programs are stressed. Each facility is encouraged to adopt those elements of the recommended program that are appropriate to its individual needs and resources

  12. Evaluate of environment quality for γ irradiation facilities using fuzzy comprehensive judgment method

    International Nuclear Information System (INIS)

    Ha Yiming

    2002-01-01

    The environment quality of Jining Irradiation Centre new γ radiation facility was evaluated by fuzzy comprehensive judgment method. The result showed that the place of γ radiation facility was well and the measures of radiate shelter and environment protect were effective. The environment quality of its area was not obvious change and the result of environment evaluation was first-rate

  13. [Quality management of nuclear medicine facilities and experience during JCI certification].

    Science.gov (United States)

    Huang, Zhongke; Lou, Cen; Chen, Liang

    2010-03-01

    In 2003, JCI certification was introduced to create our new hospital quality management system. Our department imaging facilities management level and service quality markedly improved through JCI certification and re-evaluation. It played an important role in improving the efficiency and extending the life of medical facilities, reducing maintenance costs.

  14. Microscale air quality impacts of distributed power generation facilities.

    Science.gov (United States)

    Olaguer, Eduardo P; Knipping, Eladio; Shaw, Stephanie; Ravindran, Satish

    2016-08-01

    The electric system is experiencing rapid growth in the adoption of a mix of distributed renewable and fossil fuel sources, along with increasing amounts of off-grid generation. New operational regimes may have unforeseen consequences for air quality. A three-dimensional microscale chemical transport model (CTM) driven by an urban wind model was used to assess gaseous air pollutant and particulate matter (PM) impacts within ~10 km of fossil-fueled distributed power generation (DG) facilities during the early afternoon of a typical summer day in Houston, TX. Three types of DG scenarios were considered in the presence of motor vehicle emissions and a realistic urban canopy: (1) a 25-MW natural gas turbine operating at steady state in either simple cycle or combined heating and power (CHP) mode; (2) a 25-MW simple cycle gas turbine undergoing a cold startup with either moderate or enhanced formaldehyde emissions; and (3) a data center generating 10 MW of emergency power with either diesel or natural gas-fired backup generators (BUGs) without pollution controls. Simulations of criteria pollutants (NO2, CO, O3, PM) and the toxic pollutant, formaldehyde (HCHO), were conducted assuming a 2-hr operational time period. In all cases, NOx titration dominated ozone production near the source. The turbine scenarios did not result in ambient concentration enhancements significantly exceeding 1 ppbv for gaseous pollutants or over 1 µg/m(3) for PM after 2 hr of emission, assuming realistic plume rise. In the case of the datacenter with diesel BUGs, ambient NO2 concentrations were enhanced by 10-50 ppbv within 2 km downwind of the source, while maximum PM impacts in the immediate vicinity of the datacenter were less than 5 µg/m(3). Plausible scenarios of distributed fossil generation consistent with the electricity grid's transformation to a more flexible and modernized system suggest that a substantial amount of deployment would be required to significantly affect air quality on

  15. Pain treatment facilities: do we need quantity or quality?

    NARCIS (Netherlands)

    de Meij, N.; Koke, A.; van der Weijden, T.; van Kleef, M.; Patijn, J.

    2014-01-01

    Rationale, aims and objectives: Chronic pain patients referred to a pain treatment facility have no guarantee that they will receive a proper diagnostic procedure or treatment. To obtain information about organizational aspects of pain treatment facilities and the content of their daily pain

  16. B Cell Tolerance in Health and Disease

    Directory of Open Access Journals (Sweden)

    Murali Gururajan

    2014-02-01

    Full Text Available B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-reactive B cells. This review summarizes the major mechanisms of B cell tolerance, which include clonal deletion, anergy and receptor editing. In the bone marrow presentation of antigen in membrane bound form is more effective than soluble form and the role of dendritic cells in this process is discussed. Toll like receptor derived signals affect activation of B cells by certain ligands such as nucleic acids and have been shown to play crucial roles in the development of autoimmunity in several animal models. In the periphery availability of BAFF, a B cell survival factor plays a critical role in the survival of self-reactive B cells. Antibodies against BAFF have been found to be effective therapeutic agents in lupus like autoimmune diseases. Recent developments are targeting anergy to control the growth of chronic lymphocytic leukemia cells.

  17. Transcriptional circuits in B cell transformation.

    Science.gov (United States)

    Hu, Yeguang; Yoshida, Toshimi; Georgopoulos, Katia

    2017-07-01

    Loss of IKAROS in committed B cell precursors causes a block in differentiation while at the same time augments aberrant cellular properties, such as bone marrow stromal adhesion, self-renewal and resistance to glucocorticoid-mediated cell death. B cell acute lymphoblastic leukaemias originating from these early stages of B cell differentiation and associated with IKAROS mutations share a high-risk cellular phenotype suggesting that deregulation of IKAROS-based mechanisms cause a highly malignant disease process. Recent studies show that IKAROS is critical for the activity of super-enhancers at genes required for pre-B cell receptor (BCR) signalling and differentiation, working either downstream of or in parallel with B cell master regulators such as EBF1 and PAX5. IKAROS also directly represses a cryptic regulatory network of transcription factors prevalent in mesenchymal and epithelial precursors that includes YAP1, TEAD1/2, LHX2 and LMO2, and their targets, which are not normally expressed in lymphocytes. IKAROS prevents not only expression of these 'extra-lineage' transcription factors but also their cooperation with endogenous B cell master regulators, such as EBF1 and PAX5, leading to the formation of a de novo for lymphocytes super-enhancer network. IKAROS coordinates with the Polycomb repression complex (PRC2) to provide stable repression of associated genes during B cell development. However, induction of regulatory factors normally repressed by IKAROS starts a feed-forward loop that activates de-novo enhancers and elevates them to super-enhancer status, thereby diminishing PRC2 repression and awakening aberrant epithelial-like cell properties in B cell precursors. Insight into IKAROS-based transcriptional circuits not only sets new paradigms for cell differentiation but also provides new approaches for classifying and treating high-risk human B-ALL that originates from these early stages of B cell differentiation.

  18. B cell remote-handled waste shipment cask alternatives study

    International Nuclear Information System (INIS)

    RIDDELLE, J.G.

    1999-01-01

    The decommissioning of the 324 Facility B Cell includes the onsite transport of grouted remote-handled radioactive waste from the 324 Facility to the 200 Areas for disposal. The grouted waste has been transported in the leased ATG Nuclear Services 3-82B Radioactive Waste Shipping Cask (3-82B cask). Because the 3-82B cask is a U.S. Nuclear Regulatory Commission (NRC)-certified Type B shipping cask, the lease cost is high, and the cask operations in the onsite environment may not be optimal. An alternatives study has been performed to develop cost and schedule information on alternative waste transportation systems to assist in determining which system should be used in the future. Five alternatives were identified for evaluation. These included continued lease of the 3-82B cask, fabrication of a new 3-82B cask, development and fabrication of an onsite cask, modification of the existing U.S. Department of Energy-owned cask (OH-142), and the lease of a different commercially available cask. Each alternative was compared to acceptance criteria for use in the B Cell as an initial screening. Only continued leasing of the 3-82B cask, fabrication of a new 3-82B cask, and the development and fabrication of an onsite cask were found to meet all of the B Cell acceptance criteria

  19. Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heizmann, Beate [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Sellars, MacLean [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Macias-Garcia, Alejandra [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Institute for Medical Engineering and Science at MIT, Cambridge, MA 02139 (United States); Chan, Susan, E-mail: scpk@igbmc.fr [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Kastner, Philippe, E-mail: scpk@igbmc.fr [Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 67404 Illkirch (France); Faculté de Médecine, Université de Strasbourg, Strasbourg (France)

    2016-02-12

    The Ikaros transcription factor is essential for early B cell development, but its effect on mature B cells is debated. We show that Ikaros is required to limit the response of naive splenic B cells to B cell receptor signals. Ikaros deficient follicular B cells grow larger and enter cell cycle faster after anti-IgM stimulation. Unstimulated mutant B cells show deregulation of positive and negative regulators of signal transduction at the mRNA level, and constitutive phosphorylation of ERK, p38, SYK, BTK, AKT and LYN. Stimulation results in enhanced and prolonged ERK and p38 phosphorylation, followed by hyper-proliferation. Pharmacological inhibition of ERK and p38 abrogates the increased proliferative response of Ikaros deficient cells. These results suggest that Ikaros functions as a negative regulator of follicular B cell activation.

  20. Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways

    International Nuclear Information System (INIS)

    Heizmann, Beate; Sellars, MacLean; Macias-Garcia, Alejandra; Chan, Susan; Kastner, Philippe

    2016-01-01

    The Ikaros transcription factor is essential for early B cell development, but its effect on mature B cells is debated. We show that Ikaros is required to limit the response of naive splenic B cells to B cell receptor signals. Ikaros deficient follicular B cells grow larger and enter cell cycle faster after anti-IgM stimulation. Unstimulated mutant B cells show deregulation of positive and negative regulators of signal transduction at the mRNA level, and constitutive phosphorylation of ERK, p38, SYK, BTK, AKT and LYN. Stimulation results in enhanced and prolonged ERK and p38 phosphorylation, followed by hyper-proliferation. Pharmacological inhibition of ERK and p38 abrogates the increased proliferative response of Ikaros deficient cells. These results suggest that Ikaros functions as a negative regulator of follicular B cell activation.

  1. Study of the Relevance of the Quality of Care, Operating Efficiency and Inefficient Quality Competition of Senior Care Facilities.

    Science.gov (United States)

    Lin, Jwu-Rong; Chen, Ching-Yu; Peng, Tso-Kwei

    2017-09-11

    The purpose of this research is to examine the relation between operating efficiency and the quality of care of senior care facilities. We designed a data envelopment analysis, combining epsilon-based measure and metafrontier efficiency analyses to estimate the operating efficiency for senior care facilities, followed by an iterative seemingly unrelated regression to evaluate the relation between the quality of care and operating efficiency. In the empirical studies, Taiwan census data was utilized and findings include the following: Despite the greater operating scale of the general type of senior care facilities, their average metafrontier technical efficiency is inferior to that of nursing homes. We adopted senior care facility accreditation results from Taiwan as a variable to represent the quality of care and examined the relation of accreditation results and operating efficiency. We found that the quality of care of general senior care facilities is negatively related to operating efficiency; however, for nursing homes, the relationship is not significant. Our findings show that facilities invest more in input resources to obtain better ratings in the accreditation report. Operating efficiency, however, does not improve. Quality competition in the industry in Taiwan is inefficient, especially for general senior care facilities.

  2. Lipid rafts and B cell signaling.

    Science.gov (United States)

    Gupta, Neetu; DeFranco, Anthony L

    2007-10-01

    B cells comprise an essential component of the humoral immune system. They are equipped with the unique ability to synthesize and secrete pathogen-neutralizing antibodies, and share with professional antigen presenting cells the ability to internalize foreign antigens, and process them for presentation to helper T cells. Recent evidence indicates that specialized cholesterol- and glycosphingolipid-rich microdomains in the plasma membrane commonly referred to as lipid rafts, serve to compartmentalize key signaling molecules during the different stages of B cell activation including B cell antigen receptor (BCR)-initiated signal transduction, endocytosis of BCR-antigen complexes, loading of antigenic peptides onto MHC class II molecules, MHC-II associated antigen presentation to helper T cells, and receipt of helper signals via the CD40 receptor. Here we review the recent literature arguing for a role of lipid rafts in the spatial organization of B cell function.

  3. The early history of B cells.

    Science.gov (United States)

    Cooper, Max D

    2015-03-01

    The separate development of functionally intertwined lineages of lymphocytes known as B cells and T cells is now recognized as a fundamental organizing principle of the adaptive immune system in all vertebrates. Immunologists strive to define the different sublineages of the clonally diverse B cells and T cells, how they interact with each other and how they interact with innate lymphoid cells and other elements of the innate immune system to counter infections, cancer and the development of autoimmune and inflammatory diseases. On the 50th anniversary of the recognition of B cells as a discrete cell lineage, this Timeline article recounts some of the milestones marking the development of the concept that B cells are a functionally and developmentally distinct arm of the adaptive immune system.

  4. Conceptual designs for waste quality checking facilities for low level and intermediate level radioactive wastes and hazardous waste

    International Nuclear Information System (INIS)

    Driver, S.; Griffiths, M.; Leonard, C.D.; Smith, D.L.G.

    1992-01-01

    This report summarises work carried out on the design of facilities for the quality checking of Intermediate and Low Level Radioactive Waste and Hazardous Waste. The procedures used for the quality checking of these categories of waste are summarised. Three building options are considered: a separate LLW facility, a combined facility for LLW and HW and a Waste Quality Checking Facility for the three categories of waste. Budget Cost Estimates for the three facilities are given based on 1991 prices. (author)

  5. Memory in the B-cell compartment: antibody affinity maturation.

    OpenAIRE

    Neuberger, M S; Ehrenstein, M R; Rada, C; Sale, J; Batista, F D; Williams, G; Milstein, C

    2000-01-01

    In the humoral arm of the immune system, the memory response is not only more quickly elicited and of greater magnitude than the primary response, but it is also different in quality. In the recall response to antigen, the antibodies produced are of higher affinity and of different isotype (typically immunoglobulin G rather than immunoglobulin M). This maturation rests on the antigen dependence of B-cell maturation and is effected by programmed genetic modifications of the immunoglobulin gene...

  6. Determinants of quality of shared sanitation facilities in informal settlements: case study of Kisumu, Kenya.

    Science.gov (United States)

    Simiyu, Sheillah; Swilling, Mark; Cairncross, Sandy; Rheingans, Richard

    2017-01-11

    Shared facilities are not recognised as improved sanitation due to challenges of maintenance as they easily can be avenues for the spread of diseases. Thus there is need to evaluate the quality of shared facilities, especially in informal settlements, where they are commonly used. A shared facility can be equated to a common good whose management depends on the users. If users do not work collectively towards keeping the facility clean, it is likely that the quality may depreciate due to lack of maintenance. This study examined the quality of shared sanitation facilities and used the common pool resource (CPR) management principles to examine the determinants of shared sanitation quality in the informal settlements of Kisumu, Kenya. Using a multiple case study design, the study employed both quantitative and qualitative methods. In both phases, users of shared sanitation facilities were interviewed, while shared sanitation facilities were inspected. Shared sanitation quality was a score which was the dependent variable in a regression analysis. Interviews during the qualitative stage were aimed at understanding management practices of shared sanitation users. Qualitative data was analysed thematically by following the CPR principles. Shared facilities, most of which were dirty, were shared by an average of eight households, and their quality decreased with an increase in the number of households sharing. The effect of numbers on quality is explained by behaviour reflected in the CPR principles, as it was easier to define boundaries of shared facilities when there were fewer users who cooperated towards improving their shared sanitation facility. Other factors, such as defined management systems, cooperation, collective decision making, and social norms, also played a role in influencing the behaviour of users towards keeping shared facilities clean and functional. Apart from hardware factors, quality of shared sanitation is largely due to group behaviour of users

  7. Determinants of quality of shared sanitation facilities in informal settlements: case study of Kisumu, Kenya

    Directory of Open Access Journals (Sweden)

    Sheillah Simiyu

    2017-01-01

    Full Text Available Abstract Background Shared facilities are not recognised as improved sanitation due to challenges of maintenance as they easily can be avenues for the spread of diseases. Thus there is need to evaluate the quality of shared facilities, especially in informal settlements, where they are commonly used. A shared facility can be equated to a common good whose management depends on the users. If users do not work collectively towards keeping the facility clean, it is likely that the quality may depreciate due to lack of maintenance. This study examined the quality of shared sanitation facilities and used the common pool resource (CPR management principles to examine the determinants of shared sanitation quality in the informal settlements of Kisumu, Kenya. Methods Using a multiple case study design, the study employed both quantitative and qualitative methods. In both phases, users of shared sanitation facilities were interviewed, while shared sanitation facilities were inspected. Shared sanitation quality was a score which was the dependent variable in a regression analysis. Interviews during the qualitative stage were aimed at understanding management practices of shared sanitation users. Qualitative data was analysed thematically by following the CPR principles. Results Shared facilities, most of which were dirty, were shared by an average of eight households, and their quality decreased with an increase in the number of households sharing. The effect of numbers on quality is explained by behaviour reflected in the CPR principles, as it was easier to define boundaries of shared facilities when there were fewer users who cooperated towards improving their shared sanitation facility. Other factors, such as defined management systems, cooperation, collective decision making, and social norms, also played a role in influencing the behaviour of users towards keeping shared facilities clean and functional. Conclusion Apart from hardware factors, quality

  8. Quality of Maternity Care at Health Facilities in Eritrea in 2008 ...

    African Journals Online (AJOL)

    Objective: To examine the quality of maternal health services at health facilities in Eritrea. Methods: The study was a cross-sectional survey of all hospitals and health centers and a random sample of a third of health stations. Extensive interviews with health providers and facility managers were undertaken using structured ...

  9. Establishment and maintenance of B cell identity.

    Science.gov (United States)

    Grosschedl, Rudolf

    2013-01-01

    B lymphocyte differentiation is dependent on an intricate interplay of transcription factors and signaling pathways to establish a lineage-specific program of gene expression. Functional perturbations of several transcription factors by gain- or loss-of-function experiments indicated that E2A, EBF1, and FoxO1 are required for the specification of the B cell lineage, whereas Pax5 antagonizes alternative cell fates by repressing genes that allow for responsiveness to T lymphoid- and myeloid-promoting signals. However, genome-wide analysis of EBF1-binding sites and their functional interrogation indicated that EBF1 is involved in both activation of the B cell program and repression of alternative cell fates. Recent studies indicate that EBF1 function is required throughout the B cell lineage until the onset of plasma cell differentiation and includes a role in the maintenance of B cell identity. Thus, early B cell differentiation requires intertwined networks of transcription factors in which EBF1 collaborates with E2A and FoxO1 to activate the B lineage program and acts together with Pax5 to antagonize alternative cell fates. Copyright © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.

  10. B cell phenotypes in patients with rheumatoid arthritis relapsing after rituximab: expression of B cell-activating factor-binding receptors on B cell subsets.

    Science.gov (United States)

    Becerra, E; De La Torre, I; Leandro, M J; Cambridge, G

    2017-12-01

    Serum levels of B cell-activating factor (BAFF) rise following rituximab (RTX) therapy in patients with rheumatoid arthritis (RA). Initiation of naive B cell return to the periphery and autoreactive B cell expansion leading to relapse after RTX may therefore be linked to interactions between BAFF and BAFF-binding receptors (BBR). Relationships between serum BAFF and BBR expression [(BAFFR, calcium signal modulating cyclophilic ligand interactor (TACI) and B cell maturation antigen (BCMA)] were determined on B cell subsets, defined using immunoglobulin (Ig)D/CD38. Twenty pre-RTX and 18 RA patients relapsing after B cell depletion were included. Results were analysed with respect to timing of relapse up to 7 months after peripheral B cell return (≥ 5 B cells/μl) and to serum BAFF levels. After B cell return, B cell populations from relapsing patients had significantly lower BAFFR + expression compared to HC and pre-RTX patients. The percentage of BAFFR + B cells increased with time after B cell return and was correlated inversely with serum BAFF levels. BAFFR expression remained reduced. The percentage of TACI + memory B cells were lower in RA patients after RTX compared with healthy controls (HC). BCMA expression (% and expression) did not differ between patients and HC. Relapse following B cell return appeared largely independent of the percentage of BAFFR + or percentage of BCMA + B cells or serum BAFF levels. The lower percentage of TACI + memory B cells may reduce inhibitory signalling for B cell differentiation. In patients relapsing at longer periods after B cell return, recovery of the B cell pool was more complete, suggesting that selection or expansion of autoreactive B cells may be needed to precipitate relapse. © 2017 British Society for Immunology.

  11. Inputs to quality: supervision, management, and community involvement in health facilities in Egypt in 2004

    Directory of Open Access Journals (Sweden)

    Krumholz Harlan M

    2011-10-01

    Full Text Available Abstract Background As low- and middle-income countries experience economic development, ensuring quality of health care delivery is a central component of health reform. Nevertheless, health reforms in low- and middle-income countries have focused more on access to services rather than the quality of these services, and reporting on quality has been limited. In the present study, we sought to examine the prevalence and regional variation in key management practices in Egyptian health facilities within three domains: supervision of the facility from the Ministry of Health and Population (MOHP, managerial processes, and patient and community involvement in care. Methods We conducted a cross-sectional analysis of data from 559 facilities surveyed with the Egyptian Service Provision Assessment (ESPA survey in 2004, the most recent such survey in Egypt. We registered on the Measure Demographic and Health Survey (DHS website http://legacy.measuredhs.com/login.cfm to gain access to the survey data. From the ESPA sampled 559 MOHP facilities, we excluded a total of 79 facilities because they did not offer facility-based 24-hour care or have at least one physician working in the facility, resulting in a final sample of 480 facilities. The final sample included 76 general service hospitals, 307 rural health units, and 97 maternal and child health and urban health units (MCH/urban units. We used standard frequency analyses to describe facility characteristics and tested the statistical significance of regional differences using chi-square statistics. Results Nearly all facilities reported having external supervision within the 6 months preceding the interview. In contrast, key facility-level managerial processes, such as having routine and documented management meetings and applying quality assurance approaches, were uncommon. Involvement of communities and patients was also reported in a minority of facilities. Hospitals and health units located in Urban

  12. B-Cell-Activating Factor and the B-Cell Compartment in HIV/SIV Infection

    Science.gov (United States)

    Borhis, Gwenoline; Trovato, Maria; Chaoul, Nada; Ibrahim, Hany M.; Richard, Yolande

    2017-01-01

    With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs). In this context, we paid a particular attention to B-cell-activating factor (BAFF), a key cytokine in B-cell development and immune response that is overproduced during HIV/SIV infection. As it does in autoimmune diseases, BAFF excess might contribute to the abnormal rescue of self-reactive B-cells at several checkpoints of the B-cell development and impair memory B-cell generation and functions. In this review, we first point out what is known about the functions of BAFF/a proliferation-inducing ligand and their receptors [B-cell maturation, transmembrane activator and CAML interactor (TACI), and BAFF-R], in physiological and pathophysiological settings, in mice and humans. In particular, we highlight recent results on the previously underappreciated regulatory functions of TACI and on the highly regulated production of soluble TACI and BAFF-R that act as decoy receptors. In light of recent data on BAFF, TACI, and BAFF-R, we then revisit the altered phenotypes and functions of B-cell subsets during the acute and chronic phase of HIV/SIV infection. Given the atypical phenotype and reduced functions of memory B-cells in HIV/SIV infection, we particularly discuss the GC reaction, a key checkpoint where self-reactive B-cells are eliminated and pathogen-specific memory B-cells and plasmablasts/cells are generated in physiological settings. Through its capacity to differentially bind and process BAFF-R and

  13. Characterising B cell numbers and memory B cells in HIV infected and uninfected Malawian adults

    Directory of Open Access Journals (Sweden)

    Gordon Stephen

    2010-09-01

    Full Text Available Abstract Background Untreated human immunodeficiency virus (HIV disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain. Methods A cross-sectional study was performed. We recruited HIV-uninfected and HIV-infected Malawian adults both on and off antiretroviral therapy attending the Queen Elizabeth Central hospital in Malawi. Using flow cytometry, we enumerated B cells and characterized memory B cells and compared these measurements by the different recruitment groups. Results Overall 64 participants were recruited - 20 HIV uninfected (HIV-, 30 HIV infected ART naïve (HIV+N and 14 HIV-infected ART treated (HIV+T. ART treatment had been taken for a median of 33 months (Range 12-60 months. Compared to HIV- the HIV+N adults had low absolute number of naïve resting B cells (111 vs. 180 cells/μl p = 0.008; reduced memory B cells (27 vs. 51 cells/μl p = 0.0008. The HIV+T adults had B-cell numbers similar to HIV- except for memory B cells that remained significantly lower (30 vs. 51 cells/μl p = 0.02. In the HIV+N group we did not find an association between CD4 count and B cell numbers. Conclusions HIV infected Malawian adults have abnormal B-cell numbers. Individuals treated with ART show a return to normal in B-cell numbers but a persistent deficit in the memory subset is noted. This has important implications for long term susceptibility to co-infections and should be evaluated further in a larger cohort study.

  14. Memory B Cells of Mice and Humans.

    Science.gov (United States)

    Weisel, Florian; Shlomchik, Mark

    2017-04-26

    We comprehensively review memory B cells (MBCs), covering the definition of MBCs and their identities and subsets, how MBCs are generated, where they are localized, how they are maintained, and how they are reactivated. Whereas naive B cells adopt multiple fates upon stimulation, MBCs are more restricted in their responses. Evolving work reveals that the MBC compartment in mice and humans consists of distinct subpopulations with differing effector functions. We discuss the various approaches to define subsets and subset-specific roles. A major theme is the need to both deliver faster effector function upon reexposure and readapt to antigenically variant pathogens while avoiding burnout, which would be the result if all MBCs generated only terminal effector function. We discuss cell-intrinsic differences in gene expression and signaling that underlie differences in function between MBCs and naive B cells and among MBC subsets and how this leads to memory responses.

  15. Application of quality assurance to radioactive waste disposal facilities

    International Nuclear Information System (INIS)

    1996-08-01

    Nuclear power generation and the use of radioactive materials in medicine, research and industry produce radioactive wastes. In order to assure that wastes are managed safely, the implementation of appropriate management control is necessary. This IAEA publication deals with quality assurance principles for safe disposal. This report may assist managers responsible for safe disposal of radioactive waste in achieving quality in their work; and to regulatory bodies to provide guidance for their licensee waste disposal programmes. 17 refs

  16. DOE standard: Filter test facility quality program plan

    International Nuclear Information System (INIS)

    1999-02-01

    This standard was developed primarily for application in US Department of Energy programs. It contains specific direction for HEPA filter testing performed at a DOE-accepted HEPA Filter Test Facility (FTF). Beneficial comments (recommendations, additions, deletions) and any pertinent data that may improve this document should be sent to the Office of Nuclear Safety Policy and Standards (EH-31), US Department of Energy, Washington, DC 20585, by letter or by using the self-addressed Document Improvement Proposal form (DOE F 1300.3) appearing at the end of this document

  17. The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells

    Science.gov (United States)

    Saulep-Easton, Damien; Vincent, Fabien B.; Quah, Pin Shie; Wei, Andrew; Ting, Stephen B.; Croce, Carlo M.; Tam, Constantine; Mackay, Fabienne

    2015-01-01

    Interleukin (IL)-10-producing B cells (B10 cells) have emerged as important regulatory players with immunosuppressive roles. Chronic lymphocytic leukemia (CLL) B cells also secrete IL-10 and share features of B10 cells, suggesting a possible contribution of CLL B cells to immunosuppression in CLL patients. Factors controlling the emergence of B10 cells are not known. B cell-activating factor of the tumour necrosis factor (TNF) family (BAFF) is critical for B cell maturation and survival, and is implicated in the development and progression of CLL. We sought to investigate the role of BAFF in the emergence of IL-10-producing B regulatory cells in healthy donors and CLL patients. Here, we report that BAFF signaling promotes IL-10 production by CLL B cells in a mouse model of CLL and in CLL patients. Moreover, BAFF-mediated IL-10 production by normal and CLL B cells is mediated via its receptor TACI. Our work uncovered a major targetable pathway important for the generation of regulatory B cells that is detrimental to immunity in CLL. PMID:26139429

  18. Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction

    Directory of Open Access Journals (Sweden)

    Emmanuelle Dugas-Bourdages

    2014-01-01

    Full Text Available Persistent polyclonal B cell lymphocytosis (PPBL is a rare disorder, diagnosed primarily in adult female smokers and characterized by an expansion of CD19+CD27+IgM+ memory B cells, by the presence of binucleated lymphocytes, and by a moderate elevation of serum IgM. The clinical course is usually benign, but it is not known whether or not PPBL might be part of a process leading to the emergence of a malignant proliferative disorder. In this study we sought to investigate the functional response of B cells from patients with PPBL by use of an optimal memory B cell culture model based on the CD40-CD154 interaction. We found that the proliferation of PPBL B cells was almost as important as that of B cells from normal controls, resulting in high immunoglobulin secretion with in vitro isotypic switching. We conclude that the CD40-CD154 activation pathway is functional in the memory B cell population of PPBL patients, suggesting that the disorder may be due to either a dysfunction of other cells in the microenvironment or a possible defect in another B cell activation pathway.

  19. Review of Regulatory Quality Assurance Requirements for the Operation of Nuclear R and D Facilities

    International Nuclear Information System (INIS)

    Kwon, Hyuk Il; Lim, Nam Jin

    2005-01-01

    Korea Atomic Energy Research Institute (KAERI) has many R and D facilities in operation, including HANARO research reactor, radioactive waste treatment facility (RWTF), post-irradiation examination facility (PIEF) and irradiated material test facility (IMEF). Recently, nation-wide interest is focused on the safety and security of major industrial facilities. Safe operation of nuclear facilities is imperative because of the consequence of public disaster by radiological release/ contamination, in case of an accident. Recently, Ministry of Science and Technology (MOST) of the Korean government announced amendments of Atomic Energy laws to enforce requirements of the physical protection and radiological emergency. In this paper, the context of amended Atomic Energy laws were reviewed to confirm quality assurance measures and identify additional QA activities, if any, that is required by the amendment

  20. Quality Assurance Program description, Defense Waste Processing Facility (DWPF)

    International Nuclear Information System (INIS)

    Maslar, S.R.

    1992-01-01

    This document describes the Westinghouse Savannah River Company's (WSRC) Quality Assurance Program for Defense Waste Processing at the Savannah River Site (SRS). WSRC is the operating contractor for the US Department of Energy (DOE) at the SRS. The following objectives are achieved through developing and implementing the Quality Assurance Program: (1) Ensure that the attainment of quality (in accomplishing defense high-level waste processing objectives at the SRS) is at a level commensurate with the government's responsibility for protecting public health and safety, the environment, the public investment, and for efficiently and effectively using national resources. (2) Ensure that high-level waste from qualification and production activities conform to requirements defined by OCRWM. These activities include production processes, equipment, and services; and products that are planned, designed, procured, fabricated, installed, tested, operated, maintained, modified, or produced

  1. Improving the Quality of Services in Residential Treatment Facilities: A Strength-Based Consultative Review Process

    Science.gov (United States)

    Pavkov, Thomas W.; Lourie, Ira S.; Hug, Richard W.; Negash, Sesen

    2010-01-01

    This descriptive case study reports on the positive impact of a consultative review methodology used to conduct quality assurance reviews as part of the Residential Treatment Center Evaluation Project. The study details improvement in the quality of services provided to youth in unmonitored residential treatment facilities. Improvements were…

  2. 75 FR 78952 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

    Science.gov (United States)

    2010-12-17

    ... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants; Commonwealth of Virginia; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator (HMIWI) Units, Negative... Quality, 629 East Main Street, Richmond, Virginia 23219. FOR FURTHER INFORMATION CONTACT: James B. Topsale...

  3. 75 FR 78916 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

    Science.gov (United States)

    2010-12-17

    ... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants, Commonwealth of Virginia; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator (HMIWI) Units, Negative... 19103. Copies of the State submittal are available at the Virginia Department of Environmental Quality...

  4. Quality assurance for systems at the Lawrence Livermore Laboratory tritium facility

    International Nuclear Information System (INIS)

    Dow, J.P.

    1976-01-01

    A quality-assurance program for tritium-handling systems at the Lawrence Livermore Laboratory tritium facility has been developed. Operational guidelines governing system design, construction, and testing have been written. A certified-material storeroom has been established to procure and distribute high-quality materials. Ten systems are currently being modified under the new guidelines

  5. First Dutch Consensus of Pain Quality Indicators for Pain Treatment Facilities

    NARCIS (Netherlands)

    Meij, N. de; Grotel, M. van; Patijn, J.; Weijden, T.T. van der; Kleef, M. van

    2016-01-01

    BACKGROUND: There is a general consensus about the need to define and improve the quality of pain treatment facilities. Although guidelines and recommendations to improve the quality of pain practice management have been launched, provision of appropriate pain treatment is inconsistent and the

  6. Interaction of Staphylococci with Human B cells.

    Directory of Open Access Journals (Sweden)

    Tyler K Nygaard

    Full Text Available Staphylococcus aureus is a leading cause of human infections worldwide. The pathogen produces numerous molecules that can interfere with recognition and binding by host innate immune cells, an initial step required for the ingestion and subsequent destruction of microbes by phagocytes. To better understand the interaction of this pathogen with human immune cells, we compared the association of S. aureus and S. epidermidis with leukocytes in human blood. We found that a significantly greater proportion of B cells associated with S. epidermidis relative to S. aureus. Complement components and complement receptors were important for the binding of B cells with S. epidermidis. Experiments using staphylococci inactivated by ultraviolet radiation and S. aureus isogenic deletion mutants indicated that S. aureus secretes molecules regulated by the SaeR/S two-component system that interfere with the ability of human B cells to bind this bacterium. We hypothesize that the relative inability of B cells to bind S. aureus contributes to the microbe's success as a human pathogen.

  7. Immunoglobulins, antibody repertoire and B cell development

    Czech Academy of Sciences Publication Activity Database

    Butler, J. E.; Zhao, Y.; Šinkora, Marek; Wertz, N.; Kacskovics, I.

    2009-01-01

    Roč. 33, č. 3 (2009), s. 321-333 ISSN 0145-305X R&D Projects: GA ČR GA523/07/0088 Institutional research plan: CEZ:AV0Z50200510 Keywords : swine * immunoglobulin * b cell Subject RIV: EC - Immunology Impact factor: 3.290, year: 2009

  8. Interaction of Staphylococci with Human B cells

    Science.gov (United States)

    Nygaard, Tyler K.; Kobayashi, Scott D.; Freedman, Brett; Porter, Adeline R.; Voyich, Jovanka M.; Otto, Michael; Schneewind, Olaf; DeLeo, Frank R.

    2016-01-01

    Staphylococcus aureus is a leading cause of human infections worldwide. The pathogen produces numerous molecules that can interfere with recognition and binding by host innate immune cells, an initial step required for the ingestion and subsequent destruction of microbes by phagocytes. To better understand the interaction of this pathogen with human immune cells, we compared the association of S. aureus and S. epidermidis with leukocytes in human blood. We found that a significantly greater proportion of B cells associated with S. epidermidis relative to S. aureus. Complement components and complement receptors were important for the binding of B cells with S. epidermidis. Experiments using staphylococci inactivated by ultraviolet radiation and S. aureus isogenic deletion mutants indicated that S. aureus secretes molecules regulated by the SaeR/S two-component system that interfere with the ability of human B cells to bind this bacterium. We hypothesize that the relative inability of B cells to bind S. aureus contributes to the microbe’s success as a human pathogen. PMID:27711145

  9. Software quality assurance plan for the National Ignition Facility integrated computer control system

    International Nuclear Information System (INIS)

    Woodruff, J.

    1996-11-01

    Quality achievement is the responsibility of the line organizations of the National Ignition Facility (NIF) Project. This Software Quality Assurance Plan (SQAP) applies to the activities of the Integrated Computer Control System (ICCS) organization and its subcontractors. The Plan describes the activities implemented by the ICCS section to achieve quality in the NIF Project's controls software and implements the NIF Quality Assurance Program Plan (QAPP, NIF-95-499, L-15958-2) and the Department of Energy's (DOE's) Order 5700.6C. This SQAP governs the quality affecting activities associated with developing and deploying all control system software during the life cycle of the NIF Project

  10. Preventing Heel Pressure Ulcers: Sustained Quality Improvement Initiative in a Canadian Acute Care Facility.

    Science.gov (United States)

    Hanna-Bull, Debbie

    2016-01-01

    The setting for this quality improvement initiative designed to reduce the prevalence of facility-acquired heel pressure ulcers was a regional, acute-care, 490-bed facility in Ontario, Canada, responsible for dialysis, vascular, and orthopedic surgery. An interdisciplinary skin and wound care team designed an evidence-based quality improvement initiative based on a systematic literature review and standardization of heel offloading methods. The prevalence of heel pressure ulcers was measured at baseline (immediately prior to implementation of initiative) and at 1 and 4 years following implementation. The prevalence of facility-acquired heel pressure ulcers was 5.8% when measured before project implementation. It was 4.2% at 1 year following implementation and 1.6% when measured at the end of the 4-year initiative. Outcomes demonstrate that the initiative resulted in a continuous and sustained reduction in facility-acquired heel pressure ulcer incidence over a 4-year period.

  11. Inpatient Psychiatric Facility Follow-Up After Hospitalization for Mental Illness (FUH) Quality Measure Data – National

    Data.gov (United States)

    U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

  12. Inpatient Psychiatric Facility Follow-Up After Hospitalization for Mental Illness (FUH) Quality Measure Data – by State

    Data.gov (United States)

    U.S. Department of Health & Human Services — Psychiatric facilities that are eligible for the Inpatient Psychiatric Facility Quality Reporting (IPFQR) program are required to meet all program requirements,...

  13. LLL's Quality Assurance Program and the design of specific systems: Tritium Handling Facility

    International Nuclear Information System (INIS)

    Dow, J.P.

    1975-01-01

    Lawrence Livermore Laboratory operates a Tritium Handling Facility for several programs. Besides the tritium work for the weapons program, basic research is conducted on all phases of tritium. Additional work is being conducted for the laser fusion program and the controlled thermonuclear program. The Quality Assurance Program for the tritium facility and how it is being implemented on specific tritium handling systems are described. The program is intended to prevent or mitigate the consequences of accidents by rigidly controlling the design, fabrication, procurement, construction and operation of safety-related critical structures, systems, and components of such facilities. (CH)

  14. 242-A Evaporator/Liquid Effluent Retention Facility data quality objectives

    International Nuclear Information System (INIS)

    Von Bargen, B.H.

    1994-01-01

    The purpose of data quality objectives (DQO) is to determine the most cost effective methods of gathering the essential data necessary to make decisions to support successful operation of the facility. The essential data is defined by such information as sample amount, sample location, required analyses, and how sampling and analyses are performed. Successful operation is defined as meeting the campaign objectives while operating within established requirements. This DQO document addresses that portion of the system from 242-A Evaporator candidate feed tanks through discharge of process condensate to the Liquid Effluent Retention of Facility (LERF). Later revisions will incorporate and integrate the entire system, including the Effluent Treatment Facility (ETF)

  15. Defining B cell immunodominance to viruses.

    Science.gov (United States)

    Angeletti, Davide; Gibbs, James S; Angel, Matthew; Kosik, Ivan; Hickman, Heather D; Frank, Gregory M; Das, Suman R; Wheatley, Adam K; Prabhakaran, Madhu; Leggat, David J; McDermott, Adrian B; Yewdell, Jonathan W

    2017-04-01

    Immunodominance (ID) defines the hierarchical immune response to competing antigens in complex immunogens. Little is known regarding B cell and antibody ID despite its importance in immunity to viruses and other pathogens. We show that B cells and serum antibodies from inbred mice demonstrate a reproducible ID hierarchy to the five major antigenic sites in the influenza A virus hemagglutinin globular domain. The hierarchy changed as the immune response progressed, and it was dependent on antigen formulation and delivery. Passive antibody transfer and sequential infection experiments demonstrated 'original antigenic suppression', a phenomenon in which antibodies suppress memory responses to the priming antigenic site. Our study provides a template for attaining deeper understanding of antibody ID to viruses and other complex immunogens.

  16. B Cell-Activating Factor Regulates Different Aspects of B Cell Functionality and Is Produced by a Subset of Splenic B Cells in Teleost Fish

    Science.gov (United States)

    Tafalla, Carolina; González, Lucia; Castro, Rosario; Granja, Aitor G.

    2017-01-01

    In mammals, B cell functionality is greatly influenced by cytokines released by innate cells, such as macrophages or dendritic cells, upon the early recognition of common pathogen patterns through invariant receptors. B cell-activating factor (BAFF) is one of these innate B cell-helper signals and plays a key role in the survival and differentiation of B cells. Although, evolutionarily, teleost fish constitute the first animal group in which adaptive immunity based on Ig receptors is present, fish still rely greatly on innate responses. In this context, we hypothesized that BAFF would play a key role in the control of B cell responses in fish. Supporting this, our results show that teleost BAFF recapitulates mammalian BAFF stimulating actions on B cells, upregulating the expression of membrane MHC II, improving the survival of fish naïve B cells and antibody-secreting cells, and increasing the secretion of IgM. Surprisingly, we also demonstrate that BAFF is not only produced in fish by myeloid cells but is also produced by a subset of splenic B cells. Thus, if this B cell-produced BAFF proves to be actively regulating this same B cell subset, our findings point to an ancient mechanism to control B cell differentiation and survival in lower vertebrates, which has been silenced in mammals in physiological conditions, but reemerges under pathological conditions, such as B cell lymphomas and autoimmune diseases. PMID:28360916

  17. A facility for long term evaluation and quality assurance of LHCb Vertex Detector modules

    CERN Document Server

    Marinho, F; Dimattia, R; Doherty, F; Dumps, R; Gersabeck, M; Melone, J; Parkes, C; Saavedra, A; Tobin, M

    2007-01-01

    This note describes the facility developed for long term evaluation and quality assurance of the LHCb Vertex Detector modules, known as the 'Glasgow Burn-in System'. This facility was developed to ensure that the modules conform to stringent quality levels. The system was able to uncover any weaknesses that could be introduced during the manufacturing and assembly of the components or during the transport of the modules to CERN. The system consisted of: a high resolution microscope for visual inspections; and a burn-in system to operate cooled modules in vacuum. The main components of the burn-in system were a vacuum system, a cooling system and a DAQ system.

  18. Primary Hepatosplenic Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    M.R. Morales-Polanco

    2008-03-01

    Full Text Available Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment.

  19. Quality of Tuberculosis Care in Private Health Facilities of Addis Ababa, Ethiopia

    Directory of Open Access Journals (Sweden)

    Gezahegn Gebrekidan

    2014-01-01

    Full Text Available Ensuring provision of good quality tuberculosis (TB care, especially in private for profit health facilities, is an important component of TB control strategy to reduce poor medical practice which results in multidrug resistant TB (MDR-TB. The aim of this study was to investigate quality of TB care in private health facilities of Addis Ababa. A facility based cross-sectional study was conducted based on Donabedian’s structure-process-outcome model of health care quality. Quality of care was determined by adherence to National TB Program guidelines, treatment success rate, and client satisfaction. Exit interview was conducted on 292 patients on the intensive phase of treatment and 384 patient records were reviewed in eight private health facilities. Initial diagnostic AFB test was done for 95.4% of pulmonary TB patients. Most important components of TB care recommended by national guidelines were delivered for a significant proportion of patients. Majority (75% of the clients were found to be satisfied with each component of TB care. The treatment success rate was 90.9%. The quality of TB care was fairly good. However, only 77.7% of the patients were counseled for HIV testing. Strengthening HIV counseling and testing, tackling shortage of streptomycin and laboratory reagent at private TB clinic is crucial.

  20. Quality Assessment of Family Planning Sterilization Services at Health Care Facilities: Case Record Audit.

    Science.gov (United States)

    Mathur, Medha; Goyal, Ram Chandra; Mathur, Navgeet

    2017-05-01

    Quality of sterilization services is a matter of concern in India because population control is a necessity. Family Planning Sterilization (FPS) services provided at public health care facilities need to be as per Standard Operating Procedures. To assess the quality of FPS services by audit of case records at selected health care facilities. This cross-sectional study was conducted for two and a half year duration at selected public health care facilities of central India by simple random sampling where FPS services were provided. As per the standards of Government of India, case records were audited and compliance was calculated to assess the quality of services. Results of record audit were satisfactory but important criteria like previous contraceptive history and postoperative counselling were found to be deviated from standards. At Primary Health Centres (PHCs) only 89.5% and at Community Health Centres (CHCs) 58.7% of records were having details of previous contraceptive history. Other criteria like mental illness (only 70% at CHCs) assessment were also inadequate. Although informed consent was found to be having 100% compliance in all records. Quality of care in FPS services is the matter of concern in present scenario for better quality of services. This study may enlighten the policy makers regarding improvements needed for providing quality care.

  1. 78 FR 40015 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

    Science.gov (United States)

    2013-07-03

    ... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants; District of Columbia; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator Units AGENCY: Environmental... negative declaration for hospital/medical/infectious waste incinerator (HMIWI) units within the District of...

  2. 77 FR 3389 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

    Science.gov (United States)

    2012-01-24

    ... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants, State of West Virginia; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator Units, Plan Revision... final action to approve a revision to the West Virginia hospital/medical/infectious waste incinerator...

  3. 78 FR 40087 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

    Science.gov (United States)

    2013-07-03

    ... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants; District of Columbia; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator Units AGENCY: Environmental...) section 111(d)/129 negative declaration for the District of Columbia for hospital/medical/infectious waste...

  4. 75 FR 73967 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

    Science.gov (United States)

    2010-11-30

    ... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants, State of Delaware; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator (HMIWI) Units, Negative Declaration... Environmental Control, 89 Kings Highway, P.O. Box 1401, Dover, Delaware 19903. FOR FURTHER INFORMATION CONTACT...

  5. 75 FR 73996 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

    Science.gov (United States)

    2010-11-30

    ... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants; State of Delaware; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator (HMIWI) Units, Negative Declaration... Resources and Environmental Control, 89 Kings Highway, P.O. Box 1401, Dover, Delaware 19903. FOR FURTHER...

  6. 77 FR 3422 - Approval and Promulgation of State Air Quality Plans for Designated Facilities and Pollutants...

    Science.gov (United States)

    2012-01-24

    ... Promulgation of State Air Quality Plans for Designated Facilities and Pollutants; State of West Virginia; Control of Emissions From Existing Hospital/Medical/Infectious Waste Incinerator Units, Plan Revision... revision to the West Virginia hospital/medical/infectious waste incinerator (HMIWI) Section 111(d)/ 129...

  7. Students' Perceived Quality of Library Facilities and Services in Nigerian Private Universities

    Science.gov (United States)

    Oluwunmi, A. O.; Durodola, O. D.; Ajayi, C. A.

    2016-01-01

    In a highly competitive academic environment, students are becoming more selective and demanding in their choice of University. Hence, it is essential for educational institutions, particularly privately-owned institutions, to be interested in getting feedback on the quality of their facilities and services. With a focus on four private…

  8. B-Cell-Activating Factor and Autoimmune Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Samia Ragheb

    2011-01-01

    Full Text Available BAFF is a potent B-cell survival factor, and it plays an essential role in B-cell homeostasis and B-cell function in the periphery. Both normal and autoreactive B cells are BAFF dependent; however, excess BAFF promotes the survival, growth, and maturation of autoreactive B cells. When overexpressed, BAFF protects B cells from apoptosis, thereby contributing to autoimmunity. Three independent studies have shown higher BAFF levels in the circulation of MG patients. BAFF may play an important role in the pathogenesis of MG. BAFF antagonists may well provide new treatment options for MG patients, particularly those patients with thymic lymphoid follicular hyperplasia.

  9. NKT Cell Responses to B Cell Lymphoma.

    Science.gov (United States)

    Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B; Page, Carly; Younger, Kenisha M; Tiper, Irina V; Frieman, Matthew; Kimball, Amy S; Webb, Tonya J

    2014-06-01

    Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

  10. Regulatory quality assurance requirements for the operation of nuclear R and D facilities in Korea

    International Nuclear Information System (INIS)

    Kwon, H.I.; Lim, N.J.

    2006-01-01

    Full text: Korea Atomic Energy Research Institute (KAERI) has many R and D facilities in operation. including HANARO research reactor, radioactive waste treatment facility (RWTF), post-irradiation examination facility (PIEF) and irradiated material test facility (IMEF). Recently. nation-wide interest is focused on the safety and security of major industrial facilities. Safe operation of nuclear facilities is imperative because of the consequence of public disaster by radiological release/contamination, in case of an accident. Recently, Ministry of Science and Technology (MOST) of the Korean government announced amendments of Atomic Energy laws to enforce requirements of the physical protection and radiological emergency. All provisions on nuclear safety regulation and radiation protection are entrusted to the Atomic Energy Act(AEA). The Act is enacted as the main law concerning the safety regulation of nuclear installations, and is supplemented by the Enforcement Decree and Enforcement Regulation of the Act. These Atomic Energy laws include provisions on the construction permission and the operation license of nuclear installations, such as nuclear power reactors, research reactors, nuclear ships, nuclear fuel fabrication facilities, spent fuel treatment facilities, etc. Regulatory requirements for the regulatory inspection and the safety measures for operation are also defined in the laws. The Notice of the MOST prescribes specific issues including regulatory requirements and technical standards, as entrusted by the AEA, the Decree and the Regulation. Detailed QA requirements for nuclear installations are specified differently, depending upon the type of facility. The guidelines for safety reviews and regulatory inspections are developed by the Korea Institute of Nuclear Safety (KINS), which is an exclusive organization for safety regulation of nuclear installations in Korea. In this paper, the context of the Atomic Energy laws were reviewed to confirm the

  11. Quality of newborn care: a health facility assessment in rural Ghana using survey, vignette and surveillance data

    NARCIS (Netherlands)

    Vesel, Linda; Manu, Alexander; Lohela, Terhi J.; Gabrysch, Sabine; Okyere, Eunice; ten Asbroek, Augustinus H. A.; Hill, Zelee; Agyemang, Charlotte Tawiah; Owusu-Agyei, Seth; Kirkwood, Betty R.

    2013-01-01

    To assess the structural capacity for, and quality of, immediate and essential newborn care (ENC) in health facilities in rural Ghana, and to link this with demand for facility deliveries and admissions. Health facility assessment survey and population-based surveillance data. Seven districts in

  12. Multi-Function Waste Tank Facility Quality Assurance Program Plan, Project W-236A. Revision 2

    Energy Technology Data Exchange (ETDEWEB)

    Hall, L.R.

    1995-05-30

    This document describes the Quality Assurance (QA) program for the Multi-Function Waste Tank Facility (MWTF) Project. The purpose of this QA program is to control project activities in such a manner as to achieve the mission of the MWTF Project in a safe and reliable manner. The QA program for the MWTF Project is founded on DOE Order 5700.6C, Quality Assurance, and implemented through the use of ASME NQA-1, Quality Assurance Program Requirements for Nuclear Facilities (ASME 1989 with addenda la-1989, lb-1991 and lc-1992). This document describes the program and planned actions which the Westinghouse Hanford Company (WHC) will implement to demonstrate and ensure that the project meets the requirements of DOE Order 5700.6C through the interpretive guidance of ASME NQA-1.

  13. Multi-Function Waste Tank Facility Quality Assurance Program Plan, Project W-236A. Revision 2

    International Nuclear Information System (INIS)

    Hall, L.R.

    1995-01-01

    This document describes the Quality Assurance (QA) program for the Multi-Function Waste Tank Facility (MWTF) Project. The purpose of this QA program is to control project activities in such a manner as to achieve the mission of the MWTF Project in a safe and reliable manner. The QA program for the MWTF Project is founded on DOE Order 5700.6C, Quality Assurance, and implemented through the use of ASME NQA-1, Quality Assurance Program Requirements for Nuclear Facilities (ASME 1989 with addenda la-1989, lb-1991 and lc-1992). This document describes the program and planned actions which the Westinghouse Hanford Company (WHC) will implement to demonstrate and ensure that the project meets the requirements of DOE Order 5700.6C through the interpretive guidance of ASME NQA-1

  14. The effects of health facility access and quality on family planning decisions in urban Senegal.

    Science.gov (United States)

    Cronin, Christopher J; Guilkey, David K; Speizer, Ilene S

    2018-03-01

    Research in developing countries is rarely focused on examining how supply side factors affect family planning decisions due to a lack of facility-level data. When these data exist, analyses tend to focus on rural environments. In this paper, we study the effects that health facility access and quality have on contraceptive use and desired number of children for women in urban Senegal. Unlike related studies focusing on rural environments, we find no evidence that greater access to health facilities and pharmacies increases contraceptive use among urban women. However, we do find that contraceptive use among urban women is higher with greater facility quality. For example, we find that increasing the proportion of pharmacies employing multiple pharmacists from 0% to 50% would increase contraceptive use by 6.0 percentage points, and increasing the proportion of facilities with family planning guidelines/protocols from 50% to 100% would increase use by 2.1 percentage points. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Quality assurance project plan for the UMTRA technical assistance contractor hydrochemistry facility. Final report

    International Nuclear Information System (INIS)

    1993-07-01

    The Uranium Mill Tailings Remedial Action (UMTRA) hydrochemistry facility is used to perform a limited but important set of services for the UMTRA Project. Routine services include support of field-based hydrological and geochemical operations and water sampling activities. Less commonly, the hydrology and geochemistry staff undertake special studies and site characterization studies at this facility. It is also used to train hydrologists, geochemists, and groundwater sampling crews. A review of this Quality Assurance Project Plan (QAPP) shall be accomplished once each calendar year. This review will be targeted to be accomplished not sooner than 6 months and not later than 18 months after the last review

  16. Negative signaling in B cells: SHIP Grbs Shc.

    Science.gov (United States)

    Tridandapani, S; Kelley, T; Cooney, D; Pradhan, M; Coggeshall, K M

    1997-09-01

    Negative signaling in B cells is initiated by co-crosslinking of the antigen receptor and the Fcy receptor, resulting in cessation of B-cell signaling events and, in turn, inhibiting B-cell proliferation and antibody secretion. Here, a competitive role is proposed for SHIP in blocking the interaction of Shc with the Grb2-Sos complex of proteins that lead to Ras activation in B cells.

  17. A brief history of T cell help to B cells.

    Science.gov (United States)

    Crotty, Shane

    2015-03-01

    In celebration of the 50th anniversary of the discovery of B cells, I take a look back at the history of T cell help to B cells, which was discovered 47 years ago. In addition, I summarize and categorize the distinct molecules that are expressed by CD4(+) T cells that constitute 'help' to B cells, and particularly the molecules expressed by T follicular helper (TFH) cells, which are the specialized providers of help to B cells.

  18. Software quality assurance plan for the National Ignition Facility integrated computer control system

    Energy Technology Data Exchange (ETDEWEB)

    Woodruff, J.

    1996-11-01

    Quality achievement is the responsibility of the line organizations of the National Ignition Facility (NIF) Project. This Software Quality Assurance Plan (SQAP) applies to the activities of the Integrated Computer Control System (ICCS) organization and its subcontractors. The Plan describes the activities implemented by the ICCS section to achieve quality in the NIF Project`s controls software and implements the NIF Quality Assurance Program Plan (QAPP, NIF-95-499, L-15958-2) and the Department of Energy`s (DOE`s) Order 5700.6C. This SQAP governs the quality affecting activities associated with developing and deploying all control system software during the life cycle of the NIF Project.

  19. National Ignition Facility quality assurance plan for laser materials and optical technology

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, C.R.

    1996-05-01

    Quality achievement is the responsibility of the line organizations of the National Ignition Facility (NIF) Project. This subtier Quality Assurance Plan (QAP) applies to activities of the Laser Materials & Optical Technology (LM&OT) organization and its subcontractors. It responds to the NIF Quality Assurance Program Plan (QAPP, L-15958-2, NIF-95-499) and Department of Energy (DOE) Order 5700.6C. This Plan is organized according to 10 Quality Assurance (QA) criteria and subelements of a management system as outlined in the NIF QAPP. This Plan describes how those QA requirements are met. This Plan is authorized by the Associate Project Leader for the LM&OT organization, who has assigned responsibility to the Optics QA engineer to maintain this plan, with the assistance of the NIF QA organization. This Plan governs quality-affecting activities associated with: design; procurement; fabrication; testing and acceptance; handling and storage; and installation of NIF Project optical components into mounts and subassemblies.

