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1.
Front Med (Lausanne) ; 11: 1330457, 2024.
Article in English | MEDLINE | ID: mdl-38572162

ABSTRACT

Introduction: Vacuum extraction is generally considered an operator-dependent task, with most attention directed toward the obstetrician's technical abilities (1-3). Little is known about the effect of the team and non-technical skills on clinical outcomes in vacuum-assisted delivery. This study aimed to investigate whether the non-technical skills of obstetricians were correlated with their level of clinical performance via the analysis of video recordings of teams conducting actual vacuum extractions. Methods: We installed between two or three video cameras in each delivery room at Aarhus University Hospital and Horsens Regional Hospital and obtained 60 videos of teams managing vacuum extraction. Appropriate consent was obtained. Two raters carefully reviewed the videos and assessed the teams' non-technical skills using the Assessment of Obstetric Team Performance (AOTP) checklist, rating all items on a Likert scale score from 1 to 5 (1 = poor; 3 = average; and 5 = excellent). This resulted in a total score ranging from 18 to 90. Two different raters independently assessed the teams' clinical performance (adherence to clinical guidelines) using the TeamOBS-Vacuum-Assisted Delivery (VAD) checklist, rating each item (0 = not done, 1 = done incorrectly; and 2 = done correctly). This resulted in a total score with the following ranges (low clinical performance: 0-59; average: 60-84; and high: 85-100). Interrater agreement was analyzed using intraclass correlation (ICC), and the risk of high or low clinical performance was analyzed on a logit scale to meet the assumption of normality. Results: Teams that received excellent non-technical scores had an 81% probability of achieving high clinical performance, whereas this probability was only 12% among teams with average non-technical scores (p < 0.001). Teams with a high clinical performance often had excellent behavior in the non-technical items of "team interaction," "anticipation," "avoidance fixation," and "focused communication." Teams with a low or average clinical performance often neglected to consider analgesia, had delayed abandonment of the attempted vaginal delivery and insufficient use of appropriate fetal monitoring. Interrater reliability was high for both rater-teams, with an ICC for the non-technical skills of 0.83 (95% confidence interval [CI]: 0.71-0.88) and 0.84 for the clinical performance (95% CI: 0.74-0.90). Conclusion: Although assisted vaginal delivery by vacuum extraction is generally considered to be an operator-dependent task, our findings suggest that teamwork and effective team interaction play crucial roles in achieving high clinical performance. Teamwork helped the consultant anticipate the next step, avoid fixation, ensure adequate analgesia, and maintain thorough fetal monitoring during delivery.

2.
BJOG ; 126(8): 1015-1023, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30771263

ABSTRACT

OBJECTIVE: Little is known about how teams' non-technical performance influences clinical performance in obstetric emergencies such as postpartum haemorrhage. DESIGN: Video review - observational study. SETTING: A university hospital (5000 deliveries) and a regional hospital (2000 deliveries) in Denmark. POPULATION: Obstetric teams managing real-life postpartum haemorrhage. METHODS: We systematically assessed 99 video recordings of obstetric teams managing real-life major postpartum haemorrhage. Exposure was the non-technical score (AOTP); outcomes were the clinical performance score (TeamOBS) and the delayed transfer to the operating theatre (defined as blood loss >1500 ml in the delivery room). RESULTS: Teams with an excellent non-technical score performed significantly better than teams with a poor non-technical score: 83.7 versus 0.3% chance of a high clinical performance score (P < 0.001), 0.2 versus 80% risk of a low clinical performance score (P < 0.001), and 3.5 versus 31.7% risk of delayed transfer to the operating theatre (P = 0.008). The results remained robust when adjusting for potential confounders such as bleeding velocity, aetiology, time of day, team size, and hospital. The specific non-technical skills associated with high clinical performance were vigilance, role assignment, problem-solving, management of disruptive behavior, and leadership. Communication with the patient and closing the loop were of minor importance. All performance assessments showed good reliability: the intraclass correlation was 0.97 (95% CI 0.96-0.98) for the non-technical score and 0.84 (95% CI 0.76-0.89) for the clinical performance score. CONCLUSION: Video review offers a new method and new perspectives for research in obstetric teams to identify how teams become effective and safe; the skills identified in this study can be included in future obstetric training programmes. TWEETABLE ABSTRACT: Non-technical performance is important for teams managing postpartum haemorrhage; video review of 99 obstetric teams.