  20. Correlations between quality ratings of skilled nursing facilities and multidrug-resistant urinary tract infections.

    Science.gov (United States)

    Gucwa, Azad L; Dolar, Veronika; Ye, Chao; Epstein, Stephanie

    2016-11-01

    The purpose of this study was to determine risk factors for the acquisition of urinary tract infections (UTIs) and multidrug-resistant organisms (MDROs) in residents of skilled nursing facilities (SNFs). Using the informational database provided by the Centers for Medicare and Medicaid Services (CMS), a retrospective logistic regression was performed on 1,523 urine cultures from 12 SNFs located in Long Island, New York. Of the 1,142 positive urine cultures, Escherichia coli was most prevalent. Additionally, 164 (14.4%) of the UTIs were attributed to an MDRO. In multivariate logistic regression, sex and overall quality rating predicted the occurrence of UTIs, whereas identification of MDROs was dependent on the level of nursing care received. The mean predicted probability of UTIs and receipt of contaminated samples was inversely dependent on the facility's rating, where the likelihood increased as overall quality ratings decreased. The CMS's quality rating system may provide some insight into the status of infection control practices in SNFs. The results of this study suggest that potential consumers should focus on the overall star ratings and the competency of the nursing staff in these facilities rather than on individual quality measures. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  1. Assessing the quality of care in a new nation: South Sudan's first national health facility assessment.

    Science.gov (United States)

    Berendes, Sima; Lako, Richard L; Whitson, Donald; Gould, Simon; Valadez, Joseph J

    2014-10-01

    We adapted a rapid quality of care monitoring method to a fragile state with two aims: to assess the delivery of child health services in South Sudan at the time of independence and to strengthen local capacity to perform regular rapid health facility assessments. Using a two-stage lot quality assurance sampling (LQAS) design, we conducted a national cross-sectional survey among 156 randomly selected health facilities in 10 states. In each of these facilities, we obtained information on a range of access, input, process and performance indicators during structured interviews and observations. Quality of care was poor with all states failing to achieve the 80% target for 14 of 19 indicators. For example, only 12% of facilities were classified as acceptable for their adequate utilisation by the population for sick-child consultations, 16% for staffing, 3% for having infection control supplies available and 0% for having all child care guidelines. Health worker performance was categorised as acceptable in only 6% of cases related to sick-child assessments, 38% related to medical treatment for the given diagnosis and 33% related to patient counselling on how to administer the prescribed drugs. Best performance was recorded for availability of in-service training and supervision, for seven and ten states, respectively. Despite ongoing instability, the Ministry of Health developed capacity to use LQAS for measuring quality of care nationally and state-by-state, which will support efficient and equitable resource allocation. Overall, our data revealed a desperate need for improving the quality of care in all states. © 2014 John Wiley & Sons Ltd.

  2. Intravascular Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Maria S. Khan MD, FACP

    2014-03-01

    Full Text Available Case Presentation . A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH 1231 IU/L. Except for a positive DNA test for Epstein–Barr virus (EBV infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion . Intravascular large cell B-cell lymphoma (IVLBCL is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH

  3. B Cell Receptor-Mediated Internalization of Salmonella: A Novel Pathway for Autonomous B Cell Activation and Antibody Production

    NARCIS (Netherlands)

    Souwer, Yuri; Griekspoor, Alexander; Jorritsma, Tineke; de Wit, Jelle; Janssen, Hans; Neefjes, Jacques; van Ham, S. Marieke

    2009-01-01

    The present paradigm is that primary B cells are nonphagocytosing cells. In this study, we demonstrate that human primary B cells are able to internalize bacteria when the bacteria are recognized by the BCR. BCR-mediated internalization of Salmonella typhimurium results in B cell differentiation and

  4. Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming

    NARCIS (Netherlands)

    Kwakkenbos, Mark J.; Diehl, Sean A.; Yasuda, Etsuko; Bakker, Arjen Q.; van Geelen, Caroline M. M.; Lukens, Michaël; van Bleek, Grada M.; Widjojoatmodjo, Myra N.; Bogers, Willy M. J. M.; Mei, Henrik; Radbruch, Andreas; Scheeren, Ferenc A.; Spits, Hergen; Beaumont, Tim

    The B cell lymphoma-6 (Bcl-6) and Bcl-xL proteins are expressed in germinal center B cells and enable them to endure the proliferative and mutagenic environment of the germinal center. By introducing these genes into peripheral blood memory B cells and culturing these cells with two factors produced

  5. Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming

    NARCIS (Netherlands)

    Kwakkenbos, Mark J.; Diehl, Sean A.; Yasuda, Etsuko; Bakker, Arjen Q.; van Geelen, Caroline M. M.; Lukens, Michaël V.; van Bleek, Grada M.; Widjojoatmodjo, Myra N.; Bogers, Willy M. J. M.; Mei, Henrik; Radbruch, Andreas; Scheeren, Ferenc A.; Spits, Hergen; Beaumont, Tim

    2010-01-01

    The B cell lymphoma-6 (Bcl-6) and Bcl-xL proteins are expressed in germinal center B cells and enable them to endure the proliferative and mutagenic environment of the germinal center. By introducing these genes into peripheral blood memory B cells and culturing these cells with two factors produced

  6. Improved method for predicting linear B-cell epitopes

    OpenAIRE

    Larsen, Jens Erik Pontoppidan; Lund, Ole; Nielsen, Morten

    2006-01-01

    Background B-cell epitopes are the sites of molecules that are recognized by antibodies of the immune system. Knowledge of B-cell epitopes may be used in the design of vaccines and diagnostics tests. It is therefore of interest to develop improved methods for predicting B-cell epitopes. In this paper, we describe an improved method for predicting linear B-cell epitopes. Results In order to do this, three data sets of linear B-cell epitope annotated proteins were constructed. A data set was co...

  7. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2.

    Science.gov (United States)

    Hodson, Daniel J; Shaffer, Arthur L; Xiao, Wenming; Wright, George W; Schmitz, Roland; Phelan, James D; Yang, Yandan; Webster, Daniel E; Rui, Lixin; Kohlhammer, Holger; Nakagawa, Masao; Waldmann, Thomas A; Staudt, Louis M

    2016-04-05

    The requirement for the B-cell transcription factor OCT2 (octamer-binding protein 2, encoded by Pou2f2) in germinal center B cells has proved controversial. Here, we report that germinal center B cells are formed normally after depletion of OCT2 in a conditional knockout mouse, but their proliferation is reduced and in vivo differentiation to antibody-secreting plasma cells is blocked. This finding led us to examine the role of OCT2 in germinal center-derived lymphomas. shRNA knockdown showed that almost all diffuse large B-cell lymphoma (DLBCL) cell lines are addicted to the expression of OCT2 and its coactivator OCA-B. Genome-wide chromatin immunoprecipitation (ChIP) analysis and gene-expression profiling revealed the broad transcriptional program regulated by OCT2 that includes the expression of STAT3, IL-10, ELL2, XBP1, MYC, TERT, and ADA. Importantly, genetic alteration of OCT2 is not a requirement for cellular addiction in DLBCL. However, we detected amplifications of the POU2F2 locus in DLBCL tumor biopsies and a recurrent mutation of threonine 223 in the DNA-binding domain of OCT2. This neomorphic mutation subtly alters the DNA-binding preference of OCT2, leading to the transactivation of noncanonical target genes including HIF1a and FCRL3 Finally, by introducing mutations designed to disrupt the OCT2-OCA-B interface, we reveal a requirement for this protein-protein interface that ultimately might be exploited therapeutically. Our findings, combined with the predominantly B-cell-restricted expression of OCT2 and the absence of a systemic phenotype in our knockout mice, suggest that an OCT2-targeted therapeutic strategy would be efficacious in both major subtypes of DLBCL while avoiding systemic toxicity.

  8. Quality assurance and quality control for the confinement physics research facility (CPRF) and ZTH experiment

    International Nuclear Information System (INIS)

    Kewish, R.W. Jr.

    1989-01-01

    In compliance with DOE order 5700.6B, which establishes policies to assure quality achievement in DOE programs, the authors instituted a quality assurance and quality control program whose primary goal is to assure that reliable components are available with which to assemble the CPRF/ZTH experiment. The Code of Federal Regulations 10 CFR 50, Appendix B, and the ANSI standard N45.2 were used as a primary source of guidance in establishing a plan for our QA program. Accepted codes, such as the National Electric Code (NEC), and standards adopted by organizations such as ANSI, IEEE, ASME, and NEMA were used in the design and production of components in keeping with the primary goal of the CPRF program. In setting up the CPRF/ZTH quality assurance program it was their intention to have these standards apply to all suppliers, both within and outside the Laboratory. 5 refs., 5 figs

  9. Quality assurance guidance for a low-level radioactive waste disposal facility

    International Nuclear Information System (INIS)

    Pittiglio, C.L. Jr.; Hedges, D.

    1991-04-01

    This document provides guidance to an applicant on meeting the quality control (QC) requirements of 10 CFR 61.12(j) for a low-level radioactive waste (LLRW) disposal facility. The QC requirements, plus audits and managerial controls requirements, establish the need for developing a quality assurance (QA) program and the guidance provided herein. The criteria developed for this document are similar to the criteria developed for Appendix B to Title 10 of the Code of Federal Regulations (10 CFR) Part 50. Although Appendix B is not a regulatory requirement for an LLRW disposal facility, the criteria that were developed for 10 CFR Part 50 are basic to any QA program. This document establishes QA guidance for the design, construction, and operation of those structures, engineered or natural systems, and components whose function is required to meet the performance objectives of Subpart C of 10 CFR Part 61 and to limit exposure to or release of radioactivity. 7 refs

  10. Measuring Inpatient Rehabilitation Facility Quality of Care: Discharge Self-Care Functional Status Quality Measure.

    Science.gov (United States)

    Pardasaney, Poonam K; Deutsch, Anne; Iriondo-Perez, Jeniffer; Ingber, Melvin J; McMullen, Tara

    2017-03-28

    To describe the calculation and psychometric properties of the discharge self-care functional status quality measure implemented in the Centers for Medicare & Medicaid Services' (CMS) Inpatient Rehabilitation Facility (IRF) Quality Reporting Program on October 1, 2016. Medicare fee-for-service (FFS) patients from 38 IRFs that participated in the CMS Post-Acute Care Payment Reform Demonstration were included in this cohort study. Data came from the Continuity Assessment Record and Evaluation Item Set, IRF-Patient Assessment Instrument, and Medicare claims. For each patient, we calculated an expected discharge self-care score, risk-adjusted for demographic and baseline clinical characteristics. The performance score of each IRF equaled the percentage of patient stays where the observed discharge self-care score met or exceeded the expected score. We assessed the measure's discriminatory ability across IRFs and reliability. IRFs. Medicare FFS patients aged ≥21 years (N=4769). Not applicable. Facility-level discharge self-care quality measure performance score. A total of 4769 patient stays were included; 57% of stays were in women, and 12.1% were in patients aged care score in the overall demonstration sample. The quality measure showed strong reliability, with intraclass correlation coefficients of .91. The discharge self-care quality measure showed strong discriminatory ability and reliability, representing an important initial step in evaluation of IRF self-care outcomes. A wide range in performance scores suggested a gap in quality of care across IRFs. Future work should include testing the measure with nationwide data from all IRFs. Published by Elsevier Inc.

  11. Results of RCRA groundwater quality assessment at the 216-B-3 Pond Facility

    International Nuclear Information System (INIS)

    Barnett, D.B.; Teel, S.S.

    1997-06-01

    This document describes a groundwater quality assessment of the 216-B-3 pond system, a Resources Conservation and Recovery act of 1976 (RCRA) waste facility. In 1990, sampling and chemical analysis of groundwater underlying the facility indicated that the contamination indicator parameters, total organic halogens (TOX), and total organic carbon (TOC) had exceeded established limits in two wells. This discovery placed the facility into RCRA groundwater assessment status and subsequently led to a more detailed hydrochemical analysis of groundwater underlying the facility. Comprehensive chemical analyses of groundwater samples from 1994 through 1996 revealed one compound, tris (2-chloroethyl) phosphate (TRIS2CH), that may have contributed to elevated TOX concentrations. No compound was identified as a contributor to TOC. Detailed evaluations of TOX, TOC, and TRIS2CH and comparison of occurrences of these parameters led to conclusions that (1) with few exceptions, these constituents occur at low concentrations below or near limits of quantitation; (2) it is problematic whether the low concentrations of TRIS2CH represent a contaminant originating from the facility or if it is a product of well construction; and (3) given the low and diminishing concentration of TOX, TOC, and TRIS2CH, no further investigation into the occurrent of these constituents is justified. Continued groundwater monitoring should include an immediate recalculation of background critical means of upgradient/downgradient comparisons and a return to seminannual groundwater monitoring under a RCRA indicator parameter evaluation program

  12. Factors Influencing the Choice and Quality Assessment of Hotel Facilities in Poland

    Directory of Open Access Journals (Sweden)

    Ozimek Irena

    2017-06-01

    Full Text Available The aim of this study was to investigate the effect of selected factors on the choice of hotel facilities by customers. Particular attention was focused on the perception of the quality of services by consumers. The field research, the results of which are presented in the article, was conducted on a nationwide sample of 1,000 persons aged from 15 to 70 according to the author’s questionnaire.

  13. The regulatory roles of B cell subsets in transplantation.

    Science.gov (United States)

    Chu, Zhulang; Zou, Weilong; Xu, Yanan; Sun, Qiquan; Zhao, Yong

    2018-02-01

    B cells mediate allograft rejection through antigen presentation, and production of cytokines and antibodies. More and more immunosuppressive agents specifically targeting B cells and plasma cells have been applied in clinical transplantation. However, recent studies have indicated the regulatory roles of B cells. Therefore, it is vital to clarify the different effects of B cell subsets in organ transplantation so that we can completely understand the diverse functions of B cells in transplantation. Areas covered: This review focuses on the regulatory roles of B cells in transplantation. B cell subsets with immune modulation and factors mediating immunosuppressive functions of regulatory B (Breg) cells were analyzed. Therapies targeting B cells and the application of B cells for transplant tolerance induction were discussed. Expert commentary: Besides involving rejection, B cells could also play regulatory roles in transplantation. Breg cells and the related markers may be used to predict the immune tolerant state in transplant recipients. New therapeutic strategies targeting B cells should be explored to promote tolerance induction with less impact on the host's protective immunity in organ transplanted patients.

  14. Quality assurance guidance for low-level radioactive waste disposal facility: Final report

    International Nuclear Information System (INIS)

    Pittiglio, C.L. Jr.

    1989-01-01

    This document provides guidance to an applicant on meeting the quality control (QC) requirements for a low-level waste (LLW) disposal facility. The QC requirements are the basis for developing of a quality assurance (QA) program and for the guidance provided herein. The criteria are basic to any QA program. The document specifically establishes QA guidance for the design, construction, and operation of those structures, systems, components, as well as, for site characterization activities necessary to meet the performance objectives and to limit exposure to our release of radioactivity. 7 refs

  15. Glandular dose and image quality control in mammography facilities with computerized radiography systems

    International Nuclear Information System (INIS)

    Dantas, Marcelino Vicente de Almeida

    2010-01-01

    Breast cancer is the most common cancer among women, and early detection is critical to its diagnosis and treatment. To date, the most effective method for early detection of breast cancer has been x-ray mammography for which the screen/film (SF) technique has been the gold standard. However, even though SF combinations have been improved and optimized over the years for breast imaging, there are some critical limitations, including a narrow exposure range, image artifacts, film processing problems, and inflexibility in image processing and film management. In recent years, digital mammography has been introduced in cancer screening programmes with the screen/film techniques gradually being phased out. Computed radiography (CR), also commonly known as photostimulable phosphor (PSP) imaging or storage phosphor, employs reusable imaging plates and associated hardware and software to acquire and to display digital projection radiographs. In this work, a protocol model was tested for performing image quality control and average glandular dose (AGD) evaluation in 19 institutions with computed radiography systems for mammography. The protocol was validated through tests at the Laboratorio de Radioprotecao Aplicada a Mamografia (LARAM) from the Centro de Desenvolvimento da Tecnologia Nuclear (CDTN). The image quality visual evaluation of CDMAM phantom showed that 53% of the facilities were able to produce images of excellent quality. Furthermore, the automated evaluation of image quality, using the analyze software cdcom.exe, showed that 57% of the images were considered to be of good quality. The detector linearity test showed that the CR response is very linear, where 95% of facilities evaluated were considered to be compliant. For the image noise was found that only 20% of facilities are in agreement with the parameters established for this test. The average glandular doses, which patients may be getting to perform an examination, were below the action levels

  16. Recommendations for a Software Quality Assurance Plan for the CMR Facility at LANL

    International Nuclear Information System (INIS)

    Adams, K.; Matthews, S. D.; McQueen, M. A.

    1998-01-01

    The Nuclear Materials Technology (NMT) organizations 1 and 3 within the Chemical and Metallurgical Research (CMR) facility at the Los Alamos National Laboratory are working to achieve Waste Isolation Pilot Plant (WIPP) certification to enable them to transport their TRU waste to WIPP. This document is intended to provide not only recommendations to address the necessary software quality assurance activities to enable the NMT-1 and NMT-3 organizations to be WIPP compliant but is also meant to provide a template for the final Software Quality Assurance Plan (SQAP). This document specifically addresses software quality assurance for all software used in support of waste characterization and analysis. Since NMT-1 and NMT-3 currently have several operational software products that are used for waste characterization and analysis, these software quality assurance recommendations apply to the operations, maintenance and retirement of the software and the creation and development of any new software required for waste characterization and analyses

  17. Standard guide for establishing a quality assurance program for uranium conversion facilities

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2004-01-01

    1.1 This guide provides guidance and recommended practices for establishing a comprehensive quality assurance program for uranium conversion facilities. 1.2 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate health and safety practices and determine the applicability of regulatory limitations prior to use. 1.3 The basic elements of a quality assurance program appear in the following order: FUNCTION SECTION Organization 5 Quality Assurance Program 6 Design Control 7 Instructions, Procedures & Drawings 8 Document Control 9 Procurement 10 Identification and Traceability 11 Processes 12 Inspection 13 Control of Measuring and Test Equipment 14 Handling, Storage and Shipping 15 Inspection, Test and Operating Status 16 Control of Nonconforming Items 17 Corrective Actions 18 Quality Assurance Records 19 Audits 20 TABLE 1 NQA-1 Basic Requirements Relat...

  18. Copanlisib and Nivolumab in Treating Participants With Recurrent or Refractory Diffuse Large B-cell Lymphoma or Primary Mediastinal Large B-cell Lymphoma

    Science.gov (United States)

    2018-03-29

    Diffuse Large B-Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  19. Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells

    Science.gov (United States)

    Patzelt, Thomas; Keppler, Selina J.; Gorka, Oliver; Thoene, Silvia; Wartewig, Tim; Reth, Michael; Förster, Irmgard; Lang, Roland; Buchner, Maike; Ruland, Jürgen

    2018-01-01

    The transcription factor Foxp1 is critical for early B cell development. Despite frequent deregulation of Foxp1 in B cell lymphoma, the physiological functions of Foxp1 in mature B cells remain unknown. Here, we used conditional gene targeting in the B cell lineage and report that Foxp1 disruption in developing and mature B cells results in reduced numbers and frequencies of follicular and B-1 B cells and in impaired antibody production upon T cell-independent immunization in vivo. Moreover, Foxp1-deficient B cells are impaired in survival even though they exhibit an increased capacity to proliferate. Transcriptional analysis identified defective expression of the prosurvival Bcl-2 family gene Bcl2l1 encoding Bcl-xl in Foxp1-deficient B cells, and we identified Foxp1 binding in the regulatory region of Bcl2l1. Transgenic overexpression of Bcl2 rescued the survival defect in Foxp1-deficient mature B cells in vivo and restored peripheral B cell numbers. Thus, our results identify Foxp1 as a physiological regulator of mature B cell survival mediated in part via the control of Bcl-xl expression and imply that this pathway might contribute to the pathogenic function of aberrant Foxp1 expression in lymphoma. PMID:29507226

  20. Waste Management facilities cost information: System Cost Model Software Quality Assurance Plan. Revision 2

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, B.L.; Lundeen, A.S.

    1996-02-01

    In May of 1994, Lockheed Idaho Technologies Company (LITCO) in Idaho Falls, Idaho and subcontractors developed the System Cost Model (SCM) application. The SCM estimates life-cycle costs of the entire US Department of Energy (DOE) complex for designing; constructing; operating; and decommissioning treatment, storage, and disposal (TSD) facilities for mixed low-level, low-level, transuranic, and mixed transuranic waste. The SCM uses parametric cost functions to estimate life-cycle costs for various treatment, storage, and disposal modules which reflect planned and existing facilities at DOE installations. In addition, SCM can model new facilities based on capacity needs over the program life cycle. The SCM also provides transportation costs for truck and rail, which include transport of contact-handled, remote-handled, and alpha (transuranic) wastes. The user can provide input data (default data is included in the SCM) including the volume and nature of waste to be managed, the time period over which the waste is to be managed, and the configuration of the waste management complex (i.e., where each installation`s generated waste will be treated, stored, and disposed). Then the SCM uses parametric cost equations to estimate the costs of pre-operations (designing), construction costs, operation management, and decommissioning these waste management facilities. For the product to be effective and useful the SCM users must have a high level of confidence in the data generated by the software model. The SCM Software Quality Assurance Plan is part of the overall SCM project management effort to ensure that the SCM is maintained as a quality product and can be relied on to produce viable planning data. This document defines tasks and deliverables to ensure continued product integrity, provide increased confidence in the accuracy of the data generated, and meet the LITCO`s quality standards during the software maintenance phase. 8 refs., 1 tab.

  1. Waste Management facilities cost information: System Cost Model Software Quality Assurance Plan. Revision 2

    International Nuclear Information System (INIS)

    Peterson, B.L.; Lundeen, A.S.

    1996-02-01

    In May of 1994, Lockheed Idaho Technologies Company (LITCO) in Idaho Falls, Idaho and subcontractors developed the System Cost Model (SCM) application. The SCM estimates life-cycle costs of the entire US Department of Energy (DOE) complex for designing; constructing; operating; and decommissioning treatment, storage, and disposal (TSD) facilities for mixed low-level, low-level, transuranic, and mixed transuranic waste. The SCM uses parametric cost functions to estimate life-cycle costs for various treatment, storage, and disposal modules which reflect planned and existing facilities at DOE installations. In addition, SCM can model new facilities based on capacity needs over the program life cycle. The SCM also provides transportation costs for truck and rail, which include transport of contact-handled, remote-handled, and alpha (transuranic) wastes. The user can provide input data (default data is included in the SCM) including the volume and nature of waste to be managed, the time period over which the waste is to be managed, and the configuration of the waste management complex (i.e., where each installation's generated waste will be treated, stored, and disposed). Then the SCM uses parametric cost equations to estimate the costs of pre-operations (designing), construction costs, operation management, and decommissioning these waste management facilities. For the product to be effective and useful the SCM users must have a high level of confidence in the data generated by the software model. The SCM Software Quality Assurance Plan is part of the overall SCM project management effort to ensure that the SCM is maintained as a quality product and can be relied on to produce viable planning data. This document defines tasks and deliverables to ensure continued product integrity, provide increased confidence in the accuracy of the data generated, and meet the LITCO's quality standards during the software maintenance phase. 8 refs., 1 tab

  2. Primary cardiac diffuse large B-cell lymphoma with activated B-cell-like phenotype

    Directory of Open Access Journals (Sweden)

    Vijaya Gadage

    2011-01-01

    Full Text Available Primary cardiac lymphoma (PCL is a rare and fatal disorder. It may often mimic other common cardiac tumors like cardiac myxoma because of similarities in the clinical presentation. We report a case of PCL of diffuse large B-cell type, in a 38-year-old, immunocompetent male who presented with superior vena cava syndrome that was excised as a myxoma. Histology revealed a large cell population diffusely and strongly expressing CD45, CD20, MUM1/IRF4 and FOXP1 hinting at an activated B-cell (ABC-like phenotype. After four cycles of Rituximab with CHOP (cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone the tumor regressed completely but the patient had a relapse and subsequently succumbed to the disease confirming the aggressive nature. The aggressive behavior of PCL may be possibly linked to its ABC-like origin.

  3. Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging

    Directory of Open Access Journals (Sweden)

    Daniela Frasca

    2017-08-01

    Full Text Available Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.

  4. Good Practices for Water Quality Management in Research Reactors and Spent Fuel Storage Facilities

    International Nuclear Information System (INIS)

    2011-01-01

    Water is the most common fluid used to remove the heat produced in a research reactor (RR). It is also the most common media used to store spent fuel elements after being removed from the reactor core. Spent fuel is stored either in the at-reactor pool or in away-from-reactor wet facilities, where the fuel elements are maintained until submission to final disposal, or until the decay heat is low enough to allow migration to a dry storage facility. Maintaining high quality water is the most important factor in preventing degradation of aluminium clad fuel elements, and other structural components in water cooled research reactors. Excellent water quality in spent fuel wet storage facilities is essential to achieve optimum storage performance. Experience shows the remarkable success of many research reactors where the water chemistry has been well controlled. In these cases, aluminium clad fuel elements and aluminium pool liners show few, if any, signs of either localized or general corrosion, even after more than 30 years of exposure to research reactor water. In contrast, when water quality was allowed to degrade, the fuel clad and the structural parts of the reactor have been seriously corroded. The driving force to prepare this publication was the recognition that, even though a great deal of information on research reactor water quality is available in the open literature, no comprehensive report addressing the rationale of water quality management in research reactors has been published to date. This report is designed to provide a comprehensive catalogue of good practices for the management of water quality in research reactors. It also presents a brief description of the corrosion process that affects the components of a research reactor. Further, the report provides a basic understanding of water chemistry and its influence on the corrosion process; specifies requirements and operational limits for water purification systems of RRs; describes good practices

  5. Continuous quality improvement in substance abuse treatment facilities: How much does it cost?

    Science.gov (United States)

    Hunt, Priscillia; Hunter, Sarah B; Levan, Deborah

    2017-06-01

    Continuous quality improvement (CQI) has grown in the U.S. since the 1970s, yet little is known about the costs to implement CQI in substance abuse treatment facilities. This paper is part of a larger group randomized control trial in a large urban county evaluating the impact of Plan-Study-Do-Act (PDSA)-CQI designed for community service organizations (Hunter, Ober, Paddock, Hunt, & Levan, 2014). Operated by one umbrella organization, each of the eight facilities of the study, four residential and four outpatient substance abuse treatment facilities, selected their own CQI Actions, including administrative- and clinical care-related Actions. Using an activity-based costing approach, we collected labor and supplies and equipment costs directly attributable to CQI Actions over a 12-month trial period. Our study finds implementation of CQI and meeting costs of this trial per facility were approximately $2000 to $10,500 per year ($4500 on average), or $10 to $60 per admitted client. We provide a description of the sources of variation in these costs, including differing intensity of the CQI Actions selected, which should help decision makers plan use of PDSA-CQI. Copyright © 2017. Published by Elsevier Inc.

  6. Quality Assistance Objectives for Nondestructive Assay at the Waste Receiving and Processing (WRAP) Facility

    International Nuclear Information System (INIS)

    CANTALOUB, M.G.

    2000-01-01

    The Waste Receiving and Processing (WRAP) facility, located on the Word Site in southeast Washington, is a key link in the certification of transuranic (TRU) waste for shipment to the Waste Isolation Pilot Plant (WIPP). Waste characterization is one of the vital functions performed at WRAP, and nondestructive assay (NDA) measurements of TRU waste containers is one of two required methods used for waste characterization. The Waste Acceptance Criteria for the Waste Isolation Pilot Plant, DOE/WIPP-069 (WIPP-WAC) delineates the quality assurance objectives which have been established for NDA measurement systems. Sites must demonstrate that the quality assurance objectives can be achieved for each radioassay system over the applicable ranges of measurement. This report summarizes the validation of the WRAP NDA systems against the radioassay quality assurance objectives or QAOs. A brief description of the each test and significant conclusions are included. Variables that may have affected test outcomes and system response are also addressed

  7. Quality Assurance Objectives for Nondestructive Assay at the Waste Receiving and Processing (WRAP) Facility

    International Nuclear Information System (INIS)

    CANTALOUB, M.G.; WILLS, C.E.

    2000-01-01

    The Waste Receiving and Processing (WRAP) facility, located on the Hanford Site in southeast Washington, is a key link in the certification of transuranic (TRU) waste for shipment to the Waste Isolation Pilot Plant (WIPP). Waste characterization is one of the vital functions performed at WRAP, and nondestructive assay (NDA) measurements of TRU waste containers is one of two required methods used for waste characterization. The Waste Acceptance Criteria for the Waste Isolation Pilot Plant, DOEMPP-069 (WIPP-WAC) delineates the quality assurance objectives which have been established for NDA measurement systems. Sites must demonstrate that the quality assurance objectives can be achieved for each radioassay system over the applicable ranges of measurement. This report summarizes the validation of the WRAP NDA systems against the radioassay quality assurance objectives or QAOs. A brief description of the each test and significant conclusions are included. Variables that may have affected test outcomes and system response are also addressed

  8. FFTF [fast flux tests facility] metal fuel pin sodium bond quality verification

    International Nuclear Information System (INIS)

    Pitner, A.L.

    1989-01-01

    The Fast Flux Tests Facility (FFTF) Series III driver fuel design consists of U-10 Zr fuel slugs contained in a ferritic alloy cladding. A liquid-metal, sodium bond between the fuel and cladding is required to prevent unacceptable temperatures during operation. Excessive voiding or porosity in the sodium thermal bond could result in localized fuel melting during irradiation. It is therefore imperative that bond quality be verified during fabrication of these metal fuel pins prior to irradiation. Cladding stripping of two spare metal fuel pins was successfully performed to inspect the quality of the sodium thermal bond and to compare observed defects in the bond with eddy current measurements. Bond quality was found to be generally good, thereby confirming the fabrication process used to bond the fuel and cladding with liquid-metal sodium to be acceptable. Observed porosity distribution in the sodium bond correlated well with eddy current indications

  9. Brucella abortus-infected B cells induce osteoclastogenesis.

    Science.gov (United States)

    Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

    2016-09-01

    Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Targeting HIV-1 Envelope Glycoprotein Trimers to B Cells by Using APRIL Improves Antibody Responses

    NARCIS (Netherlands)

    Melchers, Mark; Bontjer, Ilja; Tong, Tommy; Chung, Nancy P. Y.; Klasse, Per Johan; Eggink, Dirk; Montefiori, David C.; Gentile, Maurizio; Cerutti, Andrea; Olson, William C.; Berkhout, Ben; Binley, James M.; Moore, John P.; Sanders, Rogier W.

    2012-01-01

    An HIV-1 vaccine remains elusive, in part because various factors limit the quantity and quality of the antibodies raised against the viral envelope glycoprotein complex (Env). We hypothesized that targeting Env vaccines directly to B cells, by fusing them to molecules that bind and activate these

  11. Anti-B cell antibody therapies for inflammatory rheumatic diseases

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Jayne, David R W

    2014-01-01

    Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus...... and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies....

  12. Sleep quality in residents of assisted living facilities: effect on quality of life, functional status, and depression.

    Science.gov (United States)

    Martin, Jennifer L; Fiorentino, Lavinia; Jouldjian, Stella; Josephson, Karen R; Alessi, Cathy A

    2010-05-01

    To describe sleep patterns in older adults living in assisted living facilities (ALFs) and to explore the relationship between sleep disturbance and quality of life, functional status, and depression over 6 months of follow-up. Prospective, observational cohort study. Eighteen ALFs in the Los Angeles area. One hundred twenty-one ALF residents aged 65 and older (mean age 85.3, 86% female, 88% non-Hispanic white). Data were collected at baseline and 3 and 6 months after enrollment. Data collected were demographics, physical and cognitive functioning, depression, quality of life, comorbidities, medications, and subjective (i.e., questionnaires) and objective (i.e., 3 days and nights of wrist actigraphy) measures of sleep. Sixty-five percent of participants reported clinically significant sleep disturbance on the Pittsburgh Sleep Quality Index, and objective wrist actigraphy confirmed poor sleep quality. In regression analyses including sleep variables and other predictors, more self-reported sleep disturbance at baseline was associated with worse health-related quality of life (Medical Outcomes Study 12-item Short Form Survey Mental Component Summary score) and worse depressive symptoms five-item Geriatric Depression Scale at follow-up. Worse nighttime sleep (according to actigraphy) at baseline was associated with worse activities of daily living functioning and more depressive symptoms at follow-up. Sleep disturbance is common in older ALF residents, and poor sleep is associated with declining functional status and quality of life and greater depression over 6 months of follow-up. Studies are needed to determine whether improving sleep in ALF residents will result in improvements in these outcomes. Well-established treatments should be adapted for use in ALFs and systematically evaluated in future research.

  13. B cells in multiple sclerosis therapy-A comprehensive review.

    Science.gov (United States)

    Rahmanzadeh, R; Weber, M S; Brück, W; Navardi, S; Sahraian, M A

    2018-03-07

    For decades, B cells were ignored in multiple sclerosis (MS) pathogenesis, and the disease was always regarded as a T cell-mediated disorder. Recent evidence shows that there is an antigen-driven B-cell response in the central nervous system of patients with MS, and memory B cells/plasma cells are detectable in MS lesions. The striking efficacy of B cell-depleting therapies in reducing the inflammatory activity of the disease highlights that B cells may play more pathogenetic roles than expected. B cells express several unique characteristic markers on their surface, for example, CD19, CD20 molecules, that provide selective targets for monoclonal antibodies. In this respect, several B cell-targeted therapies emerged, including anti-CD20 antibodies (rituximab, ocrelizumab, and ofatumumab), anti-CD19 antibody (inebilizumab), and agents targeting the BAFF/APRIL signaling pathway (atacicept, belimumab, and LY2127399). In this review, we discuss, in detail, the immunobiology of B cells and their protective and destructive roles in MS pathogenesis. In the second part, we list the completed and ongoing clinical trials investigating the safety and efficacy of B cell-related monoclonal antibodies in MS. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Regulatory T cells and B cells: implication on autoimmune diseases

    OpenAIRE

    Wang, Ping; Zheng, Song Guo

    2013-01-01

    The regulatory T (Treg) cells play an important role in the maintenance of homeostasis and the prevention of autoimmune diseases. Although most studies are focusing on the role of Treg cells in T cells and T cells-mediated diseases, these cells also directly affect B cells and other non-T cells. This manuscript updates the role of Treg cells on the B cells and B cell-mediated diseases. In addition, the mechanisms whereby Treg cells suppress B cell responses have been discussed.

  15. Atypical B cell receptor signaling: straddling immune diseases and cancer.

    Science.gov (United States)

    Faris, Mary

    2013-08-01

    The B-cell receptor (BCR) signaling pathway plays an essential role in the survival, proliferation, differentiation and trafficking of lymphocytic. Recent findings associate aberrant BCR signaling with specific disease pathologies, including B-cell malignancies and autoimmune disorders. Inhibition of the BCR signaling pathway may therefore provide promising new strategies for the treatment of B-cell diseases. This special issue of International Reviews of Immunology focuses on atypical B-cell receptor signaling, its role in immune diseases and cancer, and its implications for potential therapeutic intervention.

  16. Fingolimod induces BAFF and expands circulating transitional B cells without activating memory B cells and plasma cells in multiple sclerosis.

    Science.gov (United States)

    Miyazaki, Yusei; Niino, Masaaki; Takahashi, Eri; Suzuki, Masako; Mizuno, Masanori; Hisahara, Shin; Fukazawa, Toshiyuki; Amino, Itaru; Nakano, Fumihito; Nakamura, Masakazu; Akimoto, Sachiko; Minami, Naoya; Fujiki, Naoto; Doi, Shizuki; Shimohama, Shun; Terayama, Yasuo; Kikuchi, Seiji

    2018-02-01

    Patients with multiple sclerosis (MS) who are treated with fingolimod have an increased proportion of transitional B cells in the circulation, but the underlying mechanism is not known. We hypothesized that B cell-activating factor of the tumor necrosis factor family (BAFF) is involved in the process. Compared with healthy controls and untreated MS patients, fingolimod-treated MS patients had significantly higher serum concentrations of BAFF, which positively correlated with the proportions and the absolute numbers of transitional B cells in blood. Despite the elevated concentrations of BAFF in fingolimod-treated MS patients, serum levels of soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor, and B cell maturation antigen were not elevated. Our results show that fingolimod induces BAFF in the circulation and expands transitional B cells, but does not activate memory B cells or plasma cells in MS, which is favorable for the treatment of this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Quality of Hospice Care at Home Versus in an Assisted Living Facility or Nursing Home.

    Science.gov (United States)

    Unroe, Kathleen T; Stump, Timothy E; Effler, Shannon; Tu, Wanzhu; Callahan, Christopher M

    2018-04-01

    To describe differences in perceived quality of hospice care for individuals living at home or in a nursing home (NH) or assisted living facility (ALF) through analysis of after-death surveys of family members. Retrospective cohort study using hospice medical record data and Family Evaluation of Hospice Care (FEHC) survey data. Large, national hospice provider. Individuals who died while receiving routine hospice care and family caregivers who completed after-death quality-of-care surveys. Survey results for 7,510 individuals were analyzed using analysis of variance and chi-square tests. Logistic regression was used to assess relationship between location of care and overall service quality. The overall survey response rate was 27%; 34.5% of families of individuals in ALFs in hospice, 27.4% of those at home, and 22.9% of those in NHs returned the survey (P quality as excellent. Hospice care in the NH was less likely to be perceived as excellent. There were significant differences in characteristics of individuals whose family members did and did not return surveys, which has implications for use of after-death surveys to evaluate hospice quality. Lower perceived quality of hospice care in NHs may be related to general dissatisfaction with receiving care in this setting. Survey results have the potential to set priorities for quality improvement, choice of provider, and potentially reimbursement. Underlying causes of differences of perceived quality in different settings of care should be examined. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

  18. The Development of a Quality Management Framework for Evaluating Medical Device Reprocessing Practice in Healthcare Facilities.

    Science.gov (United States)

    Lorv, Bailey; Horodyski, Robin; Welton, Cynthia; Vail, John; Simonetto, Luca; Jokanovic, Danilo; Sharma, Richa; Mahoney, Angela Rea; Savoy-Bird, Shay; Bains, Shalu

    2017-01-01

    There is increasing awareness of the importance of medical device reprocessing (MDR) for the provision of safe patient care. Although industry service standards are available to guide MDR practices, there remains a lack of published key performance indicators (KPIs) and targets that are necessary to evaluate MDR quality for feedback and improvement. This article outlines the development of an initial framework that builds on established guidelines and includes service standards, KPIs and targets for evaluating MDR operations. This framework can support healthcare facilities in strengthening existing practices and enables a platform for collaboration towards better MDR performance management.

  19. T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection.

    Science.gov (United States)

    Pallikkuth, Suresh; de Armas, Lesley; Rinaldi, Stefano; Pahwa, Savita

    2017-01-01

    T follicular helper (Tfh) cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging. Although many of the HIV-associated defects improve with antiretroviral therapy (ART), excess immune activation and antigen-specific B and T cell responses including Tfh function are still impaired in virologically controlled HIV-infected persons on ART. Interestingly, HIV infected individuals experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV infection and highlight the impact of chronic HIV infection and aging on Tfh-B cell interactions.

  20. T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection

    Directory of Open Access Journals (Sweden)

    Suresh Pallikkuth

    2017-10-01

    Full Text Available T follicular helper (Tfh cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging. Although many of the HIV-associated defects improve with antiretroviral therapy (ART, excess immune activation and antigen-specific B and T cell responses including Tfh function are still impaired in virologically controlled HIV-infected persons on ART. Interestingly, HIV infected individuals experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV infection and highlight the impact of chronic HIV infection and aging on Tfh–B cell interactions.

  1. Quality control assessment of diagnostic x-ray facilities in Ghana

    International Nuclear Information System (INIS)

    Amoako, J.K.; Charles, D.F.; Oppong-Adu, C.; Schandorf, C.

    2009-01-01

    Twenty-three X-ray machines located at 20 different hospitals in Ghana were assessed for quality assurance and control. The radiographic parameters evaluated were tube voltage and current, tube output consistency variation with kilovoltage (kV) and current-time (mAs) factor, exposure time accuracy and beam quality as measured by half-value layer. The photographic parameters assessed were type of films, level of film fogging, film speed, contrast index and film processing temperature. Twenty two of the machines were ∼ 99 % output consistency with standard kVp and mAs. Twelve of the machines had output linearity deviation of less than the acceptable 5 %, while 22 machines were within the accepted kVp deviation of 5 %. The film processing temperature at most hospitals exceeded the required level, due to the absence of air conditioners in the darkrooms. The darkroom quality control at all the facilities was very high. Fogging of films was minimal as indicated by the Base + Fog value of 0.3, speed index of film was ∼ 1.65 and contrast index was comparable to the acceptable value of 1.5. The level of timer accuracy was greater than 95 % for all the X-ray machines with the exception of one. The general quality control status of all the X-ray machines and darkrooms assessed were acceptable and within the quality assurance standards. (au)

  2. Radiation doses and some aspects of image quality in mammography facilities in New Zealand

    International Nuclear Information System (INIS)

    Williamson, B.D.P.; Poletti, J.L.

    1990-02-01

    Until recently, mammography in New Zealand was performed largely with adapted conventional x-ray machines with tungsten anode x-ray tubes. Over the last several years these have virtually all been replaced by dedicated mammography machines with molybdenum anode x-ray tubes. To assess current trends in radiation doses to patients and central aspects of image quality, some 37 mammography x-ray machines were surveyed during 1988-89. The mean glandular dose per film for 30 and 45 mm thick breast-equivalent phantoms was determined using thermoluminescent dosimetry. Imagings of simulated microcalcifications (specks) and a contrast-detail phantom were assessed. Accuracy of calibration of the x-ray machines and quality of film processing were also tested. Details of the survey results are given. Mean glandular tissue doses per cranio-caudal films were generally well within the recommended guidelines. Mammography facilities differed in their ability to delete simulated calcification specks. Mammographic equipment was found to be generally well adjusted. Speed and contrast of film processing were found to vary widely implying that this is a major cause of the variations in dose and image quality. An annex outlines a quality assurance programme for maintenance of optimal physical image quality and control of radiation doses. 55 refs., 21 tabs., 17 figs., 2 ills

  3. National Ignition Facility quality assurance plan for laser materials and optical technology

    International Nuclear Information System (INIS)

    Wolfe, C.R.

    1996-05-01

    Quality achievement is the responsibility of the line organizations of the National Ignition Facility (NIF) Project. This subtier Quality Assurance Plan (QAP) applies to activities of the Laser Materials ampersand Optical Technology (LM ampersand OT) organization and its subcontractors. It responds to the NIF Quality Assurance Program Plan (QAPP, L-15958-2, NIF-95-499) and Department of Energy (DOE) Order 5700.6C. This Plan is organized according to 10 Quality Assurance (QA) criteria and subelements of a management system as outlined in the NIF QAPP. This Plan describes how those QA requirements are met. This Plan is authorized by the Associate Project Leader for the LM ampersand OT organization, who has assigned responsibility to the Optics QA engineer to maintain this plan, with the assistance of the NIF QA organization. This Plan governs quality-affecting activities associated with: design; procurement; fabrication; testing and acceptance; handling and storage; and installation of NIF Project optical components into mounts and subassemblies

  4. Using Value Stream Mapping to improve quality of care in low-resource facility settings.

    Science.gov (United States)

    Ramaswamy, Rohit; Rothschild, Claire; Alabi, Funmi; Wachira, Eric; Muigai, Faith; Pearson, Nick

    2017-11-01

    Jacaranda Health (JH) is a Kenya-based organization that attempts to provide affordable, high-quality maternal and newborn healthcare through a chain of private health facilities in Nairobi. JH needed to adopted quality improvement as an organization-wide strategy to optimize effectiveness and efficiency. Value Stream Mapping, a Lean Management tool, was used to engage staff in prioritizing opportunities to improve clinical outcomes and patient-centered quality of care. Implementation was accomplished through a five-step process: (i) leadership engagement and commitment; (ii) staff training; (iii) team formation; (iv) process walkthrough; and (v) construction and validation. The Value Stream Map allowed the organization to come together and develop an end-to-end view of the process of care at JH and to select improvement opportunities for the entire system. The Value Stream Map is a simple visual tool that allows organizations to engage staff at all levels to gain commitment around quality improvement efforts. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  5. B-cell-mediated strategies to fight chronic allograft rejection

    Directory of Open Access Journals (Sweden)

    Ali H Dalloul

    2013-12-01

    Full Text Available Solid organs have been transplanted for decades. Since the improvement in graft selection and in medical and surgical procedures, the likelihood of graft function after one year is now close to 90%. Nonetheless even well-matched recipients continue to need medications for the rest of their lives hence adverse side effects and enhanced morbidity. Understanding Immune rejection mechanisms, is of increasing importance since the greater use of living-unrelated donors and genetically unmatched individuals. Chronic rejection is devoted to T-cells, however the role of B-cells in rejection has been appreciated recently by the observation that B-cell depletion improve graft survival. By contrast however, B-cells can be beneficial to the grafted tissue. This protective effect is secondary to either the secretion of protective antibodies or the induction of B-cells that restrain excessive inflammatory responses, chiefly by local provision of IL-10, or inhibit effector T-cells by direct cellular interactions. As a proof of concept B-cell-mediated infectious transplantation tolerance could be achieved in animal models, and evidence emerged that the presence of such B-cells in transplanted patients correlate with a favorable outcome. Among these populations, regulatory B-cells constitute a recently described population. These cells may develop as a feedback mechanism to prevent uncontrolled reactivity to antigens and inflammatory stimuli. The difficult task for the clinician, is to quantify the respective ratios and functions of tolerant vs effector B-cells within a transplanted organ, at a given time point in order to modulate B-cell-directed therapy. Several receptors at the B-cell membrane as well as signaling molecules, can now be targeted for this purpose. Understanding the temporal expansion of regulatory B-cells in grafted patients and the stimuli that activate them will help in the future to implement specific strategies aimed at fighting chronic

  6. How B cells influence bone biology in health and disease.

    Science.gov (United States)

    Horowitz, Mark C; Fretz, Jackie A; Lorenzo, Joseph A

    2010-09-01

    It is now well established that important regulatory interactions occur between the cells in the hematopoietic, immune and skeletal systems (osteoimmunology). B lymphocytes (B cells) are responsible for the generation and production of antibodies or immunoglobulins in the body. Together with T cells these lymphocytes comprise the adaptive immune system, which allows an individual to develop specific responses to an infection and retain memory of that infection, allowing for a faster and more robust response if that same infection occurs again. In addition to this immune function, B cells have a close and multifaceted relationship with bone cells. B cells differentiate from hematopoietic stem cells (HSCs) in supportive niches found on endosteal bone surfaces. Cells in the osteoblast lineage support HSC and B cell differentiation in these niches. B cell differentiation is regulated, at least in part, by a series of transcription factors that function in a temporal manner. While these transcription factors are required for B cell differentiation, their loss causes profound changes in the bone phenotype. This is due, in part, to the close relationship between macrophage/osteoclast and B cell differentiation. Cross talk between B cells and bone cells is reciprocal with defects in the RANKL-RANK, OPG signaling axis resulting in altered bone phenotypes. While the role of B cells during normal bone remodeling appears minimal, activated B cells play an important role in many inflammatory diseases with associated bony changes. This review examines the relationship between B cells and bone cells and how that relationship affects the skeleton and hematopoiesis during health and disease. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Safety assessment and quality control of medical x-ray facilities in some hospitals in Ghana

    International Nuclear Information System (INIS)

    Darko, E.O.; Charles, D.F.

    1998-01-01

    Safety assessment and quality control measurements of diagnostic x-ray installations were carried out in five hospitals in Ghana. The study was focused on the siting, design and construction of the buildings housing the x-ray units, assessment of safety systems and devices and measurements of the technical performance, and film processing conditions. The location, inadequacies in the design/construction, unavailability of relevant safety systems and devices, violation of basic safety principles and poor performance of some of the x-ray facilities indicate the need to improve quality control programmes, safety culture and enforcement of regulatory standards in diagnostic x-ray examinations in Ghana. (author). 8 refs., 11 tabs., 8 figs

  8. Challenges and barriers to managing quality in an end-stage renal disease facility.

    Science.gov (United States)

    VanValkenburgh, D; Snyder, S

    1994-08-01

    The End-Stage Renal Disease Program is underfunded and overregulated. Objective parameters of end points of care do not correlate to specific clinical practice patterns. We do not have consensus between payers, providers, and patients as to what the objectives of the End-Stage Renal Disease Program are or should be. This report will address the need for an integrated health care delivery system that would benefit the end-stage renal disease patient and the barriers to designing such a system. The quality improvement program of a five-unit dialysis system will be described. The deficiencies of the quality improvement program and the limitation of the facilities to improve outcome will be discussed, and constructive alternatives to achieve an integrated health care delivery system that promotes improvement in patient outcomes will be suggested.

  9. Groundwater quality assessment plan for the Metallurgical Laboratory Hazardous Waste Management Facility

    Energy Technology Data Exchange (ETDEWEB)

    Jerome, K.M.

    1990-10-01

    The Metallurgical Laboratory Hazardous Waste Management Facility (MLHWMF) will be closed under interim status regulation and permitted as a hazardous waste management facility by a Post Closure Part B Permit under 40 CFR 264. This report discusses the ground water quality assessment plan for the MLHWMF. The Metallurgical Laboratory Hazardous Waste Management Facility consists of the process sewer line leading to the Metallurgical Laboratory basin from the fence, the Metallurgical Laboratory basin, the drainage outfall to the Carolina bay, and the Carolina bay itself. The Metallurgical Laboratory HWMF received F001, F003, F007, and D011 waste. F001 waste includes spent halogenated solvents used in degreasing (trichloroethylene, 1,1,1-trichloroethane, and carbon tetrachloride). F003 waste includes spent nonhalogenated solvents (acetone), and F007 waste is spent cyanide plating bath solution. At present forty-three constituents are analyzed per sample. Trichloroethylene, tetrachloroethylene, and total radium are the only constituents that were reported above Primary Drinking Water Standards (PDWS) during the second quarter of 1990. Listed in this report are the constituents that are being analyzed at present. Appendix A presents the trends for the analyzed constituents from the fourth quarter of 1988 to the second quarter of 1990. 5 figs., 5 tabs.

  10. Process Evaluation of a Quality Improvement Project to Decrease Hospital Readmissions From Skilled Nursing Facilities.

    Science.gov (United States)

    Meehan, Thomas P; Qazi, Daniel J; Van Hoof, Thomas J; Ho, Shih-Yieh; Eckenrode, Sheila; Spenard, Ann; Pandolfi, Michelle; Johnson, Florence; Quetti, Deborah

    2015-08-01

    To describe and evaluate the impact of quality improvement (QI) support provided to skilled nursing facilities (SNFs) by a Quality Improvement Organization (QIO). Retrospective, mixed-method, process evaluation of a QI project intended to decrease preventable hospital readmissions from SNFs. Five SNFs in Connecticut. SNF Administrators, Directors of Nursing, Assistant Directors of Nursing, Admissions Coordinators, Registered Nurses, Certified Nursing Assistants, Receptionists, QIO Quality Improvement Consultant. QIO staff provided training and technical assistance to SNF administrative and clinical staff to establish or enhance QI infrastructure and implement an established set of QI tools [Interventions to Reduce Acute Care Transfers (INTERACT) tools]. Baseline SNF demographic, staffing, and hospital readmission data; baseline and follow-up SNF QI structure (QI Committee), processes (general and use of INTERACT tools), and outcome (30-day all-cause hospital readmission rates); details of QIO-provided training and technical assistance; QIO-perceived barriers to quality improvement; SNF leadership-perceived barriers, accomplishments, and suggestions for improvement of QIO support. Success occurred in establishing QI Committees and targeting preventable hospital readmissions, as well as implementing INTERACT tools in all SNFs; however, hospital readmission rates decreased in only 2 facilities. QIO staff and SNF leaders noted the ongoing challenge of engaging already busy SNF staff and leadership in QI activities. SNF leaders reported that they appreciated the training and technical assistance that their institutions received, although most noted that additional support was needed to bring about improvement in readmission rates. This process evaluation documented mixed clinical results but successfully identified opportunities to improve recruitment of and provision of technical support to participating SNFs. Recommendations are offered for others who wish to conduct

  11. Piloting laboratory quality system management in six health facilities in Nigeria.

    Directory of Open Access Journals (Sweden)

    Henry Mbah

    Full Text Available Achieving accreditation in laboratories is a challenge in Nigeria like in most African countries. Nigeria adopted the World Health Organization Regional Office for Africa Stepwise Laboratory (Quality Improvement Process Towards Accreditation (WHO/AFRO- SLIPTA in 2010. We report on FHI360 effort and progress in piloting WHO-AFRO recognition and accreditation preparedness in six health facility laboratories in five different states of Nigeria.Laboratory assessments were conducted at baseline, follow up and exit using the WHO/AFRO- SLIPTA checklist. From the total percentage score obtained, the quality status of laboratories were classified using a zero to five star rating, based on the WHO/AFRO quality improvement stepwise approach. Major interventions include advocacy, capacity building, mentorship and quality improvement projects.At baseline audit, two of the laboratories attained 1- star while the remaining four were at 0- star. At follow up audit one lab was at 1- star, two at 3-star and three at 4-star. At exit audit, four labs were at 4- star, one at 3-star and one at 2-star rating. One laboratory dropped a 'star' at exit audit, while others consistently improved. The two weakest elements at baseline; internal audit (4% and occurrence/incidence management (15% improved significantly, with an exit score of 76% and 81% respectively. The elements facility and safety was the major strength across board throughout the audit exercise.This effort resulted in measurable and positive impact on the laboratories. We recommend further improvement towards a formal international accreditation status and scale up of WHO/AFRO- SLIPTA implementation in Nigeria.

  12. Laboratory facility design and microbial indoor air quality in selected hospital laboratories.

    Science.gov (United States)

    Luksamijarulkul, Pipat; Kiennukul, Nuchanard; Vatthanasomboon, Pisit

    2014-05-01

    Hospital laboratory is one of workplace areas contaminated with a variety of biohazards. A cross sectional study was conducted to assess the microbial air quality and facility design in the laboratories of four selected governmental hospitals (Hospitals A, B, C, and D) in Bangkok, Thailand. One hundred eighty-eight indoor air samples were collected from 40 laboratory rooms to investigate bacterial and fungal counts using the Millipore air tester. Forty air samples were collected from the waiting areas of those laboratories, and 16 outdoor air samples were collected to use for comparison. Additionally, those laboratory facilities were assessed following biosafety facility design (10 items). Results indicated that the facility design of laboratory in the Hospital A met most of items of the biosafety facility criteria. The rest met only seven items of the criteria. Means +/- standard deviation (SD) of bacterial counts of 253.1 +/- 247.7 cfu/m3, 236.8 +/- 200.1 cfu/m3, 304.4 +/- 264.2 cfu/m3, and 146.7 +/- 127.0 cfu/m3, and fungal counts of 500.8 +/- 64.2 cfu/ m3, 425.0 +/- 21.2 cfu/m3, 357.0 +/- 121.2 cfu/m3, and 355.7 +/- 86.8 cfu/m3 were found in hospital laboratories A, B, C and D, respectively. The isolated colonies of bacteria and fungi were identified as group or genus. It was found that the most common bacteria was Staphylococcus spp (84.1%, 76.0%, 72.1% and 80.5%, respectively), whereas, the most common fungi were Aspergillus spp and septate hyphae fungi (42.0%, 37.5%, 39.5%, and 45.7%; vs 38.6%, 56.2%, 52.1%, and 37.2%, respectively). These data may be valuable to develop interventions to improve the microbial indoor air quality among hospital laboratories and for preventing the laboratory-acquired infections.

  13. Bidirectional regulation between B cells and T cells

    NARCIS (Netherlands)

    Margry, B.

    2014-01-01

    B cells were often thought of as simple precursors of end-stage effector cells that are merely in charge of antibody production. Research in the last decades has shown that B cells possess important other roles as well, including their involvement in the regulation and functioning of T cell-mediated

  14. DNA breaks early in replication in B cell cancers

    Science.gov (United States)

    Research by scientists at the NCI has identified a new class of DNA sites in cells that break early in the replication process. They found that these break sites correlate with damage often seen in B cell cancers, such as diffuse large B cell lymphoma.

  15. A fine romance: T follicular helper cells and B cells.

    Science.gov (United States)

    King, Cecile

    2011-06-24

    T follicular helper (Tfh) cells help B cells to generate affinity-matured antibodies. Three papers in this issue of Immunity (Choi et al., 2011; Kerfoot et al., 2011; Kitano et al., 2011) provide information about the reciprocal relationship between B cells and Tfh cells. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Resource Competition Determines Selection of B Cell Repertoires

    NARCIS (Netherlands)

    Boer, R.J. de; Freitas, A.A. (António); Perelson, A.S. (Alan)

    2001-01-01

    Previous experiments with mouse chimeras demonstrated that cellular competition for antigen- specific survival signals plays a crucial role in the maintenance of the naive B cell repertoire. Transgenic (Tg) B cell populations in these chimeras have a shortened lifespan and poor competitive

  17. Fear and overprotection in Australian residential aged-care facilities: The inadvertent impact of regulation on quality continence care.

    Science.gov (United States)

    Ostaszkiewicz, Joan; O'Connell, Beverly; Dunning, Trisha

    2016-06-01

    Most residents in residential aged-care facilities are incontinent. This study explored how continence care was provided in residential aged-care facilities, and describes a subset of data about staffs' beliefs and experiences of the quality framework and the funding model on residents' continence care. Using grounded theory methodology, 18 residential aged-care staff members were interviewed and 88 hours of field observations conducted in two facilities. Data were analysed using a combination of inductive and deductive analytic procedures. Staffs' beliefs and experiences about the requirements of the quality framework and the funding model fostered a climate of fear and risk adversity that had multiple unintended effects on residents' continence care, incentivising dependence on continence management, and equating effective continence care with effective pad use. There is a need to rethink the quality of continence care and its measurement in Australian residential aged-care facilities. © 2015 AJA Inc.

  18. Water, sanitation and hygiene infrastructure and quality in rural healthcare facilities in Rwanda.

    Science.gov (United States)

    Huttinger, Alexandra; Dreibelbis, Robert; Kayigamba, Felix; Ngabo, Fidel; Mfura, Leodomir; Merryweather, Brittney; Cardon, Amelie; Moe, Christine

    2017-08-03

    WHO and UNICEF have proposed an action plan to achieve universal water, sanitation and hygiene (WASH) coverage in healthcare facilities (HCFs) by 2030. The WASH targets and indicators for HCFs include: an improved water source on the premises accessible to all users, basic sanitation facilities, a hand washing facility with soap and water at all sanitation facilities and patient care areas. To establish viable targets for WASH in HCFs, investigation beyond 'access' is needed to address the state of WASH infrastructure and service provision. Patient and caregiver use of WASH services is largely unaddressed in previous studies despite being critical for infection control. The state of WASH services used by staff, patients and caregivers was assessed in 17 rural HCFs in Rwanda. Site selection was non-random and predicated upon piped water and power supply. Direct observation and semi-structured interviews assessed drinking water treatment, presence and condition of sanitation facilities, provision of soap and water, and WASH-related maintenance and record keeping. Samples were collected from water sources and treated drinking water containers and analyzed for total coliforms, E. coli, and chlorine residual. Drinking water treatment was reported at 15 of 17 sites. Three of 18 drinking water samples collected met the WHO guideline for free chlorine residual of >0.2 mg/l, 6 of 16 drinking water samples analyzed for total coliforms met the WHO guideline of <1 coliform/100 mL and 15 of 16 drinking water samples analyzed for E. coli met the WHO guideline of <1 E. coli/100 mL. HCF staff reported treating up to 20 L of drinking water per day. At all sites, 60% of water access points (160 of 267) were observed to be functional, 32% of hand washing locations (46 of 142) had water and soap and 44% of sanitary facilities (48 of 109) were in hygienic condition and accessible to patients. Regular maintenance of WASH infrastructure consisted of cleaning; no HCF had on

  19. A Novel VHH Antibody Targeting the B Cell-Activating Factor for B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Wen Wu

    2014-05-01

    Full Text Available Objective: To construct an immune alpaca phage display library, in order to obtain a single domain anti-BAFF (B cell-activating factor antibody. Methods: Using phage display technology, we constructed an immune alpaca phage display library, selected anti-BAFF single domain antibodies (sdAbs, cloned three anti-BAFF single-domain antibody genes into expression vector pSJF2, and expressed them efficiently in Escherichia coli. The affinity of different anti-BAFF sdAbs were measured by Bio layer interferometry. The in vitro biological function of three sdAbs was investigated by cell counting kit-8 (CCK-8 assay and a competitive enzyme-linked immunosorbent assay (ELISA. Results: We obtained three anti-BAFF single domain antibodies (anti-BAFF64, anti-BAFF52 and anti-BAFFG3, which were produced in high yield in Escherichia coli and inhibited tumor cell proliferation in vitro. Conclusion: The selected anti-BAFF antibodies could be candidates for B-cell lymphoma therapies.

  20. Comparison of EBV DNA viral load in whole blood, plasma, B-cells and B-cell culture supernatant.

    Science.gov (United States)

    Ouedraogo, David Eric; Bollore, Karine; Viljoen, Johannes; Foulongne, Vincent; Reynes, Jacques; Cartron, Guillaume; Vendrell, Jean-Pierre; Van de Perre, Philippe; Tuaillon, Edouard

    2014-05-01

    Epstein-Barr virus (EBV) genome quantitation in whole blood is used widely for therapeutic monitoring of EBV-associated disorders in immunosuppressed individuals and in patients with EBV-associated lymphoma. However, the most appropriate biological material to be used for EBV DNA quantitation remains a subject of debate. This study compare the detection rate and levels of EBV DNA from whole blood, plasma, enriched B-cells, and B-cell short-term culture supernatant using quantitative real-time PCR. Samples were collected from 33 subjects with either HIV infection or B-cell lymphoma. Overall, EBV DNA was detected in 100% of enriched B-cell samples, in 82% of B-cell culture supernatants, in 57% of plasma, and 42% of whole blood samples. A significant correlation for EBV viral load was found between enriched B-cell and B-cell culture supernatant material (ρ = 0.92; P < 0.0001), but no significant correlation existed between EBV DNA levels in whole blood and enriched B-cells (ρ = -0.02; P = 0.89), whole blood and plasma (ρ = 0.24; P = 0.24), or enriched B-cells and plasma (ρ = 0.08; P = 0.77). Testing of enriched B-cells appeared to be the most sensitive method for detection of EBV DNA as well as for exploration of the cellular reservoir. Quantitation of EBV DNA in plasma and B-cell culture supernatant may be of interest to assess EBV reactivation dynamics and response to treatment as well as to decipher EBV host-pathogen interactions in various clinical scenarios. © 2013 Wiley Periodicals, Inc.

  1. Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor.

    Directory of Open Access Journals (Sweden)

    Konstantinos Samitas

    Full Text Available B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive.A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF and their receptors (CD127 and BAFFR, BCMA, TACI, respectively were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein and in vitro (colony forming cell assay. Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL of asthmatic patients and healthy controls.Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4 and co-stimulation (CD40, CD86 and are resistant to apoptosis (Bax. Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics.Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.

  2. Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79 Fluorescence Reporter Transgenes.

    Science.gov (United States)

    Liu, Xingjun; Li, Yue-Sheng; Shinton, Susan A; Rhodes, Jennifer; Tang, Lingjuan; Feng, Hui; Jette, Cicely A; Look, A Thomas; Hayakawa, Kyoko; Hardy, Richard R

    2017-09-01

    CD79a and CD79b proteins associate with Ig receptors as integral signaling components of the B cell Ag receptor complex. To study B cell development in zebrafish, we isolated orthologs of these genes and performed in situ hybridization, finding that their expression colocalized with IgH-μ in the kidney, which is the site of B cell development. CD79 transgenic lines were made by linking the promoter and upstream regulatory segments of CD79a and CD79b to enhanced GFP to identify B cells, as demonstrated by PCR analysis of IgH-μ expression in sorted cells. We crossed these CD79-GFP lines to a recombination activating gene (Rag)2:mCherry transgenic line to identify B cell development stages in kidney marrow. Initiation of CD79:GFP expression in Rag2:mCherry + cells and the timing of Ig H and L chain expression revealed simultaneous expression of both IgH-μ- and IgL-κ-chains, without progressing through the stage of IgH-μ-chain alone. Rag2:mCherry + cells without CD79:GFP showed the highest Rag1 and Rag2 mRNAs compared with CD79a and CD79b:GFP + B cells, which showed strongly reduced Rag mRNAs. Thus, B cell development in zebrafish does not go through a Rag hi CD79 + IgH-μ + pre-B cell stage, different from mammals. After the generation of CD79:GFP + B cells, decreased CD79 expression occurred upon differentiation to Ig secretion, as detected by alteration from membrane to secreted IgH-μ exon usage, similar to in mammals. This confirmed a conserved role for CD79 in B cell development and differentiation, without the requirement of a pre-B cell stage in zebrafish. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. Defining B Cell Chromatin: Lessons from EBF1.

    Science.gov (United States)

    Boller, Sören; Li, Rui; Grosschedl, Rudolf

    2018-04-01

    Hematopoiesis is regulated by signals from the microenvironment, transcription factor networks, and changes of the epigenetic landscape. Transcription factors interact with and shape chromatin to allow for lineage- and cell type-specific changes in gene expression. During B lymphopoiesis, epigenetic regulation is observed in multilineage progenitors in which a specific chromatin context is established, at the onset of the B cell differentiation when early B cell factor 1 (EBF1) induces lineage-specific changes in chromatin, during V(D)J recombination and after antigen-driven activation of B cells and terminal differentiation. In this review, we discuss the epigenetic changes underlying B cell differentiation, focusing on the role of transcription factor EBF1 in B cell lineage priming. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Quality Assurance Project Plan for Closure of the Central Facilities Area Sewage Treatment Plant Lagoon 3 and Land Application Area

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Michael G. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-10-01

    This quality assurance project plan describes the technical requirements and quality assurance activities of the environmental data collection/analyses operations to close Central Facilities Area Sewage treatment Plant Lagoon 3 and the land application area. It describes the organization and persons involved, the data quality objectives, the analytical procedures, and the specific quality control measures to be employed. All quality assurance project plan activities are implemented to determine whether the results of the sampling and monitoring performed are of the right type, quantity, and quality to satisfy the requirements for closing Lagoon 3 and the land application area.

  5. Production and quality assurance automation in the Goddard Space Flight Center Flight Dynamics Facility

    Science.gov (United States)

    Chapman, K. B.; Cox, C. M.; Thomas, C. W.; Cuevas, O. O.; Beckman, R. M.

    1994-01-01

    The Flight Dynamics Facility (FDF) at the NASA Goddard Space Flight Center (GSFC) generates numerous products for NASA-supported spacecraft, including the Tracking and Data Relay Satellites (TDRS's), the Hubble Space Telescope (HST), the Extreme Ultraviolet Explorer (EUVE), and the space shuttle. These products include orbit determination data, acquisition data, event scheduling data, and attitude data. In most cases, product generation involves repetitive execution of many programs. The increasing number of missions supported by the FDF has necessitated the use of automated systems to schedule, execute, and quality assure these products. This automation allows the delivery of accurate products in a timely and cost-efficient manner. To be effective, these systems must automate as many repetitive operations as possible and must be flexible enough to meet changing support requirements. The FDF Orbit Determination Task (ODT) has implemented several systems that automate product generation and quality assurance (QA). These systems include the Orbit Production Automation System (OPAS), the New Enhanced Operations Log (NEOLOG), and the Quality Assurance Automation Software (QA Tool). Implementation of these systems has resulted in a significant reduction in required manpower, elimination of shift work and most weekend support, and improved support quality, while incurring minimal development cost. This paper will present an overview of the concepts used and experiences gained from the implementation of these automation systems.

  6. Dairy cow handling facilities and the perception of Beef Quality Assurance on Colorado dairies.

    Science.gov (United States)

    Adams, A E; Olea-Popelka, F J; Grandin, T; Woerner, D R; Roman-Muniz, I N

    2014-02-01

    A survey was conducted on Colorado dairies to assess attitudes and practices regarding Dairy Beef Quality Assurance (DBQA). The objectives were to (1) assess the need for a new handling facility that would allow all injections to be administered via DBQA standards; (2) establish if Colorado dairy producers are concerned with DBQA; and (3) assess differences in responses between dairy owners and herdsmen. Of the 95 dairies contacted, 20 (21%) agreed to participate, with a median herd size of 1,178. When asked to rank the following 7 traits--efficiency, animal safety, human safety, ease of animal handling, ease of operation, inject per Beef Quality Assurance (BQA) procedures, and cost--in order of priority when designing a new handling facility, human and animal safety were ranked highest in priority (first or second) by the majority of participants, with ease of animal handling and efficiency ranked next. Interestingly, the administration of injections per BQA standards was ranked sixth or seventh by most participants. Respondents estimated the average annual income from the sale of cull cows to be 4.6% of all dairy income, with 50% receiving at least one carcass discount or condemnation in the past 12 mo. Although almost all of the participating dairy farmers stated that the preferred injection site for medications was the neck region, a significant number admitted to using alternate injection sites. In contrast, no difference was found between responses regarding the preferred and actual location for intravenous injections. Although most participating producers are aware of BQA injection guidelines, they perceive efficiency as more important, which could result in injections being administered in locations not promoted by BQA. Dairy owners and herdsmen disagreed in whether or not workers had been injured in the animal handling area in the last 12 mo. Handling facilities that allow for an efficient and safe way to administer drugs according to BQA guidelines and

  7. Marginal zone B-cells, a gatekeeper of innate immunity

    Directory of Open Access Journals (Sweden)

    Moncef eZOUALI

    2011-12-01

    Full Text Available To maintain the integrity of an organism constantly challenged by pathogens, the immune system is endowed with a variety of cell types. B-lymphocytes were initially thought to only play a role in the adaptative branch of immunity. However, a number of converging observations revealed that two B-cell subsets, marginal zone (MZ and B1 cells, exhibit unique developmental and functional characteristics, and can contribute to innate immune responses. In addition to their capacity to mount local antibody response against type 2 T-independent (TI-2 antigens, MZ B-cells can participate to T-dependent (TD immune response through the capture and import of blood-borne antigens to follicular areas of the spleen. Here, we discuss the multiple roles of MZ B-cells in rodents and primates. We also summarize studies —performed in transgenic mice expressing fully human antibodies on their B-cells and macaques whose infection with Simian Immunodeficiency Virus (SIV represents a suitable model for HIV-1 infection in humans— showing that infectious agents have developed strategies to subvert MZ B-cell functions. In these two experimental models, we observed that two microbial superantigens for B-cells (protein A from Staphylococcus aureus and protein L from Peptostreptococcus magnus as well as inactivated AT-2 virions of HIV-1 and infectious SIV preferentially deplete innate-like B-cells —MZ B-cells and/or B1 B-cells— with different consequences on TI and TD antibody responses. These data revealed that viruses and bacteria have developed strategies to deplete innate-like B-cells during the acute phase of infection and to impair the antibody response. Unraveling the intimate mechanisms responsible for targeting MZ B-cells in humans will be important for understanding disease pathogenesis and for designing novel vaccine strategies.

  8. Quality of care and its determinants in longer term mental health facilities across Europe; a cross-sectional analysis

    NARCIS (Netherlands)

    Killaspy, Helen; Cardoso, Graca; White, Sarah; Wright, Christine; Caldas de Almeida, Jose Miguel; Turton, Penny; Taylor, Tatiana L.; Schuetzwohl, Matthias; Schuster, Mirjam; Cervilla, Jorge A.; Brangier, Paulette; Raboch, Jiri; Kalisova, Lucie; Onchev, Georgi; Alexiev, Spiridon; Mezzina, Roberto; Ridente, Pina; Wiersma, Durk; Visser, Ellen; Kiejna, Andrzej; Adamowski, Tomasz; Ploumpidis, Dimitris; Gonidakis, Fragiskos; King, Michael

    2016-01-01

    Background: The Quality Indicator for Rehabilitative Care (QuIRC) is an international, standardised quality tool for the evaluation of mental health facilities that provide longer term care. Completed by the service manager, it comprises 145 items that assess seven domains of care: living

  9. Choices in scale, guided by quality or legislation? : The influence of institutional factors on assisted living facilities

    NARCIS (Netherlands)

    Dort Spierings

    2011-01-01

    Since the eighties, Dutch residents of care homes have been housed in Assisted Living Facilities (ALFs) in order to age in place and live with higher social quality of housing. Scale, group mix and social quality of housing of these ALFs has not yet been explored. Initiators decide on experience and

  10. Prolactin Rescues Immature B-Cells from Apoptosis Induced by B-Cell Receptor Cross-Linking

    Directory of Open Access Journals (Sweden)

    Rocio Flores-Fernández

    2016-01-01

    Full Text Available Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE. In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease.

  11. Prolactin Rescues Immature B-Cells from Apoptosis Induced by B-Cell Receptor Cross-Linking

    Science.gov (United States)

    Flores-Fernández, Rocio; Blanco-Favela, Francisco; Fuentes-Pananá, Ezequiel M.; Chávez-Sánchez, Luis; Gorocica-Rosete, Patricia; Pizaña-Venegas, Alberto; Chávez-Rueda, Adriana Karina

    2016-01-01

    Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease. PMID:27314053

  12. B-cell Lymphoma in retrieved femoral heads: a long term follow up

    Directory of Open Access Journals (Sweden)

    van Kemenade Folkert J

    2009-05-01

    Full Text Available Abstract Background A relatively high incidence of pathological conditions in retrieved femoral heads, including a group of patients having low grade B-cell lymphoma, has been described before. At short term follow up none of these patients with low-grade B-cell lymphoma showed evidence of systemic disease. However, the long term follow up of these patients is not known. Methods From November 1994 up to and including December 2005 we screened all femoral heads removed at the time of primary total hip replacement histopathologically and included them in the bone banking protocol according to the guidelines of the American Associations of Tissue Banks (AATB and the European Association of Musculo-Skeletal Transplantation (EAMST. We determined the percentage of B-cell lymphoma in all femoral heads and in the group that fulfilled all criteria of the bone banking protocol and report on the long-term follow-up. Results Of 852 femoral heads fourteen (1.6% were highly suspicious for low-grade B-cell lymphoma. Of these 852 femoral heads, 504 were eligible for bone transplantation according to the guidelines of the AATB and the EAMST. Six femoral heads of this group of 504 were highly suspicious for low-grade B-cell lymphoma (1.2%. At long term follow up two (0.2% of all patients developed systemic malignant disease and one of them needed medical treatment for her condition. Conclusion In routine histopathological screening we found variable numbers of low-grade B-cell lymphoma throughout the years, even in a group of femoral heads that were eligible for bone transplantation. Allogenic transmission of malignancy has not yet been reported on, but surviving viruses are proven to be transmissible. Therefore, we recommend the routine histopathological evaluation of all femoral heads removed at primary total hip arthroplasty as a tool for quality control, whether the femoral head is used for bone banking or not.

  13. Service Quality and Consumer Perception on Retail Banking Facilities and Employees' Courtesy in Malaysia and New Zealand

    OpenAIRE

    Moha Asri Abdullah; Noor Hazilah Abd Manaf; Kamru Ahsan; Ferdous Azam

    2014-01-01

    Service quality and consumer perception are the issues being focused solicitously by the business community today. With the expansion of the banking sector and extensive market formation, scopes of different acuity and satisfaction level for consumers seem to impose a mingle game of their perception on service quality especially in retail banking. However, this study is focused on the service quality and consumer perception on retail banking facilities and employees' courtesy in Malaysia and ...

  14. Gallium arsenide exposure impairs splenic B cell accessory function.

    Science.gov (United States)

    Gondre-Lewis, Timothy A; Hartmann, Constance B; Caffrey, Rebecca E; McCoy, Kathleen L

    2003-03-01

    Gallium arsenide (GaAs) is utilized in industries for its semiconductor and optical properties. Chemical exposure of animals systemically suppresses several immune functions. The ability of splenic B cells to activate antigen-specific helper CD4(+) T cell hybridomas was assessed, and various aspects of antigen-presenting cell function were examined. GaAs-exposed murine B cells were impaired in processing intact soluble protein antigens, and the defect was antigen dependent. In contrast, B cells after exposure competently presented peptides to the T cells, which do not require processing. Cell surface expression of major histocompatibility complex (MHC) class II molecules and several costimulatory molecules on splenic B cells, which are critical for helper T cell activation, was not affected by chemical exposure. GaAs exposure also did not influence the stability of MHC class II heterodimers, suggesting that the defect may precede peptide exchange. GaAs-exposed B cells contained a normal level of aspartyl cathepsin activity; however, proteolytic activities of thiol cathepsins B and L were approximately half the control levels. Furthermore, two cleavage fragments of invariant chain, a molecular chaperone of MHC class II molecules, were increased in GaAs-exposed B cells, indicative of defective degradation. Thus, diminished thiol proteolytic activity in B cells may be responsible for their impaired antigen processing and invariant chain degradation, which may contribute to systemic immunosuppression caused by GaAs exposure.

  15. Dosimetry and image quality in digital mammography facilities in the State of Minas Gerais, Brazil

    Science.gov (United States)

    da Silva, Sabrina Donato; Joana, Geórgia Santos; Oliveira, Bruno Beraldo; de Oliveira, Marcio Alves; Leyton, Fernando; Nogueira, Maria do Socorro

    2015-11-01

    According to the National Register of Health Care Facilities (CNES), there are approximately 477 mammography systems operating in the state of Minas Gerais, Brazil, of which an estimated 200 are digital apparatus using mainly computerized radiography (CR) or direct radiography (DR) systems. Mammography is irreplaceable in the diagnosis and early detection of breast cancer, the leading cause of cancer death among women worldwide. A high standard of image quality alongside smaller doses and optimization of procedures are essential if early detection is to occur. This study aimed to determine dosimetry and image quality in 68 mammography services in Minas Gerais using CR or DR systems. The data of this study were collected between the years of 2011 and 2013. The contrast-to-noise ratio proved to be a critical point in the image production chain in digital systems, since 90% of services were not compliant in this regard, mainly for larger PMMA thicknesses (60 and 70 mm). Regarding the image noise, only 31% of these were compliant. The average glandular dose found is of concern, since more than half of the services presented doses above acceptable limits. Therefore, despite the potential benefits of using CR and DR systems, the employment of this technology has to be revised and optimized to achieve better quality image and reduce radiation dose as much as possible.

  16. Air quality investigations of the Sandia National Laboratories Sol se Mete Aerial Cable Facility

    Energy Technology Data Exchange (ETDEWEB)

    Gutman, W.M.; Silver, R.J. [New Mexico State Univ., Las Cruces, NM (United States). Physical Science Lab.

    1994-12-01

    The air quality implications of the test and evaluation activities at the Sandia National Laboratories Sol se Mete Aerial Cable Facility are examined. All facets of the activity that affect air quality are considered. Air contaminants produced directly include exhaust products of rocket motors used to accelerate test articles, dust and gas from chemical explosives, and exhaust gases from electricity generators in the test arenas. Air contaminants produced indirectly include fugitive dust and exhaust contaminants from vehicles used to transport personnel and material to the test area, and effluents produced by equipment used to heat the project buildings. Both the ongoing program and the proposed changes in the program are considered. Using a reliable estimate of th maximum annual testing level, the quantities of contaminants released by project activities ar computed either from known characteristics of test items or from EPA-approved emission factors Atmospheric concentrations of air contaminants are predicted using EPA dispersion models. The predicted quantities and concentrations are evaluated in relation to Federal, New Mexico, an Bernalillo County air quality regulations and the human health and safety standards of the American Conference of Governmental Industrial Hygienists.

  17. Air quality investigations of the Sandia National Laboratories Sol se Mete Aerial Cable Facility

    International Nuclear Information System (INIS)

    Gutman, W.M.; Silver, R.J.

    1994-12-01

    The air quality implications of the test and evaluation activities at the Sandia National Laboratories Sol se Mete Aerial Cable Facility are examined. All facets of the activity that affect air quality are considered. Air contaminants produced directly include exhaust products of rocket motors used to accelerate test articles, dust and gas from chemical explosives, and exhaust gases from electricity generators in the test arenas. Air contaminants produced indirectly include fugitive dust and exhaust contaminants from vehicles used to transport personnel and material to the test area, and effluents produced by equipment used to heat the project buildings. Both the ongoing program and the proposed changes in the program are considered. Using a reliable estimate of th maximum annual testing level, the quantities of contaminants released by project activities ar computed either from known characteristics of test items or from EPA-approved emission factors Atmospheric concentrations of air contaminants are predicted using EPA dispersion models. The predicted quantities and concentrations are evaluated in relation to Federal, New Mexico, an Bernalillo County air quality regulations and the human health and safety standards of the American Conference of Governmental Industrial Hygienists

  18. Predicting linear B-cell epitopes using string kernels

    Science.gov (United States)

    EL-Manzalawy, Yasser; Dobbs, Drena; Honavar, Vasant

    2008-01-01

    The identification and characterization of B-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. Therefore, computational tools for reliably predicting linear B-cell epitopes are highly desirable. We evaluated Support Vector Machine (SVM) classifiers trained utilizing five different kernel methods using fivefold cross-validation on a homology-reduced data set of 701 linear B-cell epitopes, extracted from Bcipep database, and 701 non-epitopes, randomly extracted from SwissProt sequences. Based on the results of our computational experiments, we propose BCPred, a novel method for predicting linear B-cell epitopes using the subsequence kernel. We show that the predictive performance of BCPred (AUC = 0.758) outperforms 11 SVM-based classifiers developed and evaluated in our experiments as well as our implementation of AAP (AUC = 0.7), a recently proposed method for predicting linear B-cell epitopes using amino acid pair antigenicity. Furthermore, we compared BCPred with AAP and ABCPred, a method that uses recurrent neural networks, using two data sets of unique B-cell epitopes that had been previously used to evaluate ABCPred. Analysis of the data sets used and the results of this comparison show that conclusions about the relative performance of different B-cell epitope prediction methods drawn on the basis of experiments using data sets of unique B-cell epitopes are likely to yield overly optimistic estimates of performance of evaluated methods. This argues for the use of carefully homology-reduced data sets in comparing B-cell epitope prediction methods to avoid misleading conclusions about how different methods compare to each other. Our homology-reduced data set and implementations of BCPred as well as the APP method are publicly available through our web-based server, BCPREDS, at: http://ailab.cs.iastate.edu/bcpreds/. PMID:18496882

  19. Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis.

    Science.gov (United States)

    Mahanonda, Rangsini; Champaiboon, Chantrakorn; Subbalekha, Keskanya; Sa-Ard-Iam, Noppadol; Rattanathammatada, Warattaya; Thawanaphong, Saranya; Rerkyen, Pimprapa; Yoshimura, Fuminobu; Nagano, Keiji; Lang, Niklaus P; Pichyangkul, Sathit

    2016-08-01

    The presence of inflammatory infiltrates with B cells, specifically plasma cells, is the hallmark of periodontitis lesions. The composition of these infiltrates in various stages of homeostasis and disease development is not well documented. Human tissue biopsies from sites with gingival health (n = 29), gingivitis (n = 8), and periodontitis (n = 21) as well as gingival tissue after treated periodontitis (n = 6) were obtained and analyzed for their composition of B cell subsets. Ag specificity, Ig secretion, and expression of receptor activator of NF-κB ligand and granzyme B were performed. Although most of the B cell subsets in healthy gingiva and gingivitis tissues were CD19(+)CD27(+)CD38(-) memory B cells, the major B cell component in periodontitis was CD19(+)CD27(+)CD38(+)CD138(+)HLA-DR(low) plasma cells, not plasmablasts. Plasma cell aggregates were observed at the base of the periodontal pocket and scattered throughout the gingiva, especially apically toward the advancing front of the lesion. High expression of CXCL12, a proliferation-inducing ligand, B cell-activating factor, IL-10, IL-6, and IL-21 molecules involved in local B cell responses was detected in both gingivitis and periodontitis tissues. Periodontitis tissue plasma cells mainly secreted IgG specific to periodontal pathogens and also expressed receptor activator of NF-κB ligand, a bone resorption cytokine. Memory B cells resided in the connective tissue subjacent to the junctional epithelium in healthy gingiva. This suggested a role of memory B cells in maintaining periodontal homeostasis. Copyright © 2016 by The American Association of Immunologists, Inc.

  20. Review of alternative residual contamination guides for the 324 Building B-Cell Cleanout Project. Phase 1

    International Nuclear Information System (INIS)

    Vargo, G.J.; Durham, J.S.; Brackenbush, L.W.

    1995-09-01

    This report provides a proposed residual contamination guide (RCG) for the 324 Building B-Cell Cleanout Project, Phase 1, at the Hanford Site. The RCG is expressed as a fraction of the amount of highly dispersible radioactive material that would result in offsite doses equal to the Pacific Northwest Laboratory radiological risk guidelines following the worst credible accident scenario for release of the holdup material. The proposed RCG is 10 -1 to 10 -2 of the PNL radiological risk guidelines. As part of the development of the RCG, a number of factors were considered. These include the need to provide an appropriate level of flexibility for other activities within the 324 Building that could contribute to the facility's overall radiological risk, uncertainties inherent in safety analyses, and the possible contribution of other 300 Area facilities to overall radiological risk. Because of these factors and the nature of the cleanout project, the RCG is expressed as a range rather than a point value. This report also provides guidance on determining conformance to the RCG, including inspection and measurement techniques, quality assurance requirements, and consideration of uncertainty

  1. Invasin of Yersinia pseudotuberculosis activates human peripheral B cells.

    OpenAIRE

    Lundgren, E; Carballeira, N; Vazquez, R; Dubinina, E; Bränden, H; Persson, H; Wolf-Watz, H

    1996-01-01

    The Yersinia pseudotuberculosis cell surface-located protein invasin was found to promote binding between the pathogen and resting peripheral B cells via beta 1 integrin receptors (CD29). B cells responded by expressing several activation markers and by growing, In contrast, T cells did not react, although these cells express CD29. An isogenic invA mutant failed to activate B cells. The mutation could be complemented by providing the invA+ gene in trans. Purified invasin alone did not activat...

  2. Evaluation on construction quality of pit filler material of cavern type radioactive waste disposal facility

    International Nuclear Information System (INIS)

    Takechi, Shin-ichi; Yokozeki, Kosuke; Shimbo, Hiroshi; Terada, Kenji; Akiyama, Yoshihiro; Yada, Tsutomu; Tsuji, Yukikazu

    2014-01-01

    The pit filler material of the underground cavern-type radioactive waste disposal facility, which is poured directly around the radioactive waste packages where high temperature environment is assumed by their decay heat, is concerned to be adversely affected on the filling behavior and its hardened properties. There also are specific issues that required quality of construction must be achieved by unmanned construction with remote operation, because the pit filler construction shall be done under radiation environment. In this paper, the mix proportion of filler material is deliberated with filling experiments simulating high temperature environment, and also the effect of temperature on hardened properties are confirmed with high temperature curing test. Subsequently, the feasibility of unmanned construction method of filler material by pumping, and by movable bucket, are comparatively discussed through a real size demonstration. (author)

  3. Factors associated with quality of life of people with dementia in long-term care facilities: a systematic review.

    Science.gov (United States)

    Beerens, Hanneke C; Zwakhalen, Sandra M G; Verbeek, Hilde; Ruwaard, Dirk; Hamers, Jan P H

    2013-09-01

    Quality of life has become an important outcome measure in dementia research. Currently there is no convincing evidence about which factors are associated with quality of life of people with dementia living in long-term care facilities. This study aims to investigate which factors are associated with quality of life, including factors associated with change over time, of people with dementia living in long-term care facilities. A systematic literature review was performed. Cochrane, Pubmed, CINAHL, Web of Science, and PsycINFO were searched. Three researchers independently assessed studies for eligibility. The inclusion criteria were: (1) the primary focus was on factors related to quality of life; (2) the study was performed in long-term care facilities; (3) the study regarded quality of life as multidimensional construct. Methodological quality of studies included in the review was assessed with a quality criteria checklist. Ten cross-sectional and three longitudinal articles were included in the review. In cross-sectional studies, depressive symptoms were negatively related to self-rated quality of life of people with dementia. The association between depressive symptoms and proxy-rated quality of life was less clear. Behavioural disturbances, especially agitation, appeared to be negatively related to proxy-rated quality of life. There appeared to be a negative relation between quality of life, activities of daily living and cognition, although this could not be confirmed in all studies. In longitudinal studies, depressive symptoms were negatively related and cognition was positively related to self-rated quality of life, whereas dependency and depressive symptoms were negatively related to proxy-rated quality of life. There are only few high quality studies that investigate associations of (change in) quality of life of people with dementia living in long-term care facilities. Our results suggest that depressive symptoms and agitation are related to lower

  4. Improving the beam quality of the neutron radiography facility using the SLOWPOKE-2 at the Royal Military College of Canada

    International Nuclear Information System (INIS)

    Lewis, W.J.; Bennett, L.G.I.; Teshima, P.

    1996-01-01

    At the SLOWPOKE-2 Facility at the Royal Military College of Canada, a neutron radiography facility has been designed and installed, and the beam quality has been improved by performing a series of radiographs using American standard for testing and materials (ASTM) E 545 indicators. Other means of determining the progress such as bubble detectors and activation foils were used. Modifications to the nosepiece of the beam tube including shielding and linings for fast neutron and gamma radiation were made. (orig.)

  5. B cell development in the bone marrow is regulated by homeostatic feedback exerted by mature B cells

    Directory of Open Access Journals (Sweden)

    Gitit eShahaf

    2016-03-01

    Full Text Available Cellular homeostasis in the B cell compartment is strictly imposed to balance cell production and cell loss. However, it is not clear whether B cell development in the bone marrow (BM is an autonomous process or subjected to regulation by the peripheral B cell compartment. To specifically address this question, we used mice transgenic for human CD20, where effective depletion of B lineage cells is obtained upon administration of mouse-anti-human CD20 antibodies, in the absence of any effect on other cell lineages and/or tissues. We followed the kinetics of B cell return to equilibrium by BrdU labeling and flow cytometry and analyzed the resulting data by mathematical modeling. Labeling was much faster in depleted mice. Compared to control mice, B cell-depleted mice exhibited a higher proliferation rate in the pro-/pre-B compartment, and higher cell death and lower differentiation in the immature B cell compartment. We validated the first result by analysis of the expression of Ki67, the nuclear protein expressed in proliferating cells, and the second using Annexin-V staining. Collectively, our results suggest that B lymphopoiesis is subjected to homeostatic feedback mechanisms imposed by mature B cells in the peripheral compartment.

  6. B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies.

    Science.gov (United States)

    Xiao, Gang; Chan, Lai N; Klemm, Lars; Braas, Daniel; Chen, Zhengshan; Geng, Huimin; Zhang, Qiuyi Chen; Aghajanirefah, Ali; Cosgun, Kadriye Nehir; Sadras, Teresa; Lee, Jaewoong; Mirzapoiazova, Tamara; Salgia, Ravi; Ernst, Thomas; Hochhaus, Andreas; Jumaa, Hassan; Jiang, Xiaoyan; Weinstock, David M; Graeber, Thomas G; Müschen, Markus

    2018-04-05

    B cell activation during normal immune responses and oncogenic transformation impose increased metabolic demands on B cells and their ability to retain redox homeostasis. While the serine/threonine-protein phosphatase 2A (PP2A) was identified as a tumor suppressor in multiple types of cancer, our genetic studies revealed an essential role of PP2A in B cell tumors. Thereby, PP2A redirects glucose carbon utilization from glycolysis to the pentose phosphate pathway (PPP) to salvage oxidative stress. This unique vulnerability reflects constitutively low PPP activity in B cells and transcriptional repression of G6PD and other key PPP enzymes by the B cell transcription factors PAX5 and IKZF1. Reflecting B-cell-specific transcriptional PPP-repression, glucose carbon utilization in B cells is heavily skewed in favor of glycolysis resulting in lack of PPP-dependent antioxidant protection. These findings reveal a gatekeeper function of the PPP in a broad range of B cell malignancies that can be efficiently targeted by small molecule inhibition of PP2A and G6PD. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Cloning of B cell-specific membrane tetraspanning molecule BTS possessing B cell proliferation-inhibitory function.

    Science.gov (United States)

    Suenaga, Tadahiro; Arase, Hisashi; Yamasaki, Sho; Kohno, Masayuki; Yokosuka, Tadashi; Takeuchi, Arata; Hattori, Takamichi; Saito, Takashi

    2007-11-01

    Lymphocyte proliferation is regulated by signals through antigen receptors, co-stimulatory receptors, and other positive and negative modulators. Several membrane tetraspanning molecules are also involved in the regulation of lymphocyte growth and death. We cloned a new B cell-specific tetraspanning (BTS) membrane molecule, which is similar to CD20 in terms of expression, structure and function. BTS is specifically expressed in the B cell line and its expression is increased after the pre-B cell stage. BTS is expressed in intracellular granules and on the cell surface. Overexpression of BTS in immature B cell lines induces growth retardation through inhibition of cell cycle progression and cell size increase without inducing apoptosis. This inhibitory function is mediated predominantly by the N terminus of BTS. The development of mature B cells is inhibited in transgenic mice expressing BTS, suggesting that BTS is involved in the in vivo regulation of B cells. These results indicate that BTS plays a role in the regulation of cell division and B cell growth.

  8. Comparison of the geometric accuracy of radiotherapy facilities by various manufacturers, performed within the programme of quality audits

    International Nuclear Information System (INIS)

    Pridal, I.; Klaclova, T.; Gremlica, D.; Zackova, H.; Snobr, J.

    1998-01-01

    The evaluation of geometric parameters of radiotherapy facilities is discussed, these parameters being of importance for focusing the target volume and for achieving the required standard of treatment. During quality audits at radiotherapy systems various shortcomings were found as regards the accuracy of irradiation. A part of the shortcomings was due to inadequate setting of the facility parameters; another, however, was related to the mechanical design of the treatment units. The latter problems cannot be easily eliminated and have to be taken into account when using the respective facilities

  9. COMPUTATION MODELING OF TCDD DISRUPTION OF B CELL TERMINAL DIFFERENTIATION

    Science.gov (United States)

    In this study, we established a computational model describing the molecular circuit underlying B cell terminal differentiation and how TCDD may affect this process by impinging upon various molecular targets.

  10. Diversity among memory B cells: origin, consequences, and utility.

    Science.gov (United States)

    Tarlinton, David; Good-Jacobson, Kim

    2013-09-13

    Immunological memory is the residuum of a successful immune response that in the B cell lineage comprises long-lived plasma cells and long-lived memory B cells. It is apparent that distinct classes of memory B cells exist, distinguishable by, among other things, immunoglobulin isotype, location, and passage through the germinal center. Some of this variation is due to the nature of the antigen, and some appears to be inherent to the process of forming memory. Here, we consider the heterogeneity in development and phenotype of memory B cells and whether particular functions are partitioned into distinct subsets. We consider also how understanding the details of generating memory may provide opportunities to develop better, functionally targeted vaccines.

  11. Parathyroid hormone resistance and B cell lymphopenia in propionic acidemia.

    Science.gov (United States)

    Griffin, T A; Hostoffer, R W; Tserng, K Y; Lebovitz, D J; Hoppel, C L; Mosser, J L; Kaplan, D; Kerr, D S

    1996-07-01

    The mechanisms of hypocalcemia, recurrent infections and hypogammaglobulinemia associated with metabolic decompensation of propionic acidemia due to propionyl-CoA carboxylase deficiency have not been defined. A 7-week-old infant with this disorder presented with severe hypocalcemia and B cell lymphopenia during an episode of metabolic acidosis and hyperammonemia. Hypocalcemia (1.1 mmol l-1) was associated with elevated serum intact parathyroid hormone (122 ng l-1), hyperphosphatemia, hypophosphaturia and hypercalcuria, indicating parathyroid hormone resistance. B cell lymphopenia (20 cells microliters-1) was associated with transient neutropenia, anemia and subsequent hypogamma-globulinemia (IgG < 294 mg dl-1, IgM < 8 mg dl-1, IgA < 8 mg dl-1), while T cells were normal. Parathyroid hormone resistance and B cell lymphopenia resolved following treatment with hemodialysis, diet and carnitine. These complications may be due to interference with parathyroid hormone renal tubular action and B cell maturation/proliferation by accumulated organic acids.

  12. Recent advances in B-cell epitope prediction methods

    Science.gov (United States)

    2010-01-01

    Identification of epitopes that invoke strong responses from B-cells is one of the key steps in designing effective vaccines against pathogens. Because experimental determination of epitopes is expensive in terms of cost, time, and effort involved, there is an urgent need for computational methods for reliable identification of B-cell epitopes. Although several computational tools for predicting B-cell epitopes have become available in recent years, the predictive performance of existing tools remains far from ideal. We review recent advances in computational methods for B-cell epitope prediction, identify some gaps in the current state of the art, and outline some promising directions for improving the reliability of such methods. PMID:21067544

  13. 'Big bang' of B-cell development revealed.

    Science.gov (United States)

    Murre, Cornelis

    2018-01-15

    Earlier studies have identified transcription factors that specify B-cell fate, but the underlying mechanisms remain to be revealed. Two new studies by Miyai and colleagues (pp. 112-126) and Li and colleagues (pp. 96-111) in this issue of Genes & Development provide new and unprecedented insights into the genetic and epigenetic mechanisms that establish B-cell identity. © 2018 Murre; Published by Cold Spring Harbor Laboratory Press.

  14. Long Noncoding RNA Expression during Human B-Cell Development.

    Directory of Open Access Journals (Sweden)

    Andreas Petri

    Full Text Available Long noncoding RNAs (lncRNAs have emerged as important regulators of diverse cellular processes, but their roles in the developing immune system are poorly understood. In this study, we analysed lncRNA expression during human B-cell development by array-based expression profiling of eleven distinct flow-sorted B-cell subsets, comprising pre-B1, pre-B2, immature, naive, memory, and plasma cells from bone marrow biopsies (n = 7, and naive, centroblast, centrocyte, memory, and plasmablast cells from tonsil tissue samples (n = 6, respectively. A remapping strategy was used to assign the array probes to 37630 gene-level probe sets, reflecting recent updates in genomic and transcriptomic databases, which enabled expression profiling of 19579 long noncoding RNAs, comprising 3947 antisense RNAs, 5277 lincRNAs, 7625 pseudogenes, and 2730 additional lncRNAs. As a first step towards inferring the functions of the identified lncRNAs in developing B-cells, we analysed their co-expression with well-characterized protein-coding genes, a method known as "guilt by association". By using weighted gene co-expression network analysis, we identified 272 lincRNAs, 471 antisense RNAs, 376 pseudogene RNAs, and 64 lncRNAs within seven sub-networks associated with distinct stages of B-cell development, such as early B-cell development, B-cell proliferation, affinity maturation of antibody, and terminal differentiation. These data provide an important resource for future studies on the functions of lncRNAs in development of the adaptive immune response, and the pathogenesis of B-cell malignancies that originate from distinct B-cell subpopulations.

  15. Mandatory quality assurance programmes for diagnostic radiology facilities in Ontario, Canada

    International Nuclear Information System (INIS)

    Rainbow, A.J.

    1989-01-01

    Regulations made under the Healing Arts Radiation Protection (HARP) Act, Government of Ontario, Canada, were promulgated in the form of a safety Code in November, 1985. These regulations require a minimum technical quality assurance (QA) programme for all diagnostic radiology facilities in the Province. The mandatory QA programme requires certain tests and procedures to be carried out at specified intervals. The tests include photographic quality control, patient entrance exposure measurement, collimation, half-value layer, phototiming parameters, fluoroscopic parameters including maximum patient entrance exposure rate, resolution, limit timer and automatic brightness control, and tomographic parameters including fulcrum accuracy, thickness of cut and mechanical stability. Records of the results of these tests must be kept for at least 6 years. A set of HARP guidelines published in June 1987 includes a description of appropriate measuring methods for each test together with a set of forms for recording the results of such tests. The regulations specify limiting values for a number of equipment performance parameters, including the maximum allowable patient skin entrance exposure values for common radiographic projections. (author)

  16. An Assessment of Subsurface Intake Systems: Planning and Impact on Feed Water Quality for SWRO Facilities

    KAUST Repository

    Dehwah, Abdullah

    2017-12-01

    Subsurface intake systems are known to improve the feed water quality for SWRO plants. However, a little is known about the feasibility of implementation in coastal settings, the degree of water quality improvements provided by these systems, and the internal mechanisms of potential fouling compounds removal within subsurface intake systems. A new method was developed to assess the feasibility of using different subsurface intake systems in coastal areas and was applied to Red Sea coastline of Saudi Arabia. The methodology demonstrated that five specific coastal environments could support well intake systems use for small-capacity SWRO plants, whereas large-capacity SWRO facilities could use seabed gallery intake systems. It was also found that seabed intake system could run with no operational constraints based on the high evaporation rates and associated diurnal salinity changes along the coast line. Performance of well intake systems in several SWRO facilities along the Red Sea coast showed that the concentrations of organic compounds were reduced in the feed water, similar or better than traditional pretreatment methodologies. Nearly all algae, up to 99% of bacteria, between 84 and 100% of the biopolymer fraction of NOM, and a high percentage of TEP were removed during transport through the aquifer. These organics cause membrane biofouling and using well intakes showed a 50-75% lower need to clean the SWRO membranes compared to conventional open-ocean intakes. An assessment of the effectiveness of seabed gallery intake systems was conducted through a long-term bench-scale column experiment. The simulation of the active layer (upper 1 m) showed that it is highly effective at producing feed water quality improvements and acts totally different compared to slow sand filtration systems treating freshwater. No development of a “schmutzdecke” layer occurred and treatment was not limited to the top 10 cm, but throughout the full column thickness. Algae and

  17. Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia*

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Vigolo, Michele; Willen, Laure; Tardivel, Aubry; Smulski, Cristian R.; Zheng, Timothy S.; Gommerman, Jennifer; Hess, Henry; Gottenberg, Jacques-Eric; Mackay, Fabienne; Donzé, Olivier

    2016-01-01

    B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro. A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo. These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice. PMID:27451394

  18. Data quality maintenance of the Patient Master Index (PMI): a "snap-shot" of public healthcare facility PMI data quality and linkage activities.

    Science.gov (United States)

    Williams, Kelly; Robinson, Kerin; Toth, Alexandra

    Patient (or person) master index (PMI) data quality activities in public, acute healthcare facilities in the state of Victoria, Australia were evaluated in terms of health information management-information technology best practice including data standards and practice guidelines. The findings indicate that, whilst data quality and linkage activities are undertaken, many are limited in scope or effectiveness. In view of published evidence that: (i) duplicate patient files pose significant risks by reducing information available for clinical decision-making; and (ii) quality and clinical risk management require, as a measurable outcome, continuous monitoring of duplicate files, improvements to PMI data quality practices are recommended.

  19. Perceived quality of care for common childhood illnesses: facility versus community based providers in Uganda.

    Directory of Open Access Journals (Sweden)

    Agnes Nanyonjo

    Full Text Available OBJECTIVE: To compare caretakers' perceived quality of care (PQC for under-fives treated for malaria, pneumonia and diarrhoea by community health workers (CHWs and primary health facility workers (PHFWs. METHODS: Caretaker rated PQC for children aged (2-59 months treated by either CHWs or PHFWs for a bought of malaria, pneumonia or diarrhoea was cross-sectionally compared in quality domains of accessibility, continuity, comprehensiveness, integration, clinical interaction, interpersonal treatment and trust. Child samples were randomly drawn from CHW (419 and clinic (399 records from eight Midwestern Uganda districts. An overall PQC score was predicted through factor analysis. PQC scores were compared for CHWs and PHFWs using Wilcoxon rank-sum test. Multinomial logistic regression models were used to specify the association between categorized PQC and service providers for each quality domain. Finally, overall PQC was dichotomized into "high" and "low" based on median score and relative risks (RR for PQC-service provider association were modeled in a "modified" Poisson regression model. RESULTS: Mean (SD overall PQC was significantly higher for CHWs 0.58 (0 .66 compared to PHFWs -0.58 (0.94, p<0.0001. In "modified" Poisson regression, the proportion of caretakers reporting high PQC was higher for CHWS compared to PHFWs, RR=3.1, 95%CI(2.5-3.8. In multinomial models PQC was significantly higher for CHWs compared to PHFWs in all domains except for continuity. CONCLUSION: PQC was significantly higher for CHWs compared to PHFWs in this resource constrained setting. CHWs should be tapped human resources for universal health coverage while scaling up basic child intervention as PQC might improve intervention utilization.

  20. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Assessment of quality of prescribing in patients of hypertension at primary and secondary health care facilities using the Prescription Quality Index (PQI) tool.

    Science.gov (United States)

    Suthar, Jalpa Vashishth; Patel, Varsha J

    2014-01-01

    To determine the quality of prescribing in hypertension in primary and secondary health care settings using the Prescription Quality Index (PQI) tool and to assess the reliability of this tool. An observational cross-sectional study was carried out for 6 months in order to assess quality of prescribing of antihypertensive drugs using Prescription Quality Index (PQI) at four primary (PHC) and two secondary (SHC) health care facilities. Patients attending these facilities for at least 3 months were included. Complete medical history and prescriptions received were noted. Total and criteria wise PQI scores were derived for each prescription. Prescriptions were categorized as poor (score of ≤31), medium (score 32-33) and high quality (score 34-43) based on PQI total score. Psychometric analysis using factor analysis was carried out to assess reliability and validity. Total 73 hypertensive patients were included. Mean age was 61.2 ± 11 years with 35 (48%) patients above 65 years of age. Total PQI score was 26 ± 11. There was a significant difference in PQI score between PHC and SHC (P hypertensive patients was poor, somewhat better in primary as compared to secondary health care facility. PQI is reliable for measuring prescribing quality in hypertension in Indian set up.

  2. Associations Among Health Care Workplace Safety, Resident Satisfaction, and Quality of Care in Long-Term Care Facilities.

    Science.gov (United States)

    Boakye-Dankwa, Ernest; Teeple, Erin; Gore, Rebecca; Punnett, Laura

    2017-11-01

    We performed an integrated cross-sectional analysis of relationships between long-term care work environments, employee and resident satisfaction, and quality of patient care. Facility-level data came from a network of 203 skilled nursing facilities in 13 states in the eastern United States owned or managed by one company. K-means cluster analysis was applied to investigate clustered associations between safe resident handling program (SRHP) performance, resident care outcomes, employee satisfaction, rates of workers' compensation claims, and resident satisfaction. Facilities in the better-performing cluster were found to have better patient care outcomes and resident satisfaction; lower rates of workers compensation claims; better SRHP performance; higher employee retention; and greater worker job satisfaction and engagement. The observed clustered relationships support the utility of integrated performance assessment in long-term care facilities.

  3. Quality of Maternity Care at Health Facilities in Eritrea in 2008

    African Journals Online (AJOL)

    normal deliveries, provision of basic EmOC and referral of mothers and newborns with complications. Table 1 summarizes the maternity services that are provided by type of health facility and Zoba, as reported by the health personnel in the facilities. Table 1: Availability of EmOC functions by type of health facilities. EmOC ...

  4. Quality of Longer Term Mental Health Facilities in Europe : Validation of the Quality Indicator for Rehabilitative Care against Service Users' Views

    NARCIS (Netherlands)

    Killaspy, Helen; White, Sarah; Wright, Christine; Taylor, Tatiana L.; Turton, Penny; Kallert, Thomas; Schuster, Mirjam; Cervilla, Jorge A.; Brangier, Paulette; Raboch, Jiri; Kalisova, Lucie; Onchev, Georgi; Alexiev, Spiridon; Mezzina, Roberto; Ridente, Pina; Wiersma, Durk; Visser, Ellen; Kiejna, Andrzej; Piotrowski, Patryk; Ploumpidis, Dimitris; Gonidakis, Fragiskos; Caldas-de-Almeida, Jose Miguel; Cardoso, Graca; King, Michael

    2012-01-01

    Background: The Quality Indicator for Rehabilitative Care (QuIRC) is a staff rated, international toolkit that assesses care in longer term hospital and community based mental health facilities. The QuIRC was developed from review of the international literature, an international Delphi exercise

  5. Why give birth in health facility? Users’ and providers’ accounts of poor quality of birth care in Tanzania

    Science.gov (United States)

    2013-01-01

    Background In Tanzania, half of all pregnant women access a health facility for delivery. The proportion receiving skilled care at birth is even lower. In order to reduce maternal mortality and morbidity, the government has set out to increase health facility deliveries by skilled care. The aim of this study was to describe the weaknesses in the provision of acceptable and adequate quality care through the accounts of women who have suffered obstetric fistula, nurse-midwives at both BEmOC and CEmOC health facilities and local community members. Methods Semi-structured interviews involving 16 women affected by obstetric fistula and five nurse-midwives at maternity wards at both BEmOC and CEmOC health facilities, and Focus Group Discussions with husbands and community members were conducted between October 2008 and February 2010 at Comprehensive Community Based Rehabilitation in Tanzania and Temeke hospitals in Dar es Salaam, and Mpwapwa district in Dodoma region. Results Health care users and health providers experienced poor quality caring and working environments in the health facilities. Women in labour lacked support, experienced neglect, as well as physical and verbal abuse. Nurse-midwives lacked supportive supervision, supplies and also seemed to lack motivation. Conclusions There was a consensus among women who have suffered serious birth injuries and nurse midwives staffing both BEmOC and CEmOC maternity wards that the quality of care offered to women in birth was inadequate. While the birth accounts of women pointed to failure of care, the nurses described a situation of disempowerment. The bad birth care experiences of women undermine the reputation of the health care system, lower community expectations of facility birth, and sustain high rates of home deliveries. The only way to increase the rate of skilled attendance at birth in the current Tanzanian context is to make facility birth a safer alternative than home birth. The findings from this study

  6. Quality assurance for BNCT at nuclear facilities. A necessary burden or the unavoidable seal of approval

    International Nuclear Information System (INIS)

    Moss, R.; Morrissey, J.; Sauerwein, W.; Hideghety, K.; Rassow, J.; Stecher-Rasmussen, F.

    2000-01-01

    The BNCT clinical trial at the HFR Petten is performed on a completely multi-national basis. The irradiation facility is located in one country (The Netherlands), is operated by an international team of experts under the leadership of a radiotherapist from another country (Germany) and treats patients coming from different European countries. In gaining the necessary approval, it became apparent, especially in the many discussions with the (Dutch) Health authorities that Quality Assurance (QA) would be and is a critical aspect. This is even more so, in the case of BNCT, where it was not only a (relatively) new experimental treatment (in 1996/97) about to be performed for the first time in Europe, but it was to be performed in a non-hospital environment and furthermore in a nuclear research reactor. It was necessary therefore to comply, as closely as possible, with similarly accepted practices in conventional radiotherapy. Despite QA being a sometimes burdensome task, this paper nevertheless raises the issue as to whether it is necessary or whether it is the seal of approval for BNCT as an acceptable mode of treatment in mainstream radiotherapy. (author)

  7. Geotechnical quality control: low-level radioactive waste and uranium mill tailings disposable facilities

    International Nuclear Information System (INIS)

    Johnson, H.V.; Spigolon, S.J.; Lutton, R.J.