Subject(s)
Clinical Competence , Obstetrics/standards , Patient Care Team/standards , Postpartum Hemorrhage , Work Performance , Communication , Denmark , Female , Humans , Leadership , Obstetrics/methods , Pregnancy , Process Assessment, Health Care , Video Recording
3.
BMC Cancer ; 18(1): 936, 2018 Sep 29.
Article in English | MEDLINE | ID: mdl-30268109

ABSTRACT

BACKGROUND: Cancer research has made great progress in the recent years. With the increasing number of options in diagnosis and therapy the implementation of tumorboards (TUBs) has become standard procedure in the treatment of cancer patients. Adherence tests on tumor board decisions are intended to enable quality assurance and enhancement for work in tumor boards in order to continuously optimize treatment options for cancer patients. METHODS: Subject of this study was the adherence of the recommendations made in three of 14 tumorboards, which take place weekly in the Center for Integrated Oncology (CIO) at the University Hospital Bonn. In total, therapy recommendations of 3815 patient cases were checked on their implementation. A classification into four groups has been made according to the degree of implementation. A second classification followed regarding the reasons for differences between the recommendation and the therapy which the patient actually received. RESULTS: The study showed that 80.1% of all recommendations in the three TUBs were implemented. 8.3% of all recommendations showed a deviance. Most important reasons for the deviances were patient wish (36.5%), patient death (26%) and doctoral decision, due to the patient's comorbidities or side effects of the treatment (24.1%).Interestingly, deviance in all three tumor boards in total significantly decreased over time. CONCLUSIONS: Aim of the study was to clarify the use of tumor boards and find approaches to make them more efficient. Based on the results efficiency might be optimized by increased consideration of patients` preferences, improved presentation of patient-related data, more detailed documentation and further structuring of the tumor board meetings.


Subject(s)
Guideline Adherence , Integrative Oncology , Interdisciplinary Research/organization & administration , Neoplasms/therapy , Germany , Humans
4.
Gesundheitswesen ; 78(S 01): e103-e109, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27300092

ABSTRACT

Objective: The aim of this study was to evaluate the degree of implementation of recommendations for patient safety in ambulatory surgical care and their benefit as perceived by surgeons in the ambulatory sector. Based on 2 practice recommendations issued by the Association of Statutory Health Insurance Physicians in Westphalia-Lippe, recommendations were formulated specifically for ambulatory surgery and distributed in 2013 to all physicians licensed to conduct ambulatory surgery in Westphalia-Lippe. Methods: We conducted a written survey covering all safety measures addressed by the 2 practice recommendations and assessed the degree of implementation and the perceived benefit for each of these measures as well as the strengths of the recommendations and the challenges of implementing them. The survey was distributed in late 2014 to 2 454 surgeons in the ambulatory setting. The survey period was 7 weeks. The analysis of the quantitative data was mainly descriptive and we conducted thematic summaries of free text answers to open-ended questions. Results: The participation rate was 17% (n=405). The recommendations were known to 86% of the respondents. The majority of recommended safety measures had been implemented systemically in more than 50% of the participating institutions. An increased interprofessional awareness of patient safety measurements was reported as the main impact of the recommendations. Respondents indicated further need for information and practice recommendations concerning the following topics: risk and error management, implementation of the Medical Devices Act, hygiene in medical practice and processing of instruments. Conclusion: This study highlights the valuable contribution practice recommendations can make to patient safety improvement in ambulatory surgical care. Their dissemination to other regions as well as to other ambulatory care settings such as family practice can therefore be recommended.

6.
Br J Anaesth ; 110(4): 529-44, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23454826

ABSTRACT

There is a growing literature on the relationship between team processes and clinical performance. The purpose of this review is to summarize these articles and examine the impact of team process behaviours on clinical performance. We conducted a literature search in five major databases. Inclusion criteria were: English peer-reviewed papers published between January 2001 and May 2012, which showed or tried to show (i) a statistical relationship of a team process variable and clinical performance or (ii) an improvement of a performance variable through a team process intervention. Study quality was assessed using predefined quality indicators. For every study, we calculated the relevant effect sizes. We included 28 studies in the review, seven of which were intervention studies. Every study reported at least one significant relationship between team processes or an intervention and performance. Also, some non-significant effects were reported. Most of the reported effect sizes were large or medium. The study quality ranged from medium to high. The studies are highly diverse regarding the specific team process behaviours investigated and also regarding the methods used. However, they suggest that team process behaviours do influence clinical performance and that training results in increased performance. Future research should rely on existing theoretical frameworks, valid, and reliable methods to assess processes such as teamwork or coordination and focus on the development of adequate tools to assess process performance, linking them with outcomes in the clinical setting.