    1983-06-01

    Among the many responsibilities, the owner or licensee establishes and oversees the quality control (QC) of geotechnical aspects during construction, operation, and closure of low-level radioactive waste (LLW) or uranium mill tailings disposal facilities. This report first focuses on geotechnical QC practices by identifying the geotechnical parameters that should be considered along with appropriate laboratory and field testing and observation techniques. Advantages and disadvantages of the tests are discussed. Preference is given to those standard testing techniques (e.g., ASTM and AASHTO) that are in widespread use and easily accessible to industry. Next, guidance is provided on establishing a geotechnical QC program. The frequency of testing is discussed along with specifications for appropriate field and observation control. Methods of relating laboratory testing and field testing are recommended. Various factors influencing QC and reports/documentation control are discussed. Finally, verification studies for confirming site characteristics and soil engineering properties related to design assumptions are explained. It is the intent of this report to provide a document that summarizes all elements necessary to properly implement a QC plan. To this end and since NRC's involvement will only be through its random inspection and enforcement function and is expected to be limited during the licensee's execution of the QC program (after licensing), emphasis is placed throughout this report on the need for proper QC documentation

  8. Change in quality of life of people with dementia recently admitted to long-term care facilities.

    Science.gov (United States)

    Beerens, Hanneke C; Zwakhalen, Sandra M G; Verbeek, Hilde; Ruwaard, Dirk; Ambergen, Antonius W; Leino-Kilpi, Helena; Stephan, Astrid; Zabalegui, Adelaida; Soto, Maria; Saks, Kai; Bökberg, Christina; Sutcliffe, Caroline L; Hamers, Jan P H

    2015-06-01

    To assess which factors are associated with change in quality of life of people with dementia who have recently been admitted to long-term care facilities. Many people with dementia will be admitted to long-term care facilities at some point during their disease. It is currently unknown which factors are associated with improvement and/or deterioration of quality of life immediately following admission. An observational and longitudinal survey. Data on 343 people with dementia who have been recently admitted to long-term care facilities across eight European countries were collected between November 2010-April 2012. Quality of life was assessed by people with dementia and their proxies using the 'Quality of Life-Alzheimer's Disease scale'. Explanatory variables included cognitive status, comorbidities, activities of daily living, depressive symptoms and neuropsychiatric symptoms. Descriptive and multilevel regression analyses were performed. Better cognitive abilities at baseline were associated with a decrease in self-reported quality of life. Greater dependency and more depressive symptoms at baseline were associated with declined proxy-reported quality of life. Furthermore, an increased dependency and an increase of depressive symptoms between baseline and follow-up were associated with a decreased proxy-reported quality of life. On an individual level, three groups were identified, namely people whose quality of life: (1) decreased; (2) stayed the same; and (3) increased. Cognitive functioning, functional rehabilitation and treatment of depressive symptoms should receive special attention. However, quality of life of people with dementia does not necessarily decrease after institutionalization. © 2014 John Wiley & Sons Ltd.

  9. Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia.

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Vigolo, Michele; Willen, Laure; Tardivel, Aubry; Smulski, Cristian R; Zheng, Timothy S; Gommerman, Jennifer; Hess, Henry; Gottenberg, Jacques-Eric; Mackay, Fabienne; Donzé, Olivier; Schneider, Pascal

    2016-09-16

    B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Dataset of transcriptional landscape of B cell early activation

    Directory of Open Access Journals (Sweden)

    Alexander S. Garruss

    2015-09-01

    Full Text Available Signaling via B cell receptors (BCR and Toll-like receptors (TLRs result in activation of B cells with distinct physiological outcomes, but transcriptional regulatory mechanisms that drive activation and distinguish these pathways remain unknown. At early time points after BCR and TLR ligand exposure, 0.5 and 2 h, RNA-seq was performed allowing observations on rapid transcriptional changes. At 2 h, ChIP-seq was performed to allow observations on important regulatory mechanisms potentially driving transcriptional change. The dataset includes RNA-seq, ChIP-seq of control (Input, RNA Pol II, H3K4me3, H3K27me3, and a separate RNA-seq for miRNA expression, which can be found at Gene Expression Omnibus Dataset GSE61608. Here, we provide details on the experimental and analysis methods used to obtain and analyze this dataset and to examine the transcriptional landscape of B cell early activation.

  11. The cell biology of T-dependent B cell activation

    DEFF Research Database (Denmark)

    Owens, T; Zeine, R

    1989-01-01

    The requirement that CD4+ helper T cells recognize antigen in association with class II Major Histocompatibility Complex (MHC) encoded molecules constrains T cells to activation through intercellular interaction. The cell biology of the interactions between CD4+ T cells and antigen-presenting cells...... includes multipoint intermolecular interactions that probably involve aggregation of both polymorphic and monomorphic T cell surface molecules. Such aggregations have been shown in vitro to markedly enhance and, in some cases, induce T cell activation. The production of T-derived lymphokines that have been...... implicated in B cell activation is dependent on the T cell receptor for antigen and its associated CD3 signalling complex. T-dependent help for B cell activation is therefore similarly MHC-restricted and involves T-B intercellular interaction. Recent reports that describe antigen-independent B cell...

  12. Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Matilde Cacciatore

    2012-01-01

    Full Text Available Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas.

  13. The role of B cells in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Marina D Kraaij

    2008-09-01

    Full Text Available Marina D Kraaij, Jacob M van LaarMusculoskeletal Research Group, Institute of Cellular Medicine, School of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United KingdomAbstract: Systemic sclerosis (SSc is a connective disease characterized by features of autoimmunity, vasculopathy, inflammation, and fibrosis. The disease typically starts with Raynaud’s phenomenon, followed by skin thickening in the extremities due to inflammation and fibrosis. Fibrosis results from excessive collagen production by fibroblasts, which constitutes the final common pathway of complex cellular interactions including B cells. Several studies have indicated that B cells may play a role in SSc. Lesional skin infiltrates from SSc patients consist of a variety of cells, including eosinophils, neutrophils, lymphocytes, plasma cells, and macrophages. Autoantibodies of several specificities are present in the serum of SSc patients of which antitopoisomerase 1 is the most common, and evidence has been gathered for a potential pathogenic role of some autoantibodies, eg, anti-PDGF antibodies. The blood of SSc patients contains an increased proportion of naïve B cells but a decreased proportion of memory B cells. Furthermore, serum levels of interleukin-6, an important pro-inflammatory cytokine, have been shown to correlate with skin fibrosis. Animal models of SSc have provided more in-depth information on the role of B lymphocytes, eg, through disruption of B cell function. In this review we will discuss the evidence that B cells are involved in the pathogenesis of SSc.Keywords: B lymphocyte, systemic sclerosis, fibrosis

  14. Grb2 and GRAP connect the B cell antigen receptor to Erk MAP kinase activation in human B cells.

    Science.gov (United States)

    Vanshylla, Kanika; Bartsch, Caren; Hitzing, Christoffer; Krümpelmann, Laura; Wienands, Jürgen; Engels, Niklas

    2018-03-09

    The B cell antigen receptor (BCR) employs enzymatically inactive adaptor proteins to facilitate activation of intracellular signaling pathways. In animal model systems, adaptor proteins of the growth factor receptor-bound 2 (Grb2) family have been shown to serve critical functions in lymphocytes. However, the roles of Grb2 and the Grb2-related adaptor protein (GRAP) in human B lymphocytes remain unclear. Using TALEN-mediated gene targeting, we show that in human B cells Grb2 and GRAP amplify signaling by the immunoglobulin tail tyrosine (ITT) motif of mIgE-containing BCRs and furthermore connect immunoreceptor tyrosine-based activation motif (ITAM) signaling to activation of the Ras-controlled Erk MAP kinase pathway. In contrast to mouse B cells, BCR-induced activation of Erk in human B cells is largely independent of phospholipase C-ɣ activity and diacylglycerol-responsive members of Ras guanine nucleotide releasing proteins. Together, our results demonstrate that Grb2 family adaptors are critical regulators of ITAM and ITT signaling in naïve and IgE-switched human B cells.

  15. IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate

    Science.gov (United States)

    Noviski, Mark; Mueller, James L; Satterthwaite, Anne; Garrett-Sinha, Lee Ann; Brombacher, Frank

    2018-01-01

    Naive B cells co-express two BCR isotypes, IgM and IgD, with identical antigen-binding domains but distinct constant regions. IgM but not IgD is downregulated on autoreactive B cells. Because these isotypes are presumed to be redundant, it is unknown how this could impose tolerance. We introduced the Nur77-eGFP reporter of BCR signaling into mice that express each BCR isotype alone. Despite signaling strongly in vitro, IgD is less sensitive than IgM to endogenous antigen in vivo and developmental fate decisions are skewed accordingly. IgD-only Lyn−/− B cells cannot generate autoantibodies and short-lived plasma cells (SLPCs) in vivo, a fate thought to be driven by intense BCR signaling induced by endogenous antigens. Similarly, IgD-only B cells generate normal germinal center, but impaired IgG1+ SLPC responses to T-dependent immunization. We propose a role for IgD in maintaining the quiescence of autoreactive B cells and restricting their differentiation into autoantibody secreting cells. PMID:29521626

  16. Primary Mediastinal Large B-cell Lymphoma Exhibiting Endobronchial Involvement.

    Science.gov (United States)

    Shimada, Midori; Fukuda, Minoru; Horio, Kensuke; Suyama, Takayuki; Kitazaki, Takeshi; Hashiguchi, Kohji; Fukuda, Masaaki; Shigematsu, Kazuto; Nakamura, Yoichi; Honda, Takuya; Ashizawa, Kazuto; Mukae, Hiroshi

    Primary mediastinal large B-cell lymphoma (PMLBCL) is one of the subtypes of diffuse large B-cell lymphoma. We experienced a rare case of PMLBCL that exhibited endobronchial involvement. A 33-year-old Japanese female with the chief complaints of epigastralgia, back pain, and nausea visited a primary care hospital. Computed tomography of the chest and abdomen demonstrated a bulky mass in the left anterior mediastinum, multiple pulmonary nodules, axillary lymph node swelling, and a pancreatic tumor. Fiberoptic bronchoscopy showed a white-tinged irregularly shaped endobronchial tumor accompanied by capillary vessel dilation in the left upper lobar bronchus. Taken together, these findings resulted in a diagnosis of PMLBCL.

  17. A Literature Revision in Primary Cutaneous B-cell Lymphoma.

    Science.gov (United States)

    Selva, R La; Violetti, S Alberti; Delfino, C; Grandi, V; Cicchelli, S; Tomasini, C; Fierro, M T; Berti, E; Pimpinelli, N; Quaglino, P

    2017-01-01

    The term "Primary Cutaneous B-Cell Lymphoma" (PCBCL) comprehends a variety of lymphoproliferative disorders characterized by a clonal proliferation of B-cells primarily involving the skin. The absence of evident extra-cutaneous disease must be confirmed after six-month follow-up in order to exclude a nodal non-Hodgkin's lymphoma (NHL) with secondary cutaneous involvement, which may have a completely different clinical behavior and prognosis. In this article, we have summarized the clinico-pathological features of main types of PCBCL and we outline the guidelines for management based on a review of the available literature.

  18. Reprogramming of B cells into macrophages: mechanistic insights

    OpenAIRE

    Di Tullio, Alessandro, 1982-

    2012-01-01

    Our earlier work has shown that pre-B cells can be converted into macrophages by the transcription factor C/EBPα at very high frequencies and also that a clonal pre-B cell line with an inducible form of C/EBPα can be converted into macrophage-like cells. Using these systems we have performed a systematic analysis of the questions whether during transdifferentiation the cells retrodifferentiate to a precursor cell state and whether cell cycle is required for reprogramming. As for the first ...

  19. Essential role of EBF1 in the generation and function of distinct mature B cell types

    OpenAIRE

    Vilagos, Bojan; Hoffmann, Mareike; Souabni, Abdallah; Sun, Qiong; Werner, Barbara; Medvedovic, Jasna; Bilic, Ivan; Minnich, Martina; Axelsson, Elin; Jaritz, Markus; Busslinger, Meinrad

    2012-01-01

    The transcription factor EBF1 is essential for lineage specification in early B cell development. In this study, we demonstrate by conditional mutagenesis that EBF1 is required for B cell commitment, pro–B cell development, and subsequent transition to the pre–B cell stage. Later in B cell development, EBF1 was essential for the generation and maintenance of several mature B cell types. Marginal zone and B-1 B cells were lost, whereas follicular (FO) and germinal center (GC) B cells were redu...

  20. Family Satisfaction With Nursing Home Care: The Role of Facility Characteristics and Resident Quality-of-Life Scores

    Science.gov (United States)

    Shippee, Tetyana P.; Henning-Smith, Carrie; Gaugler, Joseph E.; Held, Robert; Kane, Robert L.

    2018-01-01

    This article explores the factor structure of a new family satisfaction with nursing home care instrument and determines the relationship of resident quality of life (QOL) and facility characteristics with family satisfaction. Data sources include (1) family satisfaction interviews (n = 16,790 family members), (2) multidimensional survey of resident QOL (n = 13,433 residents), and (3) facility characteristics (n = 376 facilities). We used factor analysis to identify domains of family satisfaction and multivariate analyses to identify the role of facility-level characteristics and resident QOL on facility-mean values of family satisfaction. Four distinct domains were identified for family satisfaction: “care,” “staff,” “environment,” and “food.” Chain affiliation, higher resident acuity, more deficiencies, and large size were all associated with less family satisfaction, and resident QOL was a significant (albeit weak) predictor of family satisfaction. Results suggest that family member satisfaction is distinct from resident QOL but is associated with resident QOL and facility characteristics. PMID:26534835

  1. Early B-cell factor 1 regulates the expansion of B-cell progenitors in a dose-dependent manner.

    Science.gov (United States)

    Åhsberg, Josefine; Ungerbäck, Jonas; Strid, Tobias; Welinder, Eva; Stjernberg, Jenny; Larsson, Malin; Qian, Hong; Sigvardsson, Mikael

    2013-11-15

    Transcription factor doses are of importance for normal and malignant B-lymphocyte development; however, the understanding of underlying mechanisms and functional consequences of reduced transcription factor levels is limited. We have analyzed progenitor and B-lineage compartments in mice carrying heterozygote mutations in the E2a, Ebf1, or Pax5 gene. Although lymphoid progenitors from Ebf1 or Pax5 heterozygote mice were specified and lineage-restricted in a manner comparable with Wt progenitors, this process was severely impaired in E2a heterozygote mutant mice. This defect was not significantly enhanced upon combined deletion of E2a with Ebf1 or Pax5. Analysis of the pre-B-cell compartment in Ebf1 heterozygote mice revealed a reduction in cell numbers. These cells expressed Pax5 and other B-lineage-associated genes, and global gene expression analysis suggested that the reduction of the pre-B-cell compartment was a result of impaired pre-B-cell expansion. This idea was supported by a reduction in IL2Rα-expressing late pre-B-cells as well as by cell cycle analysis and by the finding that the complexity of the VDJ rearrangement patterns was comparable in Wt and Ebf1(+/-) pre-B-cells, although the number of progenitors was reduced. Heterozygote deletion of Ebf1 resulted in impaired response to IL7 in vitro and reduced expression levels of pre-BCR on the cell surface, providing possible explanations for the observed stage-specific reduction in cellular expansion. Thus, transcription factor doses are critical for specification as well as expansion of B-lymphoid progenitors, providing increased insight into the molecular regulation of B-cell development.

  2. Early B-cell Factor 1 Regulates the Expansion of B-cell Progenitors in a Dose-dependent Manner*

    Science.gov (United States)

    Åhsberg, Josefine; Ungerbäck, Jonas; Strid, Tobias; Welinder, Eva; Stjernberg, Jenny; Larsson, Malin; Qian, Hong; Sigvardsson, Mikael

    2013-01-01

    Transcription factor doses are of importance for normal and malignant B-lymphocyte development; however, the understanding of underlying mechanisms and functional consequences of reduced transcription factor levels is limited. We have analyzed progenitor and B-lineage compartments in mice carrying heterozygote mutations in the E2a, Ebf1, or Pax5 gene. Although lymphoid progenitors from Ebf1 or Pax5 heterozygote mice were specified and lineage-restricted in a manner comparable with Wt progenitors, this process was severely impaired in E2a heterozygote mutant mice. This defect was not significantly enhanced upon combined deletion of E2a with Ebf1 or Pax5. Analysis of the pre-B-cell compartment in Ebf1 heterozygote mice revealed a reduction in cell numbers. These cells expressed Pax5 and other B-lineage-associated genes, and global gene expression analysis suggested that the reduction of the pre-B-cell compartment was a result of impaired pre-B-cell expansion. This idea was supported by a reduction in IL2Rα-expressing late pre-B-cells as well as by cell cycle analysis and by the finding that the complexity of the VDJ rearrangement patterns was comparable in Wt and Ebf1+/− pre-B-cells, although the number of progenitors was reduced. Heterozygote deletion of Ebf1 resulted in impaired response to IL7 in vitro and reduced expression levels of pre-BCR on the cell surface, providing possible explanations for the observed stage-specific reduction in cellular expansion. Thus, transcription factor doses are critical for specification as well as expansion of B-lymphoid progenitors, providing increased insight into the molecular regulation of B-cell development. PMID:24078629

  3. Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity.

    Science.gov (United States)

    Dosenovic, Pia; Kara, Ervin E; Pettersson, Anna-Klara; McGuire, Andrew T; Gray, Matthew; Hartweger, Harald; Thientosapol, Eddy S; Stamatatos, Leonidas; Nussenzweig, Michel C

    2018-04-16

    The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain superphysiologic numbers of bNAb precursor-expressing B cells, and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti-HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center (GC) B cell recruitment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the GC when there are as few as 10 such cells per mouse. However, at low precursor frequencies, the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to GCs is variable and dependent on recirculation.

  4. Targeting the BCR signalosome in B cell malignancies

    NARCIS (Netherlands)

    de Rooij, M.F.M.

    2017-01-01

    Chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM) are B-cell malignancies which are still incurable. In these lymphomas, the cells proliferate in specialized niches in lymph nodes and bone marrow, in which they are provided by stromal-derived

  5. Likelihood-Based Inference of B Cell Clonal Families.

    Directory of Open Access Journals (Sweden)

    Duncan K Ralph

    2016-10-01

    Full Text Available The human immune system depends on a highly diverse collection of antibody-making B cells. B cell receptor sequence diversity is generated by a random recombination process called "rearrangement" forming progenitor B cells, then a Darwinian process of lineage diversification and selection called "affinity maturation." The resulting receptors can be sequenced in high throughput for research and diagnostics. Such a collection of sequences contains a mixture of various lineages, each of which may be quite numerous, or may consist of only a single member. As a step to understanding the process and result of this diversification, one may wish to reconstruct lineage membership, i.e. to cluster sampled sequences according to which came from the same rearrangement events. We call this clustering problem "clonal family inference." In this paper we describe and validate a likelihood-based framework for clonal family inference based on a multi-hidden Markov Model (multi-HMM framework for B cell receptor sequences. We describe an agglomerative algorithm to find a maximum likelihood clustering, two approximate algorithms with various trade-offs of speed versus accuracy, and a third, fast algorithm for finding specific lineages. We show that under simulation these algorithms greatly improve upon existing clonal family inference methods, and that they also give significantly different clusters than previous methods when applied to two real data sets.

  6. Th1 and Th2 help for B cells

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1995-01-01

    Sustained interaction with Th1 cells has been shown to induce IL-2 responsiveness by murine B cells. This is equivalently dependent on CD40, CD54/ICAM-1 and MHC II ligation, and co-cross-linking of CD54 and MHC II in the presence of IL-5 up-regulates a functional IL-2R on B cells. We now show...... that IL-5 (125 U/ml) synergizes with Th1 cells to induce B cell responses to IL-2, that are maintained following T-cell removal, e.g. autonomous. Th1 help in the absence of IL-5 resulted in weak or undetectable responses following T cell removal. The mechanism of IL-5 synergy involved persistence of IL-2R...... anti-Ig did not circumvent the need for IL-5 for autonomous IL-2 responses. Consistent with the above, interaction with an IL-5-producing Th2 clone induced strong autonomous B cell responses to IL-2. Qualitative differences of Th2 help over that of Th1 may thus be attributable to their differential...

  7. Role of Bruton's tyrosine kinase in B cells and malignancies

    NARCIS (Netherlands)

    Pal Singh, S. (Simar); F. Dammeijer (Floris); R.W. Hendriks (Rudi)

    2018-01-01

    textabstractBruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked

  8. Btk at the Pre-B Cell Receptor Checkpoint

    NARCIS (Netherlands)

    S. Middendorp

    2004-01-01

    textabstractSignalling from the BCR or its immature form, the pre-BCR, was shown to be crucial for B cell development. Gene-targeted mice have defined differential roles of components of the (pre-) BCR complex or its downstream signalling pathways. One of the proteins involved in (pre-) BCR

  9. Lymphoma classification update: B-cell non-Hodgkin lymphomas.

    Science.gov (United States)

    Jiang, Manli; Bennani, N Nora; Feldman, Andrew L

    2017-05-01

    Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both by lineage and by stage of differentiation, the classification of lymphomas arising from these normal lymphoid populations is complex. Recent genomic data have contributed additional complexity. Areas covered: Lymphoma classification follows the World Health Organization (WHO) system, which reflects international consensus and is based on pathological, genetic, and clinical factors. A 2016 revision to the WHO classification of lymphoid neoplasms recently was reported. The present review focuses on B-cell non-Hodgkin lymphomas, the most common group of lymphomas, and summarizes recent changes most relevant to hematologists and other clinicians who care for lymphoma patients. Expert commentary: Lymphoma classification is a continually evolving field that needs to be responsive to new clinical, pathological, and molecular understanding of lymphoid neoplasia. Among the entities covered in this review, the 2016 revision of the WHO classification particularly impact the subclassification and genetic stratification of diffuse large B-cell lymphoma and high-grade B-cell lymphomas, and reflect evolving criteria and nomenclature for indolent B-cell lymphomas and lymphoproliferative disorders.

  10. Immunomodulatory effect of Mesenchymal Stem Cells on B cells

    Directory of Open Access Journals (Sweden)

    Marcella eFranquesa

    2012-07-01

    Full Text Available The research on T cell immunosuppression therapies has attracted most of the attention in clinical transplantation. However, B cells and humoral immune responses are increasingly acknowledged as crucial mediators of chronic allograft rejection. Indeed, humoral immune responses can lead to renal allograft rejection even in patients whose cell-mediated immune responses are well controlled. On the other hand, newly studied B cell subsets with regulatory effects have been linked to tolerance achievement in transplantation. Better understanding of the regulatory and effector B cell responses may therefore lead to new therapeutic approaches.Mesenchymal Stem Cells (MSC are arising as a potent therapeutic tool in transplantation due to their regenerative and immunomodulatory properties. The research on MSCs has mainly focused on their effects on T cells and although data regarding the modulatory effects of MSCs on alloantigen-specific humoral response in humans is scarce, it has been demonstrated that MSCs significantly affect B cell functioning. In the present review we will analyze and discuss the results in this field.

  11. Prognostic significance of metallothionein in B-cell lymphomas

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Borregaard, Niels

    2006-01-01

    We have investigated metallothionein (MT) I and II mRNA and protein in B-cell lymphomas with particular reference to diffuse large B-cell lymphoma (DLBCL). The mRNA profiling was performed on Affymetrix arrays and showed up-regulated MT mRNA in 15 of 48 DLBCLs, including 12 of 23 activated B......-cell (ABC) and 3 of 9 type-3 lesions. In contrast, MT mRNA was low to undetectable in 16 germinal center B-cell (GCB)-type DLBCLs. Only 1 of 15 patients with up-regulated MT mRNA achieved a sustained remission, suggesting that up-regulated MT mRNA constitutes a significant risk factor for treatment failure......, in 115 DLBCLs, MT labeling of more than 20% lymphoma cells was associated with a significantly poorer 5-year survival, independent of the age, stage, or International Prognostic Index. Taken together, it is suggested that both increased MT mRNA and MT protein expression by more than 20% lymphoma cells...

  12. Anthropometrics and prognosis in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Bendtsen, Mette Dahl; Munksgaard, Peter Svenssen; Severinsen, Marianne Tang

    2017-01-01

    Objective: The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients. Patients and methods: A total of 653 R-CHOP(-like)-treated DLBCL patients were...

  13. Altered B Cell Homeostasis in Patients with Major Depressive Disorder and Normalization of CD5 Surface Expression on Regulatory B Cells in Treatment Responders.

    Science.gov (United States)

    Ahmetspahic, Diana; Schwarte, Kathrin; Ambrée, Oliver; Bürger, Christian; Falcone, Vladislava; Seiler, Katharina; Kooybaran, Mehrdad Rahbar; Grosse, Laura; Roos, Fernand; Scheffer, Julia; Jörgens, Silke; Koelkebeck, Katja; Dannlowski, Udo; Arolt, Volker; Scheu, Stefanie; Alferink, Judith

    2018-03-01

    Pro-inflammatory activity and cell-mediated immune responses have been widely observed in patients with major depressive disorder (MDD). Besides their well-known function as antibody-producers, B cells play a key role in inflammatory responses by secreting pro- and anti-inflammatory factors. However, homeostasis of specific B cell subsets has not been comprehensively investigated in MDD. In this study, we characterized circulating B cells of distinct developmental steps including transitional, naïve-mature, antigen-experienced switched, and non-switched memory cells, plasmablasts and regulatory B cells by multi-parameter flow cytometry. In a 6-weeks follow-up, circulating B cells were monitored in a small group of therapy responders and non-responders. Frequencies of naïve lgD + CD27 - B cells, but not lgD + CD27 + memory B cells, were reduced in severely depressed patients as compared to healthy donors (HD) or mildly to moderately depressed patients. Specifically, B cells with immune-regulatory capacities such as CD1d + CD5 + B cells and CD24 + CD38 hi transitional B cells were reduced in MDD. Also Bm1-Bm5 classification in MDD revealed reduced Bm2' cells comprising germinal center founder cells as well as transitional B cells. We further found that reduced CD5 surface expression on transitional B cells was associated with severe depression and normalized exclusively in clinical responders. This study demonstrates a compromised peripheral B cell compartment in MDD with a reduction in B cells exhibiting a regulatory phenotype. Recovery of CD5 surface expression on transitional B cells in clinical response, a molecule involved in activation and down-regulation of B cell responses, further points towards a B cell-dependent process in the pathogenesis of MDD.

  14. Primary B-cell deficiencies reveal a link between human IL-17-producing CD4 T-cell homeostasis and B-cell differentiation.

    Directory of Open Access Journals (Sweden)

    Rita R Barbosa

    Full Text Available IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17 share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a putative link between Th17-cell homeostasis and B cells by studying the Th17-cell compartment in primary B-cell immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID, defined by defects in B-cell differentiation into plasma and memory B cells, are frequently associated with autoimmune and inflammatory manifestations but we found no relationship between these and Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activated non-differentiated B cells (CD21(lowCD38(low. Moreover, Congenital Agammaglobulinemia patients, lacking B cells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFF levels, a crucial cytokine for B-cell survival. Overall, our data support a relationship between Th17-cell homeostasis and B-cell maturation, with implications for the understanding of the pathogenesis of inflammatory/autoimmune diseases and the physiology of B-cell depleting therapies.

  15. Logical analysis of diffuse large B-cell lymphomas.

    Science.gov (United States)

    Alexe, G; Alexe, S; Axelrod, D E; Hammer, P L; Weissmann, D

    2005-07-01

    The goal of this study is to re-examine the oligonucleotide microarray dataset of Shipp et al., which contains the intensity levels of 6817 genes of 58 patients with diffuse large B-cell lymphoma (DLBCL) and 19 with follicular lymphoma (FL), by means of the combinatorics, optimisation, and logic-based methodology of logical analysis of data (LAD). The motivations for this new analysis included the previously demonstrated capabilities of LAD and its expected potential (1) to identify different informative genes than those discovered by conventional statistical methods, (2) to identify combinations of gene expression levels capable of characterizing different types of lymphoma, and (3) to assemble collections of such combinations that if considered jointly are capable of accurately distinguishing different types of lymphoma. The central concept of LAD is a pattern or combinatorial biomarker, a concept that resembles a rule as used in decision tree methods. LAD is able to exhaustively generate the collection of all those patterns which satisfy certain quality constraints, through a systematic combinatorial process guided by clear optimization criteria. Then, based on a set covering approach, LAD aggregates the collection of patterns into classification models. In addition, LAD is able to use the information provided by large collections of patterns in order to extract subsets of variables, which collectively are able to distinguish between different types of disease. For the differential diagnosis of DLBCL versus FL, a model based on eight significant genes is constructed and shown to have a sensitivity of 94.7% and a specificity of 100% on the test set. For the prognosis of good versus poor outcome among the DLBCL patients, a model is constructed on another set consisting also of eight significant genes, and shown to have a sensitivity of 87.5% and a specificity of 90% on the test set. The genes selected by LAD also work well as a basis for other kinds of statistical

  16. Follicular B Cell Lymphoma with Accompanying Ischemic Gastritis Completely Resolved by Rituximab.

    Science.gov (United States)

    Tariq, Anam; Mehta, Neal; Peroutka, Kathryn

    2017-06-02

    BACKGROUND Follicular B cell lymphomas account for a significant portion of all newly diagnosed non-Hodgkin's lymphomas. While involvement can be varied, the most common extranodal presentation is within the gastrointestinal tract beyond the stomach. In addition, the stomach has a diffuse multivessel vascular supply, which decreases the likelihood of developing ischemic gastritis. CASE REPORT An 89-year-old woman with history of diabetes, deep venous thromboembolism, and hypertension was referred due to a newly diagnosed retroperitoneal mass. Biopsy of a left para-aortic node was consistent with low-grade follicular B cell lymphoma. Following mainstream treatment guidelines, rituximab was administered. Approximately 12 hours later, the patient presented to the Emergency Department with intractable vomiting and nausea. After admission, an esophagogastroduodenoscopy (EGD) revealed extensive ischemic gastritis. Due to recurrent ascites requiring frequent paracenteses, and the clinical aggressiveness of the patient's underlying lymphoma, a second dose of rituximab was administered with concurrent initiation of total parenteral nutrition. Approximately 1 week later, the patient underwent a repeat EGD for quality of life planning while in hospice. The repeat EGD revealed resolved ischemic gastritis. Her diet was advanced and she was subsequently discharged home. CONCLUSIONS Rituximab alone shows promise in treating extensive follicular B cell lymphoma complicated by ischemic gastritis, which has not been previously reported in the literature.

  17. Spatial and seasonal toxicity in a stormwater management facility: evidence obtained by adapting an integrated sediment quality assessment approach.

    Science.gov (United States)

    Tixier, Guillaume; Rochfort, Quintin; Grapentine, Lee; Marsalek, Jiri; Lafont, Michel

    2012-12-15

    Stormwater ponds have been widely used to control increased surface runoff resulting from urbanization, and to enhance runoff quality. As receiving waters, they are impacted by intermittent stormwater pollution while also serving as newly created aquatic habitats, which partly offset changes of aquatic ecosystems and their biodiversity by urbanization. Thus, determining ecological risks in stormwater ponds is important for the preservation and rehabilitation of biodiversity in urban areas. Limitations of the conventional toxicity assessment techniques in stormwater ponds have led us to use the sediment quality triad approach with the specific analyses of oligochaetes. The latter analyses build on the earlier work by the Cemagref (Lyon, France) and use the oligochaetes as bioindicators of the sediment quality. This integrative approach was tested at eight sites in the Terraview-Willowfield stormwater facility in Toronto, Ontario, in all four seasons (summer 2008-spring 2009). The facility receives direct runoff from the MacDonald-Cartier freeway with a traffic intensity of 340,000 vehicles/d. Sediment chemistry results indicate that several heavy metals and PAH compounds exceeded the Ontario sediment quality guidelines in the facility. Regardless of the season, laboratory bioassays revealed a strong spatial variation in sediment toxicity along the flow path from the inlet to the outlet, agreeing with decreasing concentrations of contaminants in sediment, especially of heavy metals. However, in situ assessments of the benthic macroinvertebrate community structure and in particular of the oligochaete community revealed an overriding influence of seasonally varying toxicity. This seasonal pattern was described as high toxicity in spring and recovery in fall and corresponded to the influx and flushing-out of road salts and of several heavy metals within the facility. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  18. The Influence of Brand Image, Price, Service Quality and Facilities on Customer Satisfaction at Aston Hotel Manado

    OpenAIRE

    Taroreh, Rita N.; Mananeke, Lisbeth; Suwandi, Monica M.

    2015-01-01

    The economic condition of a country will change the mindset of people, so what happened in Indonesia it determines the public goods and services, in accordance with ability of business players and their business oriented towards the consumer. Consumers free use of money and free compare products or services and factors associated with services like the brand image, price, service quality and facilities. These days, service business in this case of hotel, have a thighter competition. As the ne...

  19. Type I CD20 Antibodies Recruit the B Cell Receptor for Complement-Dependent Lysis of Malignant B Cells

    NARCIS (Netherlands)

    Engelberts, Patrick J.; Voorhorst, Marleen; Schuurman, Janine; van Meerten, Tom; Bakker, Joost M.; Vink, Tom; Mackus, Wendy J. M.; Breij, Esther C. W.; Derer, Stefanie; Valerius, Thomas; van de Winkel, Jan G. J.; Parren, Paul W. H. I.; Beurskens, Frank J.

    2016-01-01

    Human IgG1 type I CD20 Abs, such as rituximab and ofatumumab (OFA), efficiently induce complement-dependent cytotoxicity (CDC) of CD20(+) B cells by binding of C1 to hexamerized Fc domains. Unexpectedly, we found that type I CD20 Ab F(ab ')2 fragments, as well as C1q-binding-deficient IgG mutants,

  20. Development of a Quality of Meals and Meal Service Set of Indicators for Residential Facilities for Elderly.

    Science.gov (United States)

    Van Damme, N; Buijck, B; Van Hecke, A; Verhaeghe, S; Goossens, E; Beeckman, D

    2016-01-01

    To develop a content validated set of indicators to evaluate the quality of meals and meal service in residential facilities for elderly. Inadequate food intake is an important risk factor for malnutrition in residential facilities for elderly. Through better meeting the needs and preferences of residents and optimization of meals and meal service, residents' food intake can improve. No indicators were available which could help to guide strategies to improve the quality of meals and meal service. The indicator set was developed according to the Indicator Development Manual of the Dutch Institute for Health Care Improvement (CBO). The working group consisted of three nurse researchers and one expert in gastrology and had expertise in elderly care, malnutrition, indicator development, and food quality. A preliminary list of potential indicators was compiled using the literature and the working group's expertise. Criteria necessary to measure the indicator in practice were developed for each potential indicator. In a double Delphi procedure, the list of potential indicators and respective criteria were analyzed for content validity, using a multidisciplinary expert panel of 11 experts in elderly meal care. A preliminary list of 20 quality indicators, including 45 criteria, was submitted to the expert panel in a double Delphi procedure. After the second Delphi round, 13 indicators and 25 criteria were accepted as having content validity. The content validity index (CVI) ranged from 0.83 to 1. The indicator set consisted of six structural, four result, and three outcome indicators covering the quality domains food, service and choice, as well as nutritional screening. The criteria measure diverse aspects of meal care which are part of the responsibility of kitchen staff and health care professionals. The 'quality of meals and meal service' set of indicators is a resource to map meal quality in residential facilities for elderly. As soon as feasibility tests in practice

  1. Assessment of the quality of clinical documentation in India's JSY cash transfer program for facility births in Madhya Pradesh.

    Science.gov (United States)

    Chaturvedi, Sarika; Randive, Bharat; Raven, Joanna; Diwan, Vishal; De Costa, Ayesha

    2016-02-01

    To gain insight into the quality of care in facilities implementing the Janani Suraksha Yojana (JSY) cash transfer program in Madhya Pradesh, India, by reviewing the level of documentation in the clinical records of women who delivered. The present retrospective, descriptive study reviewed case records of women who delivered at 73 primary, secondary, and tertiary level facilities in three districts of Madhya Pradesh between 2012 and 2013. Twenty elements of care were assessed encompassing clinical history and admission details, care during delivery and postnatal period, and discharge details. A total of 1239 records were reviewed. The extent of documentation varied among the elements assessed-e.g. 24 (1.9%) records documented advice at discharge, 171 (13.8%) documented postnatal blood pressure, 437 (35.3%) documented fetal heart rate, and 1220 (98.5%) documented admission date. The extent of documentation was better at higher level facilities. The quality of clinical documentation in the JSY program was found to be unacceptably poor in Madhya Pradesh. Improving staff skills and practices in clinical documentation and record keeping will be required to enable clinical processes to be assessed and quality of care to be improved. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Quality of antimalarial drugs and antibiotics in Papua New Guinea: a survey of the health facility supply chain.

    Directory of Open Access Journals (Sweden)

    Manuel W Hetzel

    Full Text Available Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT. In Papua New Guinea (PNG, Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG.Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC. Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3 contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4% primaquine, 3/70 (4.3% amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions.This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the

  3. Quality of Antimalarial Drugs and Antibiotics in Papua New Guinea: A Survey of the Health Facility Supply Chain

    Science.gov (United States)

    Hetzel, Manuel W.; Page-Sharp, Madhu; Bala, Nancy; Pulford, Justin; Betuela, Inoni; Davis, Timothy M. E.; Lavu, Evelyn K.

    2014-01-01

    Background Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG. Methods and Findings Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions. Conclusions This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory

  4. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Xu-Monette, Z.Y.; Li, L; Byrd, J.C.; Jabbar, K.J.; Manyam, G.C.; Winde, C. Maria de; Brand, M. van den; Tzankov, A.; Visco, C.; Wang, J; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Richards, K.L.; Hsi, E.D.; Choi, W.W.; Huh, J.; Ponzoni, M.; Ferreri, A.J.; Moller, M.B.; Parsons, B.M.; Winter, J.N.; Wang, M.; Hagemeister, F.B.; Piris, M.A.; Krieken, J.H. van; Medeiros, L.J.; Li, Y.; Spriel, A.B. van; Young, K.H.

    2016-01-01

    CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its

  5. The B cell antigen receptor and overexpression of MYC can cooperate in the genesis of B cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Yosef Refaeli

    2008-06-01

    Full Text Available A variety of circumstantial evidence from humans has implicated the B cell antigen receptor (BCR in the genesis of B cell lymphomas. We generated mouse models designed to test this possibility directly, and we found that both the constitutive and antigen-stimulated state of a clonal BCR affected the rate and outcome of lymphomagenesis initiated by the proto-oncogene MYC. The tumors that arose in the presence of constitutive BCR differed from those initiated by MYC alone and resembled chronic B cell lymphocytic leukemia/lymphoma (B-CLL, whereas those that arose in response to antigen stimulation resembled large B-cell lymphomas, particularly Burkitt lymphoma (BL. We linked the genesis of the BL-like tumors to antigen stimulus in three ways. First, in reconstruction experiments, stimulation of B cells by an autoantigen in the presence of overexpressed MYC gave rise to BL-like tumors that were, in turn, dependent on both MYC and the antigen for survival and proliferation. Second, genetic disruption of the pathway that mediates signaling from the BCR promptly killed cells of the BL-like tumors as well as the tumors resembling B-CLL. And third, growth of the murine BL could be inhibited by any of three distinctive immunosuppressants, in accord with the dependence of the tumors on antigen-induced signaling. Together, our results provide direct evidence that antigenic stimulation can participate in lymphomagenesis, point to a potential role for the constitutive BCR as well, and sustain the view that the constitutive BCR gives rise to signals different from those elicited by antigen. The mouse models described here should be useful in exploring further the pathogenesis of lymphomas, and in preclinical testing of new therapeutics.

  6. Unusual B cell morphology in inflammatory bowel disease.

    Science.gov (United States)

    Defendenti, Caterina; Grosso, Silvia; Atzeni, Fabiola; Croce, Annamaria; Senesi, Olivia; Saibeni, Simone; Bollani, Simona; Almasio, Piero Luigi; Bruno, Savino; Sarzi-Puttini, Piercarlo

    2012-07-15

    B lymphocytes express various different types of surface immunoglobulins that are largely unrelated to other hematological lines, although some reports have described a relationship between malignant B cells and other cells such as macrophages. Multiple genes of hematopoietic lineage, including transcription factors, are co-expressed in hematopoietic stem cells and progenitors, a phenomenon referred to as "lineage priming". Changes in the expression levels and timing of transcription factors can induce the lineage conversion of committed cells, which indicates that the regulation of transcription factors might be particularly critical for maintaining hierarchical hematopoietic development. The aim of this study was to evaluate the surface markers of particular IgM-positive and irregularly nucleated cells detected in patients with inflammatory bowel disease (IBD), and to assess their association with diagnosis and inflammatory cell recruitment. Small intestine, colon and rectal biopsy specimens of 96 IBD patients were studied. Immunoglobulin-producing cells (IPCs) were analyzed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The specimens positive for B cells with irregular nuclei were assessed using monoclonal antibodies specific for CD79, and λ and κ chains in order to confirm their B cell nature. CD15+ cells, an important marker of inflammatory cell recruitment, were also evaluated. Statistical correlations were sought between the histological findings and clinical expression. 34 (35.4%) of the 96 patients (64 with ulcerative colitis and 32 with Crohn's disease) presented a periglandial localization of IPCs with irregular nuclei, which showed surface markers specific for the B cell subset, such as IgM and CD79, but quantitative differences in λ and κ chains. These specimens also contained CD15-positive cells, which are usually absent in healthy controls. The quantitative aspects and localization of the CD15

  7. Improving the indoor air quality of respiratory type of medical facility by zeolite filtering.

    Science.gov (United States)

    Shen, Jyun-Hong; Wang, Yeoung-Sheng; Lin, Jhan-Ping; Wu, Sheng-Hung; Horng, Jao-Jia

    2014-01-01

    This study investigated the indoor air quality (IAQ) conditions of carbon dioxide (CO2), carbon monoxide (CO), ozone (O3), formaldehyde (HCHO), total volatile organic compounds (TVOCs), and bio-aerosols (bacteria and fungi) in a respiratory type of medical facility in Chia-Yi County in southern Taiwan. Among those IAQ conditions, the concentrations of CO, O3, and HCHO exceeded the regulation values of the Taiwan Environmental Protection Administration (EPA) mostly in the morning. The concentrations of bacteria and fungi did not exceed the regulation values but still posed potential health and environment problems for workers, patients, and visitors. Therefore, self-made silver-coated zeolite (AgZ) was used as a filter material in air cleaners to remove bio-aerosols in the respiratory care ward (RCW), and the removals were still effective after 120 hr. The cumulative bio-aerosol removals for bacteria and fungi were 900 and 1,088 colony-forming units (CFU) g(-1) after 24 hr and were above 3,100 and 2,700 CFU g(-1) after 120 hr. From the research results, it is suggested that AgZ filtering could be used as a feasible engineering measure for hospitals to control their bacteria and fungi parameters in IAQ management. Hospitals should maintain their environmental management and monitoring programs and use different engineering measures to improve different IAQ parameters. This study investigated the IAQ conditions in the field at a hospital in Chia-Yi County in southern Taiwan. Although concentrations of most parameters were still within the regulation values, the concentrations of CO, O3, and HCHO were partially exceeded. We propose a method using an air cleaner with silver-coated zeolite (AgZ) as a possible engineering measure, and there were effective reductions of bacteria and fungi to lower levels with antibacterial effects after 120 hr. Furthermore, this study implies that hospitals should continuously maintain environmental monitoring programs and adopt optimal

  8. Quality of Longer Term Mental Health Facilities in Europe: Validation of the Quality Indicator for Rehabilitative Care against Service Users’ Views

    Science.gov (United States)

    Killaspy, Helen; White, Sarah; Wright, Christine; Taylor, Tatiana L.; Turton, Penny; Kallert, Thomas; Schuster, Mirjam; Cervilla, Jorge A.; Brangier, Paulette; Raboch, Jiri; Kalisova, Lucie; Onchev, Georgi; Alexiev, Spiridon; Mezzina, Roberto; Ridente, Pina; Wiersma, Durk; Visser, Ellen; Kiejna, Andrzej; Piotrowski, Patryk; Ploumpidis, Dimitris; Gonidakis, Fragiskos; Caldas-de-Almeida, José Miguel; Cardoso, Graça; King, Michael

    2012-01-01

    Background The Quality Indicator for Rehabilitative Care (QuIRC) is a staff rated, international toolkit that assesses care in longer term hospital and community based mental health facilities. The QuIRC was developed from review of the international literature, an international Delphi exercise with over 400 service users, practitioners, carers and advocates from ten European countries at different stages of deinstitutionalisation, and review of the care standards in these countries. It can be completed in under an hour by the facility manager and has robust content validity, acceptability and inter-rater reliability. In this study, we investigated the internal validity of the QuIRC. Our aim was to identify the QuIRC domains of care that independently predicted better service user experiences of care. Method At least 20 units providing longer term care for adults with severe mental illness were recruited in each of ten European countries. Service users completed standardised measures of their experiences of care, quality of life, autonomy and the unit’s therapeutic milieu. Unit managers completed the QuIRC. Multilevel modelling allowed analysis of associations between service user ratings as dependent variables with unit QuIRC domain ratings as independent variables. Results 1750/2495 (70%) users and the managers of 213 units from across ten European countries participated. QuIRC ratings were positively associated with service users’ autonomy and experiences of care. Associations between QuIRC ratings and service users’ ratings of their quality of life and the unit’s therapeutic milieu were explained by service user characteristics (age, diagnosis and functioning). A hypothetical 10% increase in QuIRC rating resulted in a clinically meaningful improvement in autonomy. Conclusions Ratings of the quality of longer term mental health facilities made by service managers were positively associated with service users’ autonomy and experiences of care

  9. Quality of longer term mental health facilities in Europe: validation of the quality indicator for rehabilitative care against service users' views.

    Directory of Open Access Journals (Sweden)

    Helen Killaspy

    Full Text Available BACKGROUND: The Quality Indicator for Rehabilitative Care (QuIRC is a staff rated, international toolkit that assesses care in longer term hospital and community based mental health facilities. The QuIRC was developed from review of the international literature, an international Delphi exercise with over 400 service users, practitioners, carers and advocates from ten European countries at different stages of deinstitutionalisation, and review of the care standards in these countries. It can be completed in under an hour by the facility manager and has robust content validity, acceptability and inter-rater reliability. In this study, we investigated the internal validity of the QuIRC. Our aim was to identify the QuIRC domains of care that independently predicted better service user experiences of care. METHOD: At least 20 units providing longer term care for adults with severe mental illness were recruited in each of ten European countries. Service users completed standardised measures of their experiences of care, quality of life, autonomy and the unit's therapeutic milieu. Unit managers completed the QuIRC. Multilevel modelling allowed analysis of associations between service user ratings as dependent variables with unit QuIRC domain ratings as independent variables. RESULTS: 1750/2495 (70% users and the managers of 213 units from across ten European countries participated. QuIRC ratings were positively associated with service users' autonomy and experiences of care. Associations between QuIRC ratings and service users' ratings of their quality of life and the unit's therapeutic milieu were explained by service user characteristics (age, diagnosis and functioning. A hypothetical 10% increase in QuIRC rating resulted in a clinically meaningful improvement in autonomy. CONCLUSIONS: Ratings of the quality of longer term mental health facilities made by service managers were positively associated with service users' autonomy and experiences of care

  10. Quality of longer term mental health facilities in Europe: validation of the quality indicator for rehabilitative care against service users' views.

    Science.gov (United States)

    Killaspy, Helen; White, Sarah; Wright, Christine; Taylor, Tatiana L; Turton, Penny; Kallert, Thomas; Schuster, Mirjam; Cervilla, Jorge A; Brangier, Paulette; Raboch, Jiri; Kalisova, Lucie; Onchev, Georgi; Alexiev, Spiridon; Mezzina, Roberto; Ridente, Pina; Wiersma, Durk; Visser, Ellen; Kiejna, Andrzej; Piotrowski, Patryk; Ploumpidis, Dimitris; Gonidakis, Fragiskos; Caldas-de-Almeida, José Miguel; Cardoso, Graça; King, Michael

    2012-01-01

    The Quality Indicator for Rehabilitative Care (QuIRC) is a staff rated, international toolkit that assesses care in longer term hospital and community based mental health facilities. The QuIRC was developed from review of the international literature, an international Delphi exercise with over 400 service users, practitioners, carers and advocates from ten European countries at different stages of deinstitutionalisation, and review of the care standards in these countries. It can be completed in under an hour by the facility manager and has robust content validity, acceptability and inter-rater reliability. In this study, we investigated the internal validity of the QuIRC. Our aim was to identify the QuIRC domains of care that independently predicted better service user experiences of care. At least 20 units providing longer term care for adults with severe mental illness were recruited in each of ten European countries. Service users completed standardised measures of their experiences of care, quality of life, autonomy and the unit's therapeutic milieu. Unit managers completed the QuIRC. Multilevel modelling allowed analysis of associations between service user ratings as dependent variables with unit QuIRC domain ratings as independent variables. 1750/2495 (70%) users and the managers of 213 units from across ten European countries participated. QuIRC ratings were positively associated with service users' autonomy and experiences of care. Associations between QuIRC ratings and service users' ratings of their quality of life and the unit's therapeutic milieu were explained by service user characteristics (age, diagnosis and functioning). A hypothetical 10% increase in QuIRC rating resulted in a clinically meaningful improvement in autonomy. Ratings of the quality of longer term mental health facilities made by service managers were positively associated with service users' autonomy and experiences of care. Interventions that improve quality of care in these

  11. SU-F-T-169: A Periodic Quality Assurance Program for a Spot-Scanning Proton Treatment Facility

    Energy Technology Data Exchange (ETDEWEB)

    Mundy, D; Tryggestad, E; Beltran, C; Furutani, K; Gilson, G; Ito, S; Johnson, J; Kruse, J; Remmes, N; Tasson, A; Whitaker, T; Herman, M [Mayo Clinic, Rochester, MN (United States)

    2016-06-15

    Purpose: To develop daily and monthly quality assurance (QA) programs in support of a new spot-scanning proton treatment facility using a combination of commercial and custom equipment and software. Emphasis was placed on efficiency and evaluation of key quality parameters. Methods: The daily QA program was developed to test output, spot size and position, proton beam energy, and image guidance using the Sun Nuclear Corporation rf-DQA™3 device and Atlas QA software. The program utilizes standard Atlas linear accelerator tests repurposed for proton measurements and a custom jig for indexing the device to the treatment couch. The monthly QA program was designed to test mechanical performance, image quality, radiation quality, isocenter coincidence, and safety features. Many of these tests are similar to linear accelerator QA counterparts, but many require customized test design and equipment. Coincidence of imaging, laser marker, mechanical, and radiation isocenters, for instance, is verified using a custom film-based device devised and manufactured at our facility. Proton spot size and position as a function of energy are verified using a custom spot pattern incident on film and analysis software developed in-house. More details concerning the equipment and software developed for monthly QA are included in the supporting document. Thresholds for daily and monthly tests were established via perturbation analysis, early experience, and/or proton system specifications and associated acceptance test results. Results: The periodic QA program described here has been in effect for approximately 9 months and has proven efficient and sensitive to sub-clinical variations in treatment delivery characteristics. Conclusion: Tools and professional guidelines for periodic proton system QA are not as well developed as their photon and electron counterparts. The program described here efficiently evaluates key quality parameters and, while specific to the needs of our facility

  12. SU-F-T-169: A Periodic Quality Assurance Program for a Spot-Scanning Proton Treatment Facility

    International Nuclear Information System (INIS)

    Mundy, D; Tryggestad, E; Beltran, C; Furutani, K; Gilson, G; Ito, S; Johnson, J; Kruse, J; Remmes, N; Tasson, A; Whitaker, T; Herman, M

    2016-01-01

    Purpose: To develop daily and monthly quality assurance (QA) programs in support of a new spot-scanning proton treatment facility using a combination of commercial and custom equipment and software. Emphasis was placed on efficiency and evaluation of key quality parameters. Methods: The daily QA program was developed to test output, spot size and position, proton beam energy, and image guidance using the Sun Nuclear Corporation rf-DQA™3 device and Atlas QA software. The program utilizes standard Atlas linear accelerator tests repurposed for proton measurements and a custom jig for indexing the device to the treatment couch. The monthly QA program was designed to test mechanical performance, image quality, radiation quality, isocenter coincidence, and safety features. Many of these tests are similar to linear accelerator QA counterparts, but many require customized test design and equipment. Coincidence of imaging, laser marker, mechanical, and radiation isocenters, for instance, is verified using a custom film-based device devised and manufactured at our facility. Proton spot size and position as a function of energy are verified using a custom spot pattern incident on film and analysis software developed in-house. More details concerning the equipment and software developed for monthly QA are included in the supporting document. Thresholds for daily and monthly tests were established via perturbation analysis, early experience, and/or proton system specifications and associated acceptance test results. Results: The periodic QA program described here has been in effect for approximately 9 months and has proven efficient and sensitive to sub-clinical variations in treatment delivery characteristics. Conclusion: Tools and professional guidelines for periodic proton system QA are not as well developed as their photon and electron counterparts. The program described here efficiently evaluates key quality parameters and, while specific to the needs of our facility

  13. Quality of caesarean delivery services and documentation in first-line referral facilities in Afghanistan: a chart review

    Directory of Open Access Journals (Sweden)

    Kim Young-Mi

    2012-03-01

    Full Text Available Abstract Background Increasing appropriate use and documentation of caesarean section (CS has the potential to decrease maternal and perinatal mortality in settings with low CS rates. We analyzed data collected as part of a comprehensive needs assessment of emergency obstetric and newborn care (EmONC facilities in Afghanistan to gain a greater understanding of the clinical indications, timeliness, and outcomes of CS deliveries. Methods Records were reviewed at 78 government health facilities expected to function as EmONC providers that were located in secure areas of the country. Information was collected on the three most recent CS deliveries in the preceding 12 months at facilities with at least one CS delivery in the preceding three months. After excluding 16 facilities with no recent CS deliveries, the sample includes 173 CS deliveries at 62 facilities. Results No CS deliveries were performed in the previous three months at 21% of facilities surveyed; all of these were lower-level facilities. Most CS deliveries (88% were classified as emergencies, and only 12% were referrals from another facility. General anesthesia was used in 62% of cases, and spinal or epidural anesthesia in 34%. Only 28% of cases were managed with a partograph. Surgery began less than one hour after the decision for a CS delivery in just 30% of emergency cases. Among the 173 cases, 27 maternal deaths, 28 stillbirths, and 3 early neonatal deaths were documented. In cases of maternal and fetal death, the most common indications for CS delivery were placenta praevia or abruption and malpresentation. In 62% of maternal deaths, the fetus was stillborn or died shortly after birth. In 48% of stillbirths, the fetus had a normal heart rate at the last check. Information on partograph use was missing in 38% of cases, information on parity missing in 23% of cases and indications for cesareans missing in 9%. Conclusions Timely referral within and to EmONC facilities would decrease

  14. Rituximab and chemotherapy in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Sonet, Anne; Bosly, André

    2009-06-01

    Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

  15. Bisphosphonates target B cells to enhance humoral immune responses

    Science.gov (United States)

    Tonti, Elena; Jiménez de Oya, Nereida; Galliverti, Gabriele; Moseman, E. Ashley; Di Lucia, Pietro; Amabile, Angelo; Sammicheli, Stefano; De Giovanni, Marco; Sironi, Laura; Chevrier, Nicolas; Sitia, Giovanni; Gennari, Luigi; Guidotti, Luca G.; von Andrian, Ulrich H.; Iannacone, Matteo

    2013-01-01

    Summary Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4+ and γδ T cells, neutrophils or dendritic cells and their effect does not rely on local macrophage depletion nor does it depend upon Toll-like receptor signaling or the inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. These data establish bisphosphonates as a novel class of adjuvants that boost humoral immune responses. PMID:24120862

  16. Bisphosphonates Target B Cells to Enhance Humoral Immune Responses

    Directory of Open Access Journals (Sweden)

    Elena Tonti

    2013-10-01

    Full Text Available Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens, and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4+ and γδ T cells, neutrophils, or dendritic cells, and their effect does not rely on local macrophage depletion, Toll-like receptor signaling, or the inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. These data establish bisphosphonates as an additional class of adjuvants that boost humoral immune responses.

  17. Antibody B cell responses in HIV-1 infection.

    Science.gov (United States)

    Mouquet, Hugo

    2014-11-01

    In rare cases, B cells can supply HIV-1-infected individuals with unconventional antibodies equipped to neutralize the wide diversity of viral variants. Innovations in single-cell cloning, high-throughput sequencing, and structural biology methods have enabled the capture and thorough characterization of these exceptionally potent broadly neutralizing antibodies (bNAbs). Here, I review the recent findings in humoral responses to HIV-1, focusing on the interplay between naturally occurring bNAbs and the virus both at systemic and mucosal levels. In this context, I discuss how an improved understanding of bNAb generation may provide invaluable insight into the fundamental mechanisms governing adaptive B cell responses to viruses, and how this knowledge is currently contributing to the development of vaccine and therapeutic strategies against HIV-1. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Quality of child healthcare at primary healthcare facilities: a national assessment of the Integrated Management of Childhood Illnesses in Afghanistan.

    Science.gov (United States)

    Mansoor, Ghulam Farooq; Chikvaidze, Paata; Varkey, Sherin; Higgins-Steele, Ariel; Safi, Najibullah; Mubasher, Adela; Yusufi, Khaksar; Alawi, Sayed Alisha

    2017-02-01

    To assess quality of the national Integrated Management of Childhood Illness (IMCI) program services provided for sick children at primary health facilities in Afghanistan. Mixed methods including cross-sectional study. Thirteen (of thirty-four) provinces in Afghanistan. Observation of case management and re-examination of 177 sick children, exit interviews with caretakers and review of equipment/supplies at 44 health facilities. Introduction and scale up of Integrated Management of Childhood Illnesses at primary health care facilities. Care of sick children according to IMCI guidelines, health worker skills and essential health system elements. Thirty-two (71%) of the health workers were trained in IMCI and five (11%) received supervision in clinical case management during the past 6 months. On average, 5.4 out of 10 main assessment tasks were performed during cases observed, the index being higher in children seen by trained providers than untrained (6.3 vs 3.5, 95% CI 5.8-6.8 vs 2.9-4.1). In all, 74% of the 104 children who needed oral antibiotics received prescriptions, while 30% received complete and correct advice and 30% were overprescribed, and more so by untrained providers. Home care counseling was associated with provider training status (41.3% by trained and 24.5% by untrained). Essential oral and pre-referral injectable medicine and equipment/supplies were available in 66%, 23%, and 45% of health facilities, respectively. IMCI training improved assessment, rational use of antibiotics and counseling; further investment in IMCI in Afghanistan, continuing provider capacity building and supportive supervision for improved quality of care and counseling for sick children is needed, especially given high burden treatable childhood illness. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  19. Complement-dependent transport of antigen into B cell follicles

    DEFF Research Database (Denmark)

    Gonzalez, Santiago F.; Lukacs-Kornek, Veronika; Kuligowski, Michael P.

    2010-01-01

    an additional novel pathway in which complement C3 and its receptors enhance humoral immunity through delivery of Ag to the B cell compartment. In this review, we discuss this pathway and highlight several novel exceptions recently found with a model influenza vaccine, such as mannose-binding lectin...... opsonization of influenza and uptake by macrophages, and the capture of virus by dendritic cells residing in the medullary compartment of peripheral lymph nodes....

  20. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Schmitz, Roland; Wright, George W; Huang, Da Wei; Johnson, Calvin A; Phelan, James D; Wang, James Q; Roulland, Sandrine; Kasbekar, Monica; Young, Ryan M; Shaffer, Arthur L; Hodson, Daniel J; Xiao, Wenming; Yu, Xin; Yang, Yandan; Zhao, Hong; Xu, Weihong; Liu, Xuelu; Zhou, Bin; Du, Wei; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Connors, Joseph M; Campo, Elias; Lopez-Guillermo, Armando; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa M; Tay Kuang Wei, Kevin; Zelenetz, Andrew D; Leonard, John P; Bartlett, Nancy L; Tran, Bao; Shetty, Jyoti; Zhao, Yongmei; Soppet, Dan R; Pittaluga, Stefania; Wilson, Wyndham H; Staudt, Louis M

    2018-04-12

    Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88 L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).

  1. Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Devesh Kumawat

    2018-01-01

    Full Text Available A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

  2. The Influence of Facility and Service Quality towards Customer Satisfaction and its Impact on Customer Loyalty in Borobudur Hotel in Jakarta

    Directory of Open Access Journals (Sweden)

    Rianto Nurtjahjo

    2017-05-01

    Full Text Available Hotel developments currently grow very rapidly. The emergence of new hotels increases the competition in the hospitality industry. This research aimed to determine the influence of the facilities, the quality of service to customer satisfaction and its impact on customer loyalty in Borobudur Hotel in Jakarta. Data collection was done by distributing questionnaires directly to 360 customers in Borobudur Hotel in Jakarta. The analysis technique used path analysis. The results of this research indicate that the variables of facilities, service quality and customer satisfaction significantly affect customer loyalty variables simultaneously or partially. In addition, facilities and quality of service variable have a significant effect on customer satisfaction variables.

  3. Factors Affecting Quality of Laboratory Services in Public and Private Health Facilities in Addis Ababa, Ethiopia

    OpenAIRE

    Mesfin, Eyob Abera; Taye, Binyam; Belay, Getachew; Ashenafi, Aytenew; Girma, Veronica

    2017-01-01

    Background Quality laboratory service is an essential component of health care system but in Sub-Saharan Africa such as Ethiopia, laboratories quality system remains weak due to several factors and it needs more attention to strengthen its capacity and quality system. Methodology A cross sectional study was conducted using a questionnaire to assess factors affecting the quality of laboratory service at private and public health institutions in Addis Ababa. Results A total of 213 laboratory pr...

  4. Altered B cell homeostasis and Toll-like receptor 9-driven response in patients affected by autoimmune polyglandular syndrome Type 1: Altered B cell phenotype and dysregulation of the B cell function in APECED patients.

    Science.gov (United States)

    Perri, Valentina; Gianchecchi, Elena; Scarpa, Riccardo; Valenzise, Mariella; Rosado, Maria Manuela; Giorda, Ezio; Crinò, Antonino; Cappa, Marco; Barollo, Susi; Garelli, Silvia; Betterle, Corrado; Fierabracci, Alessandra

    2017-02-01

    APECED is a T-cell mediated disease with increased frequencies of CD8+ effector and reduction of FoxP3+ T regulatory cells. Antibodies against affected organs and neutralizing to cytokines are found in the peripheral blood. The contribution of B cells to multiorgan autoimmunity in Aire-/- mice was reported opening perspectives on the utility of anti-B cell therapy. We aimed to analyse the B cell phenotype of APECED patients compared to age-matched controls. FACS analysis was conducted on PBMC in basal conditions and following CpG stimulation. Total B and switched memory (SM) B cells were reduced while IgM memory were increased in patients. In those having more than 15 years from the first clinical manifestation the defect included also mature and transitional B cells; total memory B cells were increased, while SM were unaffected. In patients with shorter disease duration, total B cells were unaltered while SM and IgM memory behaved as in the total group. A defective B cell proliferation was detected after 4day-stimulation. In conclusion APECED patients show, in addition to a significant alteration of the B cell phenotype, a dysregulation of the B cell function involving peripheral innate immune mechanisms particularly those with longer disease duration. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. [Bone marrow involvement in primary mediastinal B-cell lymphoma].

    Science.gov (United States)

    Magomedova, A U; Fastova, E A; Kovrigina, A M; Obukhova, T N; Skidan, N I; Mangasarova, Ya K; Vorobyev, A I; Kravchenko, S K

    Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct type of large B-cell lymphoma. In this type of the disease, the neoplastic process is located in the anterior and superior mediastinum, frequently with compression of the superior vena cava and with tumor invasion into the adjacent organs and tissues: the pericardium, lung, pleura, etc. Despite the fact that in PMBCL progression, there may be involvement of extranodal organs, such as the kidney, adrenal glands, liver, and central nervous system, bone marrow (BM) injury is generally absent. Since BM injury in patients with diffuse large B-cell lymphoma is an independent poor prognostic indicator, there is reason to believe that BM involvement in PMBCL affects the prognosis. These cases may need intensified induction therapy followed by autologous hematopoietic stem cell transplantation; and BM injury should be monitored during the therapy. The paper gives reports of clinical cases of bone marrow involvement in 2 PMBCL patients treated at the National Research Center for Hematology, Ministry of Health of the Russian Federation.

  6. The acquisition of cytokine responsiveness by murine B cells

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1994-01-01

    The mechanism whereby small resting (high buoyant density) murine B cells are induced to express interleukin-2 receptors (IL-2R) and to respond to IL-2 was addressed by staining with anti-IL-2R alpha and -IL-2R beta monoclonal antibodies (mAb), and using receptor-specific cDNA probes. Resting B...... cells expressed undetectable levels of both IL-2R alpha and beta chains on their surface and did not respond to IL-2, even at supra-physiological concentrations. Sepharose-coupled, but not streptavidin-cross-linked, plastic-adsorbed or soluble, anti-mu up-regulated the expression of IL-2R alpha and beta...... chains and mRNA to levels comparable to those seen in activated T cells. Anti-mu-stimulated B cells responded to IL-2 by incorporation of [3H]thymidine and high rate immunoglobulin (Ig) secretion. Both IL-5 (at optimal concentration) and suboptimal lipopolysaccharide (LPS; 20 ng/ml) induced surface...

  7. Quantitative regulation of B cell division destiny by signal strength.

    Science.gov (United States)

    Turner, Marian L; Hawkins, Edwin D; Hodgkin, Philip D

    2008-07-01

    Differentiation to Ab secreting and isotype-switched effector cells is tightly linked to cell division and therefore the degree of proliferation strongly influences the nature of the immune response. The maximum number of divisions reached, termed the population division destiny, is stochastically distributed in the population and is an important parameter in the quantitative outcome of lymphocyte responses. In this study, we further assessed the variables that regulate B cell division destiny in vitro in response to T cell- and TLR-dependent stimuli. Both the concentration and duration of stimulation were able to regulate the average maximum number of divisions undergone for each stimulus. Notably, a maximum division destiny was reached during provision of repeated saturating stimulation, revealing that an intrinsic limit to proliferation exists even under these conditions. This limit was linked directly to division number rather than time of exposure to stimulation and operated independently of the survival regulation of the cells. These results demonstrate that a B cell population's division destiny is regulable by the stimulatory conditions up to an inherent maximum value. Division destiny is a crucial parameter in regulating the extent of B cell responses and thereby also the nature of the immune response mounted.

  8. Large anaplastic spinal B-cell lymphoma in a cat.

    Science.gov (United States)

    Flatland, Bente; Fry, Michael M; Newman, Shelley J; Moore, Peter F; Smith, Joanne R; Thomas, William B; Casimir, Roslyn H

    2008-12-01

    A 5-year-old female spayed domestic shorthair cat was presented for evaluation of tetraparesis. The neurologic lesion was localized to the cervical spinal segment (C1-C6). A left axillary mass was identified, and the results of fine needle aspiration cytology indicated malignant round cell neoplasia of possible histiocytic origin. The cells were large, had marked anisocytosis and anisokaryosis, occasional bi- and multinucleation, and cytoplasmic vacuolation. Euthanasia was performed due to the poor prognosis associated with severe, progressive neurologic signs and a malignant neoplasm. Postmortem examination revealed spinal cord compression and an extradural mass at the C1-C2 spinal segment, with neoplastic cells in the adjacent vertebral bodies, surrounding skeletal muscle, left axillary lymph node, and bone marrow from the right femur. The initial histologic diagnosis was anaplastic sarcoma, but immunohistochemical results indicated the cells were CD20+ and CD45R+ and CD3-, compatible with a diagnosis of B-cell lymphoma. CD79a staining was nonspecific and uninterpretable. Weak to moderate CD18 positivity and E-cadherin positivity were also observed. Clonality of the B-cell population could not be demonstrated using PCR testing for antigen receptor gene rearrangement. To the authors' knowledge, this is the first reported case of a feline spinal anaplastic B-cell lymphoma exhibiting bi- and multinucleated cells. The prognostic significance of this cell morphology and immunophenotype is unknown.

  9. Lenalidomide in Diffuse Large B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Annalisa Chiappella

    2012-01-01

    Full Text Available Diffuse Large B-cell Lymphomas (DLBCL are the most frequent Non-Hodgkin Lymphomas (NHL. The addition of Rituximab to the standard chemotherapy CHOP improved the outcome in this patients, but so far 40% of patients experienced relapse or progressive disease. Lenalidomide, an immunomodulatory agent, had direct tumoricidal and antiangiogenetic actions on tumor cells and was able to modulate tumor-cell microenvironment, with the restoration of impaired T-cell activity and the formation of immuno-synapsis. Based on these actions, lenalidomide represented an active drug on aggressive relapsed NHL. In this review, the most relevant clinical trials for the use of lenalidomide in DLBCL were reported. Monotherapy with lenalidomide showed an activity in term of overall response rate, with acceptable hematological and extrahematological toxicities in relapsed/refractory aggressive NHL. The role of lenalidomide as salvage therapy in both cell of origin patterns in DLBCL (germinal center B-cell/activated B-cell was reported in preliminary data. Preliminary data regarding the role of lenalidomide in addition to chemoimmunotherapy (R-CHOP in first line clinical trials were discussed; data of safety, feasibility and efficacy were promising.

  10. CD3-positive B cells: a storage-dependent phenomenon.

    Directory of Open Access Journals (Sweden)

    Angela Nagel

    Full Text Available The majority of clinical studies requires extensive management of human specimen including e.g. overnight shipping of blood samples in order to convey the samples in a central laboratory or to simultaneously analyze large numbers of patients. Storage of blood samples for periods of time before in vitro/ex vivo testing is known to influence the antigen expression on the surface of lymphocytes. In this context, the present results show for the first time that the T cell antigen CD3 can be substantially detected on the surface of human B cells after ex vivo storage and that the degree of this phenomenon critically depends on temperature and duration after blood withdrawal. The appearance of CD3 on the B cell surface seems to be a result of contact-dependent antigen exchange between T and B lymphocytes and is not attributed to endogenous production by B cells. Since cellular subsets are often classified by phenotypic analyses, our results indicate that ex vivo cellular classification in peripheral blood might result in misleading interpretations. Therefore, in order to obtain results reflecting the in vivo situation, it is suggested to minimize times of ex vivo blood storage after isolation of PBMC. Moreover, to enable reproducibility of results between different research groups and multicenter studies, we would emphasize the necessity to specify and standardize the storage conditions, which might be the basis of particular findings.

  11. The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

    Science.gov (United States)

    van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

    2017-03-01

    The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

  12. Clients’ satisfaction with quality of childbirth services: A comparative study between public and private facilities in Limuru Sub-County, Kiambu, Kenya

    Science.gov (United States)

    2018-01-01

    Background This study intended to compare the clients’ satisfaction with the quality of childbirth services in a private and public facility amongst mothers who have delivered within the last twenty four to seventy hours. Methods This was a cross-sectional comparative research design with both quantitative and qualitative data collection and analysis methods. Data were collected through a focused group discussion guide and structured questionnaire collecting information on clients’ satisfaction with quality of childbirth services. The study was conducted amongst women of reproductive age (WRA) between 15–49 years in Tigoni District hospital (public hospital) and Limuru Nursing home (private hospital). For quantitative data we conducted descriptive analysis and Mann-Whitney test using SPSS version 20.0 while qualitative data was manually analyzed manually using thematic analysis. Results A higher proportion of clients from private facility 98.1% were attended within 0–30 minutes of arrival to the facility as compared to 87% from public facility. The overall mean score showed that the respondents in public facility gave to satisfaction with the services was 4.46 out of a maximum of 5.00 score while private facility gave 4.60. The level of satisfaction amongst respondents in the public facility on pain relief after delivery was statistically significantly higher than the respondents in private facilities (U = 8132.50, ppublic facility on functional equipment was statistically significantly higher than the respondents in private facilities (U = 9206.50, p = 0.001). Moreover, level of satisfaction with the way staff responded to questions and concerns during labour and delivery was statistically significantly higher than the respondents in private facilities (U = 9964.50, p = 0.022). Conclusion In overall, majority of clients from both public and private facilities expressed satisfaction with quality of services from admission till discharge in both public and

  13. Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

    Science.gov (United States)

    2018-03-12

    ALK-Positive Large B-Cell Lymphoma; Atypical Burkitt/Burkitt-Like Lymphoma; Burkitt-Like Lymphoma With 11q Aberration; Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; EBV-Positive Mucocutaneous Ulcer; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Human Herpesvirus 8-Positive Neoplastic Cells Present; Intravascular Large B-Cell Lymphoma; Large B-Cell Lymphoma With IRF4 Rearrangement; Plasmablastic Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma; Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Primary Effusion Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Lymphomatoid Granulomatosis; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Small Intestinal High Grade B-Cell Lymphoma, Not Otherwise Specified; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  14. R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    2018-03-27

    CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

  15. a System Dynamics Model to Study the Importance of Infrastructure Facilities on Quality of Primary Education System in Developing Countries

    Science.gov (United States)

    Pedamallu, Chandra Sekhar; Ozdamar, Linet; Weber, Gerhard-Wilhelm; Kropat, Erik

    2010-06-01

    The system dynamics approach is a holistic way of solving problems in real-time scenarios. This is a powerful methodology and computer simulation modeling technique for framing, analyzing, and discussing complex issues and problems. System dynamics modeling and simulation is often the background of a systemic thinking approach and has become a management and organizational development paradigm. This paper proposes a system dynamics approach for study the importance of infrastructure facilities on quality of primary education system in developing nations. The model is proposed to be built using the Cross Impact Analysis (CIA) method of relating entities and attributes relevant to the primary education system in any given community. We offer a survey to build the cross-impact correlation matrix and, hence, to better understand the primary education system and importance of infrastructural facilities on quality of primary education. The resulting model enables us to predict the effects of infrastructural facilities on the access of primary education by the community. This may support policy makers to take more effective actions in campaigns.

  16. Racial differences in B cell receptor signaling pathway activation.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Mathi, Kavita; Pos, Zoltan; Wang, Ena; Hawtin, Rachael E; Marincola, Francesco M; Cesano, Alessandra

    2012-06-06

    Single-cell network profiling (SCNP) is a multi-parametric flow cytometry-based approach that simultaneously measures basal and modulated intracellular signaling activity in multiple cell subpopulations. Previously, SCNP analysis of a broad panel of immune signaling pathways in cell subsets within PBMCs from 60 healthy donors identified a race-associated difference in B cell anti-IgD-induced PI3K pathway activity. The present study extended this analysis to a broader range of signaling pathway components downstream of the B cell receptor (BCR) in European Americans and African Americans using a subset of donors from the previously analyzed cohort of 60 healthy donors. Seven BCR signaling nodes (a node is defined as a paired modulator and intracellular readout) were measured at multiple time points by SCNP in PBMCs from 10 healthy donors [5 African Americans (36-51 yrs), 5 European Americans (36-56 yrs), all males]. Analysis of BCR signaling activity in European American and African American PBMC samples revealed that, compared to the European American donors, B cells from African Americans had lower anti-IgD induced phosphorylation of multiple BCR pathway components, including the membrane proximal proteins Syk and SFK as well as proteins in the PI3K pathway (S6 and Akt), the MAPK pathways (Erk and p38), and the NF-κB pathway (NF-κB). In addition to differences in the magnitude of anti-IgD-induced pathway activation, racial differences in BCR signaling kinetic profiles were observed. Further, the frequency of IgD+ B cells differed by race and strongly correlated with BCR pathway activation. Thus, the race-related difference in BCR pathway activation appears to be attributable at least in part to a race-associated difference in IgD+ B cell frequencies. SCNP analysis enabled the identification of statistically significant race-associated differences in BCR pathway activation within PBMC samples from healthy donors. Understanding race-associated contrasts in immune

  17. Racial differences in B cell receptor signaling pathway activation

    Directory of Open Access Journals (Sweden)

    Longo Diane M

    2012-06-01

    Full Text Available Abstract Background Single-cell network profiling (SCNP is a multi-parametric flow cytometry-based approach that simultaneously measures basal and modulated intracellular signaling activity in multiple cell subpopulations. Previously, SCNP analysis of a broad panel of immune signaling pathways in cell subsets within PBMCs from 60 healthy donors identified a race-associated difference in B cell anti-IgD-induced PI3K pathway activity. Methods The present study extended this analysis to a broader range of signaling pathway components downstream of the B cell receptor (BCR in European Americans and African Americans using a subset of donors from the previously analyzed cohort of 60 healthy donors. Seven BCR signaling nodes (a node is defined as a paired modulator and intracellular readout were measured at multiple time points by SCNP in PBMCs from 10 healthy donors [5 African Americans (36-51 yrs, 5 European Americans (36-56 yrs, all males]. Results Analysis of BCR signaling activity in European American and African American PBMC samples revealed that, compared to the European American donors, B cells from African Americans had lower anti-IgD induced phosphorylation of multiple BCR pathway components, including the membrane proximal proteins Syk and SFK as well as proteins in the PI3K pathway (S6 and Akt, the MAPK pathways (Erk and p38, and the NF-κB pathway (NF-κB. In addition to differences in the magnitude of anti-IgD-induced pathway activation, racial differences in BCR signaling kinetic profiles were observed. Further, the frequency of IgD+ B cells differed by race and strongly correlated with BCR pathway activation. Thus, the race-related difference in BCR pathway activation appears to be attributable at least in part to a race-associated difference in IgD+ B cell frequencies. Conclusions SCNP analysis enabled the identification of statistically significant race-associated differences in BCR pathway activation within PBMC samples from

  18. Model for deployment of a Quality Assurance System in the nuclear fuel cycle facilities using Project Management techniques

    International Nuclear Information System (INIS)

    Lage, Ricardo F.; Ribeiro, Saulo F.Q.

    2015-01-01

    The Nuclear Safety is the main goal in any nuclear facility. In this sense the Norm CNEN-NN-1.16 classifies the quality assurance issue as a management system to be deployed and implemented by the organization to achieving security goals. Quality Assurance is a set of systematic and planned actions necessary to provide adequate confidence ensuring that a structure, system, component or installation will work satisfactorily in s. Hence, the Quality Assurance System (QAS) is a complete and comprehensive methodology, going far beyond a management plan quality from the perspective of project management. The fundamental of QAS requirements is all activities that influence the quality, involving organizational, human resources, procurement, nuclear safety, projects, procedures and communication. Coordination of all these elements requires a great effort by the team responsible because it usually involves different areas and different levels of hierarchy within the organization. The objectives and desired benefits should be well set for everyone to understand what it means to be achieved and how to achieve. The support of senior management is critical at this stage, providing guidelines and resources necessary to get the job elapse clearly and efficiently, on time, cost and certain scope. The methodology of project management processes can be applied to facilitate and expedite the implementation of this system. Many of the principles of the QAS are correlated with knowledge areas of project management. The proposed model for implementation of a QAS in the nuclear fuel cycle facilities considered the best project management practices according to the Project Management Book of Knowledge (PMBOK - 5th edition) of the Project Management Institute (PMI). This knowledge is considered very good practices around the world. Since the model was defined, the deployment process becomes more practical and efficient, providing reduction in deployment time, better management of human

  19. Quality of care and its determinants in longer term mental health facilities across Europe; a cross-sectional analysis.

    Science.gov (United States)

    Killaspy, Helen; Cardoso, Graça; White, Sarah; Wright, Christine; Caldas de Almeida, José Miguel; Turton, Penny; Taylor, Tatiana L; Schützwohl, Matthias; Schuster, Mirjam; Cervilla, Jorge A; Brangier, Paulette; Raboch, Jiri; Kalisova, Lucie; Onchev, Georgi; Alexiev, Spiridon; Mezzina, Roberto; Ridente, Pina; Wiersma, Durk; Visser, Ellen; Kiejna, Andrzej; Adamowski, Tomasz; Ploumpidis, Dimitris; Gonidakis, Fragiskos; King, Michael

    2016-02-11

    The Quality Indicator for Rehabilitative Care (QuIRC) is an international, standardised quality tool for the evaluation of mental health facilities that provide longer term care. Completed by the service manager, it comprises 145 items that assess seven domains of care: living environment; treatments and interventions; therapeutic environment; self-management and autonomy; social interface; human rights; and recovery based practice. We used the QuIRC to investigate associations between characteristics of longer term mental health facilities across Europe and the quality of care they delivered to service patients. QuIRC assessments were completed for 213 longer term mental health units in ten countries that were at various stages of deinstitutionalisation of their mental health services. Associations between QuIRC domain scores and unit descriptive variables were explored using simple and multiple linear regression that took into account clustering at the unit and country level. We found wide variation in QuIRC domain scores between individual units, but across countries, fewer than a quarter scored below 50 % on any domains. The quality of care was higher in units that were smaller, of mixed sex, that had a defined expected maximum length of stay and in which not all patients were severely disabled. This is the first time longer term mental health units across a number of European countries have been compared using a standardised measure. Further use of the QuIRC will allow greater understanding of the quality of care in these units across Europe and provide an opportunity to monitor pan-European quality standards of care for this vulnerable patient group.

  20. Model for deployment of a Quality Assurance System in the nuclear fuel cycle facilities using Project Management techniques

    Energy Technology Data Exchange (ETDEWEB)

    Lage, Ricardo F.; Ribeiro, Saulo F.Q., E-mail: rflage@gmail.com, E-mail: quintao.saulo@gmail.com [Industrias Nucleares do Brasil (INB), Rio de Janeiro, RJ (Brazil)

    2015-07-01

    The Nuclear Safety is the main goal in any nuclear facility. In this sense the Norm CNEN-NN-1.16 classifies the quality assurance issue as a management system to be deployed and implemented by the organization to achieving security goals. Quality Assurance is a set of systematic and planned actions necessary to provide adequate confidence ensuring that a structure, system, component or installation will work satisfactorily in s. Hence, the Quality Assurance System (QAS) is a complete and comprehensive methodology, going far beyond a management plan quality from the perspective of project management. The fundamental of QAS requirements is all activities that influence the quality, involving organizational, human resources, procurement, nuclear safety, projects, procedures and communication. Coordination of all these elements requires a great effort by the team responsible because it usually involves different areas and different levels of hierarchy within the organization. The objectives and desired benefits should be well set for everyone to understand what it means to be achieved and how to achieve. The support of senior management is critical at this stage, providing guidelines and resources necessary to get the job elapse clearly and efficiently, on time, cost and certain scope. The methodology of project management processes can be applied to facilitate and expedite the implementation of this system. Many of the principles of the QAS are correlated with knowledge areas of project management. The proposed model for implementation of a QAS in the nuclear fuel cycle facilities considered the best project management practices according to the Project Management Book of Knowledge (PMBOK - 5th edition) of the Project Management Institute (PMI). This knowledge is considered very good practices around the world. Since the model was defined, the deployment process becomes more practical and efficient, providing reduction in deployment time, better management of human

  1. Type i CD20 antibodies recruit the B cell receptor for complement-dependent lysis of malignant B cells

    DEFF Research Database (Denmark)

    Engelberts, P. J.; Voorhorst, M.; Schuurman, J.

    2016-01-01

    . We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR- B cell lines. A direct relationship...... between BCR expression and accessory CDC was established by transfecting the BCR into CD20+ cells: OFA-F(ab')2 fragments were able to induce CDC in the CD20+BCR+ cell population, but not in the CD20+BCR- population. Importantly, OFA-F(ab')2 fragments were able to induce CDC ex vivo in malignant B cells...... isolated from patients with mantle cell lymphoma and Waldenström macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab-induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC...

  2. Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription- independent poising of chromatin.

    Science.gov (United States)

    Treiber, Thomas; Mandel, Elizabeth M; Pott, Sebastian; Györy, Ildiko; Firner, Sonja; Liu, Edison T; Grosschedl, Rudolf

    2010-05-28

    The transcription factor early B cell factor-1 (Ebf1) is a key determinant of B lineage specification and differentiation. To gain insight into the molecular basis of Ebf1 function in early-stage B cells, we combined a genome-wide ChIP sequencing analysis with gain- and loss-of-function transcriptome analyses. Among 565 genes that are occupied and transcriptionally regulated by Ebf1, we identified large sets involved in (pre)-B cell receptor and Akt signaling, cell adhesion, and migration. Interestingly, a third of previously described Pax5 targets was found to be occupied by Ebf1. In addition to Ebf1-activated and -repressed genes, we identified targets at which Ebf1 induces chromatin changes that poise the genes for expression at subsequent stages of differentiation. Poised chromatin states on specific targets could also be established by Ebf1 expression in T cells but not in NIH 3T3 cells, suggesting that Ebf1 acts as a "pioneer" factor in a hematopoietic chromatin context. Copyright 2010 Elsevier Inc. All rights reserved.

  3. The Desirable Scale", impact of scale on group mix and social quality in assisted living facilities.

    NARCIS (Netherlands)

    Dort Spierings

    2012-01-01

    In order to be able to age in place, Dutch elderly are being housed in Assisted Living Facilities (ALFs) for over 25 years. Here they can live independently and rely on care and services. The physical scale of ALFs ranges from 30 up to 300 residents. This paper presents the findings of a multiple

  4. Producing National Ignition Facility (NIF)-quality beams on the Nova and Beamlet lasers

    International Nuclear Information System (INIS)

    Widmayer, C.C.; Auerbach, J.M.; Ehrlich, R.B.

    1996-08-01

    The Nova and Beamlet lasers were used to simulate the beam propagation conditions that will be encountered during the National Ignition Facility operation. Perturbation theory predicts that there is a 5mm scale length propagation mode that experiences large nonlinear power growth. This mode was observed in the tests. Further tests have confirmed that this mode can be suppressed with improved spatial filtering

  5. Characterization of Regulatory B Cells in Graves' Disease and Hashimoto's Thyroiditis

    DEFF Research Database (Denmark)

    Kristensen, Birte; Hegedüs, Laszlo; Lundy, Steven K

    2015-01-01

    A hallmark of regulatory B cells is IL-10 production, hence their designation as IL-10+ B cells. Little is known about the ability of self-antigens to induce IL-10+ B cells in Graves' disease (GD), Hashimoto's thyroiditis (HT), or other autoimmune disease. Here we pulsed purified B cells from 12 HT...... patients, 12 GD patients, and 12 healthy donors with the thyroid self-antigen, thyroglobulin (TG) and added the B cells back to the remaining peripheral blood mononuclear cells (PBMCs). This procedure induced IL-10+ B-cell differentiation in GD. A similar tendency was observed in healthy donors......, but not in cells from patients with HT. In GD, B cells primed with TG induced IL-10-producing CD4+ T cells. To assess the maximal frequency of inducible IL-10+ B cells in the three donor groups PBMCs were stimulated with PMA/ionomycin. The resulting IL-10+ B-cell frequency was similar in the three groups...

  6. Comparison of Perceived and Technical Healthcare Quality in Primary Health Facilities: Implications for a Sustainable National Health Insurance Scheme in Ghana.

    Science.gov (United States)

    Alhassan, Robert Kaba; Duku, Stephen Opoku; Janssens, Wendy; Nketiah-Amponsah, Edward; Spieker, Nicole; van Ostenberg, Paul; Arhinful, Daniel Kojo; Pradhan, Menno; Rinke de Wit, Tobias F

    2015-01-01

    Quality care in health facilities is critical for a sustainable health insurance system because of its influence on clients' decisions to participate in health insurance and utilize health services. Exploration of the different dimensions of healthcare quality and their associations will help determine more effective quality improvement interventions and health insurance sustainability strategies, especially in resource constrained countries in Africa where universal access to good quality care remains a challenge. To examine the differences in perceptions of clients and health staff on quality healthcare and determine if these perceptions are associated with technical quality proxies in health facilities. Implications of the findings for a sustainable National Health Insurance Scheme (NHIS) in Ghana are also discussed. This is a cross-sectional study in two southern regions in Ghana involving 64 primary health facilities: 1,903 households and 324 health staff. Data collection lasted from March to June, 2012. A Wilcoxon-Mann-Whitney test was performed to determine differences in client and health staff perceptions of quality healthcare. Spearman's rank correlation test was used to ascertain associations between perceived and technical quality care proxies in health facilities, and ordered logistic regression employed to predict the determinants of client and staff-perceived quality healthcare. Negative association was found between technical quality and client-perceived quality care (coef. = -0.0991, pquality proxies, suggesting some level of unbalanced commitment to quality improvement and potential information asymmetry between clients and service providers. Overall, the findings suggest that increased efforts towards technical quality care alone will not necessarily translate into better client-perceived quality care and willingness to utilize health services in NHIS-accredited health facilities. There is the need to intensify client education and balanced

  7. Essential role of EBF1 in the generation and function of distinct mature B cell types.

    Science.gov (United States)

    Vilagos, Bojan; Hoffmann, Mareike; Souabni, Abdallah; Sun, Qiong; Werner, Barbara; Medvedovic, Jasna; Bilic, Ivan; Minnich, Martina; Axelsson, Elin; Jaritz, Markus; Busslinger, Meinrad

    2012-04-09

    The transcription factor EBF1 is essential for lineage specification in early B cell development. In this study, we demonstrate by conditional mutagenesis that EBF1 is required for B cell commitment, pro-B cell development, and subsequent transition to the pre-B cell stage. Later in B cell development, EBF1 was essential for the generation and maintenance of several mature B cell types. Marginal zone and B-1 B cells were lost, whereas follicular (FO) and germinal center (GC) B cells were reduced in the absence of EBF1. Activation of the B cell receptor resulted in impaired intracellular signaling, proliferation and survival of EBF1-deficient FO B cells. Immune responses were severely reduced upon Ebf1 inactivation, as GCs were formed but not maintained. ChIP- and RNA-sequencing of FO B cells identified EBF1-activated genes that encode receptors, signal transducers, and transcriptional regulators implicated in B cell signaling. Notably, ectopic expression of EBF1 efficiently induced the development of B-1 cells at the expense of conventional B cells. These gain- and loss-of-function analyses uncovered novel important functions of EBF1 in controlling B cell immunity.

  8. Ia-restricted B-B cell interaction. I. The MHC haplotype of bone marrow cells present during B cell ontogeny dictates the self-recognition specificity of B cells in the polyclonal B cell activation by a B cell differentiation factor, B151-TRF2

    International Nuclear Information System (INIS)

    Ono, S.; Takahama, Y.; Hamaoka, T.

    1987-01-01

    We have demonstrated that B cell recognition of Ia molecules is involved in polyclonal B cell differentiation by B151-TRF2. The present study was undertaken to examine the Ia recognition specificity of B151-TRF2-responsive B cells in fully major histocompatibility complex (MHC)-allogeneic P1----P2, semiallogeneic P1----(P1 x P2)F1, and double donor (P1 + P2)----(P1 x P2)F1 and (P1 + P2)----P1 radiation bone marrow chimeras. The B cells from both P1----P2 and P1----(P1 x P2)F1 chimeras could give rise to in vitro immunoglobulin M-producing cells upon stimulation with B151-TRF2 comparable in magnitude to that of normal P1 B cells, and their responses were inhibited by anti-I-AP1 but not by anti-I-AP2 monoclonal antibody even in the presence of mitomycin C-treated T cell-depleted P2 spleen cells as auxiliary cells. In contrast, the B151-TRF2 responses of P1 B cells isolated from both (P1 + P2)----(P1 x P2)F1 and (P1 + P2)----P1 double bone marrow chimeras became sensitive to the inhibition of not only anti-I-AP1 but also anti-I-AP2 monoclonal antibody only when the culture was conducted in the presence of P2 auxiliary cells, demonstrating that they adaptively differentiate to recognize as self-structures allogeneic as well as syngeneic Ia molecules. Moreover, the experiments utilizing B cells from H-2-congenic mice and B cell hybridoma clones as auxiliary cells revealed that B151-TRF2-responsive B cells recognize Ia molecules expressed on B cells. Taken together, these results demonstrate that B151-TRF2-responsive B cells recognize Ia molecules expressed by B cells as self-structures and that their self-recognition specificity is dictated by the MHC haplotype of bone marrow cells present during the B cell ontogeny but not by the MHC haplotype of a radiation-resistant host environment

  9. Crew Factors in Flight Operations XII: A Survey of Sleep Quantity and Quality in On-Board Crew Rest Facilities

    Science.gov (United States)

    Rosekind, Mark R.; Gregory, Kevin B.; Co, Elizabeth L.; Miller, Donna L.; Dinges, David F.

    2000-01-01

    Many aircraft operated on long-haul commercial airline flights are equipped with on-board crew rest facilities, or bunks, to allow crewmembers to rest during the flight. The primary objectives of this study were to gather data on how the bunks were used, the quantity and quality of sleep obtained by flight crewmembers in the facilities, and the factors that affected their sleep. A retrospective survey comprising 54 questions of varied format addressed demographics, home sleep habits, and bunk sleep habits. Crewmembers from three airlines with long-haul fleets carrying augmented crews consisting of B747-100/200, B747-400, and MD-11 aircraft equipped with bunks returned a total of 1404 completed surveys (a 37% response rate). Crewmembers from the three carriers were comparable demographically, although one carrier had older, more experienced flight crewmembers. Each group, on average, rated themselves as "good" or "very good" sleepers at home, and all groups obtained about the same average amount of sleep each night. Most were able to sleep in the bunks, and about two thirds indicated that these rest opportunities benefited their subsequent flight deck alertness and performance. Comfort, environment, and physiology (e.g., being ready for sleep) were identified as factors that most promoted sleep. Factors cited as interfering with sleep included random noise, thoughts, heat, and the need to use the bathroom. These factors, in turn, suggest potential improvements to bunk facilities and their use. Ratings of the three aircraft types suggested differences among facilities. Bunks in the MD-11 were rated significantly better than either of the B747 types, and the B747-400 bunks received better ratings than did the older, B747-100/200 facilities.

  10. Baboon envelope pseudotyped lentiviral vectors efficiently transduce human B cells and allow active factor IX B cell secretion in vivo in NOD/SCIDγc-/-mice.

    Science.gov (United States)

    Levy, C; Fusil, F; Amirache, F; Costa, C; Girard-Gagnepain, A; Negre, D; Bernadin, O; Garaulet, G; Rodriguez, A; Nair, N; Vandendriessche, T; Chuah, M; Cosset, F-L; Verhoeyen, E

    2016-12-01

    Essentials B cells are attractive targets for gene therapy and particularly interesting for immunotherapy. A baboon envelope pseudotyped lentiviral vector (BaEV-LV) was tested for B-cell transduction. BaEV-LVs transduced mature and plasma human B cells with very high efficacy. BaEV-LVs allowed secretion of functional factor IX from B cells at therapeutic levels in vivo. Background B cells are attractive targets for gene therapy for diseases associated with B-cell dysfunction and particularly interesting for immunotherapy. Moreover, B cells are potent protein-secreting cells and can be tolerogenic antigen-presenting cells. Objective Evaluation of human B cells for secretion of clotting factors such as factor IX (FIX) as a possible treatment for hemophilia. Methods We tested here for the first time our newly developed baboon envelope (BaEV) pseudotyped lentiviral vectors (LVs) for human (h) B-cell transduction following their adaptive transfer into an NOD/SCIDγc -/- (NSG) mouse. Results Upon B-cell receptor stimulation, BaEV-LVs transduced up to 80% of hB cells, whereas vesicular stomatitis virus G protein VSV-G-LV only reached 5%. Remarkably, BaEVTR-LVs permitted efficient transduction of 20% of resting naive and 40% of resting memory B cells. Importantly, BaEV-LVs reached up to 100% transduction of human plasmocytes ex vivo. Adoptive transfer of BaEV-LV-transduced mature B cells into NOD/SCID/γc -/- (NSG) [non-obese diabetic (NOD), severe combined immuno-deficiency (SCID)] mice allowed differentiation into plasmablasts and plasma B cells, confirming a sustained high-level gene marking in vivo. As proof of principle, we assessed BaEV-LV for transfer of human factor IX (hFIX) into B cells. BaEV-LVs encoding FIX efficiently transduced hB cells and their transfer into NSG mice demonstrated for the first time secretion of functional hFIX from hB cells at therapeutic levels in vivo. Conclusions The BaEV-LVs might represent a valuable tool for therapeutic protein

  11. Factors Affecting Quality of Laboratory Services in Public and Private Health Facilities in Addis Ababa, Ethiopia

    Science.gov (United States)

    Taye, Binyam; Belay, Getachew; Ashenafi, Aytenew; Girma, Veronica

    2017-01-01

    Background Quality laboratory service is an essential component of health care system but in Sub-Saharan Africa such as Ethiopia, laboratories quality system remains weak due to several factors and it needs more attention to strengthen its capacity and quality system. Methodology A cross sectional study was conducted using a questionnaire to assess factors affecting the quality of laboratory service at private and public health institutions in Addis Ababa. Results A total of 213 laboratory professionals participated in the study and 131 (61.5%) participants had bachelor degree. Majority, 133 (62.4%), of the professionals did not attend any work related training. Seventy five (35.2%) respondents believed that their laboratories did not provide quality laboratory services and the major reported factors affecting provision of quality services were shortage of resources (64.3%), poor management support (57.3%), poor equipment quality (53.4%), high workload (41.1%), lack of equipment calibration (38.3%) and lack of knowledge (23.3%). Moreover logistic regression analysis showed that provision of quality laboratory service was significantly associated with result verification (AOR=9.21, 95% CI=2.26, 37.48), internal quality control (AOR= 6.11, 95% CI=2.11, 17.70), turnaround time (AOR=5.11, 95% CI=1.94, 13.46), shortage of equipment (AOR=7.76, 95% CI=2.55, 23.66), communication with clinicians (AOR=3.24, 95% CI=1.25, 8.41) and lack of job description (AOR=3.67, 95% CI=1.319, 10.22). Conclusion In conclusion, the major factors that affecting the quality of laboratory service were associated with poor human resource management, poor resources provision, poor management commitment, ineffective communication system and lack of well-established quality management system. PMID:29075171

  12. Factors Affecting Quality of Laboratory Services in Public and Private Health Facilities in Addis Ababa, Ethiopia.

    Science.gov (United States)

    Mesfin, Eyob Abera; Taye, Binyam; Belay, Getachew; Ashenafi, Aytenew; Girma, Veronica

    2017-10-01

    Quality laboratory service is an essential component of health care system but in Sub-Saharan Africa such as Ethiopia, laboratories quality system remains weak due to several factors and it needs more attention to strengthen its capacity and quality system. A cross sectional study was conducted using a questionnaire to assess factors affecting the quality of laboratory service at private and public health institutions in Addis Ababa. A total of 213 laboratory professionals participated in the study and 131 (61.5%) participants had bachelor degree. Majority, 133 (62.4%), of the professionals did not attend any work related training. Seventy five (35.2%) respondents believed that their laboratories did not provide quality laboratory services and the major reported factors affecting provision of quality services were shortage of resources (64.3%), poor management support (57.3%), poor equipment quality (53.4%), high workload (41.1%), lack of equipment calibration (38.3%) and lack of knowledge (23.3%). Moreover logistic regression analysis showed that provision of quality laboratory service was significantly associated with result verification (AOR=9.21, 95% CI=2.26, 37.48), internal quality control (AOR= 6.11, 95% CI=2.11, 17.70), turnaround time (AOR=5.11, 95% CI=1.94, 13.46), shortage of equipment (AOR=7.76, 95% CI=2.55, 23.66), communication with clinicians (AOR=3.24, 95% CI=1.25, 8.41) and lack of job description (AOR=3.67, 95% CI=1.319, 10.22). In conclusion, the major factors that affecting the quality of laboratory service were associated with poor human resource management, poor resources provision, poor management commitment, ineffective communication system and lack of well-established quality management system.

  13. Intrinsic Plasma Cell Differentiation Defects in B Cell Expansion with NF-κB and T Cell Anergy Patient B Cells

    Directory of Open Access Journals (Sweden)

    Swadhinya Arjunaraja

    2017-08-01

    Full Text Available B cell Expansion with NF-κB and T cell Anergy (BENTA disease is a novel B cell lymphoproliferative disorder caused by germline, gain-of-function mutations in the lymphocyte scaffolding protein CARD11, which drives constitutive NF-κB signaling. Despite dramatic polyclonal expansion of naive and immature B cells, BENTA patients also present with signs of primary immunodeficiency, including markedly reduced percentages of class-switched/memory B cells and poor humoral responses to certain vaccines. Using purified naive B cells from our BENTA patient cohort, here we show that BENTA B cells exhibit intrinsic defects in B cell differentiation. Despite a profound in vitro survival advantage relative to normal donor B cells, BENTA patient B cells were severely impaired in their ability to differentiate into short-lived IgDloCD38hi plasmablasts or CD138+ long-lived plasma cells in response to various stimuli. These defects corresponded with diminished IgG antibody production and correlated with poor induction of specific genes required for plasma cell commitment. These findings provide important mechanistic clues that help explain both B cell lymphocytosis and humoral immunodeficiency in BENTA disease.

  14. Determinants of Quality of Work Life among Nurses Working in Hawassa Town Public Health Facilities, South Ethiopia: A Cross-Sectional Study.

    Science.gov (United States)

    Kelbiso, Lolemo; Belay, Admasu; Woldie, Mirkuzie

    2017-01-01

    A high quality of work life (QWL) is a crucial issue for health care facilities to have qualified, dedicated, and inspired employees. Among different specialties in health care settings, nurses have a major share among other health care providers. So, they should experience a better QWL to deliver high-quality holistic care to those who need help. To assess the level of quality of work life and its predictors among nurses working in Hawassa town public health facilities, South Ethiopia. A facility based cross-sectional study was conducted on 253 nurses of two hospitals and nine health centers. The total sample size was allocated to each facility based on the number of nurses in each facility. Data were collected using a structured questionnaire. The interitem consistency of the scale used to measure QWL had Cronbach's alpha value of 0.86. A multinomial logistic regression model was fitted to identify significant predictors of quality of work life using SPSS version 20. The study showed that 67.2% of the nurses were dissatisfied with the quality of their work life. We found that educational status, monthly income, working unit, and work environment were strong predictors of quality of work life among nurses ( p quality of their work life. The findings in this study and studies reported from elsewhere pinpoint that perception of nurses about the quality of their work life can be modified if health care managers are considerate of the key issues surrounding QWL.

  15. Quality control assessment of diagnostic X-ray facilities in Ghana ...

    African Journals Online (AJOL)

    Twenty-three X-ray machines located at 20 different hospitals in Ghana were assessed for quality assurance and control. The radiographic parameters evaluated were tube voltage and current, tube output consistency variation with kilovoltage (kV) and current-time (mAs) factor, exposure time accuracy and beam quality as ...

  16. Quality of Maternity Care at Health Facilities in Eritrea in 2008

    African Journals Online (AJOL)

    Availability of care, infrastructure, continuity of care, access to a referral system, management and process of care, which collectively define quality of Maternity. Care, and has an impact on maternal and perinatal health outcomes. Quality of Maternity Care is known to have an impact on utilization of service. Extraneous.

  17. Applicability of the 5S management method for quality improvement in health-care facilities: a review.

    Science.gov (United States)

    Kanamori, Shogo; Shibanuma, Akira; Jimba, Masamine

    2016-01-01

    The 5S management method (where 5S stands for sort, set in order, shine, standardize, and sustain) was originally implemented by manufacturing enterprises in Japan. It was then introduced to the manufacturing sector in the West and eventually applied to the health sector for organizing and standardizing the workplace. 5S has recently received attention as a potential solution for improving government health-care services in low- and middle-income countries. We conducted a narrative literature review to explore its applicability to health-care facilities globally, with a focus on three aspects: (a) the context of its application, (b) its impacts, and (c) its adoption as part of government initiatives. To identify relevant research articles, we researched public health databases in English, including CINAHL, PubMed, ScienceDirect, and Web of Science. We found 15 of the 114 articles obtained from the search results to be relevant for full-text analysis of the context and impacts of the 5S application. To identify additional information particularly on its adoption as part of government initiatives, we also examined other types of resources including reference books, reports, didactic materials, government documents, and websites. The 15 empirical studies highlighted its application in primary health-care facilities and a wide range of hospital areas in Brazil, India, Jordan, Senegal, Sri Lanka, Tanzania, the UK, and the USA. The review also found that 5S was considered to be the starting point for health-care quality improvement. Ten studies presented its impacts on quality improvements; the changes resulting from the 5S application were classified into the three dimensions of safety, efficiency, and patient-centeredness. Furthermore, 5S was adopted as part of government quality improvement strategies in India, Senegal, Sri Lanka, and Tanzania. 5S could be applied to health-care facilities regardless of locations. It could be not only a tool for health workers and

  18. [Improving experimental teaching facilities and opening up of laboratories in order to raise experimental teaching quality of genetics].

    Science.gov (United States)

    Xiao, Jian-Fu; Wu, Jian-Guo; Shi, Chun-Hai

    2011-12-01

    Advanced teaching facilities and the policy of opening laboratories to students play an important role in raising the quality in the experimental teaching of Genetics. This article introduces the superiority of some advanced instruments and equipment (such as digital microscope mutual laboratory system, flow cytometry, and NIRSystems) in the experimental teaching of genetics, and illustrates with examples the significance of exposing students to experiments in developing their creative consciousness and creative ability. This article also offers some new concepts on the further improvement upon teaching in the laboratory.

  19. Utilizing integrated facility design to improve the quality of a pediatric ambulatory surgery center.

    Science.gov (United States)

    Pelly, Nicole; Zeallear, Brian; Reed, Mark; Martin, Lynn

    2013-07-01

    The aim was to use Integrated Facility Design (IFD) to design a surgery center that enhances the delivery of health care by developing processes that provide highly efficient patient, family, and provider flows while adding value and utilizing costly resources effectively. Integrated Facility Design is an adaptation of the Toyota 3P (Production, Preparation, Process) Program. The goal of IFD is to accelerate development time and lower start-up costs. The use of IFD produced a savings of $30 million in project costs and enabled a completion date 3.5 months ahead of schedule. The designed patient flow processes resulted in dramatic improvements in patient, family, and provider throughput. The use of IFD in the design of a pediatric ambulatory clinic and surgery resulted in significant cost savings and improved clinical efficiency. © 2013 John Wiley & Sons Ltd.

  20. Generation of Recombinant Monoclonal Antibodies from Immunised Mice and Rabbits via Flow Cytometry and Sorting of Antigen-Specific IgG+ Memory B Cells.

    Directory of Open Access Journals (Sweden)

    Dale O Starkie

    Full Text Available Single B cell screening strategies, which avoid both hybridoma fusion and combinatorial display, have emerged as important technologies for efficiently sampling the natural antibody repertoire of immunized animals and humans. Having access to a range of methods to interrogate different B cell subsets provides an attractive option to ensure large and diverse panels of high quality antibody are produced. The generation of multiple antibodies and having the ability to find rare B cell clones producing IgG with unique and desirable characteristics facilitates the identification of fit-for-purpose molecules that can be developed into therapeutic agents or research reagents. Here, we describe a multi-parameter flow cytometry single-cell sorting technique for the generation of antigen-specific recombinant monoclonal antibodies from single IgG+ memory B cells. Both mouse splenocytes and rabbit PBMC from immunised animals were used as a source of B cells. Reagents staining both B cells and other unwanted cell types enabled efficient identification of class-switched IgG+ memory B cells. Concurrent staining with antigen labelled separately with two spectrally-distinct fluorophores enabled antigen-specific B cells to be identified, i.e. those which bind to both antigen conjugates (double-positive. These cells were then typically sorted at one cell per well using FACS directly into a 96-well plate containing reverse transcriptase reaction mix. Following production of cDNA, PCR was performed to amplify cognate heavy and light chain variable region genes and generate transcriptionally-active PCR (TAP fragments. These linear expression cassettes were then used directly in a mammalian cell transfection to generate recombinant antibody for further testing. We were able to successfully generate antigen-specific recombinant antibodies from both the rabbit and mouse IgG+ memory B cell subset within one week. This included the generation of an anti-TNFR2 blocking

  1. Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Juan Pablo Jaworski

    Full Text Available Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig purified from previously infected animals (SHIVIG or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2-3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host's ability to eliminate HIV.

  2. Optimizing Outcomes in Primary Mediastinal B-cell Lymphoma.

    Science.gov (United States)

    Zinzani, Pier Luigi; Broccoli, Alessandro

    2016-12-01

    Primary mediastinal B-cell lymphoma is characterized by a high chance of cure, and cured patients have a long disease-free life-expectancy; however, prognosis is severe in the case of relapsed or refractory disease. The initial use of the most effective chemoimmunotherapy regimen is therefore crucial. Understanding who will benefit from postinduction radiotherapy is also of paramount importance; positron emission tomography may be a reliable guide for physicians in determining which patients will require consolidation. New drugs with mechanisms of action including the most relevant biologic features of the tumor may allow better disease control. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Diffuse Large B-Cell Lymphoma with Calf Muscle Localization

    Directory of Open Access Journals (Sweden)

    Laura Bourdeanu

    2011-01-01

    Full Text Available Although diffuse large B-cell lymphoma (DLBCL usually occurs in the lymph nodes, approximately 30–40% of the time it can have an extranodal site of involvement and it can arise in nearly every body site such as intestine, bone, breast, liver, skin, lung, and central nervous system. Muscle involvement of DLBCL is especially uncommon, comprising 0.5% of extranodal NHL. We report a case of a 72-year-old man with extranodal DLBCL of a unique manifestation in the calf muscle, involving predominantly the gastrocnemius muscle. The patient achieved complete response and remained free of local recurrence or metastasis following diagnosis.

  4. Diffuse large B-cell lymphoma of the oral cavity

    International Nuclear Information System (INIS)

    Carlos Bortoluzzi, Marcelo

    2010-01-01

    The authors report a case of diffuse large B-cell lymphoma (DLBL) of the oral cavity. The patient was a 73-year-old white man who first presented at the Division of Stomatology with a large nodular mass in the hard palate and a nodular lesion in the upper lip, which were diagnosed as DLBL. The patient was treated with eight cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), but the disease recurred 22 months after the end of the therapy. Both primary sites hard palate and upper lip were involved again and the patient was resubmitted to chemotherapy. (author)

  5. Quality Assurance Program Plan for the Waste Sampling and Characterization Facility

    Energy Technology Data Exchange (ETDEWEB)

    Grabbe, R.R.

    1995-03-02

    The objective of this Quality Assurance Plan is to provide quality assurance (QA) guidance, implementation of regulatory QA requirements, and quality control (QC) specifications for analytical service. This document follows the Department of Energy (DOE)-issued Hanford Analytical Services Quality Assurance Plan (HASQAP) and additional federal [10 US Code of Federal Regulations (CFR) 830.120] QA requirements that HASQAP does not cover. This document describes how the laboratory implements QA requirements to meet the federal or state requirements, provides what are the default QC specifications, and/or identifies the procedural information that governs how the laboratory operates. In addition, this document meets the objectives of the Quality Assurance Program provided in the WHC-CM-4-2, Section 2.1. This document also covers QA elements that are required in the Guidelines and Specifications for Preparing Quality Assurance Program Plans (QAPPs), (QAMS-004), and Interim Guidelines and Specifications for Preparing Quality Assurance Product Plans (QAMS-005) from the Environmental Protection Agency (EPA). A QA Index is provided in the Appendix A.

  6. Quality Assurance Program Plan for the Waste Sampling and Characterization Facility

    International Nuclear Information System (INIS)

    Grabbe, R.R.

    1995-01-01

    The objective of this Quality Assurance Plan is to provide quality assurance (QA) guidance, implementation of regulatory QA requirements, and quality control (QC) specifications for analytical service. This document follows the Department of Energy (DOE)-issued Hanford Analytical Services Quality Assurance Plan (HASQAP) and additional federal [10 US Code of Federal Regulations (CFR) 830.120] QA requirements that HASQAP does not cover. This document describes how the laboratory implements QA requirements to meet the federal or state requirements, provides what are the default QC specifications, and/or identifies the procedural information that governs how the laboratory operates. In addition, this document meets the objectives of the Quality Assurance Program provided in the WHC-CM-4-2, Section 2.1. This document also covers QA elements that are required in the Guidelines and Specifications for Preparing Quality Assurance Program Plans (QAPPs), (QAMS-004), and Interim Guidelines and Specifications for Preparing Quality Assurance Product Plans (QAMS-005) from the Environmental Protection Agency (EPA). A QA Index is provided in the Appendix A

  7. Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus.