Subject(s)
Patient Care Team/organization & administration , Patient Care Team/standards , Behavior , Clinical Competence , Communication , Data Collection , Data Interpretation, Statistical , Leadership , Research Design , Treatment Outcome
7.
Br J Anaesth ; 106(6): 801-6, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21429954

ABSTRACT

BACKGROUND: Recent studies in anaesthesia and intensive care indicate that a team's ability to adapt its coordination activities to changing situational demands is crucial for effective teamwork and thus, safe patient care. This study addresses the relationship between adaptation of team coordination and markers of clinical performance in response to a critical event, particularly regarding which types of coordination activities are used and which team member engages in those coordination activities. METHODS: Video recordings of 15 two-person anaesthesia teams (anaesthesia trainee plus anaesthesia nurse) performing a simulated induction of general anaesthesia were coded, using a structured observation system for coordination activities. The simulation involved a critical event-asystole during laryngoscopy. Clinical performance was assessed using two separate reaction times related to the critical event. RESULTS: Analyses of variance revealed a significant effect of the critical event on team coordination: after the occurrence of the asystole, team members adapted their coordination activities by spending more time on information management-a specific type of coordination activity (F(1,28)=15.17, P=0.001). No significant effect was found for task management. The increase in information management was related to faster decisions regarding how to respond to the critical event, but only for trainees and not for nurses. CONCLUSIONS: Our findings support the claim that adaptation of coordination activities is related to improved team performance in healthcare. Moreover, adaptation and its relationship to team performance were found to vary with regard to type of coordination activities and team member.


Subject(s)
Adaptation, Psychological , Anesthesiology/organization & administration , Clinical Competence , Patient Care Team/organization & administration , Task Performance and Analysis , Anesthesia, General/standards , Anesthesiology/education , Anesthesiology/standards , Decision Making , Education, Medical, Graduate/organization & administration , Female , Health Services Research/methods , Heart Arrest/etiology , Heart Arrest/therapy , Humans , Information Management/standards , Laryngoscopy/adverse effects , Male , Patient Care Team/standards , Patient Simulation , Reaction Time , Switzerland , Video Recording
8.
Qual Saf Health Care ; 19(6): e60, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20558472

ABSTRACT

BACKGROUND: Incident reporting systems are widely considered effective instruments for learning from incidents. However, research shows that many incidents are not reported by healthcare providers. OBJECTIVE: The lack of theoretical foundation in research on barriers to and motivators for incident reporting is addressed in this article, and a psychological framework of antecedents to staff's motivation (not) to report incidents is proposed. FRAMEWORK DEVELOPMENT: Concepts relevant for clinicians' motivation to report incidents were identified in psychological literature. Additionally, a literature review was conducted to extract barriers to incident reporting and cluster them into thematic groups. Barriers and motivators influencing clinicians' willingness to report were integrated and identified as an indicator for actual reporting behaviour. CONCLUSIONS: The proposed framework provides a basis for guiding future empirical studies that will improve our understanding of what encourages and what hinders clinicians to report incidents and, consequently, of areas for interventions to enhance reporting behaviour.


Subject(s)
Concept Formation , Mandatory Reporting , Medical Errors , Guideline Adherence , Health Personnel , Humans , Motivation
9.
Acta Anaesthesiol Scand ; 53(2): 143-51, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19032571