    Science.gov (United States)

    Gies, Vincent; Schickel, Jean-Nicolas; Jung, Sophie; Joublin, Aurélie; Glauzy, Salomé; Knapp, Anne-Marie; Soley, Anne; Poindron, Vincent; Guffroy, Aurélien; Choi, Jin-Young; Gottenberg, Jacques-Eric; Anolik, Jennifer H; Martin, Thierry; Soulas-Sprauel, Pauline; Meffre, Eric; Korganow, Anne-Sophie

    2018-03-08

    B cells play a central role in systemic lupus erythematosus (SLE) pathophysiology but dysregulated pathways leading to a break in B cell tolerance remain unclear. Since Toll-like receptor 9 (TLR9) favors the elimination of autoreactive B cells in the periphery, we assessed TLR9 function in SLE by analyzing the responses of B cells and plasmacytoid dendritic cells (pDCs) isolated from healthy donors and patients after stimulation with CpG, a TLR9 agonist. We found that SLE B cells from patients without hydroxychloroquine treatment displayed defective in vitro TLR9 responses, as illustrated by the impaired upregulation of B cell activation molecules and the diminished production of various cytokines including antiinflammatory IL-10. In agreement with CD19 controlling TLR9 responses in B cells, decreased expression of the CD19/CD21 complex on SLE B cells was detected as early as the transitional B cell stage. In contrast, TLR7 function was preserved in SLE B cells, whereas pDCs from SLE patients properly responded to TLR9 stimulation, thereby revealing that impaired TLR9 function in SLE was restricted to B cells. We conclude that abnormal CD19 expression and TLR9 tolerogenic function in SLE B cells may contribute to the break of B cell tolerance in these patients.

  8. CD47 limits antibody dependent phagocytosis against non-malignant B cells.

    Science.gov (United States)

    Gallagher, Sandra; Turman, Sean; Lekstrom, Kristen; Wilson, Susan; Herbst, Ronald; Wang, Yue

    2017-05-01

    Recent studies have demonstrated the importance of CD47 in protecting malignant B cells from antibody dependent cellular phagocytosis (ADCP). Combined treatment of anti-CD47 and -CD20 antibodies synergistically augment elimination of tumor B cells in xenograft mouse models. This has led to the development of novel reagents that can potentially enhance killing of malignant B cells in patients. B cell depleting therapy is also a promising treatment for autoimmune patients. In the current study, we aimed to investigate whether or not CD47 protects non-malignant B cells from ADCP. We show that CD47 is expressed on all B cells in mice, with the highest level on plasma cells in bone marrow and spleen. Although its expression is dispensable for B cell development in mice, CD47 on B cells limits antibody mediated phagocytosis. B cell depletion following in vivo anti-CD19 treatment is more efficient in CD47-/- mice than in wild type mice. In vitro, both naïve and activated B cells from CD47-/- mice are more sensitive to ADCP than wild type B cells. Lastly, we show in an ADCP assay that blocking CD47 can enhance anti-CD19 antibody mediated phagocytosis of wild type B cells. These results suggest that in addition to its already demonstrated benefit in cancer, targeting CD47 may be used as an adjunct in combination with B cell depletion antibodies for treatment of autoimmune diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. High sensitivity and specificity of clinical microscopy in rural health facilities in western Kenya under an external quality assurance program.

    Science.gov (United States)

    Wafula, Rebeccah; Sang, Edna; Cheruiyot, Olympia; Aboto, Angeline; Menya, Diana; O'Meara, Wendy Prudhomme

    2014-09-01

    Microscopic diagnosis of malaria is a well-established and inexpensive technique that has the potential to provide accurate diagnosis of malaria infection. However, it requires both training and experience. Although it is considered the gold standard in research settings, the sensitivity and specificity of routine microscopy for clinical care in the primary care setting has been reported to be unacceptably low. We established a monthly external quality assurance program to monitor the performance of clinical microscopy in 17 rural health centers in western Kenya. The average sensitivity over the 12-month period was 96% and the average specificity was 88%. We identified specific contextual factors that contributed to inadequate performance. Maintaining high-quality malaria diagnosis in high-volume, resource-constrained health facilities is possible. © The American Society of Tropical Medicine and Hygiene.

  10. Quality assurance grading guidelines for research and development at DOE facilities

    Energy Technology Data Exchange (ETDEWEB)

    Powell, T.B.; Morris, R.N.

    1993-01-01

    The quality assurance (QA) requirements for the US Department of Energy (DOE) are established in DOE Order 5700.6C. This order is applicable for all DOE departmental elements, management, and maintenance and operating contractors and requires that documented Quality Assurance Programs (QAPs) are prepared at all levels; it has one attachment. The DOE Office of Energy Research (DOE-ER) has issued a standard to ensure implementation of the full intent of this order in the ER community.

  11. Impact of emissions from natural gas production facilities on ambient air quality in the Barnett Shale area: a pilot study.

    Science.gov (United States)

    Zielinska, Barbara; Campbell, Dave; Samburova, Vera

    2014-12-01

    Rapid and extensive development of shale gas resources in the Barnett Shale region of Texas in recent years has created concerns about potential environmental impacts on water and air quality. The purpose of this study was to provide a better understanding of the potential contributions of emissions from gas production operations to population exposure to air toxics in the Barnett Shale region. This goal was approached using a combination of chemical characterization of the volatile organic compound (VOC) emissions from active wells, saturation monitoring for gaseous and particulate pollutants in a residential community located near active gas/oil extraction and processing facilities, source apportionment of VOCs measured in the community using the Chemical Mass Balance (CMB) receptor model, and direct measurements of the pollutant gradient downwind of a gas well with high VOC emissions. Overall, the study results indicate that air quality impacts due to individual gas wells and compressor stations are not likely to be discernible beyond a distance of approximately 100 m in the downwind direction. However, source apportionment results indicate a significant contribution to regional VOCs from gas production sources, particularly for lower-molecular-weight alkanes (air toxics combined with soot to total carbon ratios that were high for an area with little residential or commercial development may be indicative of the impact of increased heavy-duty vehicle traffic related to gas production. Implications: Rapid and extensive development of shale gas resources in recent years has created concerns about potential environmental impacts on water and air quality. This study focused on directly measuring the ambient air pollutant levels occurring at residential properties located near natural gas extraction and processing facilities, and estimating the relative contributions from gas production and motor vehicle emissions to ambient VOC concentrations. Although only a small

  12. Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.

    Science.gov (United States)

    De Silva, Nilushi S; Silva, Kathryn; Anderson, Michael M; Bhagat, Govind; Klein, Ulf

    2016-03-15

    BAFF is critical for the survival and maturation of mature B cells. BAFF, via BAFFR, activates multiple signaling pathways in B cells, including the alternative NF-κB pathway. The transcription factors RELB and NF-κB2 (p100/p52) are the downstream mediators of the alternative pathway; however, the B cell-intrinsic functions of these NF-κB subunits have not been studied in vivo using conditional alleles, either individually or in combination. We in this study report that B cell-specific deletion of relb led to only a slight decrease in the fraction of mature splenic B cells, whereas deletion of nfkb2 caused a marked reduction. This phenotype was further exacerbated upon combined deletion of relb and nfkb2 and most dramatically affected the maintenance of marginal zone B cells. BAFF stimulation, in contrast to CD40 activation, was unable to rescue relb/nfkb2-deleted B cells in vitro. RNA-sequencing analysis of BAFF-stimulated nfkb2-deleted versus normal B cells suggests that the alternative NF-κB pathway, in addition to its critical role in BAFF-mediated cell survival, may control the expression of genes involved in the positioning of B cells within the lymphoid microenvironment and in the establishment of T cell-B cell interactions. Thus, by ablating the downstream transcription factors of the alternative NF-κB pathway specifically in B cells, we identify in this study a critical role for the combined activity of the RELB and NF-κB2 subunits in B cell homeostasis that cannot be compensated for by the canonical NF-κB pathway under physiological conditions. Copyright © 2016 by The American Association of Immunologists, Inc.

  13. Interleukin-35 induces regulatory B cells that suppress autoimmune disease.

    Science.gov (United States)

    Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M; Mahdi, Rashid M; Dolinska, Monika B; Sergeev, Yuri V; Wingfield, Paul T; Kim, Sung-Hye; Egwuagu, Charles E

    2014-06-01

    Interleukin-10 (IL-10)-producing regulatory B (Breg) cells suppress autoimmune disease, and increased numbers of Breg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting CD4(+) T cells to regulatory T (Treg) cells. The mechanisms mediating the induction and development of Breg cells remain unclear. Here we show that IL-35 induces Breg cells and promotes their conversion to a Breg subset that produces IL-35 as well as IL-10. Treatment of mice with IL-35 conferred protection from experimental autoimmune uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL-35 signaling (IL-12Rβ2 KO mice) produced less Breg cells endogenously or after treatment with IL-35 and developed severe uveitis. Adoptive transfer of Breg cells induced by recombinant IL-35 suppressed EAU when transferred to mice with established disease, inhibiting pathogenic T helper type 17 (TH17) and TH1 cells while promoting Treg cell expansion. In B cells, IL-35 activates STAT1 and STAT3 through the IL-35 receptor comprising the IL-12Rβ2 and IL-27Rα subunits. As IL-35 also induced the conversion of human B cells into Breg cells, these findings suggest that IL-35 may be used to induce autologous Breg and IL-35(+) Breg cells and treat autoimmune and inflammatory disease.

  14. Engaging the lysosomal compartment to combat B cell malignancies

    DEFF Research Database (Denmark)

    Gronbaek, K.; Jaattela, M.

    2009-01-01

    The combination of rituximab, a type I anti-CD20 mAb, with conventional chemotherapy has significantly improved the outcome of patients with B cell malignancies. Regardless of this success, many patients still relapse with therapy-resistant disease, highlighting the need for the development of mAbs...... with higher capacity to induce programmed cell death. The so-called type II anti-CD20 mAbs (e.g., tositumomab) that trigger caspase-independent B cell lymphoma cell death in vitro and show superior efficacy as compared with rituximab in eradicating target cells in mouse models are emerging as the next...... generation of therapeutic anti-CD20 mAbs. In this issue of the JCI, Ivanov and colleagues identify the lysosomal compartment as a target for type II mAbs (see the related article beginning on page 2143). These data encourage the further clinical development of type II mAbs as well as other lysosome...

  15. Primary intravascular large B-cell lymphoma of pituitary

    Directory of Open Access Journals (Sweden)

    K R Anila

    2012-01-01

    Full Text Available A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and lactate dehydrogenase (LDH values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done. Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL of pituitary was made. Our patient′s condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.

  16. Modulation of B-cell receptor and microenvironment signaling by a guanine exchange factor in B-cell malignancies

    International Nuclear Information System (INIS)

    Liao, Wei; Sharma, Sanjai

    2016-01-01

    Objective: Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) cells over-express a guanine exchange factor (GEF), Rasgrf-1. This GEF increases active Ras as it catalyzes the removal of GDP from Ras so that GTP can bind and activate Ras. This study aims to study the mechanism of action of Rasgrf-1 in B-cell malignancies. Methods: N-terminus truncated Rasgrf-1 variants have a higher GEF activity as compared to the full-length transcript therefore a MCL cell line with stable over-expression of truncated Rasgrf-1 was established. The B-cell receptor (BCR) and chemokine signaling pathways were compared in the Rasgrf-1 over-expressing and a control transfected cell line. Results: Cells over-expressing truncated form of Rasgrf-1 have a higher proliferative rate as compared to control transfected cells. BCR was activated by lower concentrations of anti-IgM antibody in Rasgrf-1 over-expressing cells as compared to control cells indicating that these cells are more sensitive to BCR signaling. BCR signaling also phosphorylates Rasgrf-1 that further increases its GEF function and amplifies BCR signaling. This activation of Rasgrf-1 in over-expressing cells resulted in a higher expression of phospho-ERK, AKT, BTK and PKC-alpha as compared to control cells. Besides BCR, Rasgrf-1 over-expressing cells were also more sensitive to microenvironment stimuli as determined by resistance to apoptosis, chemotaxis and ERK pathway activation. Conclusions: This GEF protein sensitizes B-cells to BCR and chemokine mediated signaling and also upregulates a number of other signaling pathways which promotes growth and survival of these cells

  17. Case-mix and quality indicators in Chinese elder care homes: are there differences between government-owned and private-sector facilities?

    Science.gov (United States)

    Liu, Chang; Feng, Zhanlian; Mor, Vincent

    2014-02-01

    To assess the association between ownership of Chinese elder care facilities and their performance quality and to compare the case-mix profile of residents and facility characteristics in government-owned and private-sector homes. Cross-sectional study. Census of elder care homes surveyed in Nanjing (2009) and Tianjin (2010). Elder care facilities located in urban Nanjing (n = 140, 95% of all) and urban Tianjin (n = 157, 97% of all). A summary case-mix index based on activity of daily living (ADL) limitations and cognitive impairment was created to measure levels of care needs of residents in each facility. Structure, process, and outcome measures were selected to assess facility-level quality of care. A structural quality measure, understaffing relative to resident levels of care needs, which indicates potentially inadequate staffing given resident case-mix, was also developed. Government-owned homes had significantly higher occupancy rates, presumably reflecting popular demand for publicly subsidized beds, but served residents who, on average, have fewer ADL and cognitive functioning limitations than those in private-sector facilities. Across a range of structure, process, and outcome measures of quality, there is no clear evidence suggesting advantages or disadvantages of either ownership type, although when staffing-to-resident ratio is gauged relative to resident case-mix, private-sector facilities were more likely to be understaffed than government-owned facilities. In Nanjing and Tianjin, private-sector homes were more likely to be understaffed, although their residents were sicker and frailer on average than those in government facilities. It is likely that the case-mix differences are the result of selective admission policies that favor healthier residents in government facilities than in private-sector homes. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  18. Animal welfare strengthens the quality of research. 3 million euros for a ultramodern animal facility

    International Nuclear Information System (INIS)

    2015-01-01

    The Belgian Nuclear Research Center SCK-CEN has been studying the long-term effects of low radiation doses on health for over 40 years.This uses mice because more than 90 per cent of their genome is identical with that of human beings. In order to work better and more ethically, SCK-CEN has invested 3 million euros in a brand-new animal facility. This makes it possible to carry out research under the best possible conditions for both humans and mice.

  19. Polyclonal B-cell lymphocytosis with binucleated lymphocytes (PPBL

    Directory of Open Access Journals (Sweden)

    Xavier Troussard

    2008-10-01

    Full Text Available Xavier Troussard1, Edouard Cornet1, Jean-François Lesesve2, Carine Kourel3, Hossein Mossafa31Laboratoire d’Hématologie Côte de Nacre, Université Caen Basse Normandie Caen, Registre Régional des Hémopathies Malignes de Basse Normandie, France; 2Laboratoire d’Hématologie, Vandoeuvre-Les-Nancy Cedex, France; 3Département de Génétique Humaine, Laboratoire pasteur-Cerba, Cergy-Pontoise, FranceFor the Groupe Français d’Hématologie cellulaire (GFHCAbstract: Persistent polyclonal B-cell lymphocytosis (PPBL is a rare and recently described entity. The review of the literature show PPBL is diagnosed predominantly but not exclusively in women, usually smokers. PPBL is recognized by a moderate, chronic and absolute lymphocytosis (>4 × 109/l in the peripheral blood. In 10% of cases without lymphocytosis, the PPBL diagnosis has to be suggested by peripheral blood examination showing in all cases atypical binucleated lymphocytes. A polyclonal serum IgM is also associated and HLA-DR7 expression is present in most cases. Contrary to B-cell chronic lymphoproliferative disorders (B-CLPD, peripheral B cells are polyclonal with kappa and lambda light-chain expression and no clonal rearrangement of immunoglobulin heavy chain genes is usually demonstrated. The detection of an extra isochromosome for the long arm of chromosome 3 +i(3(q10 has to be considered as a specific marker of PPBL. We performed conventional cytogenetic analysis (CCA in 111 patients with typical PPBL we followed-up more than 4 years. +i(3q was detected in 34% (33/98, PCC in 8% (8/98 and both abnormalities in 31% (30/98. CCA showed neither +i(3q nor PCC in 28% (27/98. Fluorescence in situ hybridization (FISH was also performed in 84 cases and +i(3q was detected in 71% (60/84. When combining both procedures in 84 patients, +i(3q was detected in 17 patients with negative CCA and was confirmed in 43 patients with positive CCA. CCA and FISH were both negative in 24 cases. Whether

  20. Prospect, Practices and Safety for Quality Management of the Gamma Greenhouse, a Novel Facility for Chronic Gamma Radiation

    International Nuclear Information System (INIS)

    Azhar Mohamad; Sobri Hussein; Abdul Rahim Harun; Ahsanulkhaliqin Abdul Wahab

    2012-01-01

    Malaysia has a special facility for chronic irradiation, known as the Gamma Greenhouse (GGH), located at MINT-Tech Park in Jalan Dengkil, Malaysian Nuclear Agency (Nuclear Malaysia). The Gamma Greenhouse source of chronic irradiation comes from a 137 Cs double encapsulated 800 Ci Cesium-137 pencil, producing a low dose rate, which is considered to be more effective in recovering and producing useful mutants in comparison to acute irradiation at higher dose. The irradiation facility comprises an open-topped irradiation area, 30 m in diameter, protected by a partial concrete wall, with entrance maze and site topography. High safety features are in place, where the facility is protected by a sophisticated interlock system that only allows the source to be exposed when all the prerequisite safety conditions are met, and automatically returns the source to the safe storage position if any safety device is compromised. The main irradiation area is further protected by a 300 m diameter exclusion zone that is also protected by the safety interlock circuit. The facility can accommodate a wide range of plant materials such as seeds, seedlings in pots, cuttings, calluses, somatic embryos and suspension cell cultures. In practice, plant samples will be exposed to low dose gamma radiation over long periods of time (hours, weeks, months), depending on their nature and sensitivity. All procedures generate data for evaluation, which require accuracy; quality management is essential in irradiation service. The prospect of the gamma greenhouse is in research and services on induced mutation techniques for the improvement of plant varieties and microbe strains. Services are provided to academicians, planters, students and researchers working with plants and microorganisms. In addition, it is also useful in the teaching and training on breeding, nuclear and radiation technology. The activities in utilization the gamma greenhouse cover mainly Research and Development, Research

  1. Quality of Case Management for Pneumonia and Diarrhea Among Children Seen at Health Facilities in Southern Malawi.

    Science.gov (United States)

    Kobayashi, Miwako; Mwandama, Dyson; Nsona, Humphreys; Namuyinga, Ruth J; Shah, Monica P; Bauleni, Andrew; Vanden Eng, Jodi Vanden; Rowe, Alexander K; Mathanga, Don P; Steinhardt, Laura C

    2017-05-01

    Pneumonia and diarrhea are leading causes of child deaths in Malawi. Guidelines to manage childhood illnesses in resource-poor settings exist, but studies have reported low health-care worker (HCW) adherence to guidelines. We conducted a health facility survey from January to March 2015 to assess HCW management of pneumonia and diarrhea in children management quality. Descriptive statistics and multivariable logistic regression models examined patient, HCW, and health facility factors associated with recommended pneumonia and diarrhea management, using Malawi's national guidelines as the gold standard. Of 694 surveyed children 2-59 months of age at 95 health facilities, 132 (19.0%) met survey criteria for pneumonia; HCWs gave recommended antibiotic treatment to 90 (68.2%). Of 723 children < 5 years of age, 222 (30.7%) had uncomplicated diarrhea; HCWs provided recommended treatment to 94 (42.3%). In multivariable analyses, caregivers' spontaneous report of children's symptoms was associated with recommended treatment of both pneumonia (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.2-6.8, P = 0.023) and diarrhea (OR: 24.2, 95% CI: 6.0-97.0, P < 0001). Malaria diagnosis was negatively associated with recommended treatment (OR for pneumonia: 0.5, 95% CI: 0.2-1.0, P = 0.046; OR for diarrhea: 0.3, 95% CI: 0.1-0.6, P = 0.003). To improve quality of care, children should be assessed systematically, even when malaria is suspected. Renewed efforts to invigorate such a systematic approach, including HCW training, regular follow-up supervision, and monitoring HCW performance, are needed in Malawi.

  2. Impairment of mature B-cell maintenance upon combined deletion of the alternative NF-?B transcription factors RELB and NF-?B2 in B cells$

    OpenAIRE

    De Silva, Nilushi S.; Silva, Kathryn; Anderson, Michael M.; Bhagat, Govind; Klein, Ulf

    2016-01-01

    B-cell activating factor (BAFF) is critical for the survival and maturation of mature B-cells. BAFF, via the BAFF receptor (BAFFR), activates multiple signaling pathways in B-cells, including the alternative nuclear factor-?B (NF-?B) pathway. The transcription factors RELB and NF-?B2 (p100/p52) are the downstream mediators of the alternative pathway; however, the B-cell-intrinsic functions of these NF-?B subunits have not been studied in vivo using conditional alleles, either individually or ...

  3. Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice

    Science.gov (United States)

    Fournier, Emilie M.; Velez, Maria-Gabriela; Leahy, Katelyn; Swanson, Cristina L.; Rubtsov, Anatoly V.; Torres, Raul M.

    2012-01-01

    Rare dual-reactive B cells expressing two types of Ig light or heavy chains have been shown to participate in immune responses and differentiate into IgG+ cells in healthy mice. These cells are generated more often in autoreactive mice, leading us to hypothesize they might be relevant in autoimmunity. Using mice bearing Igk allotypic markers and a wild-type Ig repertoire, we demonstrate that the generation of dual-κ B cells increases with age and disease progression in autoimmune-prone MRL and MRL/lpr mice. These dual-reactive cells express markers of activation and are more frequently autoreactive than single-reactive B cells. Moreover, dual-κ B cells represent up to half of plasmablasts and memory B cells in autoimmune mice, whereas they remain infrequent in healthy mice. Differentiation of dual-κ B cells into plasmablasts is driven by MRL genes, whereas the maintenance of IgG+ cells is partly dependent on Fas inactivation. Furthermore, dual-κ B cells that differentiate into plasmablasts retain the capacity to secrete autoantibodies. Overall, our study indicates that dual-reactive B cells significantly contribute to the plasmablast and memory B cell populations of autoimmune-prone mice suggesting a role in autoimmunity. PMID:22927551

  4. Isolation and characterization of an HIV-1 envelope glycoprotein-specific B-cell from an immortalized human naïve B-cell library.

    Science.gov (United States)

    Sun, Zehua; Lu, Shiqiang; Yang, Zheng; Li, Jingjing; Zhang, Meiyun

    2017-04-01

    With the recent development of single B-cell cloning techniques, an increasing number of human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing antibodies have been isolated since 2009. However, knowledge regarding HIV-1-specific B cells in vivo is limited. In this study, an HIV-1-specific B-cell line was established using healthy PBMC donors by the highly efficient Epstein-Barr virus transformation method to generate immortalized human naïve B-cell libraries. The enrichment of HIV-1 envelope-specific B cells was observed after four rounds of cell panning with the HIV-1 envelope glycoprotein. An HIV-1 envelope-specific stable B-cell line (LCL-P4) was generated. Although this cell line acquired a lymphoblastic phenotype, no expression was observed for activation-induced cytidine deaminase, an enzyme responsible for initiating somatic hypermutation and class switch recombination in B cells. This study describes a method that enables fast isolation of HIV-1-specific B cells, and this approach may extend to isolating other B-cell-specific antigens for further experiments.

  5. EBI2 overexpression in mice leads to B1 B cell expansion and chronic lymphocytic leukemia-(CLL)-like B cell malignancies

    DEFF Research Database (Denmark)

    Niss Arfelt, Kristine; Barington, Line; Benned-Jensen, Tau

    2017-01-01

    Human and mouse chronic lymphocytic leukemia (CLL) develop from CD5+ B cells that in mice and macaques are known to define the distinct B1a B cell lineage. B1a cells are characterized by lack of germinal center development and the B1a cell population is increased in mice with reduced germinal...... center formation. As a major mediator of follicular B cell migration, the G protein-coupled receptor (GPCR) Epstein Barr virus-induced gene 2 (EBI2 or GPR183) directs B cell migration in the lymphoid follicles in response to its endogenous ligands, oxysterols. Thus, upregulation of EBI2 drives the B...

  6. Quality of Drinking Water Treated at Point of Use in Residential Healthcare Facilities for the Elderly.

    Science.gov (United States)

    Sacchetti, Rossella; De Luca, Giovanna; Guberti, Emilia; Zanetti, Franca

    2015-09-09

    Municipal tap water is increasingly treated at the point of use (POU) to improve the acceptability and palatability of its taste. The aim of this study was to assess the bacteriologic and nutritional characteristics of tap water treated at the point of use in residential healthcare facilities for the elderly. Two types of POU devices were used: microfiltered water dispensers (MWDs) and reverse-osmosis water dispensers (ROWDs). All samples of water entering the devices and leaving them were tested for the bacteriological parameters set by Italian regulations for drinking water and for opportunistic pathogens associated with various infections in healthcare settings; in addition, the degree of mineralization of the water was assessed. The results revealed widespread bacterial contamination in the POU treatment devices, particularly from potentially pathogenic species. As expected, the use of ROWDs led to a decrease in the saline content of the water. In conclusion, the use of POU treatment in healthcare facilities for the elderly can be considered advisable only if the devices are constantly and carefully maintained.

  7. Enhanced selection of high affinity DNA-reactive B cells following cyclophosphamide treatment in mice.

    Directory of Open Access Journals (Sweden)

    Daisuke Kawabata

    2010-01-01

    Full Text Available A major goal for the treatment of patients with systemic lupus erythematosus with cytotoxic therapies is the induction of long-term remission. There is, however, a paucity of information concerning the effects of these therapies on the reconstituting B cell repertoire. Since there is recent evidence suggesting that B cell lymphopenia might attenuate negative selection of autoreactive B cells, we elected to investigate the effects of cyclophosphamide on the selection of the re-emerging B cell repertoire in wild type mice and transgenic mice that express the H chain of an anti-DNA antibody. The reconstituting B cell repertoire in wild type mice contained an increased frequency of DNA-reactive B cells; in heavy chain transgenic mice, the reconstituting repertoire was characterized by an increased frequency of mature, high affinity DNA-reactive B cells and the mice expressed increased levels of serum anti-DNA antibodies. This coincided with a significant increase in serum levels of BAFF. Treatment of transgene-expressing mice with a BAFF blocking agent or with DNase to reduce exposure to autoantigen limited the expansion of high affinity DNA-reactive B cells during B cell reconstitution. These studies suggest that during B cell reconstitution, not only is negative selection of high affinity DNA-reactive B cells impaired by increased BAFF, but also that B cells escaping negative selection are positively selected by autoantigen. There are significant implications for therapy.

  8. File list: ALL.Bld.05.AllAg.Lymphoma,_B-Cell [Chip-atlas[Archive

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  20. Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells

    NARCIS (Netherlands)

    Avalos, Ana M.; Bilate, Angelina M.; Witte, Martin D.; Tai, Albert K.; He, Jiang; Frushicheva, Maria P.; Thill, Peter D.; Meyer-Wentrup, Friederike; Theile, Christopher S.; Chakraborty, Arup K.; Zhuang, Xiaowei; Ploegh, Hidde L.

    2014-01-01

    Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR.

  1. Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Lanemo Myhrinder, Anna; Hellqvist, Eva; Bergh, Ann-Charlotte

    2013-01-01

    Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface...

  2. File list: ALL.Bld.20.AllAg.Pro-B_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  4. File list: His.Bld.50.AllAg.Pro-B_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. Monocytes mediate shaving of B-cell-bound anti-CD20 antibodies

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Jungersen, Mette B; Pedersen, Charlotte D

    2011-01-01

    complex from the B-cell surface. Here, we confirm, that in vitro co-culture of human monocytes and RTX-labelled syngeneic B cells results in reduced expression of CD20/RTX complex on the B cell surface. This shaving mechanism was the result of active protease activity because EDTA and PMSF were able...

  6. Comparison of Perceived and Technical Healthcare Quality in Primary Health Facilities: Implications for a Sustainable National Health Insurance Scheme in Ghana

    NARCIS (Netherlands)

    Alhassan, R.K.; Duku, S.O.; Janssens, W.; Nketiah-Amponsah, E.; Spieker, N.; van Ostenberg, P.; Arhinful, D.K.; Pradhan, M.; Rinke de Wit, T.F.

    2015-01-01

    Background Quality care in health facilities is critical for a sustainable health insurance system because of its influence on clients’ decisions to participate in health insurance and utilize health services. Exploration of the different dimensions of healthcare quality and their associations will

  7. Comparison of Perceived and Technical Healthcare Quality in Primary Health Facilities: Implications for a Sustainable National Health Insurance Scheme in Ghana

    NARCIS (Netherlands)

    Alhassan, Robert Kaba; Duku, Stephen Opoku; Janssens, Wendy; Nketiah-Amponsah, Edward; Spieker, Nicole; van Ostenberg, Paul; Arhinful, Daniel Kojo; Pradhan, Menno; Rinke de Wit, Tobias F.

    2015-01-01

    Background Quality care in health facilities is critical for a sustainable health insurance system because of its influence on clients' decisions to participate in health insurance and utilize health services. Exploration of the different dimensions of healthcare quality and their associations will

  8. [Quality management in a clinical research facility: Evaluation of changes in quality in-house figures and the appraisal of in-house quality indicators].

    Science.gov (United States)

    Aden, Bile; Allekotte, Silke; Mösges, Ralph

    2016-12-01

    For long-term maintenance and improvement of quality within a clinical research institute, the implementation and certification of a quality management system is suitable. Due to the implemented quality management system according to the still valid DIN EN ISO 9001:2008 desired quality objectives are achieved effectively. The evaluation of quality scores and the appraisal of in-house quality indicators make an important contribution in this regard. In order to achieve this and draw quality assurance conclusions, quality indicators as sensible and sensitive as possible are developed. For this, own key objectives, the retrospective evaluation of quality scores, a prospective follow-up and also discussions establish the basis. In the in-house clinical research institute the measures introduced by the quality management led to higher efficiency in work processes, improved staff skills, higher customer satisfaction and overall to more successful outcomes in relation to the self-defined key objectives. Copyright © 2016. Published by Elsevier GmbH.

  9. The regulatory network of B-cell differentiation: a focused view of early B-cell factor 1 function.

    Science.gov (United States)

    Boller, Sören; Grosschedl, Rudolf

    2014-09-01

    During the last decades, many studies have investigated the transcriptional and epigenetic regulation of lineage decision in the hematopoietic system. These efforts led to a model in which extrinsic signals and intrinsic cues establish a permissive chromatin context upon which a regulatory network of transcription factors and epigenetic modifiers act to guide the differentiation of hematopoietic lineages. These networks include lineage-specific factors that further modify the epigenetic landscape and promote the generation of specific cell types. The process of B lymphopoiesis requires a set of transcription factors, including Ikaros, PU.1, E2A, and FoxO1 to 'prime' cis-regulatory regions for subsequent activation by the B-lineage-specific transcription factors EBF1 and Pax-5. The expression of EBF1 is initiated by the combined action of E2A and FoxO1, and it is further enhanced and maintained by several positive feedback loops that include Pax-5 and IL-7 signaling. EBF1 acts in concert with Ikaros, PU.1, Runx1, E2A, FoxO1, and Pax-5 to establish the B cell-specific transcription profile. EBF1 and Pax-5 also collaborate to repress alternative cell fates and lock cells into the B-lineage fate. In addition to the functions of EBF1 in establishing and maintaining B-cell identity, EBF1 is required to coordinate differentiation with cell proliferation and survival. © 2014 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

  10. Clients' perception of service quality of care in health facilities in ...

    African Journals Online (AJOL)

    Introduction: Clients perception of service quality is important for utilization of health services. Clients with positive perception are more likely to comply with treatment and to continue to use health care services. Assessing clients' perception of services offered is crucial for improving delivery and organization of the services.

  11. Quality of paste-abortion care _in public! health facilities in

    African Journals Online (AJOL)

    Background: Comprehensive quality Post Abortion Care (PAC) is one of the important strategies to save lives where access to safe ... Great majority of the patients responded that they were satisfied with services they have obtained. Dissatisfaction ... already enough children and being very young and being in school. (3, 4 ...

  12. Technical quality of delivery care in private- and public-sector health facilities in Enugu and Lagos States, Nigeria.

    Science.gov (United States)

    Hirose, Atsumi; Yisa, Ibrahim O; Aminu, Amina; Afolabi, Nathanael; Olasunmbo, Makinde; Oluka, George; Muhammad, Khalilu; Hussein, Julia

    2018-04-18

    Private-sector providers are increasingly being recognized as important contributors to the delivery of healthcare. Countries with high disease burdens and limited public-sector resources are considering using the private sector to achieve universal health coverage. However, evidence for the technical quality of private-sector care is lacking. This study assesses the technical quality of maternal healthcare during delivery in public- and private-sector facilities in resource-limited settings, from a systems and programmatic perspective. A summary index (the skilled attendance index, SAI), was used. Two-staged cluster sampling with stratification was used to select representative samples of case records in public- and private-sector facilities in Enugu and Lagos States, Nigeria. Information to assess criteria was extracted, and the SAI calculated. Linear regression models examined the relationship between SAI and the private and public sectors, controlling for confounders. The median SAI was 54.8% in Enugu and 85.7% in Lagos. The private for-profit sector's SAI was lower than and the private not-for-profit sector's SAI was higher than the public sector in Enugu [coefficient = -3.6 (P = 0.018) and 12.6 (P sector's SAI was higher and the private not-for-profit sector's SAI was lower than the public sector [3.71 (P = 0.005) and -3.92 (P sector was strong and there was a relatively strong regulatory body. Our findings raise important considerations relating to the quality of maternity care, the public-private mix and needs for regulation in global efforts to achieve universal healthcare.

  13. B-cell phenotype and IgD-CD27- memory B cells are affected by TNF-inhibitors and tocilizumab treatment in rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Rita A Moura

    Full Text Available The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA.Blood samples were collected from untreated early RA (ERA patients, established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors. B-cell subpopulations were characterized by flow cytometry and B-cell gene expression was analyzed by real-time PCR on isolated B-cells. Serum levels of BAFF, CXCL13 and sCD23 were determined by ELISA.The frequency of total CD19+ B cells in circulation was similar between controls and all RA groups, irrespective of treatment, but double negative (DN IgD-CD27- memory B cells were significantly increased in ERA and established RA when compared to controls. Treatment with TNF-inhibitors and tocilizumab restored the frequency of IgD-CD27- B-cells to normal levels, but did not affect other B cell subpopulations. TACI, CD95, CD5, HLA-DR and TLR9 expression on B-cells significantly increased after treatment with either TNF-inhibitors and/ or tocilizumab, but no significant changes were observed in BAFF-R, BCMA, CD69, CD86, CXCR5, CD23, CD38 and IgM expression on B-cells when comparing baseline with post-treatment follow-ups. Alterations in B-cell gene expression of BAFF-R, TACI, TLR9, FcγRIIB, BCL-2, BLIMP-1 and β2M were found in ERA and established RA patients, but no significant differences were observed after TNF-inhibitors and tocilizumab treatment when comparing baseline and follow-ups. Serum levels of CXCL13, sCD23 and BAFF were not significantly affected by treatment with TNF-inhibitors and tocilizumab.In RA patients, the use of TNF-inhibitors and/ or tocilizumab treatment affects B-cell phenotype and IgD-CD27- memory B

  14. Maternal and fetal mechanisms of B cell regulation during pregnancy: human Chorionic Gonadotropin stimulates B cells to produce IL-10 while alpha-fetoprotein drives them into apoptosis

    Directory of Open Access Journals (Sweden)

    Franziska Fettke

    2016-12-01

    Full Text Available Maternal immune tolerance towards the fetus is an essential requisite for pregnancy. While T cell functions are well documented, little is known about the participation of B cells. We have previously suggested that IL-10 producing B cells are involved in pregnancy tolerance in mice and humans. By employing murine and human systems, we report now that fetal trophoblasts positively regulate the generation of IL-10 producing B cells. We next studied the participation of hormones produced by the placenta as well as the fetal protein alpha-fetoprotein (AFP in B cell modulation. Human Chorionic Gonadotropin (hCG, but not progesterone, estrogen or a combination of both, was able to promote changes in B cell phenotype and boost their IL-10 production, which was abolished after blocking hCG. The hCG-induced B cell phenotype was not associated with augmented galactosylation, sialylation or fucosylation of IgG subclasses in their Fc. In vitro, hCG induced the synthesis of asymmetrically glycosylated antibodies in their Fab region. Interestingly, AFP had dual effects depending on the concentration. At concentrations corresponding to maternal serum levels, it did not modify the phenotype or IL-10 secretion of B cells. At fetal concentrations, however, AFP was able to drive B cells into apoptosis, which may indicate a protective mechanism to avoid maternal B cells to reach the fetus.Our data suggests that the fetus secrete factors that promote a pregnancy-friendly B cell phenotype, unraveling interesting aspects of B cell function and modulation by pregnancy hormones and fetal proteins.

  15. Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity.

    Science.gov (United States)

    Nakayama, Yumi; Kosek, Jolanta; Capone, Lori; Hur, Eun Mi; Schafer, Peter H; Ringheim, Garth E

    2017-10-01

    BAFF is a B cell survival and maturation factor implicated in the pathogenesis of systemic lupus erythematosus (SLE). In this in vitro study, we describe that soluble BAFF in combination with IL-2 and IL-21 is a T cell contact-independent inducer of human B cell proliferation, plasmablast differentiation, and IgG secretion from circulating CD27 + memory and memory-like CD27 - IgD - double-negative (DN) B cells, but not CD27 - IgD + naive B cells. In contrast, soluble CD40L in combination with IL-2 and IL-21 induces these activities in both memory and naive B cells. Blood from healthy donors and SLE patients have similar circulating levels of IL-2, whereas SLE patients exhibit elevated BAFF and DN B cells and reduced IL-21. B cell differentiation transcription factors in memory, DN, and naive B cells in SLE show elevated levels of Aiolos, whereas Ikaros levels are unchanged. Treatment with CC-220, a modulator of the cullin ring ligase 4-cereblon E3 ubiquitin ligase complex, reduces Aiolos and Ikaros protein levels and BAFF- and CD40L-induced proliferation, plasmablast differentiation, and IgG secretion. The observation that the soluble factors BAFF, IL-2, and IL-21 induce memory and DN B cell activation and differentiation has implications for extrafollicular plasmablast development within inflamed tissue. Inhibition of B cell plasmablast differentiation by reduction of Aiolos and Ikaros may have utility in the treatment of SLE, where elevated levels of BAFF and Aiolos may prime CD27 + memory and DN memory-like B cells to become Ab-producing plasmablasts in the presence of BAFF and proinflammatory cytokines. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. Separation of plasmacytoid dendritic cells from B-cell-biased lymphoid progenitor (BLP) and Pre-pro B cells using PDCA-1.

    Science.gov (United States)

    Medina, Kay L; Tangen, Sarah N; Seaburg, Lauren M; Thapa, Puspa; Gwin, Kimberly A; Shapiro, Virginia Smith

    2013-01-01

    B-cell-biased lymphoid progenitors (BLPs) and Pre-pro B cells lie at a critical juncture between B cell specification and commitment. However, both of these populations are heterogenous, which hampers investigation into the molecular changes that occur as lymphoid progenitors commit to the B cell lineage. Here, we demonstrate that there are PDCA-1(+)Siglec H(+) plasmacytoid dendritic cells (pDCs) that co-purify with BLPs and Pre-pro B cells, which express little or no CD11c or Ly6C. Removal of PDCA-1(+) pDCs separates B cell progenitors that express high levels of a Rag1-GFP reporter from Rag1-GFP(low/neg) pDCs within the BLP and Pre-pro B populations. Analysis of Flt3-ligand knockout and IL-7Rα knockout mice revealed that there is a block in B cell development at the all-lymphoid progenitor (ALP) stage, as the majority of cells within the BLP or Pre-pro B gates were PDCA-1(+) pDCs. Thus, removal of PDCA-1(+) pDCs is critical for analysis of BLP and Pre-pro B cell populations. Analysis of B cell potential within the B220(+)CD19(-) fraction demonstrated that AA4.1(+)Ly6D(+)PDCA-1(-) Pre-pro B cells gave rise to CD19(+) B cells at high frequency, while PDCA-1(+) pDCs in this fraction did not. Interestingly, the presence of PDCA-1(+) pDCs within CLPs may help to explain the conflicting results regarding the origin of these cells.

  17. Separation of plasmacytoid dendritic cells from B-cell-biased lymphoid progenitor (BLP and Pre-pro B cells using PDCA-1.

    Directory of Open Access Journals (Sweden)

    Kay L Medina

    Full Text Available B-cell-biased lymphoid progenitors (BLPs and Pre-pro B cells lie at a critical juncture between B cell specification and commitment. However, both of these populations are heterogenous, which hampers investigation into the molecular changes that occur as lymphoid progenitors commit to the B cell lineage. Here, we demonstrate that there are PDCA-1(+Siglec H(+ plasmacytoid dendritic cells (pDCs that co-purify with BLPs and Pre-pro B cells, which express little or no CD11c or Ly6C. Removal of PDCA-1(+ pDCs separates B cell progenitors that express high levels of a Rag1-GFP reporter from Rag1-GFP(low/neg pDCs within the BLP and Pre-pro B populations. Analysis of Flt3-ligand knockout and IL-7Rα knockout mice revealed that there is a block in B cell development at the all-lymphoid progenitor (ALP stage, as the majority of cells within the BLP or Pre-pro B gates were PDCA-1(+ pDCs. Thus, removal of PDCA-1(+ pDCs is critical for analysis of BLP and Pre-pro B cell populations. Analysis of B cell potential within the B220(+CD19(- fraction demonstrated that AA4.1(+Ly6D(+PDCA-1(- Pre-pro B cells gave rise to CD19(+ B cells at high frequency, while PDCA-1(+ pDCs in this fraction did not. Interestingly, the presence of PDCA-1(+ pDCs within CLPs may help to explain the conflicting results regarding the origin of these cells.

  18. Distance from health facility and mothers’ perception of quality related to skilled delivery service utilization in northern Ethiopia

    Directory of Open Access Journals (Sweden)

    Fisseha G

    2017-10-01

    birth order and having an educated partner were the significant predictors of skilled delivery service utilization.Conclusion: Implementing community-based intervention programs that will address the physical accessibility of delivery services, such as the ambulance service, road issues and waiting rooms, and improving quality maternity service will likely reduce the current problem. Keywords: distance from health facility, perception of quality, skilled delivery service utilization, Northern Ethiopia

  19. Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective.

    Science.gov (United States)

    Darwiche, Walaa; Gubler, Brigitte; Marolleau, Jean-Pierre; Ghamlouch, Hussein

    2018-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of small mature-looking CD19+ CD23+ CD5+ B-cells that accumulate in the blood, bone marrow, and lymphoid organs. To date, no consensus has been reached concerning the normal cellular counterpart of CLL B-cells and several B-cell types have been proposed. CLL B-cells have remarkable phenotypic and gene expression profile homogeneity. In recent years, the molecular and cellular biology of CLL has been enriched by seminal insights that are leading to a better understanding of the natural history of the disease. Immunophenotypic and molecular approaches (including immunoglobulin heavy-chain variable gene mutational status, transcriptional and epigenetic profiling) comparing the normal B-cell subset and CLL B-cells provide some new insights into the normal cellular counterpart. Functional characteristics (including activation requirements and propensity for plasma cell differentiation) of CLL B-cells have now been investigated for 50 years. B-cell subsets differ substantially in terms of their functional features. Analysis of shared functional characteristics may reveal similarities between normal B-cell subsets and CLL B-cells, allowing speculative assignment of a normal cellular counterpart for CLL B-cells. In this review, we summarize current data regarding peripheral B-cell differentiation and human B-cell subsets and suggest possibilities for a normal cellular counterpart based on the functional characteristics of CLL B-cells. However, a definitive normal cellular counterpart cannot be attributed on the basis of the available data. We discuss the functional characteristics required for a cell to be logically considered to be the normal counterpart of CLL B-cells.

  20. B Cell Depletion: Rituximab in Glomerular Disease and Transplantation

    Directory of Open Access Journals (Sweden)

    S. Marinaki

    2013-12-01

    Full Text Available B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

  1. Diffuse Large B Cell Lymphoma of the Breast

    Directory of Open Access Journals (Sweden)

    Feryal Karaca

    2015-03-01

    Full Text Available Primary breast lymphoma is rarely encountered in Non-Hodgkin Lymphomas. However, if early diagnosis is made, and treatment is started immediately in patients with low grade and stage, patient survival is increased. 39-year old female patient applied us due to a palpable mass. She was diagnosed with the Non-Hodgkin Lymphoma Diffuse Large B Cell Lymphoma after the investigations. Curative external radiotherapy was applied after 6 courses of CHOP-R chemotherapy to the patient with Stage-IIE favorable, and B symptoms. After 48-month follow up, patient follow up is being continued without any progression, or recurrence or metastasis. [Cukurova Med J 2015; 40(1.000: 151-157

  2. [Primary cutaneous B-cell lymphomas: study of 22 cases].

    Science.gov (United States)

    Martín Carrasco, Pablo; Morillo Andújar, Mercedes; Pérez Ruiz, Carmen; de Zulueta Dorado, Teresa; Cabrera Pérez, Rocío; Conejo-Mir, Julián

    2016-09-02

    Primary cutaneous B-cell lymphoma (CBCL) is a very low prevalence neoplasm and constitutes 25% of all primary cutaneous lymphomas. Our objective was to discover the epidemiological, clinic and histologic characteristics of CBCL in our area. Retrospective descriptive study with patients with histologic diagnosis of CBCL followed up in our department between 2004 and 2015. Twenty-two patients with CBCL were included; 65% were men and 35% were women. Follicle centre lymphoma was the most common subtype (41%). Only 3 cases presented with node involvement and one with bone marrow invasion. Five recurrences were detected and one patient died because of the CBCL. This is one of the first CBCL series in theSpanish population. The incidence, sex, age, subtype distribution, clinical features and immunohistochemical patterns are very similar to those of the other series. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. Lenalidomide in Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Catherine Thieblemont

    2012-01-01

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is the most common form of non-Hodgkin's lymphoma (NHL in adults. Even if the natural history of DLBCL has been improved with the advent of immunochemotherapy, the survival results obtained with current treatment options clearly indicate that new agents or novel approaches are needed. Lenalidomide (Revlimid, Celgene Corporation, Summit, NJ, USA, an analogue of thalidomide, is an immunomodulatory drug with pleiotropic mechanisms of action potentially adding to immunochemotherapy. We present here the biological rational for the use of lenalidomide in DLBCL in light of recent advances in the pathophysiology of the disease and the therapeutic results of the most recent trials published in literature or reported in meetings in relapsed/refractory situations as well as in first-line treatment.

  4. Cerebral toxoplasmosis in a diffuse large B cell lymphoma patient

    International Nuclear Information System (INIS)

    Savsek, Lina; Opaskar, Tanja Ros

    2016-01-01

    Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8 th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance

  5. Quality assurance for external personnel monitoring in nuclear industrial facilities, CNNC

    International Nuclear Information System (INIS)

    Zhang Yansheng; Dai Jun; Li Taosheng

    1993-01-01

    More than 6000 personnel are currently being monitored for occupational exposure in CNNC, China. Personnel monitoring is one of the important items of radiation protection. The data of individual dose are not only indispensable for radiation safety assessment but also the basis for radiation protection measures to be taken. Possibly, it could provide basic information for epidemiological studies, optimization procedure of radiation protection (risk/benefit analyses) and medical or legal purposes. Obviously, personnel monitoring and its quality assurance are very significant

  6. Comparison of Perceived and Technical Healthcare Quality in Primary Health Facilities: Implications for a Sustainable National Health Insurance Scheme in Ghana

    Science.gov (United States)

    Alhassan, Robert Kaba; Duku, Stephen Opoku; Janssens, Wendy; Nketiah-Amponsah, Edward; Spieker, Nicole; van Ostenberg, Paul; Arhinful, Daniel Kojo; Pradhan, Menno; Rinke de Wit, Tobias F.

    2015-01-01

    Background Quality care in health facilities is critical for a sustainable health insurance system because of its influence on clients’ decisions to participate in health insurance and utilize health services. Exploration of the different dimensions of healthcare quality and their associations will help determine more effective quality improvement interventions and health insurance sustainability strategies, especially in resource constrained countries in Africa where universal access to good quality care remains a challenge. Purpose To examine the differences in perceptions of clients and health staff on quality healthcare and determine if these perceptions are associated with technical quality proxies in health facilities. Implications of the findings for a sustainable National Health Insurance Scheme (NHIS) in Ghana are also discussed. Methods This is a cross-sectional study in two southern regions in Ghana involving 64 primary health facilities: 1,903 households and 324 health staff. Data collection lasted from March to June, 2012. A Wilcoxon-Mann-Whitney test was performed to determine differences in client and health staff perceptions of quality healthcare. Spearman’s rank correlation test was used to ascertain associations between perceived and technical quality care proxies in health facilities, and ordered logistic regression employed to predict the determinants of client and staff-perceived quality healthcare. Results Negative association was found between technical quality and client-perceived quality care (coef. = -0.0991, peducation and balanced commitment to technical and perceived quality improvement efforts. This will help enhance client confidence in Ghana’s healthcare system, stimulate active participation in the national health insurance, increase healthcare utilization and ultimately improve public health outcomes. PMID:26465935

  7. LISTENing to healthcare students: the impact of new library facilities on the quality of services.

    Science.gov (United States)

    Haldane, Graham C

    2003-06-01

    Following a low assessment of 'Learning resources' provision by the Quality Assurance Agency, the librarian of Homerton College, School of Health Studies commenced the LISTEN Project, a long-term study to monitor the effects of planned interventions on the quality of library provision. Surveys of entry-to-register student nurses & midwives were conducted in 1999 and 2001 by extensive questionnaires, inviting Likert-scaled and free text responses. Following a college relocation, students made greater than expected use of a new health studies library in Cambridge, and significantly less use of the local teaching hospital library. Using both a satisfaction index and a non-parametric test of mean scores, student evaluation of library services in Cambridge significantly improved following relocation. The physical accommodation and location of library services remain important to healthcare students. Identifiable improvements to the quality of services, however, will overcome initial resistance to change. Education providers must ensure the best mix of physical and electronic services for students who spend much of their time on clinical placement.

  8. Standard operating procedures for quality audits of 60Co external beam radiotherapy facilities

    International Nuclear Information System (INIS)

    Larrinaga Cortina, E.F.; Dominguez Hung, L.; Campa Menendez, R.

    2001-01-01

    The use of radiotherapy implies the necessity of rigorous quality standards in its different components, aimed to provide the best possible treatment and avoid potential patients' risks, that could even cause him death. Projects of technical cooperation developed in Cuba and supported by the International Atomic Energy Agency address the implementation of Programs of Quality Assurance (PGC) in radiotherapy services. The establishment of the National Quality Audit Program (PNAC) is a superior stage. The National Control Center for Medical Devices, as the national regulator entity for the control and supervision of medical devices in the National Health System, is responsible for the making and execution of the PNAC. The audit modality selected was the inspection visit in situ due to its intrinsic advantages, our geographical extension and the number of radiotherapy services. This paper presents the methodology for the execution of the PNAC, in form of a Normalized Procedure of Operation (PNO) that defines the objectives, scope, terms and definitions, responsibilities, composition and selection of the auditor team, security's conditions, materials and equipment, steps of the audit execution, results calculation and interpretation, records, etc. (author)

  9. Expectations and perceptions of clients concerning the quality of care provided at a Brazilian hospital facility.

    Science.gov (United States)

    Mendes, Isabel Amélia Costa; Trevizan, Maria Auxiliadora; de Godoy, Simone; Nogueira, Paula Cristina; Ventura, Carla Aparecida Arena; Furlan, Claudia Elizangela Bis

    2018-02-01

    To identify the expectations and perceptions of clients concerning the quality of hospital care provided to them and their respective companions at a private Brazilian hospital using SERVQUAL. The SERVQUAL questionnaire can provide information concerning expectations and perceptions of clients. In addition, it is able to identify the participation of frontline employees and how they contribute to the organization's end product (service delivery). In total, 172 inpatients for surgical reasons answered the SERVQUAL questionnaire. It consists of 23 pairs of statements, 22 of which are distributed into the dimensions of tangibles, reliability, responsiveness, assurance and empathy. Statement 23 refers to the overall quality of care. Exploratory analysis, internal consistency (Cronbach's alpha) and the kappa Coefficient were calculated using the Statistical Package for Social Sciences and SAS 9.2. Ethical approval was obtained from the Institutional Review Board at the Hospital das Clínicas at the University of São Paulo at Ribeirao Preto Medical School. Most participants had a bachelor's degree and were over than 60years old. Cronbach's alpha coefficients indicated good internal consistency (α=0.93) and high levels of agreement were observed (91.10%). The SERVQUAL questionnaire was sensitive to items in each dimension for which clients' perceptions surpassed their expectations. The continuous quality assessment of health services is mandatory for nursing leadership. The nursing leadership can further explore the SERVQUAL with a view to better attending to the clients' expectations. Copyright © 2017. Published by Elsevier Inc.

  10. B-cell exposure to self-antigen induces IL-10 producing B cells as well as IL-6- and TNF-α-producing B-cell subsets in healthy humans

    DEFF Research Database (Denmark)

    Langkjær, Anina; Kristensen, Birte; Hansen, Bjarke E

    2012-01-01

    Human B cells are able to secrete IL-10 after stimulation with mitogens, but their ability to produce IL-10 and regulate T-cell responses after stimulation with self-antigens is unclear. We co-cultured thyroglobulin-pulsed B cells from healthy donors with autologous T cells and observed production...... of IL-10 and TGF-β, in addition to TNF-α and IL-6. Pulsing with foreign antigen, tetanus toxoid (TT), induced a Th1-response with minimal IL-10 production. After thyroglobulin-pulsing, 1.10±0.50% of B cells and 1.00±0.20% of CD4(+) T cells produced IL-10, compared to 0.29±0.19% of B cells (P=0.01) and 0.......13±0.15% of CD4(+) T cells (P=0.006) following TT-pulsing. Thyroglobulin-stimulated, IL-10-secreting B cells were enriched within CD5(+) and CD24(high) cells. While thyroglobulin-pulsed B cells induced only modest proliferation of CD4(+) T cells, B cells pulsed with TT induced vigorous proliferation. Thus, B...

  11. EBI2 overexpression in mice leads to B1 B-cell expansion and chronic lymphocytic leukemia-like B-cell malignancies.

    Science.gov (United States)

    Niss Arfelt, Kristine; Barington, Line; Benned-Jensen, Tau; Kubale, Valentina; Kovalchuk, Alexander L; Daugvilaite, Viktorija; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Egerod, Kristoffer L; Bassi, Maria R; Spiess, Katja; Schwartz, Thue W; Wang, Hongsheng; Morse, Herbert C; Holst, Peter J; Rosenkilde, Mette M

    2017-02-16

    Human and mouse chronic lymphocytic leukemia (CLL) develops from CD5 + B cells that in mice and macaques are known to define the distinct B1a B-cell lineage. B1a cells are characterized by lack of germinal center (GC) development, and the B1a cell population is increased in mice with reduced GC formation. As a major mediator of follicular B-cell migration, the G protein-coupled receptor Epstein-Barr virus-induced gene 2 ( EBI2 or GPR183 ) directs B-cell migration in the lymphoid follicles in response to its endogenous ligands, oxysterols. Thus, upregulation of EBI2 drives the B cells toward the extrafollicular area, whereas downregulation is essential for GC formation. We therefore speculated whether increased expression of EBI2 would lead to an expanded B1 cell subset and, ultimately, progression to CLL. Here, we demonstrate that B-cell-targeted expression of human EBI2 (hEBI2) in mice reduces GC-dependent immune responses, reduces total immunoglobulin M (IgM) and IgG levels, and leads to increased proliferation and upregulation of cellular oncogenes. Furthermore, hEBI2 overexpression leads to an abnormally expanded CD5 + B1a B-cell subset (present as early as 4 days after birth), late-onset lymphoid cancer development, and premature death. These findings are highly similar to those observed in CLL patients and identify EBI2 as a promoter of B-cell malignancies.