ABSTRACT

AIMS/BACKGROUND: This review examines current research on teamwork in highly dynamic domains of healthcare such as operating rooms, intensive care, emergency medicine, or trauma and resuscitation teams with a focus on aspects relevant to the quality and safety of patient care. RESULTS: Evidence from three main areas of research supports the relationship between teamwork and patient safety: (1) Studies investigating the factors contributing to critical incidents and adverse events have shown that teamwork plays an important role in the causation and prevention of adverse events. (2) Research focusing on healthcare providers' perceptions of teamwork demonstrated that (a) staff's perceptions of teamwork and attitudes toward safety-relevant team behavior were related to the quality and safety of patient care and (b) perceptions of teamwork and leadership style are associated with staff well-being, which may impact clinician' ability to provide safe patient care. (3) Observational studies on teamwork behaviors related to high clinical performance have identified patterns of communication, coordination, and leadership that support effective teamwork. CONCLUSION: In recent years, research using diverse methodological approaches has led to significant progress in team research in healthcare. The challenge for future research is to further develop and validate instruments for team performance assessment and to develop sound theoretical models of team performance in dynamic medical domains integrating evidence from all three areas of team research identified in this review. This will help to improve team training efforts and aid the design of clinical work systems supporting effective teamwork and safe patient care.


Subject(s)
Cooperative Behavior , Interdisciplinary Communication , Patient Care Team , Safety , Attitude of Health Personnel , Communication Barriers , Emergency Service, Hospital , Goals , Group Processes , Humans , Intensive Care Units , Leadership , Medical Errors , Operating Rooms , Resuscitation
10.
Ergonomics ; 51(8): 1153-78, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18608475

ABSTRACT

Patient care in hospital settings requires coordinated team performance. Studies in other industries show that successful teams adapt their coordination processes to the situational task requirements. This prospective field study aimed to test a new observation system and investigate patterns of adaptive coordination within operating room teams. A trained observer recorded coordination activities during 24 cardiac surgery procedures. The study tested whether different patterns occur during different phases of and between different types of surgical procedures (two-way multivariate ANOVA with repeated measure). A statistically significant increase was found in clinical and coordination activities in phases of the operation with high task interdependence. The highest level of 'coordination via the work environment' (i.e. an implicit coordination mechanism) was recorded during the actual procedure on the beating heart. These findings prove the sensitivity of the observation system developed and evaluated in this study and provide insight into patterns of adaptive coordination in cardiac anaesthesia. This study furthers our understanding of adaptive coordination as a cornerstone of effective team performance in complex work environments. Using a new observation system, it describes patterns employed by health care professionals in response to changing task demands in an acute patient care setting.


Subject(s)
Adaptation, Psychological , Operating Rooms , Patient Care Team , Task Performance and Analysis , Anesthesiology , Humans
11.
Genes Immun ; 8(7): 604-12, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17713556

ABSTRACT

The inhibitory receptor FcgammaRIIb regulates B-cell functions. Genetic studies have associated Fcgr2b polymorphisms and lupus susceptibility in both humans and murine models, in which B cells express reduced FcgammaRIIb levels. Furthermore, FcgammaRIIb absence results in lupus on the appropriate genetic background, and lentiviral-mediated FcgammaRIIb overexpression prevents disease in the NZM2410 lupus mouse. The NZM2410/NZW allele Fcgr2b is, however, located in-between Sle1a and Sle1b, two potent susceptibility loci, making it difficult to evaluate Fcr2b(NZW) independent contribution. By using two congenic strains that each carries only Sle1a (B6.Sle1a(15-353)), or Fcr2b(NZW) in the absence of Sle1a or Sle1b (B6.Sle1(111-148)), we show that the Fcr2b(NZW) allele does not upregulate its expression on germinal center B cells and plasma cells, as does the C57BL/6 allele on B6.Sle1a(15-353) B cells. Furthermore, in the absence of the flanking Sle1a and Sle1b, Fcr2b(NZW) does not produce an autoimmune phenotype, but is associated with an increased number of class-switched plasma cells. These results show that while a lower level of FcgammaRIIb does not by itself induce the development of autoreactive B cells, it has the potential to amplify the contribution of autoreactive B cells induced by other lupus-susceptibility loci by enhancing the production of class-switched plasma cells.


Subject(s)
B-Lymphocytes/immunology , Germinal Center/immunology , Immunoglobulin G/biosynthesis , Receptors, IgG/genetics , Alleles , Animals , B-Lymphocytes/cytology , Dendritic Cells, Follicular/cytology , Dendritic Cells, Follicular/immunology , Gene Expression Regulation , Genetic Predisposition to Disease , Germinal Center/cytology , Germinal Center/metabolism , Immunoglobulin Class Switching , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/metabolism , Mice , Mice, Congenic , Mice, Inbred C57BL , Mice, Inbred Strains , Plasma Cells/immunology , Receptors, IgG/immunology , Receptors, IgG/metabolism , Up-Regulation
12.
Ergonomics ; 50(2): 246-60, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17419157

ABSTRACT

This study investigated the behavioural aspects of ecological validity of anaesthesia simulation environments using a task analysis approach. Six anaesthesists were observed during two cases performed in the operating room (OR), one routine and two critical incident simulation scenarios. A two-way MANOVA for repeated measures was performed with the independent variables Case (OR/SIM-R/SIM-CI) and Phase Induction/ Maintenance (Emergence), the latter being a repeated measure. Dependent variables were the proportion of each phase spent on each of the observation categories. Statistically significant main effects for Phase concerning communication, monitoring, manual tasks and documentation, for Case concerning communication and documentation, and a significant interaction effect for Phase x Case concerning manual tasks and other were found. Increased action density (i.e. amount of co-occurring activities) was observed during Induction, Emergence and the Management of simulated critical events. The similarities and differences in anaesthetists' activity patterns identified in this study will help to further improve the ecological validity of simulation environments as research settings.


Subject(s)
Anesthesiology , Computer Simulation , Operating Rooms , Task Performance and Analysis , Humans , Reproducibility of Results
13.
Acta Anaesthesiol Scand ; 49(6): 728-34, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15954950

ABSTRACT

An important element of how adverse events are handled is effective communication between health care providers and patients and their families. This review addresses the main questions: What do patients expect in the aftermath of an adverse event? What is known about the practice of open disclosure? How can organizations support health care providers in the aftermath of an adverse event, both professionally and personally? Patients clearly expect open disclosure to include an explanation of what happened, an apology for harm done, that appropriate remedial action will be taken and an explanation of what will be done to learn from the event and to prevent recurrence. Research has found that open disclosure is not very common although the ethical duty to disclose is widely acknowledged. Barriers to open disclosure include discomfort and a lack of training how to disclose, a fear of litigation, a culture of infallibility among health professionals, and inadequate systems for analysis, discussion and learning from mistakes. Significant commitment is required from health care organizations and managers to develop frameworks for open disclosure to occur, to assure its quality and to support health care providers in this process. Organizations also need to address the emotional needs of health care professionals in the aftermath of an adverse event. Last but not least, adequate systems for debriefing and incident analysis need to be in place to learn from adverse events and to avoid recurrence.


Subject(s)
Anesthesia/adverse effects , Anesthesiology/ethics , Disclosure/standards , Patients , Anesthesiology/education , Disclosure/legislation & jurisprudence , Guidelines as Topic , Humans
15.
Article in German | MEDLINE | ID: mdl-11475625

ABSTRACT

"Patient safety" and "errors in medicine" are issues gaining more and more prominence in the eyes of the public. According to newer studies, errors in medicine are among the ten major causes of death in association with the whole area of health care. A new era has begun incorporating attention to a "systems" approach to deal with errors and their causes in the health system. In other high-risk domains with a high demand for safety (such as the nuclear power industry and aviation) many strategies to enhance safety have been established. It is time to study these strategies, to adapt them if necessary and apply them to the field of medicine. These strategies include: to teach people how errors evolve in complex working domains and how types of errors are classified; the introduction of critical incident reporting systems that are free of negative consequences for the reporters; the promotion of continuous medical education; and the development of generic problem-solving skills incorporating the extensive use of realistic simulators wherever possible. Interestingly, the field of anesthesiology--within which realistic simulators were developed--is referred to as a model for the new patient safety movement. Despite this proud track record in recent times though, there is still much to be done even in the field of anesthesiology. Overall though, the most important strategy towards a long-term improvement in patient safety will be a change of "culture" throughout the entire health care system. The "culture of blame" focused on individuals should be replaced by a "safety culture", that sees errors and critical incidents as a problem of the whole organization. The acceptance of human fallability and an open-minded non-punitive analysis of errors in the sense of a "preventive and proactive safety culture" should lead to solutions at the systemic level. This change in culture can only be achieved with a strong commitment from the highest levels of an organization. Patient safety must have the highest priority in the goals of the institution: "Primum nihil nocere"--"First, do not harm".