  12. Spacelab data processing facility (SLDPF) quality assurance (QA)/data accounting (DA) expert systems - Transition from prototypes to operational systems

    Science.gov (United States)

    Basile, Lisa

    1988-01-01

    The SLDPF is responsible for the capture, quality monitoring processing, accounting, and shipment of Spacelab and/or Attached Shuttle Payloads (ASP) telemetry data to various user facilities. Expert systems will aid in the performance of the quality assurance and data accounting functions of the two SLDPF functional elements: the Spacelab Input Processing System (SIPS) and the Spacelab Output Processing System (SOPS). Prototypes were developed for each as independent efforts. The SIPS Knowledge System Prototype (KSP) used the commercial shell OPS5+ on an IBM PC/AT; the SOPS Expert System Prototype used the expert system shell CLIPS implemented on a Macintosh personal computer. Both prototypes emulate the duties of the respective QA/DA analysts based upon analyst input and predetermined mission criteria parameters, and recommended instructions and decisions governing the reprocessing, release, or holding for further analysis of data. These prototypes demonstrated feasibility and high potential for operational systems. Increase in productivity, decrease of tedium, consistency, concise historical records, and a training tool for new analyses were the principal advantages. An operational configuration, taking advantage of the SLDPF network capabilities, is under development with the expert systems being installed on SUN workstations. This new configuration in conjunction with the potential of the expert systems will enhance the efficiency, in both time and quality, of the SLDPF's release of Spacelab/AST data products.

  13. Spacelab data processing facility (SLDPF) Quality Assurance (QA)/Data Accounting (DA) expert systems: Transition from prototypes to operational systems

    Science.gov (United States)

    Basile, Lisa

    1988-01-01

    The SLDPF is responsible for the capture, quality monitoring processing, accounting, and shipment of Spacelab and/or Attached Shuttle Payloads (ASP) telemetry data to various user facilities. Expert systems will aid in the performance of the quality assurance and data accounting functions of the two SLDPF functional elements: the Spacelab Input Processing System (SIPS) and the Spacelab Output Processing System (SOPS). Prototypes were developed for each as independent efforts. The SIPS Knowledge System Prototype (KSP) used the commercial shell OPS5+ on an IBM PC/AT; the SOPS Expert System Prototype used the expert system shell CLIPS implemented on a Macintosh personal computer. Both prototypes emulate the duties of the respective QA/DA analysts based upon analyst input and predetermined mission criteria parameters, and recommended instructions and decisions governing the reprocessing, release, or holding for further analysis of data. These prototypes demonstrated feasibility and high potential for operational systems. Increase in productivity, decrease of tedium, consistency, concise historial records, and a training tool for new analyses were the principal advantages. An operational configuration, taking advantage of the SLDPF network capabilities, is under development with the expert systems being installed on SUN workstations. This new configuration in conjunction with the potential of the expert systems will enhance the efficiency, in both time and quality, of the SLDPF's release of Spacelab/AST data products.

  14. A role for gut-associated lymphoid tissue in shaping the human B cell repertoire.

    Science.gov (United States)

    Vossenkämper, Anna; Blair, Paul A; Safinia, Niloufar; Fraser, Louise D; Das, Lisa; Sanders, Theodore J; Stagg, Andrew J; Sanderson, Jeremy D; Taylor, Kirstin; Chang, Fuju; Choong, Lee M; D'Cruz, David P; Macdonald, Thomas T; Lombardi, Giovanna; Spencer, Jo

    2013-08-26

    We have tracked the fate of immature human B cells at a critical stage in their development when the mature B cell repertoire is shaped. We show that a major subset of bone marrow emigrant immature human B cells, the transitional 2 (T2) B cells, homes to gut-associated lymphoid tissue (GALT) and that most T2 B cells isolated from human GALT are activated. Activation in GALT is a previously unknown potential fate for immature human B cells. The process of maturation from immature transitional B cell through to mature naive B cell includes the removal of autoreactive cells from the developing repertoire, a process which is known to fail in systemic lupus erythematosus (SLE). We observe that immature B cells in SLE are poorly equipped to access the gut and that gut immune compartments are depleted in SLE. Thus, activation of immature B cells in GALT may function as a checkpoint that protects against autoimmunity. In healthy individuals, this pathway may be involved in generating the vast population of IgA plasma cells and also the enigmatic marginal zone B cell subset that is poorly understood in humans.

  15. B cells exposed to enterobacterial components suppress development of experimental colitis

    DEFF Research Database (Denmark)

    Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

    2012-01-01

    ). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

  16. B Cells Promote Th1- Skewed NKT Cell Response by CD1d-TCR Interaction.

    Science.gov (United States)

    Shin, Jung Hoon; Park, Se-Ho

    2013-10-01

    CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although α-galactosylceramide (α-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-γ by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.

  17. Compliance and quality control monitoring of diagnostic X-ray facilities in Dar es Salaam city, Tanzania

    Energy Technology Data Exchange (ETDEWEB)

    Nkuba, Leonid L.; Nyanda, Pendo B., E-mail: leonid.nkuba@taec.or.tz [Tanzania Atomic Energy Commission, Radiation Control Directorate, Dar es Salaam (Tanzania, United Republic of)

    2017-09-01

    The compliance evaluation and quality control measurements on 60 diagnostic X-ray units were performed. The results on legal compliance show that 25 % of X-ray facilities operated without or with an expired license. The rest of the centers were new and had already applied for license and others had valid licenses. For basic requirements compliance, 47 % of X-ray facilities did not have the changing cubicles, 37 % of X-ray facilities did not post radiation warning sign and symbols also 46 % of units were found either without protective gear or operated by unqualified personnel. The QC test results showed that 93 % had X-ray tube voltage within the tolerance limit of 10 % and HVL ≥ 2.3 mmAl, at 80 kV was observed in 98.2 % of the units, whereas 98 % of exposure had acceptable kV reproducibility within the tolerance limit of 5 %. Of the X-ray generators assessed, 93 % had tolerable mAs linearity. 93 % and 97 % had acceptable beam alignment and light beam diaphragm. Of the assessed units, 13 (93 %) had tube leakage < 1000 μGy/hr at 1m. For shielding tests, 47 % of units had radiation levels above 0.5 μSv/hr at the main door leading to the X-ray rooms and the registration area. The dose rates > 10 μSv/hr were recorded at viewing windows, walls and doors of control cubicles and behind the doors of changing cubicles. These dose rates indicating higher health risk to workers and member of public. (author)

  18. Wayfinding: a quality factor in human design approach to healthcare facilities.

    Science.gov (United States)

    Del Nord, R

    1999-01-01

    The specific aim of this paper is the systematic analysis of interactions and reciprocal conditions existing between the physical space of hospital buildings and the different categories of individuals that come in contact with them. The physical and environmental facilities of hospital architecture often influence the therapeutic character of space and the employees. If the values of the individual are to be safeguarded in this context, priority needs to be given to such factors as communication, privacy, etc. This would mean the involvement of other professional groups such as psychologists, sociologists, ergonomists, etc. at the hospital building planning stage. This paper will outline the result of some research conducted at the University Research Center "TESIS" of Florence to provide better understanding of design strategies applied to reduce the pathology of spaces within the healthcare environment. The case studies will highlight the parameters and the possible architectural solutions to wayfinding and the humanization of spaces, with particular emphasis on lay-outs, technologies, furniture and finishing design.

  19. A novel marine mesocosm facility to study global warming, water quality, and ocean acidification.

    Science.gov (United States)

    Duarte, Gustavo; Calderon, Emiliano N; Pereira, Cristiano M; Marangoni, Laura F B; Santos, Henrique F; Peixoto, Raquel S; Bianchini, Adalto; Castro, Clovis B

    2015-10-01

    We describe a completely randomizable flow-through outdoor mesocosm for climate change and ecotoxicology studies that was built with inexpensive materials. The 16 raceway tanks allow up to 6× water renewal per hour, avoiding changes in natural abiotic seawater conditions. We use an open-source hardware board (Arduino) that was adapted to control heaters and an innovative CO 2 injection system. This system reduced seawater pH up to -0.9 units and increased temperature up to +6°C in three treatments and a control. Treatments can be continuously compared with the control and vary according to diel fluctuations, thus following the diel range observed in the sea. The mesocosm facility also includes an integrated secondary system of 48 aquaria for ecotoxicology studies. We validated the reproducibility and relevance of our experimental system by analyzing the variation of the total DNA of the microbial community extracted from corals in three elevated temperature scenarios during a 40-day experiment. We also present data from temperature, acidification, and copper contamination trials, which allowed continuous, reliable, and consistent treatment manipulations.

  20. The water exercise improves health-related quality of life of frail elderly people at day service facility.

    Science.gov (United States)

    Sato, Daisuke; Kaneda, Koichi; Wakabayashi, Hitoshi; Nomura, Takeo

    2007-12-01

    The purpose of this study was to investigate the effects of water exercise at a day service facility and the effects of water exercise frequency on health-related quality of life (HRQL). Participants (n = 30) were randomly separated into three groups: two indicating exercise frequency, at once-weekly or twice-weekly, and a control group. One-hour exercise intervention sessions were carried out once or twice a week, accordingly, for 24 weeks. The water exercise session comprised a warm-up on land, activities of daily living (ADL) exercises, stretching, strength training, and relaxation in water. HRQL was evaluated using the Medical Outcomes Survey Short-Form 36 (SF-36) questionnaire, and ADL disability was assessed using the Functional Independence Measure. Significant differences were found between pre- and 6 months in both the once- and twice-weekly groups in HRQL (p service facility improved participants' HRQL for 6 months by improving exercise habits and ADL disability. Furthermore, the HRQL change differed according to exercise frequency: twice-weekly exercise showed more rapid improvement than once-weekly.

  1. Signals from activation of B-cell receptor with anti-IgD can override the stimulatory effects of excess BAFF on mature B cells in vivo.

    Science.gov (United States)

    Nguyen, Tue G; Morris, Jonathan M

    2014-09-01

    The selection and maturation of B-cell clones are critically determined by tonic signals from activated B cell receptors (BCR) and survival signals from BAFF cytokine. These finely tuned and coordinated signals provide a net positive signal that can promote the selection, maturation, proliferation and differentiation of a developing B cell. Stimulation with an anti-IgD antibody can also activate BCR but can lead to depletion and an arrest of mature B-cell development in vivo. It is not known whether survival signals from excess BAFF can override the suppressive effects of treatment with anti-IgD on mature B cells in vivo. Herein, we examined the effects of co-treatment of BAFF and anti-IgD on the mature B-cell compartment and antibody production in vivo by treating mice with either 1mg/kg BAFF or anti-IgD alone or in combination for 3 consecutive days. We found that co-treatment with anti-IgD significantly abrogated these stimulatory effects of BAFF treatment on splenic CD19+ B cells as well as mature CD19+IgD(hi)IgM+ B cells in vivo. Anti-IgD down-regulated the expression of the BCR complex (mIgM, mIgD and CD19) and the BAFF receptor TACI without regard to the presence of BAFF. Anti-IgD treatment also significantly negated BAFF-induced IgM production in vivo. Both BAFF and anti-IgD could individually stimulate IL-10 synthesis in B cells but did not affect one another. Taken together, our data suggest that activation of BCR with an anti-IgD antibody can override the stimulatory effects from excess BAFF on B cell proliferation and antibody production by down-regulating the expression of BCR complex and BAFF receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Hoxa9 collaborates with E2A-PBX1 in mouse B cell leukemia in association with Flt3 activation and decrease of B cell gene expression.

    Science.gov (United States)

    Hassawi, Mona; Shestakova, Elena A; Fournier, Marilaine; Lebert-Ghali, Charles-Étienne; Vaisson, Gratianne; Frison, Héloïse; Sinnett, Daniel; Vidal, Ramon; Thompson, Alexander; Bijl, Janet J

    2014-01-01

    The fusion protein E2A-PBX1 induces pediatric B cell leukemia in human. Previously, we reported oncogenic interactions between homeobox (Hox) genes and E2A-PBX1 in murine T cell leukemia. A proviral insertional mutagenesis screen with our E2A-PBX1 B cell leukemia mouse model identified Hoxa genes as potential collaborators to E2A-PBX1. Here we studied whether Hoxa9 could enhance E2A-PBX1 leukemogenesis. We show that Hoxa9 confers a proliferative advantage to E2A-PBX1 B cells. Transplantation experiments with E2A-PBX1 transgenic B cells overexpressing Hoxa9 isolated from bone marrow chimeras showed that Hoxa9 accelerates the generation of E2A-PBX1 B cell leukemia, but Hoxa9 is unable to transform B cells alone. Quantitative-reverse transcriptase polymerase chain reaction analysis demonstrated a strong repression of B cell specific genes in these E2A-PBX1/Hoxa9 leukemias in addition to Flt3 activation, indicating inhibition of B cell differentiation in combination with enhanced proliferation. Overexpression of Hoxa9 in established E2A-PBX1 mouse leukemic B cells resulted in a growth advantage in vitro, which was also characterized by an enhanced expression of Flt3. we show for the first time that Hoxa9 collaborates with E2A-PBX1 in the oncogenic transformation of B cells in a mouse model that involves Flt3 signaling, which is potentially relevant to human disease. Copyright © 2013 Wiley Periodicals, Inc.

  3. Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.

    Science.gov (United States)

    Ota, Yuri; Niiro, Hiroaki; Ota, Shun-Ichiro; Ueki, Naoko; Tsuzuki, Hirofumi; Nakayama, Tsuyoshi; Mishima, Koji; Higashioka, Kazuhiko; Jabbarzadeh-Tabrizi, Siamak; Mitoma, Hiroki; Akahoshi, Mitsuteru; Arinobu, Yojiro; Kukita, Akiko; Yamada, Hisakata; Tsukamoto, Hiroshi; Akashi, Koichi

    2016-03-16

    The efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation. Peripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells. RANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro. Our current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.

  4. B cell follicle-like structures in multiple sclerosis-with focus on the role of B cell activating factor

    DEFF Research Database (Denmark)

    Morten, Haugen; Frederiksen, Jette L; Vinter, Matilda Degn

    2014-01-01

    B lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). Follicle-like structures (FLS) have recently been found in the subarachnoid space in the leptomeninges in some patients with secondary progressive MS (SPMS). They contain proliferating B lymphocytes, plasma cells......, helper T lymphocytes and a network of follicular dendritic cells. FLS have been shown to correlate with increased cortical demyelination, neuronal loss, meningeal infiltration and central nervous system inflammation, as well as lower age at disease onset and progression to severe disability and death....... In this review, we will discuss the role of FLS in MS pathogenesis and disease course and the possible influence by B cell activating factor (BAFF) and C-X-C motif chemokine 13 (CXCL13)....

  5. TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Loo, Suet K; Ch'ng, Ewe S; Md Salleh, Md Salzihan

    2017-01-01

    immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly...... to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographic parameters and survival in DLBCL. METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared......-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P

  6. The Earthscope USArray Array Network Facility (ANF): Metadata, Network and Data Monitoring, Quality Assurance During the Second Year of Operations

    Science.gov (United States)

    Eakins, J. A.; Vernon, F. L.; Martynov, V.; Newman, R. L.; Cox, T. A.; Lindquist, K. L.; Hindley, A.; Foley, S.

    2005-12-01

    The Array Network Facility (ANF) for the Earthscope USArray Transportable Array seismic network is responsible for: the delivery of all Transportable Array stations (400 at full deployment) and telemetered Flexible Array stations (up to 200) to the IRIS Data Management Center; station command and control; verification and distribution of metadata; providing useful remotely accessible world wide web interfaces for personnel at the Array Operations Facility (AOF) to access state of health information; and quality control for all data. To meet these goals, we use the Antelope software package to facilitate data collection and transfer, generation and merging of the metadata, real-time monitoring of dataloggers, generation of station noise spectra, and analyst review of individual events. Recently, an Antelope extension to the PHP scripting language has been implemented which facilitates the dynamic presentation of the real-time data to local web pages. Metadata transfers have been simplified by the use of orb transfer technologies at the ANF and receiver end points. Web services are being investigated as a means to make a potentially complicated set of operations easy to follow and reproduce for each newly installed or decommissioned station. As part of the quality control process, daily analyst review has highlighted areas where neither the regional network bulletins nor the USGS global bulletin have published solutions. Currently four regional networks (Anza, BDSN, SCSN, and UNR) contribute data to the Transportable Array with additional contributors expected. The first 100 stations (42 new Earthscope stations) were operational by September 2005 with all but one of the California stations installed. By year's end, weather permitting, the total number of stations deployed is expected to be around 145. Visit http://anf.ucsd.edu for more information on the project and current status.

  7. The controversial impact of B cells subsets on immune response to pneumococcal vaccine in HIV-1 patients

    Directory of Open Access Journals (Sweden)

    Olga Tsachouridou

    2015-09-01

    Conclusions: Low concentrations of total B cells and exhausted memory B cells was the strongest independent predictor of poor pneumococcal vaccine responsiveness, emphasizing that B cell subset disturbances are associated with a poor vaccine response among HIV-infected patients.

  8. Subsurface intakes for seawater reverse osmosis facilities: Capacity limitation, water quality improvement, and economics

    KAUST Repository

    Missimer, Thomas M.

    2013-08-01

    The use of subsurface intake systems for seawater reverse osmosis (SWRO) desalination plants significantly improves raw water quality, reduces chemical usage and environmental impacts, decreases the carbon footprint, and reduces cost of treated water to consumers. These intakes include wells (vertical, angle, and radial type) and galleries, which can be located either on the beach or in the seabed. Subsurface intakes act both as intakes and as part of the pretreatment system by providing filtration and active biological treatment of the raw seawater. Recent investigations of the improvement in water quality made by subsurface intakes show lowering of the silt density index by 75 to 90%, removal of nearly all algae, removal of over 90% of bacteria, reduction in the concentrations of TOC and DOC, and virtual elimination of biopolymers and polysaccharides that cause organic biofouling of membranes. Economic analyses show that overall SWRO operating costs can be reduced by 5 to 30% by using subsurface intake systems. Although capital costs can be slightly to significantly higher compared to open-ocean intake system costs, a preliminary life-cycle cost analysis shows significant cost saving over operating periods of 10 to 30. years. © 2013 Elsevier B.V.

  9. Activity involvement and quality of life of people at different stages of dementia in long term care facilities.

    Science.gov (United States)

    Smit, Dieneke; de Lange, Jacomine; Willemse, Bernadette; Twisk, Jos; Pot, Anne Margriet

    2016-01-01

    Involvement in activities is assumed to positively influence the quality of life of people with dementia, yet activity provision in long-term care remains limited. This study aims to provide more insight into the value of activity involvement for domains of the quality of life of long-term dementia care residents, taking resident characteristics and cognitive status into account. Data were derived from 144 long-term care facilities participating in the second measurement (2010/2011) of the living arrangements for dementia study. Amongst 1144 residents, the relationship between time involved in activities (activity pursuit patterns; RAI-MDS) and quality of life (Qualidem) was studied using multilevel linear regression analyses. Analyses were adjusted for residents' age, gender, neuropsychiatric symptoms, ADL dependency and cognition. To check for effect modification of cognition, interactions terms of the variables activity involvement and cognitive status were added to the analyses. Despite resident's cognitive status, their activity involvement was significantly related to better scores on care relationship, positive affect, restless tense behaviour, social relations, and having something to do. A negative relationship existed between the activity involvement and positive self-image. The explained variance in the quality of life between residents caused by the activity involvement was small. Activity involvement seems to be a small yet important contributor to higher well-being in long-term care resident at all stages of dementia. Adjusting activities to individual preferences and capabilities might enlarge this relationship. Further research is needed to confirm this hypothesis, using measurement instruments less sensitive to recall bias and differentiating between the active and passive activity involvement.

  10. JCAR014 and Durvalumab in Treating Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-02

    BCL2 Gene Rearrangement; BCL6 Gene Rearrangement; CD19 Positive; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; High-Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; MYC Gene Rearrangement; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  11. The meteorological monitoring audit, preventative maintenance and quality assurance programs at a former nuclear weapons facility

    Energy Technology Data Exchange (ETDEWEB)

    Maxwell, D.R. [DynCorp of Colorado, Inc., Golden, CO (United States). Rocky Flats Environmental Technology Site

    1995-12-31

    The purposes of the meteorological monitoring audit, preventative maintenance, and quality assurance programs at the Rocky Flats Environmental Technology Site (Site), are to (1) support Emergency Preparedness (EP) programs at the Site in assessing the transport, dispersion, and deposition of effluents actually or potentially released into the atmosphere by Site operations; and (2) provide information for onsite and offsite projects concerned with the design of environmental monitoring networks for impact assessments, environmental surveillance activities, and remediation activities. The risk from the Site includes chemical and radioactive emissions historically related to nuclear weapons component production activities that are currently associated with storage of large quantities of radionuclides (plutonium) and radioactive waste forms. The meteorological monitoring program provides information for site-specific weather forecasting, which supports Site operations, employee safety, and Emergency Preparedness operations.

  12. The meteorological monitoring audit, preventative maintenance and quality assurance programs at a former nuclear weapons facility

    International Nuclear Information System (INIS)

    Maxwell, D.R.

    1995-01-01

    The purposes of the meteorological monitoring audit, preventative maintenance, and quality assurance programs at the Rocky Flats Environmental Technology Site (Site), are to (1) support Emergency Preparedness (EP) programs at the Site in assessing the transport, dispersion, and deposition of effluents actually or potentially released into the atmosphere by Site operations; and (2) provide information for onsite and offsite projects concerned with the design of environmental monitoring networks for impact assessments, environmental surveillance activities, and remediation activities. The risk from the Site includes chemical and radioactive emissions historically related to nuclear weapons component production activities that are currently associated with storage of large quantities of radionuclides (plutonium) and radioactive waste forms. The meteorological monitoring program provides information for site-specific weather forecasting, which supports Site operations, employee safety, and Emergency Preparedness operations

  13. [Composting facilities. 1. Microbiological quality of compost with special regard to disposable diapers].

    Science.gov (United States)

    Jager, E; Rüden, H; Zeschmar-Lahl, B

    1994-10-01

    At three different composting facilities, co-composting of used panty diapers with an addition of 10% (weight) to the usual plant input was investigated for various hygienic and microbiological parameters. In nearly any case, a sufficient degree of germ reduction above 99.9% could be observed by determination of reduction rates of B. subtilis spores. The concentrations of "total microorganisms" ranged from 3.9 x 10(5) to 3.3 x 10(11) colony forming units per gram compost (CFU/g) in composts without and from 3.3 x 10(5) to 4.7 x 10(9) CFU/g in composts with panty diapers in the input. The concentrations of "gram-negative bacteria" ranged from 3.3 x 10(4) to 1.3 x 10(9) CFU/g (without panty diapers) resp. from 3.3 x 10(5) to 3.5 x 10(8) CFU/g (with panty diapers), the concentrations of "fecal streptococci" from 1.7 x 10(3) to 7.7 x 10(7) CFU/g (without panty diapers) resp. from 1.4 x 10(4) to 1.4 x 10(8) CFU/g (with panty diapers). Facultatively pathogenic microorganisms showed a broad variety, but no common trend in composts with and without panty diapers in the input. Statistical validity of the determination of contents of microorganisms in compost samples was guaranteed by the collection and analysis of 20 parallel samples with an average sample mass of 10 to 15 kg. From the analyzed quantitative and qualitative hygienic-microbiological parameters, it can be concluded that no negative hygienic-microbiological effects, caused by the addition of 10% (weight) of used panty diapers in the input, have to be expected. Under the aspects of epidemiologic hygiene, composting of used panty diapers together with usual input materials seems to cause no increased risks under the tested conditions. Under the aspect of consumer protection, there is no increase in the risk of infection when using compost produced with addition of panty diapers, compared to compost produced without panty diaper addition to the input.

  14. SAP modulates B cell functions in a genetic background-dependent manner.

    Science.gov (United States)

    Detre, Cynthia; Yigit, Burcu; Keszei, Marton; Castro, Wilson; Magelky, Erica M; Terhorst, Cox

    2013-06-01

    Mutations affecting the SLAM-associated protein (SAP) are responsible for the X-linked lympho-proliferative syndrome (XLP), a severe primary immunodeficiency syndrome with disease manifestations that include fatal mononucleosis, B cell lymphoma and dysgammaglobulinemia. It is well accepted that insufficient help by SAP-/- CD4+ T cells, in particular during the germinal center reaction, is a component of dysgammaglobulinemia in XLP patients and SAP-/- animals. It is however not well understood whether in XLP patients and SAP-/- mice B cell functions are affected, even though B cells themselves do not express SAP. Here we report that B cell intrinsic responses to haptenated protein antigens are impaired in SAP-/- mice and in Rag-/- mice into which B cells derived from SAP-/- mice together with wt CD4+ T cells had been transferred. This impaired B cells functions are in part depending on the genetic background of the SAP-/- mouse, which affects B cell homeostasis. Surprisingly, stimulation with an agonistic anti-CD40 causes strong in vivo and in vitro B cell responses in SAP-/- mice. Taken together, the data demonstrate that genetic factors play an important role in the SAP-related B cell functions. The finding that anti-CD40 can in part restore impaired B cell responses in SAP-/- mice, suggests potentially novel therapeutic interventions in subsets of XLP patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Alterations on peripheral B cell subsets following an acute uncomplicated clinical malaria infection in children

    Directory of Open Access Journals (Sweden)

    Ng'ang'a Zipporah W

    2008-11-01

    Full Text Available Abstract Background The effects of Plasmodium falciparum on B-cell homeostasis have not been well characterized. This study investigated whether an episode of acute malaria in young children results in changes in the peripheral B cell phenotype. Methods Using flow-cytofluorimetric analysis, the B cell phenotypes found in the peripheral blood of children aged 2–5 years were characterized during an episode of acute uncomplicated clinical malaria and four weeks post-recovery and in healthy age-matched controls. Results There was a significant decrease in CD19+ B lymphocytes during acute malaria. Characterization of the CD19+ B cell subsets in the peripheral blood based on expression of IgD and CD38 revealed a significant decrease in the numbers of naive 1 CD38-IgD+ B cells while there was an increase in CD38+IgD- memory 3 B cells during acute malaria. Further analysis of the peripheral B cell phenotype also identified an expansion of transitional CD10+CD19+ B cells in children following an episode of acute malaria with up to 25% of total CD19+ B cell pool residing in this subset. Conclusion Children experiencing an episode of acute uncomplicated clinical malaria experienced profound disturbances in B cell homeostasis.

  16. Characteristics of B-cell-specific growth substance produced by Bacillus licheniformis E1.

    Science.gov (United States)

    Kim, Joo Young; Chung, Kun Sub; Park, Jeon Han; Kwak, Yi-Sub; Lee, Bong Ki

    2009-01-01

    A B cell-specific growth substance (BGS) was isolated from the slime layer of Bacillus licheniformis E1. Unlike LPS, the BGS was not affected by polymixin B, an inhibitor of LPS, or by TLR4, and resulted in the growth of B cells. When BALB/c mice were treated with the BGS, the B cell population was found to increase in both the bone marrow and the spleen, with a marked increase after 24 h in the bone marrow and after 48 h in the spleen. When using antibodies to B cell lineage-restricted surface molecules to analyze the B cell population changes resulting from treatment with the BGS, an increase in immature B cells (IgM(+) and AA4.1(+)) and mature B cells (IgM(+) and IgD(+)) was found in the bone marrow 24 h after treatment with the BGS, whereas a decrease in mature B cells and increase in IgG(+) B cells were found in the spleen. When the BGS and OVA antigen were injected into the peritoneal cavity of BALB/c mice, this resulted in a high OVA-specific antibody titer in the sera, similar to that induced by aluminum hydroxide. Therefore, it is anticipated that the mass production of the BGS by B. licheniformis E1 could be used for studies of B cells in immunology, and contribute to the development of a new adjuvant for vaccine manufacture.

  17. A two-scale model for correlation between B cell VDJ usage in zebrafish

    Science.gov (United States)

    Pan, Keyao; Deem, Michael

    2011-03-01

    The zebrafish (Danio rerio) is one of the model animals for study of immunology. The dynamics of the adaptive immune system in zebrafish is similar to that in higher animals. In this work, we built a two-scale model to simulate the dynamics of B cells in primary and secondary immune reactions in zebrafish and to explain the reported correlation between VDJ usage of B cell repertoires in distinct zebrafish. The first scale of the model consists of a generalized NK model to simulate the B cell maturation process in the 10-day primary immune response. The second scale uses a delay ordinary differential equation system to model the immune responses in the 6-month lifespan of zebrafish. The generalized NK model shows that mature B cells specific to one antigen mostly possess a single VDJ recombination. The probability that mature B cells in two zebrafish have the same VDJ recombination increases with the B cell population size or the B cell selection intensity and decreases with the B cell hypermutation rate. The ODE model shows a distribution of correlation in the VDJ usage of the B cell repertoires in two six-month-old zebrafish that is highly similar to that from experiment. This work presents a simple theory to explain the experimentally observed correlation in VDJ usage of distinct zebrafish B cell repertoires after an immune response.

  18. IL-4Rα-associated antigen processing by B cells promotes immunity in Nippostrongylus brasiliensis infection.

    Directory of Open Access Journals (Sweden)

    William G C Horsnell

    2013-10-01

    Full Text Available In this study, B cell function in protective T(H2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα⁻/⁻ mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4⁺ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88⁻/⁻ B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4⁺ T cell-mediated protective immunity against N. brasiliensis infection.

  19. B cells in chronic obstructive pulmonary disease: moving to center stage

    Science.gov (United States)

    Polverino, Francesca; Seys, Leen J. M.; Bracke, Ken R.

    2016-01-01

    Chronic inflammatory responses in the lungs contribute to the development and progression of chronic obstructive pulmonary disease (COPD). Although research studies focused initially on the contributions of the innate immune system to the pathogenesis of COPD, more recent studies have implicated adaptive immune responses in COPD. In particular, studies have demonstrated increases in B cell counts and increases in the number and size of B cell-rich lymphoid follicles in COPD lungs that correlate directly with COPD severity. There are also increases in lung levels of mediators that promote B cell maturation, activation, and survival in COPD patients. B cell products such as autoantibodies directed against lung cells, components of cells, and extracellular matrix proteins are also present in COPD lungs. These autoantibodies may contribute to lung inflammation and injury in COPD patients, in part, by forming immune complexes that activate complement components. Studies of B cell-deficient mice and human COPD patients have linked B cells most strongly to the emphysema phenotype. However, B cells have protective activities during acute exacerbations of COPD by promoting adaptive immune responses that contribute to host defense against pathogens. This review outlines the evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD and the mechanisms involved. It also reviews the potential and limitations of B cells as therapeutic targets to slow the progression of human COPD. PMID:27542809

  20. IL-4Rα-Associated Antigen Processing by B Cells Promotes Immunity in Nippostrongylus brasiliensis Infection

    Science.gov (United States)

    Hoving, Jennifer C.; Nieuwenhuizen, Natalie; McSorley, Henry J.; Ndlovu, Hlumani; Bobat, Saeeda; Kimberg, Matti; Kirstein, Frank; Cutler, Anthony J.; DeWals, Benjamin; Cunningham, Adam F.; Brombacher, Frank

    2013-01-01

    In this study, B cell function in protective TH2 immunity against N. brasiliensis infection was investigated. Protection against secondary infection depended on IL-4Rα and IL-13; but not IL-4. Protection did not associate with parasite specific antibody responses. Re-infection of B cell-specific IL-4Rα−/− mice resulted in increased worm burdens compared to control mice, despite their equivalent capacity to control primary infection. Impaired protection correlated with reduced lymphocyte IL-13 production and B cell MHC class II and CD86 surface expression. Adoptive transfer of in vivo N. brasiliensis primed IL-4Rα expressing B cells into naïve BALB/c mice, but not IL-4Rα or IL-13 deficient B cells, conferred protection against primary N. brasiliensis infection. This protection required MHC class II compatibility on B cells suggesting cognate interactions by B cells with CD4+ T cells were important to co-ordinate immunity. Furthermore, the rapid nature of these protective effects by B cells suggested non-BCR mediated mechanisms, such as via Toll Like Receptors, was involved, and this was supported by transfer experiments using antigen pulsed Myd88−/− B cells. These data suggest TLR dependent antigen processing by IL-4Rα-responsive B cells producing IL-13 contribute significantly to CD4+ T cell-mediated protective immunity against N. brasiliensis infection. PMID:24204255

  1. Induction of polyclonal B cell activation and differentiation by the AIDS retrovirus (HTLV-III/LAV)

    International Nuclear Information System (INIS)

    Higgins, S.E.; Schnittman, S.M.; Lane, H.C.; Folks, T.; Koenig, S.; Fauci, A.S.

    1986-01-01

    The immune systems of individuals infected with HTLV-III/LAV are characterized by a profound defect in cellular immunity together with paradoxical polyclonal B cell activation. The present study examined the direct effects of HTLV-III/LAV on B lymphocytes. Peripheral blood B cells from healthy donors were incubated with a variety of HTLV-III/LAV isolates for 1 h and 3 H-thymidine incorporation was measured at multiple time points. Responses ranged from 9000-28,000 cpm and peaked on day 4. This B cell activation was not enhanced by the addition of interleukin-2 to culture, was not synergistic with Staphylococcus aureus Cowan I, was not modulated by the addition of T lymphocytes to culture, and was not associated with B cell transformation. Supernatant Ig could first be detected in virus-activated cultures at day 4, plateaued by day 8, and yielded a mean of 12,500 ng IgG+IgM/ml/50,000 B cells. Thus, HTLV-III/LAV is a potent T cell independent B cell mitogen capable of inducing B cell activation, proliferation, and differentiation comparable in magnitude to that of the most potent B cell activators. This biological property of HTLV-III/LAV may help explain the profound polyclonal B cell activation observed in patients with AIDS and may provide investigators with another probe for investigating the mechanisms of B cell activation

  2. Interleukin-21 enhances rituximab activity in a cynomolgus monkey model of B cell depletion and in mouse B cell lymphoma models.

    Directory of Open Access Journals (Sweden)

    Cecile M Krejsa

    Full Text Available Rituximab, a monoclonal antibody targeting CD20 on B cells, is currently used to treat many subtypes of B cell lymphomas. However, treatment is not curative and response rates are variable. Recombinant interleukin-21 (rIL-21 is a cytokine that enhances immune effector function and affects both primary and transformed B cell differentiation. We hypothesized that the combination of rIL-21 plus rituximab would be a more efficacious treatment for B cell malignancies than rituximab alone. We cultured human and cynomolgus monkey NK cells with rIL-21 and found that their activity was increased and proteins associated with antibody dependent cytotoxicity were up-regulated. Studies in cynomolgus monkeys modeled the effects of rIL-21 on rituximab activity against CD20 B cells. In these studies, rIL-21 activated innate immune effectors, increased ADCC and mobilized B cells into peripheral blood. When rIL-21 was combined with rituximab, deeper and more durable B cell depletion was observed. In another series of experiments, IL-21 was shown to have direct antiproliferative activity against a subset of human lymphoma cell lines, and combination of murine IL-21 with rituximab yielded significant survival benefits over either agent alone in xenogeneic mouse tumor models of disseminated lymphoma. Therefore, our results do suggest that the therapeutic efficacy of rituximab may be improved when used in combination with rIL-21.

  3. CD19 CAR-targeted T cells induce long-term remission and B Cell Aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Marco L Davila

    Full Text Available Although many adults with B cell acute lymphoblastic leukemia (B-ALL are induced into remission, most will relapse, underscoring the dire need for novel therapies for this disease. We developed murine CD19-specific chimeric antigen receptors (CARs and an immunocompetent mouse model of B-ALL that recapitulates the disease at genetic, cellular, and pathologic levels. Mouse T cells transduced with an all-murine CD3ζ/CD28-based CAR that is equivalent to the one being used in our clinical trials, eradicate B-ALL in mice and mediate long-term B cell aplasias. In this model, we find that increasing conditioning chemotherapy increases tumor eradication, B cell aplasia, and CAR-modified T cell persistence. Quantification of recipient B lineage cells allowed us to estimate an in vivo effector to endogenous target ratio for B cell aplasia maintenance. In mice exhibiting a dramatic B cell reduction we identified a small population of progenitor B cells in the bone marrow that may serve as a reservoir for long-term CAR-modified T cell stimulation. Lastly, we determine that infusion of CD8+ CAR-modified T cells alone is sufficient to maintain long-term B cell eradication. The mouse model we report here should prove valuable for investigating CAR-based and other therapies for adult B-ALL.

  4. A critical role of the Thy28-MYH9 axis in B cell-specific expression of the Pax5 gene in chicken B cells.

    Directory of Open Access Journals (Sweden)

    Toshitsugu Fujita

    Full Text Available Accumulating evidence suggests that Pax5 plays essential roles in B cell lineage commitment. However, molecular mechanisms of B cell-specific expression of Pax5 are not fully understood. Here, we applied insertional chromatin immunoprecipitation (iChIP combined with stable isotope labeling using amino acids in cell culture (SILAC (iChIP-SILAC to direct identification of proteins interacting with the promoter region of the endogenous single-copy chicken Pax5 gene. By comparing B cells with macrophage-like cells trans-differentiated by ectopic expression of C/EBPβ, iChIP-SILAC detected B cell-specific interaction of a nuclear protein, Thy28/Thyn1, with the Pax5 1A promoter. Trans-differentiation of B cells into macrophage-like cells caused down-regulation of Thy28 expression. Loss-of-function of Thy28 induced decrease in Pax5 expression and recruitment of myosin-9 (MYH9, one of Thy28-interacting proteins, to the Pax5 1A promoter. Loss-of-function of MYH9 also induced decrease in Pax5 expression. Thus, our analysis revealed that Thy28 is functionally required for B cell-specific expression of Pax5 via recruitment of MYH9 to the Pax5 locus in chicken B cells.

  5. Maintaining Quality of Candidate Strains of Transgenic Mosquitoes for Studies in Containment Facilities in Disease Endemic Countries.

    Science.gov (United States)

    Mumford, John D; Leach, Adrian W; Benedict, Mark Q; Facchinelli, Luca; Quinlan, M Megan

    2018-01-01

    Transgenic mosquitoes are being developed as novel components of area-wide approaches to vector-borne disease control. Best practice is to develop these in phases, beginning with laboratory studies, before moving to field testing and inclusion in control programs, to ensure safety and prevent costly field testing of unsuitable strains. The process of identifying and developing good candidate strains requires maintenance of transgenic colonies over many generations in containment facilities. By working in disease endemic countries with target vector populations, laboratory strains may be developed and selected for properties that will enhance intended control efficacy in the next phase, while avoiding traits that introduce unnecessary risks. Candidate strains aiming toward field use must consistently achieve established performance criteria, throughout the process of scaling up from small study colonies to production of sufficient numbers for field testing and possible open release. Maintenance of a consistent quality can be demonstrated by a set of insect quality and insectary operating indicators, measured over time at predetermined intervals. These indicators: inform comparability of studies using various candidate strains at different times and locations; provide evidence of conformity relevant to compliance with terms of approval for regulated use; and can be used to validate some assumptions related to risk assessments covering the contained phase and for release into the environment.

  6. Splenectomy associated changes in IgM memory B cells in an adult spleen registry cohort.

    Directory of Open Access Journals (Sweden)

    Paul U Cameron

    Full Text Available Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591. A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140 were tested for IgM memory B cells. We also determined a changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b the kinetics of changes in haematological markers associated with splenectomy(n = 45. Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001 reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB, occurred early (median 25 days and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.

  7. Splenectomy Associated Changes in IgM Memory B Cells in an Adult Spleen Registry Cohort

    Science.gov (United States)

    Cameron, Paul U.; Jones, Penelope; Gorniak, Malgorzata; Dunster, Kate; Paul, Eldho; Lewin, Sharon; Woolley, Ian; Spelman, Denis

    2011-01-01

    Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591). A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140) were tested for IgM memory B cells. We also determined a) changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b) the kinetics of changes in haematological markers associated with splenectomy(n = 45). Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (psplenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB), occurred early (median 25 days) and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population. PMID:21829713

  8. Development and Validation of an Index to Measure the Quality of Facility-Based Labor and Delivery Care Processes in Sub-Saharan Africa.

    Directory of Open Access Journals (Sweden)

    Vandana Tripathi

    Full Text Available High quality care is crucial in ensuring that women and newborns receive interventions that may prevent and treat birth-related complications. As facility deliveries increase in developing countries, there are concerns about service quality. Observation is the gold standard for clinical quality assessment, but existing observation-based measures of obstetric quality of care are lengthy and difficult to administer. There is a lack of consensus on quality indicators for routine intrapartum and immediate postpartum care, including essential newborn care. This study identified key dimensions of the quality of the process of intrapartum and immediate postpartum care (QoPIIPC in facility deliveries and developed a quality assessment measure representing these dimensions.Global maternal and neonatal care experts identified key dimensions of QoPIIPC through a modified Delphi process. Experts also rated indicators of these dimensions from a comprehensive delivery observation checklist used in quality surveys in sub-Saharan African countries. Potential QoPIIPC indices were developed from combinations of highly-rated indicators. Face, content, and criterion validation of these indices was conducted using data from observations of 1,145 deliveries in Kenya, Madagascar, and Tanzania (including Zanzibar. A best-performing index was selected, composed of 20 indicators of intrapartum/immediate postpartum care, including essential newborn care. This index represented most dimensions of QoPIIPC and effectively discriminated between poorly and well-performed deliveries.As facility deliveries increase and the global community pays greater attention to the role of care quality in achieving further maternal and newborn mortality reduction, the QoPIIPC index may be a valuable measure. This index complements and addresses gaps in currently used quality assessment tools. Further evaluation of index usability and reliability is needed. The availability of a streamlined

  9. TGFβ activated kinase 1 (TAK1 at the crossroad of B cell receptor and Toll-like receptor 9 signaling pathways in human B cells.

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    Dániel Szili

    Full Text Available B cell development and activation are regulated by combined signals mediated by the B cell receptor (BCR, receptors for the B-cell activating factor of the tumor necrosis factor family (BAFF-R and the innate receptor, Toll-like receptor 9 (TLR9. However, the underlying mechanisms by which these signals cooperate in human B cells remain unclear. Our aim was to elucidate the key signaling molecules at the crossroads of BCR, BAFF-R and TLR9 mediated pathways and to follow the functional consequences of costimulation.Therefore we stimulated purified human B cells by combinations of anti-Ig, B-cell activating factor of the tumor necrosis factor family (BAFF and the TLR9 agonist, CpG oligodeoxynucleotide. Phosphorylation status of various signaling molecules, B cell proliferation, cytokine secretion, plasma blast generation and the frequency of IgG producing cells were investigated. We have found that BCR induced signals cooperate with BAFF-R- and TLR9-mediated signals at different levels of cell activation. BCR and BAFF- as well as TLR9 and BAFF-mediated signals cooperate at NFκB activation, while BCR and TLR9 synergistically costimulate mitogen activated protein kinases (MAPKs, ERK, JNK and p38. We show here for the first time that the MAP3K7 (TGF beta activated kinase, TAK1 is responsible for the synergistic costimulation of B cells by BCR and TLR9, resulting in an enhanced cell proliferation, plasma blast generation, cytokine and antibody production. Specific inhibitor of TAK1 as well as knocking down TAK1 by siRNA abrogates the synergistic signals. We conclude that TAK1 is a key regulator of receptor crosstalk between BCR and TLR9, thus plays a critical role in B cell development and activation.

  10. Evaluation of CD307a expression patterns during normal B-cell maturation and in B-cell malignancies by flow cytometry.

    Science.gov (United States)

    Auat, Mariangeles; Cardoso, Chandra Chiappin; Santos-Pirath, Iris Mattos; Rudolf-Oliveira, Renata Cristina Messores; Matiollo, Camila; Lange, Bárbara Gil; da Silva, Jessica Pires; Dametto, Gisele Cristina; Pirolli, Mayara Marin; Colombo, Maria Daniela Holthausen Perico; Santos-Silva, Maria Claudia

    2018-02-24

    Flow cytometric immunophenotyping is deemed a fundamental tool for the diagnosis of B-cell neoplasms. Currently, the investigation of novel immunophenotypic markers has gained importance, as they can assist in the precise subclassification of B-cell malignancies by flow cytometry. Therefore, the purpose of the present study was to evaluate the expression of CD307a during normal B-cell maturation and in B-cell malignancies as well as to investigate its potential role in the differential diagnosis of these entities. CD307a expression was assessed by flow cytometry in normal precursor and mature B cells and in 115 samples collected from patients diagnosed with precursor and mature B-cell neoplasms. CD307a expression was compared between neoplastic and normal B cells. B-acute lymphoblastic leukemia cases exhibited minimal expression of CD307a, displaying a similar expression pattern to that of normal B-cell precursors. Mantle cell lymphoma (MCL) cases showed the lowest levels of CD307a among mature B-cell neoplasms. CD307a expression was statistically lower in MCL cases than in chronic B lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL) cases. No statistical differences were observed between CD307a expression in neoplastic and normal plasma cells. These results indicate that the assessment of CD307a expression by flow cytometry could be helpful to distinguish CLL from MCL, and the latter from MZL. Although these results are not entirely conclusive, they provide a basis for further studies in a larger cohort of patients. © 2018 International Clinical Cytometry Society. © 2018 International Clinical Cytometry Society.

  11. Negative selection of self-reactive chicken B cells requires B cell receptor signaling and is independent of the bursal microenvironment.

    Science.gov (United States)

    Davani, Dariush; Pancer, Zeev; Cheroutre, Hilde; Ratcliffe, Michael J H

    2014-04-01

    Although the negative selection of self-reactive B cells in the bone marrow of mammals has been clearly demonstrated, it remains unclear in models of gut-associated B cell lymphopoiesis, such as that of the chicken (Gallus gallus). We have generated chicken surface IgM-related receptors in which the diversity region of the lamprey variable lymphocyte receptor (VLR) has been fused to the C region of chicken surface IgM (Tμ). Expression of a VLR:Tμ receptor with specificity for PE supported normal development of B cells, whereas a VLR:Tμ receptor specific to hen egg lysozyme (a self-antigen with respect to chicken B cells) induced, in vivo, complete deletion of VLR(HEL)Tμ-expressing B cells. In ovo i.v. injection of PE resulted in deletion of VLR(PE)Tμ-expressing Β cells in the embryo spleen, demonstrating that negative selection was independent of the bursal microenvironment. Although chickens transduced with a murine CD8α:chicken Igα fusion protein contained B cells expressing mCD8α:chIgα, cotransfection of the mCD8α:chIgα construct, together with thymus leukemia Ag (a natural ligand for mCD8α), resulted in reduced levels of mCD8α:chIgα-expressing B cells in inverse proportion to the levels of thymus leukemia Ag-expressing cells. Deletion of mCD8α:chIgα-expressing cells was specific for B cells and required active signaling downstream of the mCD8α:chIgα receptor. Ag-mediated negative selection of developing chicken B cells can therefore occur independently of the bursal microenvironment and is dependent on signaling downstream of the BCR.

  12. [Evaluation auditing of the quality of health care in accreditation of health facilities].

    Science.gov (United States)

    Paim, Chennyfer da Rosa Paino; Zucchi, Paola

    2011-01-01

    This article shows how many health insurance companies operating in the Greater São Paulo have been performing auditing of the quality of their health care services, professionals, and which criteria are being employed to do so. Because of the legislation decreeing that health insurance companies have legal co-responsibility for the health care services and National Health Agency control the health services National Health Agency, auditing evaluations have been implemented since then. The survey was based on electronic forms e-mailed to all health insurance companies operating in the Greater São Paulo. The sample consisted of 125 health insurance companies; 29 confirmed that had monitoring and evaluation processes; 26 performed auditing of their services regularly; from those, 20 used some type of form or protocol for technical visits; all evaluation physical and administrative structure and 22 included functional structure. Regarding the professionals audited 21 were nurses, 13 administrative assistants; 04 managers and 02 doctors. Regarding criteria for accreditation the following were highlighted: region analysis (96%), localization (88.88%) and cost (36%). We conclude that this type of auditing evaluation is rather innovative and is being gradually implemented by the health insurance companies, but is not a systematic process.

  13. Offline monitoring and data quality of the ATLAS Resistive Plate Chambers at CERN Tier0 facility

    CERN Document Server

    Guida, A; The ATLAS collaboration

    2010-01-01

    Resistive Plate Chambers (RPC) were installed in the barrel region of ATLAS detector to provide the muon trigger (and a coarse measure of the “non-bending” phi coordinate) in the region || < 1.05. The RPC are gaseous detector which measure the muon trajectory with 3 cm strips in the bending plane (r-z) and in the orthogonal direction (r-phi) with few nanoseconds time resolution. The trigger is done in both projections and has a programmable threshold from about 5 to 20 GeV transverse momentum. A total of 596 RPC chambers were installed, arranged in three cylindrical layers. They cover an area of 3650 square meters and are equipped with 368000 read-out electronic channels. The monitoring and the control of such a large subsystem is crucial to maximize the physics reach of the experiment. A dedicated tool was developed to perform the offline monitoring, to evaluate the quality of the RPC data and the detector performance. This tool is executed together with the reconstruction process at “Tier-0” ...

  14. Studying Drinking Water Quality and its Change During Transportation through Samara Water-Supply Facilities

    Science.gov (United States)

    Kichigin, V. I.; Egorova, Y. A.; Nesterenko, O. I.

    2017-11-01

    The paper investigates changes in water physico-chemical composition and its physical indicators through ζ-potential in residential buildings in eight administrative districts of Samara. The results are processed by the methods of mathematical statistics and presented at the 0.05 level of importance. The sampling points for water in the city districts were chosen with the aid of random numbers tables. It was determined that the quality of drinking water was stable and consistent with the existing standards in Zheleznodorozhniy, Samarskiy, Leninskiy, Octyabrskiy, Kirovsliy, Sovetskiy and Promyshlenniy districts of Samara. The following indicators were taken into account: pH, colour, turbidity, alkalinity, general rigidity, content of ions Ca2 +, Mg2 +. It was also established that drinking water in Kuibyshevskiy district (with all other excellent indicators) had increased mineralization due to the natural hydrological conditions of the water inlet. Some change in the size of zeta-potential of the water was detected during its transportation through the existing water-supplying networks of the city. It was shown that the link between zeta-potential and various kinds of contamination in drinking water is underexplored and requires further detailed study.

  15. Gastric Marginal Zone B Cell Lymphoma of the Duodenum

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    A. Ndzengue

    2011-10-01

    Full Text Available Small bowel lymphomas of the extranodal type occur in the young and are characteristically associated with malabsorption syndrome. We present the case of an elderly in whom there was no malabsorption and the duodenal tumor was a gastric type marginal zone B cell lymphoma also known as gastric mucosa-associated lymphoid tissue (MALT lymphoma. A 73-year-old woman presented to the emergency room with 2 weeks of general weakness, recurrent vomiting containing food particles and abdominal distension. She had been diagnosed with diabetic gastroparesis 4 years prior. CT of the abdomen and pelvis was suggestive of gastric outlet obstruction but no evidence of pancreatic or duodenal mass. Endoscopy and biopsy of the tumor obstructing the distal first part of the duodenum confirmed a gastric marginal MALT lymphoma. The patient’s symptoms improved with radiotherapy. Gastric MALT lymphoma, an extranodal lymphoma primarily described in the stomach, can also present in the small bowel and is not associated with malabsorption.

  16. EVALUATION OF CYTOKINE GENE POLYMORPHISM IN B CELL LYMPHOID MALIGNANCIES

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    E. L. Nazarova

    2014-01-01

    Full Text Available Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

  17. Antibody and B cell responses to Plasmodium sporozoites

    Directory of Open Access Journals (Sweden)

    Johanna N Dups

    2014-11-01

    Full Text Available Antibodies are capable of blocking infection of the liver by Plasmodium sporozoites. Accordingly the induction of anti-sporozoite antibodies is a major aim of various vaccine approaches to malaria. In recent years our knowledge of the specificity and quantities of antibodies required for protection has been greatly expanded by clinical trials of various whole sporozoite and subunit vaccines. Moreover, the development of humanized mouse models and transgenic parasites have also aided our ability to assess the specificity of antibodies and their ability to block infection. Nonetheless, considerable gaps remain in our knowledge - in particular in understanding what antigens are recognized by infection blocking antibodies and in knowing how we can induce robust, long-lived antibody responses. Maintaining high levels of circulating antibodies is likely to be of primary importance, as antibodies must block infection in the short time it takes for sporozoites to reach the liver from the skin. It is clear that a better understanding of the development of protective B cell-mediated immunity will aid the development and refinement of malaria vaccines.

  18. B Cell Intrinsic Mechanisms Constraining IgE Memory

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    Brice Laffleur

    2017-11-01

    Full Text Available Memory B cells and long-lived plasma cells are key elements of adaptive humoral immunity. Regardless of the immunoglobulin class produced, these cells can ensure long-lasting protection but also long-lasting immunopathology, thus requiring tight regulation of their generation and survival. Among all antibody classes, this is especially true for IgE, which stands as the most potent, and can trigger dramatic inflammatory reactions even when present in minute amounts. IgE responses and memory crucially protect against parasites and toxic components of venoms, conferring selective advantages and explaining their conservation in all mammalian species despite a parallel broad spectrum of IgE-mediated immunopathology. Long-term memory of sensitization and anaphylactic responses to allergens constitute the dark side of IgE responses, which can trigger multiple acute or chronic pathologic manifestations, some punctuated with life-threatening events. This Janus face of the IgE response and memory, both necessary and potentially dangerous, thus obviously deserves the most elaborated self-control schemes.

  19. Primary Mediastinal Large B-Cell Lymphoma during Pregnancy

    Directory of Open Access Journals (Sweden)

    Cesar A. Perez

    2012-01-01

    Full Text Available Non-Hodgkin’s Lymphoma (NHL rarely presents during pregnancy and primary mediastinal large B-cell lymphoma (PMLBCL accounts for approximately 2.5% of patients with NHL. The case of a 22-year-old woman who was diagnosed with Stage IIA PMLBCL during week 13 of her intrauterine pregnancy is described. The staging consisted in computed tomography (CT of the chest and magnetic resonance imaging (MRI of the abdomen and pelvis. She was managed with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for a total of six cycles and, because of the early presentation during the second trimester, she received the entire chemotherapy course during the pregnancy. She delivered a healthy baby at 34 weeks of pregnancy and a 18FDG-PET/CT scan demonstrated complete remission after delivery. After 20 months of follow up she remains with no evidence of disease and her 1-year-old son has shown no developmental delays or physical abnormalities. PMLBCL, although an uncommon subgroup of DLBCL, may present during pregnancy and R-CHOP should be considered as one suitable option in this complex scenario.

  20. Molecular processes involved in B cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Malouf, Camille; Ottersbach, Katrin

    2018-02-01

    B cell leukaemia is one of the most frequent malignancies in the paediatric population, but also affects a significant proportion of adults in developed countries. The majority of infant and paediatric cases initiate the process of leukaemogenesis during foetal development (in utero) through the formation of a chromosomal translocation or the acquisition/deletion of genetic material (hyperdiploidy or hypodiploidy, respectively). This first genetic insult is the major determinant for the prognosis and therapeutic outcome of patients. B cell leukaemia in adults displays similar molecular features as its paediatric counterpart. However, since this disease is highly represented in the infant and paediatric population, this review will focus on this demographic group and summarise the biological, clinical and epidemiological knowledge on B cell acute lymphoblastic leukaemia of four well characterised subtypes: t(4;11) MLL-AF4, t(12;21) ETV6-RUNX1, t(1;19) E2A-PBX1 and t(9;22) BCR-ABL1.

  1. Multifocal Extranodal Involvement of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Devrim Cabuk

    2013-01-01

    Full Text Available Endobronchial involvement of extrapulmonary malignant tumors is uncommon and mostly associated with breast, kidney, colon, and rectum carcinomas. A 68-year-old male with a prior diagnosis of colon non-Hodgkin lymphoma (NHL was admitted to the hospital with a complaint of cough, sputum, and dyspnea. The chest radiograph showed right hilar enlargement and opacity at the right middle zone suggestive of a mass lesion. Computed tomography of thorax revealed a right-sided mass lesion extending to thoracic wall with the destruction of the third and the fourth ribs and a right hilar mass lesion. Fiberoptic bronchoscopy was performed in order to evaluate endobronchial involvement and showed stenosis with mucosal tumor infiltration in right upper lobe bronchus. The pathological examination of bronchoscopic biopsy specimen reported diffuse large B-cell lymphoma and the patient was accepted as the endobronchial recurrence of sigmoid colon NHL. The patient is still under treatment of R-ICE (rituximab-ifosfamide-carboplatin-etoposide chemotherapy and partial regression of pulmonary lesions was noted after 3 courses of treatment.