Subject(s)
Anesthesiology/standards , Medical Errors/prevention & control , Safety , Anesthesia/adverse effects , Cause of Death , Humans , Medical Errors/classification , Problem Solving , Quality Assurance, Health Care
16.
J Immunol ; 167(1): 15-20, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11418626

ABSTRACT

Immunization of mice containing mutations that inactivate the TCR Cbeta and Cdelta genes with the T cell-independent (TI) type 2 Ag (4-hydroxy-3-nitrophenyl)acetyl-Ficoll induces clusters of peanut agglutinin-binding B cells in the spleen. These clusters are histologically indistinguishable from germinal centers (GCs) typical of T cell-dependent immune responses. They are located in follicles, and contain mature follicular dendritic cells, immune complex deposits, and B cells that display the phenotypic qualities of conventional GC B cells. However, the kinetics of this TI GC response differ from T cell-dependent GC responses in being rapidly induced and of short duration. Moreover, the Ab V genes expressed in TI GCs have not undergone somatic hypermutation. Therefore, T cells may be required for B cell differentiation processes associated with the intermediate and latter stages of the GC reaction, but they are dispensable for the induction and initial development of this response.


Subject(s)
Germinal Center/immunology , Lymphopenia/immunology , T-Lymphocytes/immunology , Animals , Antigens, T-Independent/immunology , B-Lymphocytes/metabolism , Base Sequence , Cell Aggregation/genetics , Cell Aggregation/immunology , Cell Differentiation/genetics , Cell Differentiation/immunology , Gene Expression Regulation/immunology , Germinal Center/pathology , Immunoglobulin Heavy Chains/biosynthesis , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/biosynthesis , Immunoglobulin Variable Region/genetics , Immunophenotyping , Lymphopenia/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Molecular Sequence Data , Mutation , Peanut Agglutinin/biosynthesis , Spleen/immunology , Spleen/pathology , T-Lymphocytes/pathology
17.
Int Immunol ; 13(4): 475-84, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11282987

ABSTRACT

We generated IgHmudelta transgenic mice using a V(H) gene that in A/J mice encodes multireactive BCR in the preimmune B cell compartment and is predominantly expressed by a memory B cell subpopulation. Most primary splenic B cells in these mice have a size, cell-surface phenotype and in vitro response profile distinct from mature follicular (B2), marginal zone (MZ) or B1 B cells, but are long-lived and appear to be slowly cycling. They reside in conventional B cell areas of the spleen and mount robust foreign antigen-driven germinal center responses, but do not efficiently differentiate to secretory phenotype. We propose that these qualities result from ongoing, low-avidity BCR-self-ligand interactions and promote entry into the memory pathway. Given these data, and the enormous diversity and characteristic multireactivity of the preimmune antibody repertoire, we also suggest that it may be more appropriate to view the primary B cell compartment as a continuum of functional and phenotypic 'layers', rather than as a group of discrete B1, B2 and MZ subsets.


Subject(s)
Antibodies/genetics , B-Lymphocytes/immunology , Cell Differentiation , Animals , Animals, Newborn , Antibodies/blood , Antigens, Differentiation, B-Lymphocyte/analysis , B-Lymphocytes/cytology , Cell Size , Immunization , Immunoglobulin Heavy Chains/genetics , Immunoglobulins/blood , Lymph Nodes/immunology , Mice , Mice, Transgenic , Receptors, Antigen, B-Cell/analysis , Spleen/cytology , Spleen/immunology , p-Azobenzenearsonate/immunology
18.
Immunity ; 14(1): 33-43, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11163228

ABSTRACT

Available evidence indicates that B cell tolerance is attained by receptor editing, anergy, or clonal deletion. Here, we describe a p-azophenylarsonate (Ars)-specific immunoglobulin transgenic mouse in which B cells become anergic as a consequence of cross-reaction with autoantigen in the bone marrow. Developing bone marrow B cells show no evidence of receptor editing but transiently upregulate activation markers and appear to undergo accelerated development. Mature B cells are present in normal numbers but are refractory to BCR-mediated induction of calcium mobilization, tyrosine phosphorylation, and antibody responses. Activation marker expression and acquisition of the anergic phenotype is prevented in bone marrow cultures by monovalent hapten. In this model, it appears that induction of anergy in B cells can be prevented by monovalent hapten competing with autoantigen for the binding site.


Subject(s)
Autoimmunity/immunology , B-Lymphocytes/immunology , Bone Marrow Cells/immunology , Clonal Anergy/immunology , Haptens/immunology , Immunoglobulins/immunology , Lymphocyte Activation/immunology , Alleles , Animals , Biomarkers , DNA, Single-Stranded/immunology , Gene Expression , Hemocyanins/immunology , Immunoglobulin delta-Chains/genetics , Immunoglobulin delta-Chains/immunology , Immunoglobulin kappa-Chains/genetics , Immunoglobulin kappa-Chains/immunology , Immunoglobulin mu-Chains/genetics , Immunoglobulin mu-Chains/immunology , Immunoglobulins/genetics , Mice , Mice, Transgenic , Transgenes , p-Azobenzenearsonate/immunology
19.
J Immunol ; 166(5): 3226-30, 2001 Mar 01.
Article in English | MEDLINE | ID: mdl-11207276

ABSTRACT

Expression of the protooncogene A-myb is restricted to the developing CNS, adult testes, breasts in late pregnancy, and germinal centers of secondary B cell follicles. The functional relevance of A-myb expression at three of these sites has been demonstrated previously via the generation and analysis of A-myb-deficient mice, which display behavioral abnormalities, male sterility, and perturbed breast development during pregnancy. In contrast, here we show that the germinal center response driven by T cell-dependent Ag immunization and the associated processes of Ab V gene somatic hypermutation, affinity maturation, and heavy chain class switching are overtly normal in A-myb-deficient mice. Nonetheless, these mice display mild splenic white pulp hypoplasia and blunted primary serum Ab responses, suggesting that although A-myb is not directly involved in the regulation of the memory B cell response, it may play a role in enhancing peripheral B cell survival or proliferative capacity.


Subject(s)
Avian Proteins , B-Lymphocytes/immunology , Germinal Center/immunology , Proto-Oncogene Proteins/deficiency , Proto-Oncogene Proteins/genetics , T-Lymphocytes/immunology , Trans-Activators/deficiency , Trans-Activators/genetics , Animals , Antibodies/blood , Antibody Formation/genetics , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , Cell Differentiation/genetics , Cell Differentiation/immunology , Chickens , Female , Germinal Center/metabolism , Germinal Center/pathology , Immunoglobulin Class Switching/genetics , Injections, Intraperitoneal , Lymphocyte Activation/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Proto-Oncogene Proteins c-myb , Spleen/abnormalities , Spleen/growth & development , Spleen/immunology , T-Lymphocytes/metabolism , gamma-Globulins/administration & dosage , gamma-Globulins/immunology
20.
Dev Immunol ; 8(3-4): 223-34, 2001.
Article in English | MEDLINE | ID: mdl-11785672

ABSTRACT

We investigated the role of apoptosis in the development of B cell memory by analyzing the (p-azophenylarsonate) Ars response in a line of A strain mice in which expression of human Bcl-2 was enforced in the B cell compartment. Previous studies of the Ars immune response in these A. Bcl-2 mice, demonstrated that a large percentage of the antibodies expressed by the Ars induced memory B cell compartment had accumulated point mutations via somatic hypermutation that increased their affinity for both Ars and the autoantigen DNA ("dual reactive" antibodies). This was in sharp contrast to normal A strain mice which displayed no dual reactive B cells in their Ars induced memory B cell compartment. These data suggested that interference with apoptotic pathways regulated by Bcl-2 allows developing memory B cells that have acquired autoreactivity to bypass a peripheral tolerance checkpoint. Further studies of these mice, reported here, demonstrate that enforced expression of Bcl-2 does not alter serum antibody affinity maturation nor positive selection of B cells expressing somatically mutated antibody with an increased affinity for Ars. Moreover, the somatic hypermutation process was unaffected in A. Bcl-2 mice. Thus, enforced expression of Bcl-2 in A. Bcl-2 mice appears to selectively alter a negative selection process that operates during memory B cell differentiation.


Subject(s)
Antibodies/immunology , B-Lymphocytes/immunology , Clonal Deletion , Proto-Oncogene Proteins c-bcl-2/physiology , p-Azobenzenearsonate/immunology , Animals , Antibodies, Antinuclear/immunology , Antibody Affinity , Autoimmunity , Base Sequence , DNA/immunology , Gene Expression , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , Immunologic Memory , Mice , Mice, Inbred A , Mice, Transgenic , Molecular Sequence Data , Mutation , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Somatic Hypermutation, Immunoglobulin , Spleen/cytology , Spleen/immunology
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