  2. B Cell Intrinsic Mechanisms Constraining IgE Memory.

    Science.gov (United States)

    Laffleur, Brice; Debeaupuis, Orianne; Dalloul, Zeinab; Cogné, Michel

    2017-01-01

    Memory B cells and long-lived plasma cells are key elements of adaptive humoral immunity. Regardless of the immunoglobulin class produced, these cells can ensure long-lasting protection but also long-lasting immunopathology, thus requiring tight regulation of their generation and survival. Among all antibody classes, this is especially true for IgE, which stands as the most potent, and can trigger dramatic inflammatory reactions even when present in minute amounts. IgE responses and memory crucially protect against parasites and toxic components of venoms, conferring selective advantages and explaining their conservation in all mammalian species despite a parallel broad spectrum of IgE-mediated immunopathology. Long-term memory of sensitization and anaphylactic responses to allergens constitute the dark side of IgE responses, which can trigger multiple acute or chronic pathologic manifestations, some punctuated with life-threatening events. This Janus face of the IgE response and memory, both necessary and potentially dangerous, thus obviously deserves the most elaborated self-control schemes.

  3. Prognostic Assessment in Patients with Indolent B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Luca Arcaini

    2012-01-01

    Full Text Available Follicular lymphoma (FL is an indolent lymphoma with long median survival. Many studies have been performed to build up prognostic scores potentially useful to identify patients with poorer outcome. In 2004, an international consortium coordinated by the International Follicular Lymphoma Prognostic Factor project was established and a new prognostic study was launched (FLIPI2 using progression-free survival (PFS as main endpoint and integrating all the modern parameters prospectively collected. Low-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Each entity is characterized by unique clinicobiologic features. Some studies have been focused on prognostic factors in single lymphoma subtypes, with the development of specific-entity scores based on retrospective series, for instance splenic marginal zone lymphoma (SMZL. A widely accepted prognostic tool for clinical usage for indolent non-follicular B-cell lymphomas is largely awaited. In this paper we summarized the current evidence regarding prognostic assessment of indolent follicular and non-follicular lymphomas.

  4. Changes in B Cell Populations and Merozoite Surface Protein-1-Specific Memory B Cell Responses after Prolonged Absence of Detectable P. falciparum Infection.

    Directory of Open Access Journals (Sweden)

    Cyrus Ayieko

    Full Text Available Clinical immunity to malaria declines in the absence of repeated parasite exposure. However, little is known about how B cell populations and antigen-specific memory B cells change in the absence of P. falciparum infection. A successful indoor residual insecticide spraying campaign in a highland area of western Kenya, led to an absence of blood-stage P. falciparum infection between March 2007 and April 2008. We assessed memory B cell responses in 45 adults at the beginning (April 2008 and end (April 2009 of a subsequent 12-month period during which none of the adults had evidence of asymptomatic parasitemia or clinical disease. Antibodies and memory B cells to the 42-kDa portion of the merozoite surface protein-1 (MSP-142 were measured using ELISA and ELISPOT assays, respectively. B cell populations were characterized by flow cytometry. From 2008 to 2009, the prevalence of MSP-142-specific memory B cells (45% vs. 55%, respectively, P = 0.32 or antibodies (91% vs. 82%, respectively, P = 0.32 did not differ significantly, although specific individuals did change from positive to negative and vice versa, particularly for memory B cells, suggesting possible low-level undetected parasitemia may have occurred in some individuals. The magnitude of MSP-142-specific memory B cells and levels of antibodies to MSP-142 also did not differ from 2008 to 2009 (P>0.10 for both. However, from 2008 to 2009 the proportions of both class-switched atypical (CD19+IgD-CD27-CD21-IgM- and class-switched activated (CD19+IgD-CD27+CD21-IgM- memory B cells decreased (both P<0.001. In contrast, class-switched resting classical memory B cells (CD19+IgD-CD27+CD21+IgM- increased (P<0.001. In this area of seasonal malaria transmission, a one- year absence of detectable P. falciparum infection was not associated with changes in the prevalence or level of MSP-142 specific memory B cells, but was associated with major changes in overall memory B cell subsets.

  5. Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells

    Directory of Open Access Journals (Sweden)

    Itziar Ubillos

    2017-08-01

    Full Text Available In persistent infections that are accompanied by chronic immune activation, such as human immunodeficiency virus, hepatitis C virus, and malaria, there is an increased frequency of a phenotypically distinct subset of memory B cells lacking the classic memory marker CD27 and showing a reduced capacity to produce antibodies. However, critical knowledge gaps remain on specific B cell changes and immune adaptation in chronic infections. We hypothesized that expansion of atypical memory B cells (aMBCs and reduction of activated peripheral marginal zone (MZ-like B cells in constantly exposed individuals might be accompanied by phenotypic changes that would confer a tolerogenic profile, helping to establish tolerance to infections. To better understand malaria-associated phenotypic abnormalities on B cells, we analyzed peripheral blood mononuclear cells from 55 pregnant women living in a malaria-endemic area of Papua Nueva Guinea and 9 Spanish malaria-naïve individuals using four 11-color flow cytometry panels. We assessed the expression of markers of B cell specificity (IgG and IgM, activation (CD40, CD80, CD86, b220, TACI, and CD150, inhibition (PD1, CD95, and CD71, and migration (CCR3, CXCR3, and CD62l. We found higher frequencies of active and resting aMBC and marked reduction of MZ-like B cells, although changes in absolute cell counts could not be assessed. Highly exposed women had higher PD1+-, CD95+-, CD40+-, CD71+-, and CD80+-activated aMBC frequencies than non-exposed subjects. Malaria exposure increased frequencies of b220 and proapoptotic markers PD1 and CD95, and decreased expression of the activation marker TACI on MZ-like B cells. The increased frequencies of inhibitory and apoptotic markers on activated aMBCs and MZ-like B cells in malaria-exposed adults suggest an immune-homeostatic mechanism for maintaining B cell development and function while simultaneously downregulating hyperreactive B cells. This mechanism would keep the B cell

  6. [Current aspects of the pathology and differentiation of extranodal marginal zone B-cell lymphoma, MALT-Type, and gastrointestinal diffuse large B-cell lymphoma].

    Science.gov (United States)

    Flossbach, L; Kestler, H A; Gress, T M; Möller, P; Barth, T F

    2010-08-01

    The marginal zone B-cell lymphoma, MALT-type (MZBL, MT) is a low-grade B-cell lymphoma which is predominantly localised in the stomach with a typical morphology and cytogenetic pattern. The coexistence of a diffuse large B-cell lymphoma (DLBCL) with an MZBL, MT in the gastrointestinal tract is defined as a composite lymphoma (ComL) and represents a fascinating model of lymphoma progression. In this review we focus on current aspects regarding the molecular characterisation of MZBL, MT and gastrointestinal DLBCL and their mutual relationships. Copyright Georg Thieme Verlag KG Stuttgart New York.

  7. Association between infrastructure and observed quality of care in 4 healthcare services: A cross-sectional study of 4,300 facilities in 8 countries.

    Science.gov (United States)

    Leslie, Hannah H; Sun, Zeye; Kruk, Margaret E

    2017-12-01

    It is increasingly apparent that access to healthcare without adequate quality of care is insufficient to improve population health outcomes. We assess whether the most commonly measured attribute of health facilities in low- and middle-income countries (LMICs)-the structural inputs to care-predicts the clinical quality of care provided to patients. Service Provision Assessments are nationally representative health facility surveys conducted by the Demographic and Health Survey Program with support from the US Agency for International Development. These surveys assess health system capacity in LMICs. We drew data from assessments conducted in 8 countries between 2007 and 2015: Haiti, Kenya, Malawi, Namibia, Rwanda, Senegal, Tanzania, and Uganda. The surveys included an audit of facility infrastructure and direct observation of family planning, antenatal care (ANC), sick-child care, and (in 2 countries) labor and delivery. To measure structural inputs, we constructed indices that measured World Health Organization-recommended amenities, equipment, and medications in each service. For clinical quality, we used data from direct observations of care to calculate providers' adherence to evidence-based care guidelines. We assessed the correlation between these metrics and used spline models to test for the presence of a minimum input threshold associated with good clinical quality. Inclusion criteria were met by 32,531 observations of care in 4,354 facilities. Facilities demonstrated moderate levels of infrastructure, ranging from 0.63 of 1 in sick-child care to 0.75 of 1 for family planning on average. Adherence to evidence-based guidelines was low, with an average of 37% adherence in sick-child care, 46% in family planning, 60% in labor and delivery, and 61% in ANC. Correlation between infrastructure and evidence-based care was low (median 0.20, range from -0.03 for family planning in Senegal to 0.40 for ANC in Tanzania). Facilities with similar infrastructure scores

  8. Association between infrastructure and observed quality of care in 4 healthcare services: A cross-sectional study of 4,300 facilities in 8 countries.

    Directory of Open Access Journals (Sweden)

    Hannah H Leslie

    2017-12-01

    Full Text Available It is increasingly apparent that access to healthcare without adequate quality of care is insufficient to improve population health outcomes. We assess whether the most commonly measured attribute of health facilities in low- and middle-income countries (LMICs-the structural inputs to care-predicts the clinical quality of care provided to patients.Service Provision Assessments are nationally representative health facility surveys conducted by the Demographic and Health Survey Program with support from the US Agency for International Development. These surveys assess health system capacity in LMICs. We drew data from assessments conducted in 8 countries between 2007 and 2015: Haiti, Kenya, Malawi, Namibia, Rwanda, Senegal, Tanzania, and Uganda. The surveys included an audit of facility infrastructure and direct observation of family planning, antenatal care (ANC, sick-child care, and (in 2 countries labor and delivery. To measure structural inputs, we constructed indices that measured World Health Organization-recommended amenities, equipment, and medications in each service. For clinical quality, we used data from direct observations of care to calculate providers' adherence to evidence-based care guidelines. We assessed the correlation between these metrics and used spline models to test for the presence of a minimum input threshold associated with good clinical quality. Inclusion criteria were met by 32,531 observations of care in 4,354 facilities. Facilities demonstrated moderate levels of infrastructure, ranging from 0.63 of 1 in sick-child care to 0.75 of 1 for family planning on average. Adherence to evidence-based guidelines was low, with an average of 37% adherence in sick-child care, 46% in family planning, 60% in labor and delivery, and 61% in ANC. Correlation between infrastructure and evidence-based care was low (median 0.20, range from -0.03 for family planning in Senegal to 0.40 for ANC in Tanzania. Facilities with similar

  9. Water management of the uranium production facility in Brazil (Caetite, BA): potential impacts over groundwater quality

    International Nuclear Information System (INIS)

    Lamego, Fernando; Santos, Robson Rodger; Silva, L. Ferreira da; Fernandes, Horst Monken

    2008-01-01

    The uranium unit of Caetite - in charge of all the 'yellow cake' produced in Brazil - is located in the semi-arid Northeast region at Bahia State. The geological uranium content of the ore is 3000 ppm, which is mainly associated with albite (NaAlSi 8 O 8 ), and its extraction is achieved by means of a Heap-Leach process. This process has a low water demand, which is supplied by a network of wells, but can contribute to change the groundwater quality and in some cases the extinguishing of wells was observed. The managing of liquid mining wastes formed by drainage waters from mine pit and solid waste piles is not enough to avoid unwarranted releases in the environment, which turn necessary the waste treatment through passing them into the industrial plant in order to reduce radionuclide concentrations. The groundwater is Na-HCO 3 type water and relative high concentration of Cl are observed in some groundwater. It seems that levels of uranium in groundwaters are mainly a consequence of the complexation of the metal by carbonates (or other anions) and not by any sort of the contamination of these waters by the drainage accumulated in the open pit. The speciation modelling allows identifying some areas where the replenishment of the aquifer is more active, but in general the recharge is a fast process run by direct infiltration. The stable isotope data (δ 2 H and δ 18 O) showed that evaporation plays a role during the infiltration, causing the groundwater salinization. These data discard the possibility that groundwater salinization was caused by discharge of deeper saline groundwater through faults associated to a regional groundwater flow system. The presence of an active shallow groundwater flow system offers better possibility for sustainable use of the groundwater resources in this semi-arid region of Brazil. (author)

  10. Regulation of B cell functions by Toll-like receptors and complement.

    Science.gov (United States)

    Kremlitzka, Mariann; Mácsik-Valent, Bernadett; Erdei, Anna

    2016-10-01

    B cell functions triggered by the clonally-rearranged antigen-specific B cell receptor (BCR) are regulated by several germ-line encoded receptors - including Toll-like receptors (TLRs) and complement receptors (CRs). Simultaneous or sequential engagement of these structures expressed either on the cell membrane or intracellularly, may fundamentally alter and fine tune activation, antibody and cytokine production of B cells. Here we review the expression and function of TLRs and various C3 fragment binding CRs on B cells, emphasizing their role in different human B cell subsets under physiological and pathological conditions. Studies underlining the importance of the crosstalk between TLRs and CRs in regulating B cell functions are also highlighted. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  11. [Insulin pump in type 2 diabetes: B-cell focused treatment].

    Science.gov (United States)

    Picková, Klára; Rušavý, Zdeněk

    Type 2 diabetes is a disorder characterized by insulin resistance and progressive deterioration of B-cell insulin secretion. B-cell protective strategies for lowering glucolipotoxicity by rapid achievement of normoglycemia using exogenous insulin improve their function and prolong diabetes remission. Insulin pump is an effective treatment method in newly diagnosed diabetes, where even short-term pump therapy is B-cell protective. Combination therapy with insulin pump and antidiabetics targeting the incretin system acts in synergy to protect the B-cell. While the positive effect of insulin pump is apparent even a year after stopping the therapy, the effect of incretins lasts only while on the medication. Short-term insulin treatment, especially delivered by insulin pump, is an effective method of B-cell protection in recent type 2 diabetes.Key words: B-cell function - diabetes mellitus - insulin pump - insulin resistance - type 2 diabetes.

  12. B lymphocyte lineage specification, commitment and epigenetic control of transcription by early B cell factor 1.

    Science.gov (United States)

    Hagman, James; Ramírez, Julita; Lukin, Kara

    2012-01-01

    Early B cell factor 1 (EBF1) is a transcription factor that is critical for both B lymphopoiesis and B cell function. EBF1 is a requisite component of the B lymphocyte transcriptional network and is essential for B lineage specification. Recent studies revealed roles for EBF1 in B cell commitment. EBF1 binds its target genes via a DNA-binding domain including a unique 'zinc knuckle', which mediates a novel mode of DNA recognition. Chromatin immunoprecipitation of EBF1 in pro-B cells defined hundreds of new, as well as previously identified, target genes. Notably, expression of the pre-B cell receptor (pre-BCR), BCR and PI3K/Akt/mTOR signaling pathways is controlled by EBF1. In this review, we highlight these current developments and explore how EBF1 functions as a tissue-specific regulator of chromatin structure at B cell-specific genes.

  13. B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis.

    Science.gov (United States)

    Bénard, Alan; Sakwa, Imme; Schierloh, Pablo; Colom, André; Mercier, Ingrid; Tailleux, Ludovic; Jouneau, Luc; Boudinot, Pierre; Al-Saati, Talal; Lang, Roland; Rehwinkel, Jan; Loxton, Andre G; Kaufmann, Stefan H E; Anton-Leberre, Véronique; O'Garra, Anne; Sasiain, Maria Del Carmen; Gicquel, Brigitte; Fillatreau, Simon; Neyrolles, Olivier; Hudrisier, Denis

    2018-03-15

    In addition to their well-known function as antibody-producing cells, B lymphocytes can markedly influence the course of infectious or noninfectious diseases via antibody-independent mechanisms. In tuberculosis (TB), B cells accumulate in lungs, yet their functional contribution to the host response remains poorly understood. To document the role of B cells in TB in an unbiased manner. We generated the transcriptome of B cells isolated from Mycobacterium tuberculosis (Mtb)-infected mice and validated the identified key pathways using in vitro and in vivo assays. The obtained data were substantiated using B cells from pleural effusion of patients with TB. B cells isolated from Mtb-infected mice displayed a STAT1 (signal transducer and activator of transcription 1)-centered signature, suggesting a role for IFNs in B-cell response to infection. B cells stimulated in vitro with Mtb produced type I IFN, via a mechanism involving the innate sensor STING (stimulator of interferon genes), and antagonized by MyD88 (myeloid differentiation primary response 88) signaling. In vivo, B cells expressed type I IFN in the lungs of Mtb-infected mice and, of clinical relevance, in pleural fluid from patients with TB. Type I IFN expression by B cells induced an altered polarization of macrophages toward a regulatory/antiinflammatory profile in vitro. In vivo, increased provision of type I IFN by B cells in a murine model of B cell-restricted Myd88 deficiency correlated with an enhanced accumulation of regulatory/antiinflammatory macrophages in Mtb-infected lungs. Type I IFN produced by Mtb-stimulated B cells favors macrophage polarization toward a regulatory/antiinflammatory phenotype during Mtb infection.

  14. Age-associated B cells (ABC) inhibit B lymphopoiesis and alter antibody repertoires in old age.

    Science.gov (United States)

    Riley, Richard L; Khomtchouk, Kelly; Blomberg, Bonnie B

    2017-11-01

    With old age (∼2y old), mice show substantial differences in B cell composition within the lymphoid tissues. In particular, a novel subset of IgM + CD21/35 lo/- CD23 - mature B cells, the age-associated B cells or ABC, increases numerically and proportionately. This occurs at the expense of other B cell subsets, including B2 follicular B cells in spleen and recirculating primary B cells in bone marrow. Our studies suggest that ABC have a distinctive antibody repertoire, as evidenced by relatively high reactivity to the self-antigens phosphorylcholine (PC) and malondialdehyde (MDA). While PC and MDA are found on apoptotic cells and oxidized lipoproteins, antibodies to these antigens are also cross-reactive with epitopes on bacterial species. In old mice, ABC express TNFα and are pro-inflammatory. ABC can inhibit growth and/or survival in pro-B cells as well as common lymphoid progenitors (CLP). In particular, ABC cause apoptosis in pro-B cells with relatively high levels of the surrogate light chain (SLC) and, consequently, promote an "SLC low" pathway of B cell differentiation in old mice. SLC together with μ heavy chain comprises the pre-B cell receptor (preBCR) critical for pre-B cell expansion and selection of the μ heavy chain Vh repertoire. The low level of SLC likely impairs normal preBCR driven proliferation and alters μ heavy chain Vh selection thereby affecting the antibody specificities of new B cells. In this manner, ABC may contribute to both qualitative and quantitative disruptions of normal B lymphopoiesis in old age. Copyright © 2017. Published by Elsevier Inc.

  15. Regulation of B cell development by posttranslational modification of Ebf1

    OpenAIRE

    Wang, Qiongman

    2016-01-01

    Early B cell differentiation is regulated via a complex transcriptional network. Ebf1 is a central part of it, regulating around 3000 target genes associated with B cell function. Among these target genes, Ebf1 plays diverse roles to activate, repress or poise gene expression. Post-translational modification represents a potential explanation for these diverse roles. Specifically, phosphorylation of Ebf1 might contribute to the diverse functions of Ebf1 during B cell development. The hypot...

  16. Uptake and presentation of myelin basic protein by normal human B cells.

    Directory of Open Access Journals (Sweden)

    Marie Klinge Brimnes

    Full Text Available B cells may play both pathogenic and protective roles in T-cell mediated autoimmune diseases such as multiple sclerosis (MS. These functions relate to the ability of B cells to bind and present antigens. Under serum-free conditions we observed that 3-4% of circulating B cells from healthy donors were capable of binding the MS-associated self-antigen myelin basic protein (MBP and of presenting the immunodominant peptide MBP85-99, as determined by staining with the mAb MK16 recognising the peptide presented by HLA-DR15-positive cells. In the presence of serum, however, the majority of B cells bound MBP in a complement-dependent manner, and almost half of the B cells became engaged in presentation of MBP85-99. Even though complement receptor 1 (CR1, CD35 and CR2 (CD21 both contributed to binding of MBP to B cells, only CR2 was important for the subsequent presentation of MBP85-99. A high proportion of MBP85-99 presenting B cells expressed CD27, and showed increased expression of CD86 compared to non-presenting B cells. MBP-pulsed B cells induced a low frequency of IL-10-producing CD4+ T cells in 3 out of 6 donors, indicating an immunoregulatory role of B cells presenting MBP-derived peptides. The mechanisms described here refute the general assumption that B-cell presentation of self-antigens requires uptake via specific B-cell receptors, and may be important for maintenance of tolerance as well as for driving T-cell responses in autoimmune diseases.

  17. Subversion of the B-cell compartment during parasitic, bacterial, and viral infections

    OpenAIRE

    Borhis, Gwenoline; Richard, Yolande

    2015-01-01

    International audience; AbstractRecent studies on HIV infection have identified new human B-cell subsets with a potentially important impact on anti-viral immunity. Current work highlights the occurrence of similar B-cell alterations in other viral, bacterial, and parasitic infections, suggesting that common strategies have been developed by pathogens to counteract protective immunity. For this review, we have selected key examples of human infections for which B-cell alterations have been de...

  18. The progeny of a single virgin B cell predominates the human recall B cell response to the capsular polysaccharide of Haemophilus influenzae type b

    DEFF Research Database (Denmark)

    Barington, T; Hougs, L; Juul, L

    1996-01-01

    of Haemophilus influenzae type b coupled to tetanus toxoid. We combined affinity purification of circulating vaccine-induced Ab-secreting cells with PCR amplification of cDNA followed by cloning and sequencing. Forty-eight and 42 kappa VJ gene transcripts were analyzed from two adults, respectively. Both......Restricted V region diversity is a key feature of Abs to many haptens and simple polysaccharides. Two possible mechanisms exist: 1) selection of many clonally unrelated B cells using very similar or identical VDJ and VJ rearrangements; and 2) selection of a heavily expanded progeny of few virgin B...... cells. How many virgin B cells eventually give rise to the total Ab response to a simple Ag is a fundamental immunologic question. In this report, we address this question in human adults by analyzing the rearranged VkappaJkappa genes of B cells responding to a single dose of the capsular polysaccharide...

  19. The Fas/CD95 receptor regulates the death of autoreactive B cells and the selection of antigen-specific B cells

    Directory of Open Access Journals (Sweden)

    Anne-Odile eHUEBER

    2012-07-01

    Full Text Available Cell death receptors have crucial roles in the regulation of immune responses. Here we review recent in vivo data confirming that the Fas death receptor (TNFSR6 on B cells is important for the regulation of autoimmunity since the impairment of only Fas function on B cells results in uncontrolled autoantibody production and autoimmunity. Fas plays a role in the elimination of the non-specific and auto-reactive B cells in germinal center, while during the selection of antigen specific B cells different escape signals ensure the resistance to Fas-mediated apoptosis. Antigen specific survival such as BCR or MHCII signal or coreceptors (CD19 cooperating with BCR inhibits the formation of death inducing signaling complex. Antigen-specific survival can be reinforced by antigen-independent signals of IL4 or CD40 overproducing the anti-apoptotic members of the Bcl-2 family proteins.

  20. The outcome of primary mediastinal large B-cell lymphoma

    International Nuclear Information System (INIS)

    Fang Hui; Li Yexiong; Qi Shunan; Liu Qingfeng; Wang Shulian; Jin Jing; Wang Weihu; Song Yongwen; Liu Xinfan; Yu Zihao

    2008-01-01

    Objective: To investigate the treatment outcome and failure in patients with primary mediastinal large B-cell lymphoma(PMBL). Methods: Between Jan. 1992 and Oct. 2006, a total of 46 patients with pathologically confirmed PMBL were reviewed, including 14 with Ann Arbor Stage I disease, 23 with Stage II disease, 3 with Stage III disease and 6 with Stage IV disease. Stage I + II disease was present in 80% of the patients. All patients were treated with chemotherapy, and 29 also received radiotherapy. Twenty-seven patients (59%) were treated with first generation regimen (CHOP), 9 (20%) with third generation regimens (MACOP-B, ProMACE/CytaBOM, m-BACOD, or ProMACE-MOPP), and 10 (22%) with high-dose chemotherapy (HDCT/APBSCT). Rituximab was administered to 16 patients (35%). For most patients who received radiotherapy, an involved field was used with a median dose of 45 Gy in 23 fractions. Results: The rate of complete remission, partial remission and progression disease was 41%, 30% and 24%, respectively. The 5-year overall survival rate (OS) for all patients was 35%. The 2- and 5-year OS was 79% and 63% for stage I + II and 51% and 0 for stage III + IV, respectively (χ 2 =4.35,P=0.037). The 2-year progression free survival rate was 63% and 11%, respectively(χ 2 =17.77, P=0.000). The 5- year OS was 80% for the patients with CR, 50% for those with PR, and 0 for those with progression disease (χ 2 =19.58, P=0.003). With a median follow-up of 22 months, progression disease and relapse occurred in 19 patients. Conclusions: Survival of patients with advanced stage PMBL is poor. Further studies are needed to confirm the optimal treatment. Radiotherapy often plays a pivotal role in local control. (authors)

  1. Gammaherpesvirus Colonization of the Spleen Requires Lytic Replication in B Cells.

    Science.gov (United States)

    Lawler, Clara; de Miranda, Marta Pires; May, Janet; Wyer, Orry; Simas, J Pedro; Stevenson, Philip G

    2018-04-01

    Gammaherpesviruses infect lymphocytes and cause lymphocytic cancers. Murid herpesvirus-4 (MuHV-4), Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus all infect B cells. Latent infection can spread by B cell recirculation and proliferation, but whether this alone achieves systemic infection is unclear. To test the need of MuHV-4 for lytic infection in B cells, we flanked its essential ORF50 lytic transactivator with loxP sites and then infected mice expressing B cell-specific Cre (CD19-Cre). The floxed virus replicated normally in Cre - mice. In CD19-Cre mice, nasal and lymph node infections were maintained; but there was little splenomegaly, and splenic virus loads remained low. Cre-mediated removal of other essential lytic genes gave a similar phenotype. CD19-Cre spleen infection by intraperitoneal virus was also impaired. Therefore, MuHV-4 had to emerge lytically from B cells to colonize the spleen. An important role for B cell lytic infection in host colonization is consistent with the large CD8 + T cell responses made to gammaherpesvirus lytic antigens during infectious mononucleosis and suggests that vaccine-induced immunity capable of suppressing B cell lytic infection might reduce long-term virus loads. IMPORTANCE Gammaherpesviruses cause B cell cancers. Most models of host colonization derive from cell cultures with continuous, virus-driven B cell proliferation. However, vaccines based on these models have worked poorly. To test whether proliferating B cells suffice for host colonization, we inactivated the capacity of MuHV-4, a gammaherpesvirus of mice, to reemerge from B cells. The modified virus was able to colonize a first wave of B cells in lymph nodes but spread poorly to B cells in secondary sites such as the spleen. Consequently, viral loads remained low. These results were consistent with virus-driven B cell proliferation exploiting normal host pathways and thus having to transfer lytically to new B cells for new proliferation. We

  2. B-CELL SUBPOPULATIONS OF PERIPHERAL BLOOD IN SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    A. I. Budkova

    2017-01-01

    Full Text Available Distinct changes of B-cell subpopulations are observed in most systemic rheumatic diseases associated with polyclonal B cell hyperreactivity. Immunosuppressive and cytostatic therapy may also differentially influence B lymphocyte subsets in these. We studied subpopulations of B cells in systemic rheumatic patients along treatment with cytostatics. We analyzed B cell phenotypes in ninety-nine blood samples from the patients with systemic lupus erythematosus (SLE, n = 25, systemic sclerosis (n = 27, Sjogren’s syndrome (n = 47 in the course of their hospital treatment. Control group consisted of 49 healthy blood donors. Phenotyping of blood B-cell subpopulations was performed by means of flow cytometry (Beckman Coulter, USA. Naïve B-cell subpopulations in SLE patients who underwent cyclophosphan treatment, were underrepresented, if compared with normal control group, whereas plasmablast levels were increased irrespectively of medication mode. B cell population exhibits a natural heterogeneity, thus making it necessary to analyze distinct B cell subpopulations as independent functional units, when studying different rheumatic diseases. The levels of plasmablasts which are active antibody producers, remain high, despite immunosuppressive therapy performed in SLE. Thus, therapy targeted against certain B cell subsets, could be able to provide a more effective treatment for the patients with systemic rheumatic diseases.

  3. B cell-independent contribution of BAFF to murine autoimmune disease.

    Science.gov (United States)

    Stohl, William; Banfalvi, Agnes

    2016-11-01

    BAFF blockade is efficacious in murine and human SLE. Whereas the attendant reduction in B cells contributes to the efficacy, it remains unresolved whether a B cell-independent component also contributes. Since accurate assessment of a B cell-independent component can only be made in a B cell-independent autoimmune disease, we investigated MOG 35-55 -induced EAE in C57BL/6 mice. Neither pharmacologic neutralization nor genetic elimination of BAFF affected disease, nor did elimination of APRIL (with or without elimination of BAFF) or constitutive over-expression of BAFF. Eliminating BAFF had no effect on disease even in mice that were genetically manipulated to maintain greater-than-normal numbers of B cells. However, elimination of BAFF in B cell-deficient mice dramatically reduced disease, thereby unmasking a B cell-independent contribution of BAFF to an autoimmune disease. Our findings raise the plausibility that BAFF contributes to SLE not only through effects on B cells but through B cell-independent pathways as well. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival.

    Science.gov (United States)

    Jacque, Emilie; Schweighoffer, Edina; Tybulewicz, Victor L J; Ley, Steven C

    2015-06-01

    B cell activating factor (BAFF) stimulation of the BAFF receptor (BAFF-R) is essential for the homeostatic survival of mature B cells. Earlier in vitro experiments with inhibitors that block MEK 1 and 2 suggested that activation of ERK 1 and 2 MAP kinases is required for BAFF-R to promote B cell survival. However, these inhibitors are now known to also inhibit MEK5, which activates the related MAP kinase ERK5. In the present study, we demonstrated that BAFF-induced B cell survival was actually independent of ERK1/2 activation but required ERK5 activation. Consistent with this, we showed that conditional deletion of ERK5 in B cells led to a pronounced global reduction in mature B2 B cell numbers, which correlated with impaired survival of ERK5-deficient B cells after BAFF stimulation. ERK5 was required for optimal BAFF up-regulation of Mcl1 and Bcl2a1, which are prosurvival members of the Bcl-2 family. However, ERK5 deficiency did not alter BAFF activation of the PI3-kinase-Akt or NF-κB signaling pathways, which are also important for BAFF to promote mature B cell survival. Our study reveals a critical role for the MEK5-ERK5 MAP kinase signaling pathway in BAFF-induced mature B cell survival and homeostatic maintenance of B2 cell numbers. © 2015 Jacque et al.

  5. Human B cells produce chemokine CXCL10 in the presence of Mycobacterium tuberculosis specific T cells

    DEFF Research Database (Denmark)

    Hoff, Soren T; Salman, Ahmed M; Ruhwald, Morten

    2015-01-01

    BACKGROUND: The role of B cells in human host response to Mycobacterium tuberculosis (Mtb) infection is still controversial, but recent evidence suggest that B cell follicle like structures within the lung may influence host responses through regulation of the local cytokine environment. A candid......BACKGROUND: The role of B cells in human host response to Mycobacterium tuberculosis (Mtb) infection is still controversial, but recent evidence suggest that B cell follicle like structures within the lung may influence host responses through regulation of the local cytokine environment...

  6. Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome.

    Science.gov (United States)

    Carsetti, Rita; Valentini, Diletta; Marcellini, Valentina; Scarsella, Marco; Marasco, Emiliano; Giustini, Ferruccio; Bartuli, Andrea; Villani, Alberto; Ugazio, Alberto G

    2015-03-01

    Children with Down syndrome (DS) have increased susceptibility to infections and a high frequency of leukemia and autoimmune disorders, suggesting that immunodeficiency and immune dysfunction are integral parts of the syndrome. A reduction in B-cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here, we compared B-cell populations of 19 children with DS with those in healthy age-matched controls. We found that all steps of peripheral B-cell development are altered in DS, with a more severe defect during the later stages of B-cell development. Transitional and mature-naïve B-cell numbers are reduced by 50% whereas switched memory B cells represent 10-15% of the numbers in age-matched controls. Serum IgM levels were slightly reduced, but all other immunoglobulin isotypes were in the normal range. The frequency of switched memory B cells specific for vaccine antigens was significantly lower in affected children than in their equivalently vaccinated siblings. In vitro switched memory B cells of patients with DS have an increased ability to differentiate into antibody-forming cells in response to TLR9 signals. Tailored vaccination schedules increasing the number of switched memory B cells may improve protection and reduce the risk of death from infection in DS. © 2014 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. B Lymphocyte Lineage Specification, Commitment and Epigenetic Control of Transcription by Early B Cell Factor 1

    OpenAIRE

    Hagman, James; Ramírez, Julita; Lukin, Kara

    2012-01-01

    Early B cell factor 1 (EBF1) is a transcription factor that is critical for both B lymphopoiesis and B cell function. EBF1 is a requisite component of the B lymphocyte transcriptional network and is essential for B lineage specification. Recent studies revealed roles for EBF1 in B cell commitment. EBF1 binds its target genes via a DNA-binding domain including a unique ‘zinc knuckle’, which mediates a novel mode of DNA recognition. Chromatin immunoprecipitation of EBF1 in pro-B cells defined h...

  8. The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh.

    Science.gov (United States)

    Solanki, Anisha; Lau, Ching-In; Saldaña, José Ignacio; Ross, Susan; Crompton, Tessa

    2017-07-03

    Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])-deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs. RNA sequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL and showed that these cells expressed reduced levels of B-lineage transcription factors and B cell receptor (BCR)/pre-BCR-signaling genes. Expression of the master regulators of B cell development Ebf1 and Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and in vitro Shh treatment or neutralization reduced or increased their expression, respectively. © 2017 Solanki et al.

  9. Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate

    OpenAIRE

    Mansson, Robert; Welinder, Eva; Åhsberg, Josefine; Lin, Yin C.; Benner, Christopher; Glass, Christopher K.; Lucas, Joseph S.; Sigvardsson, Mikael; Murre, Cornelis

    2012-01-01

    Recent studies have identified a number of transcriptional regulators, including E2A, early B-cell factor 1 (EBF1), FOXO1, and paired box gene 5 (PAX5), that promote early B-cell development. However, how this ensemble of regulators mechanistically promotes B-cell fate remains poorly understood. Here we demonstrate that B-cell development in FOXO1-deficient mice is arrested in the common lymphoid progenitor (CLP) LY6D+ cell stage. We demonstrate that this phenotype closely resembles the arres...

  10. Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma.

    Science.gov (United States)

    Bohle, V; Döring, C; Hansmann, M-L; Küppers, R

    2013-03-01

    A hallmark of classical Hodgkin lymphoma (cHL) is that the B-cell-derived Hodgkin and Reed-Sternberg (HRS) tumor cells have largely lost the B-cell-typical gene expression program. The factors causing this 'reprogramming' of HRS cells are only partly understood. As early B-cell factor 1 (EBF1), a major B-cell transcription factor, is downregulated in HRS cells, we analyzed whether this downregulation contributes to the lost B-cell phenotype and tested the consequences of EBF1 re-expression in cHL cell lines. EBF1 re-expression caused an upregulation of B-cell genes, such as CD19, CD79A and CD79B, although the B-cell genes FOXO1 and PAX5 remained lowly expressed. The re-expression of CD19, CD79A and CD79B occurred largely without demethylation of promoter CpG motifs of these genes. In the cHL cell line L-1236 fitness decreased after EBF1 re-expression. These data show that EBF1 has the ability to reintroduce part of the B-cell signature in cHL cell lines. Loss of EBF1 expression in HRS cells therefore contributes to their lost B-cell phenotype. Notably, in the cHL cell line KM-H2 destructive mutations were found in one allele of EBF1, indicating that genetic lesions may sometimes have a role in impairing EBF1 expression.

  11. Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells.

    Science.gov (United States)

    Györy, Ildiko; Boller, Sören; Nechanitzky, Robert; Mandel, Elizabeth; Pott, Sebastian; Liu, Edison; Grosschedl, Rudolf

    2012-04-01

    The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell subsets, including B1 cells and marginal zone B cells. The proliferation defect of Ebf1-deficient pro-B cells and the impaired expression of multiple cell cycle regulators are overcome by transformation with v-Abl. The survival defect of transformed Ebf1(fl/fl) pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-x(L). In mature B cells, Ebf1 deficiency interferes with signaling via the B-cell-activating factor receptor (BAFF-R)- and B-cell receptor (BCR)-dependent Akt pathways. Moreover, Ebf1 is required for germinal center formation and class switch recombination. Genome-wide analyses of Ebf1-mediated gene expression and chromatin binding indicate that Ebf1 regulates both common and distinct sets of genes in early and late stage B cells. By regulating important components of transcription factor and signaling networks, Ebf1 appears to be involved in the coordination of cell proliferation, survival, and differentiation at multiple stages of B lymphopoiesis.

  12. B-cell exhaustion in HIV infection: the role of immune activation.

    Science.gov (United States)

    Moir, Susan; Fauci, Anthony S

    2014-09-01

    To discuss a component of the pathogenic mechanisms of HIV infection in the context of phenotypic and functional alterations in B cells that are due to persistent viral replication leading to aberrant immune activation and cellular exhaustion. We explore how B-cell exhaustion arises during persistent viremia and how it compares with T-cell exhaustion and similar B-cell alterations in other diseases. HIV-associated B-cell exhaustion was first described in 2008, soon after the demonstration of persistent virus-induced T-cell exhaustion, as well as the identification of a subset B cells in tonsil tissues with immunoregulatory features similar to those observed in T-cell exhaustion. Our understanding of B-cell exhaustion has since expanded in two important areas: the role of inhibitory receptors in the unresponsiveness of exhausted B cells and the increasing evidence that similar B cells are found in other diseases that are associated with aberrant immune activation and inflammation. The phenomenon of B-cell exhaustion is now well established in HIV infection and other diseases characterized by immune activation. Over the coming years, it will be important to understand how cellular exhaustion affects the capacity of the immune system to respond to persisting primary pathogens, as well as to other microbial antigens, whether encountered as secondary infections or following immunization.

  13. Reduced PTEN involved in primary immune thrombocytopenia via contributing to B cell hyper-responsiveness.

    Science.gov (United States)

    Wang, Shixuan; Guan, Yue; Wang, Yunlong; Li, Huiyuan; Zhang, Donglei; Ju, Mankai; Hao, Yating; Song, Xuewen; Sun, Boyang; Dou, Xueqing; Yang, Renchi

    2018-01-01

    Phosphatase and tensin homolog (PTEN) is thought to mediate B cell activation by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. This pathway is important for activation, growth, and proliferation. Although enhanced B cell receptor (BCR) signaling contributes to increased B cell activity in immune thrombocytopenia (ITP), the role of PTEN is unclear. In this study, we analyzed B cells of ITP patients using flow cytometry and found that all B cell subsets, excluding memory B cells, showed lower PTEN expression than cells from healthy controls (HCs). PTEN expression was also positively-correlated with blood platelet count, although levels were lower in patients who were platelet autoantibody-positive compared with those who were negative. We next evaluated the effects of IL-21, anti-IgM, and CD40L on PTEN expression, demonstrating that they were potent inducers of PTEN expression in normal B cells. Induction of PTEN expression was lower in B cells of ITP patients. We also found that IL-21 increased the proportion of plasma cells in peripheral blood mononuclear cells (PBMCs) of ITP patients, independent of BCR signaling. This effect was reproducible using PTEN inhibitors with cells from HCs. In summary, defective PTEN expression, regulation, and function all contribute to the B cell hyper-responsiveness that associates with ITP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. B Cells Promote Th1- Skewed NKT Cell Response by CD1d-TCR Interaction

    OpenAIRE

    Shin, Jung Hoon; Park, Se-Ho

    2013-01-01

    CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although ?-galactosylceramide (?-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-? by NKT cells, concomitant with a d...

  15. High levels of SOX5 decrease proliferative capacity of human B cells, but permit plasmablast differentiation.

    Directory of Open Access Journals (Sweden)

    Mirzokhid Rakhmanov

    Full Text Available Currently very little is known about the differential expression and function of the transcription factor SOX5 during B cell maturation. We identified two new splice variants of SOX5 in human B cells, encoding the known L-SOX5B isoform and a new shorter isoform L-SOX5F. The SOX5 transcripts are highly expressed during late stages of B-cell differentiation, including atypical memory B cells, activated CD21low B cells and germinal center B cells of tonsils. In tonsillar sections SOX5 expression was predominantly polarized to centrocytes within the light zone. After in vitro stimulation, SOX5 expression was down-regulated during proliferation while high expression levels were permissible for plasmablast differentiation. Overexpression of L-SOX5F in human primary B lymphocytes resulted in reduced proliferation, less survival of CD138neg B cells, but comparable numbers of CD138+CD38hi plasmablasts compared to control cells. Thus, our findings describe for the first time a functional role of SOX5 during late B cell development reducing the proliferative capacity and thus potentially affecting the differentiation of B cells during the germinal center response.

  16. B cells produce less IL-10, IL-6 and TNF-α in myasthenia gravis.

    Science.gov (United States)

    Yilmaz, Vuslat; Oflazer, Piraye; Aysal, Fikret; Parman, Yeşim G; Direskeneli, Haner; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2015-06-01

    B cells from myasthenia gravis (MG) patients with autoantibodies (Aab) against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or with no detectable Aab were investigated as cytokine producing cells in this study. B cells were evaluated for memory phenotypes and expressions of IL-10, IL-6 and IL-12A. Induced productions of IL-10, IL-6, IL-12p40, TNF-α and LT from isolated B cells in vitro were measured by immunoassays. MG patients receiving immunosuppressive treatment had higher proportions of memory B cells compared with healthy controls and untreated patients. With CD40 stimulation MG patients produced significantly lower levels of IL-10, IL-6. With CD40 and B cell receptor stimulation of B cells, TNF-α production also decreased in addition to these cytokines. The lower levels of these cytokine productions were not related to treatment. Our results confirm a disturbance of B cell subpopulations in MG subgroups on immunosuppressive treatment. B cell derived IL-10, IL-6 and TNF-α are down-regulated in MG, irrespective of different antibody productions. Ineffective cytokine production by B cells may be a susceptibility factor in dysregulation of autoimmune Aab production.

  17. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

    OpenAIRE

    Chettiankandy, Tabita Joy; Tupkari, Jagdish Vishnu; Kumar, Keshav; Ahire, Manisha Sandeep

    2016-01-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Burkitt's lymphoma (BL), is a diagnostic provisional category in the World Health Organization 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typica...

  18. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development.

    Science.gov (United States)

    Ramadani, Faruk; Bolland, Daniel J; Garcon, Fabien; Emery, Juliet L; Vanhaesebroeck, Bart; Corcoran, Anne E; Okkenhaug, Klaus

    2010-08-10

    B cell development is controlled by a series of checkpoints that ensure that the immunoglobulin (Ig)-encoding genes produce a functional B cell receptor (BCR) and antibodies. As part of this process, recombination-activating gene (Rag) proteins regulate the in-frame assembly of the Ig-encoding genes. The BCR consists of Ig proteins in complex with the immunoreceptor tyrosine-based activation motif (ITAM)-containing Igalpha and Igbeta chains. Whereas the activation of the tyrosine kinases Src and Syk is essential for BCR signaling, the pathways that act downstream of these kinases are incompletely defined. Previous work has revealed a key role for the p110delta isoform of phosphatidylinositol 3-kinase (PI3K) in agonist-induced BCR signaling; however, early B cell development and mature B cell survival, which depend on agonist-independent or "tonic" BCR signaling, are not substantially affected by a deficiency in p110delta. Here, we show that p110alpha, but not p110beta, compensated in the absence of p110delta to promote early B cell development in the bone marrow and B cell survival in the spleen. In the absence of both p110alpha and p110delta activities, pre-BCR signaling failed to suppress the production of Rag proteins and to promote developmental progression of B cell progenitors. Unlike p110delta, however, p110alpha did not contribute to agonist-induced BCR signaling. These studies indicate that either p110alpha or p110delta can mediate tonic signaling from the BCR, but only p110delta can contribute to antigen-dependent activation of B cells.

  19. Active chronic sarcoidosis is characterized by increased transitional blood B cells, increased IL-10-producing regulatory B cells and high BAFF levels.

    Directory of Open Access Journals (Sweden)

    Anne Saussine

    Full Text Available BACKGROUND: Sarcoidosis is a multisystemic disease of unknown etiology characterized by a disproportionate Th1 granulomatous immune response in the organs involved. Plasmatic hypergammaglobulinemia and B cell accumulation in granulomatous lesions suggest the possible role of humoral immune responses in the pathogenesis of sarcoidosis. The purpose of this study is to describe B cell peripheral compartment in sarcoidosis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed blood B cell subsets and BAFF levels in 33 patients with chronic sarcoidosis (active sarcoidosis n = 18; inactive sarcoidosis n = 15 and 18 healthy donors. Active chronic sarcoidosis patients had significantly less circulating memory B cells (p<0.01, more transitional (p<0.01 and increased numbers of IL-10-producing regulatory B cells (p<0.05 compared with healthy donors and patients with inactive sarcoidosis. BAFF serum levels were significantly higher in patients with active sarcoidosis (p<0.01 versus healthy donors and inactive sarcoidosis patients and strongly correlated with serum hypergammaglobulinemia (r = 0.53, p<0.01 and angiotensin converting enzyme levels (r = 0.61, p = <0.01. CONCLUSIONS/SIGNIFICANCE: These data show that there is an altered B cell homeostasis in active sarcoidosis and suggest BAFF antagonist drugs as potential new treatments of this disease.

  20. Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells.

    Science.gov (United States)

    Schwartz, Anton M; Putlyaeva, Lidia V; Covich, Milica; Klepikova, Anna V; Akulich, Kseniya A; Vorontsov, Ilya E; Korneev, Kirill V; Dmitriev, Sergey E; Polanovsky, Oleg L; Sidorenko, Svetlana P; Kulakovskiy, Ivan V; Kuprash, Dmitry V

    2016-10-01

    Signaling lymphocytic activation molecule family member 1 (SLAMF1)/CD150 is a co-stimulatory receptor expressed on a variety of hematopoietic cells, in particular on mature lymphocytes activated by specific antigen, costimulation and cytokines. Changes in CD150 expression level have been reported in association with autoimmunity and with B-cell chronic lymphocytic leukemia. We characterized the core promoter for SLAMF1 gene in human B-cell lines and explored binding sites for a number of transcription factors involved in B cell differentiation and activation. Mutations of SP1, STAT6, IRF4, NF-kB, ELF1, TCF3, and SPI1/PU.1 sites resulted in significantly decreased promoter activity of varying magnitude, depending on the cell line tested. The most profound effect on the promoter strength was observed upon mutation of the binding site for Early B-cell factor 1 (EBF1). This mutation produced a 10-20 fold drop in promoter activity and pinpointed EBF1 as the master regulator of human SLAMF1 gene in B cells. We also identified three potent transcriptional enhancers in human SLAMF1 locus, each containing functional EBF1 binding sites. Thus, EBF1 interacts with specific binding sites located both in the promoter and in the enhancer regions of the SLAMF1 gene and is critical for its expression in human B cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Quality of nutrition services in primary health care facilities: Implications for integrating nutrition into the health system in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Sk Masum Billah

    Full Text Available In 2011, the Bangladesh Government introduced the National Nutrition Services (NNS by leveraging the existing health infrastructure to deliver nutrition services to pregnant woman and children. This study examined the quality of nutrition services provided during antenatal care (ANC and management of sick children younger than five years.Service delivery quality was assessed across three dimensions; structural readiness, process and outcome. Structural readiness was assessed by observing the presence of equipment, guidelines and register/reporting forms in ANC rooms and consulting areas for sick children at 37 primary healthcare facilities in 12 sub-districts. In addition, the training and knowledge relevant to nutrition service delivery of 95 healthcare providers was determined. The process of nutrition service delivery was assessed by observing 381 ANC visits and 826 sick children consultations. Satisfaction with the service was the outcome and was determined by interviewing 541 mothers/caregivers of sick children.Structural readiness to provide nutrition services was higher for ANC compared to management of sick children; 73% of ANC rooms had >5 of the 13 essential items while only 13% of the designated areas for management of sick children had >5 of the 13 essential items. One in five (19% healthcare providers had received nutrition training through the NNS. Delivery of the nutrition services was poor: <30% of women received all four key antenatal nutrition services, 25% of sick children had their weight checked against a growth-chart and <1% had their height measured. Nevertheless, most mothers/caregivers rated their satisfaction of the service above average.Strengthening the provision of equipment and increasing the coverage of training are imperative to improve nutrition services. Inherent barriers to implementing nutrition services in primary health care, especially high caseloads during the management of sick under-five children, should

  2. Development of a Risk-adjustment Model for the Inpatient Rehabilitation Facility Discharge Self-care Functional Status Quality Measure.

    Science.gov (United States)

    Deutsch, Anne; Pardasaney, Poonam; Iriondo-Perez, Jeniffer; Ingber, Melvin J; Porter, Kristie A; McMullen, Tara

    2017-07-01

    Functional status measures are important patient-centered indicators of inpatient rehabilitation facility (IRF) quality of care. We developed a risk-adjusted self-care functional status measure for the IRF Quality Reporting Program. This paper describes the development and performance of the measure's risk-adjustment model. Our sample included IRF Medicare fee-for-service patients from the Centers for Medicare & Medicaid Services' 2008-2010 Post-Acute Care Payment Reform Demonstration. Data sources included the Continuity Assessment Record and Evaluation Item Set, IRF-Patient Assessment Instrument, and Medicare claims. Self-care scores were based on 7 Continuity Assessment Record and Evaluation items. The model was developed using discharge self-care score as the dependent variable, and generalized linear modeling with generalized estimation equation to account for patient characteristics and clustering within IRFs. Patient demographics, clinical characteristics at IRF admission, and clinical characteristics related to the recent hospitalization were tested as risk adjusters. A total of 4769 patient stays from 38 IRFs were included. Approximately 57% of the sample was female; 38.4%, 75-84 years; and 31.0%, 65-74 years. The final model, containing 77 risk adjusters, explained 53.7% of variance in discharge self-care scores (Pcare function was the strongest predictor, followed by admission cognitive function and IRF primary diagnosis group. The range of expected and observed scores overlapped very well, with little bias across the range of predicted self-care functioning. Our risk-adjustment model demonstrated strong validity for predicting discharge self-care scores. Although the model needs validation with national data, it represents an important first step in evaluation of IRF functional outcomes.

  3. BAFF and BAFF receptor levels correlate with B cell subset activation and redistribution in controlled human malaria infection

    NARCIS (Netherlands)

    Scholzen, A.; Teirlinck, A.C.; Bijker, E.M.; Roestenberg, M.; Hermsen, C.C.; Hoffman, S.L.; Sauerwein, R.W.

    2014-01-01

    Characteristic features of Plasmodium falciparum malaria are polyclonal B cell activation and an altered composition of the blood B cell compartment, including expansion of CD21(-)CD27(-) atypical memory B cells. BAFF is a key cytokine in B cell homeostasis, but its potential contribution to the

  4. Dialysis Facility Compare

    Data.gov (United States)

    U.S. Department of Health & Human Services — Dialysis Facility Compare helps you find detailed information about Medicare-certified dialysis facilities. You can compare the services and the quality of care that...

  5. Peripheral CD5+ B Cells in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

    Science.gov (United States)

    Unizony, Sebastian; Lim, Noha; Phippard, Deborah J.; Carey, Vincent J.; Miloslavsky, Eli M.; Tchao, Nadia K.; Iklé, David; Asare, Adam L.; Merkel, Peter A.; Monach, Paul A.; Seo, Philip; St Clair, E. William; Langford, Carol A.; Spiera, Robert; Hoffman, Gary S.; Kallenberg, Cees G. M.; Specks, Ulrich; Stone, John H.

    2015-01-01

    Objective CD5+ B cells have been conceptualized as a possible surrogate for Breg cells. The aim of the present study was to determine the utility of CD5+ B cells as biomarkers in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Methods The absolute and relative numbers (percentages) of CD5+ B cells (explanatory variables) were measured longitudinally during 18 months in 197 patients randomized to receive either rituximab (RTX) or cyclophosphamide (CYC) followed by azathioprine (AZA) for the treatment of AAV (Rituximab in ANCA-Associated Vasculitis [RAVE] trial). Outcome variables included disease activity (status of active disease versus complete remission), responsiveness to induction therapy, disease relapse, disease severity, and, in RTX-treated patients, relapse-free survival according to the percentage of CD5+ B cells detected upon B cell repopulation. Results CD5+ B cell numbers were comparable between the treatment groups at baseline. After an initial decline, absolute CD5+ B cell numbers progressively increased in patients in the RTX treatment arm, but remained low in CYC/AZA-treated patients. In both groups, the percentage of CD5+ B cells increased during remission induction and slowly declined thereafter. During relapse, the percentage of CD5+ B cells correlated inversely with disease activity in RTX-treated patients, but not in patients who received CYC/AZA. No significant association was observed between the numbers of CD5+ B cells and induction treatment failure or disease severity. The dynamics of the CD5+ B cell compartment did not anticipate disease relapse. Following B cell repopulation, the percentage of CD5+ B cells was not predictive of time to flare in RTX-treated patients. Conclusion The percentage of peripheral CD5+ B cells might reflect disease activity in RTX-treated patients. However, sole staining for CD5 as a putative surrogate marker for Breg cells did not identify a subpopulation of B cells with clear potential for

  6. IL-15 expression on RA synovial fibroblasts promotes B cell survival.

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    Marta Benito-Miguel

    Full Text Available INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001. IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05. Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

  7. Flow Cytometry Analysis of Peripheral Blood B Cell Distribution of Patients with Multiple Sclerosis

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    Vuslat Yılmaz

    2017-12-01

    Full Text Available Objective: Multiple sclerosis (MS is a central nervous system (CNS disease characterized by autoimmune inflammation and neurodegeneration. Damage to the CNS is thought to be mediated predominantly by activated pro-inflammatory T cells and antibody secreting B cells. Strong evidence of B cell functions in MS pathogenesis has come from trials of B cell- depleting treatment. In this study, the peripheral blood frequencies of B cell subsets were measured using flow cytometry in patients to determine the disease-specific B cell differences that might be associated with the evolution to progressive forms of MS. Materials and Methods: Peripheral blood mononuclear cells were separated from patients and healthy controls [relapsing-remitting MS (RRMS and secondary progressive MS (SPMS]. Cells were stained with anti-human monoclonal antibodies (CD19-APC, CD27-FITC, IgD-APC/Cy7, CD138-PE, CD24-PerCP and CD38-Alexa fluor 700, and analyzed using flow cytometry Results: There were no significant differences between the MS group and healthy controls by means of peripheral blood frequencies of B cells, immature, naïve, classic memory, plasma, plasmablasts, and regulatory B cells. Only higher naïve B cell frequency tendency was determined in patients with RRMS as compared with patients with SPMS and healthy controls. Conclusion: Peripheral blood B cell subset measurements are not likely to be used as a biomarker for prediction of disease progression. Although B cells have a well-known pathogenic significance, B cell population alterations do not occur during the progression of the disease

  8. Alteration of B cell subsets and the receptor for B cell activating factor (BAFF) in paediatric patients with type 1 diabetes.

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    Parackova, Zuzana; Klocperk, Adam; Rataj, Michal; Kayserova, Jana; Zentsova, Irena; Sumnik, Zdenek; Kolouskova, Stanislava; Sklenarova, Jana; Pruhova, Stepanka; Obermannova, Barbora; Petruzelkova, Lenka; Lebl, Jan; Kalina, Tomas; Sediva, Anna

    2017-09-01

    Lately, mounting evidence has shown that B cells pla