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1.
GMS J Med Educ ; 39(2): Doc19, 2022.
Article in English | MEDLINE | ID: mdl-35692362

ABSTRACT

Introduction: Starting in 2013, a five-year, competence-based postgraduate programme, the "Seminartage Weiterbildung Allgemeinmedizin" (SemiWAM®) for continuing education in general practice, was developed and offered in Bavaria. This evaluation reports on the experiences of SemiWAM® after a first cycle. Material and methods: Process reflection based on the cycle of Kern: In addition to qualitative findings, results of the evaluation forms (mean values with standard deviation) are presented. The evaluation form contained questions on organisational issues, content of presentation, didactic preparation of the supervisor, transfer to real life practice as well as demographic variables. All questions were voted on a six-point Likert scale from "1=very satisfied" to "6=very dissatisfied". Results: The reflection showed three crucial entry points: Choosing "reason for encounter" as a content precondition to ensure target audience needs, the close didactic supervision of supervisor, and the continuous growth of supervisor team with newly qualified GP. The evaluation results for the overall assessment (MW 1.11-1.60), the didactic concept (MW 1.30-1.87), as well as the transfer into daily life practice (MW 1.48-2.35) reflect the high quality of the SemiWAM®. Discussion: The SemiWAM® curriculum presented can be easily transferred to comparable structures in Germany that accompany specialty training, such as the competence centres for residency training in general practice. The process evaluation based on the core cycle also provides important support for the agile implementation of these or similar programmes.


Subject(s)
General Practice , Internship and Residency , Clinical Competence , Curriculum , Family Practice/education , General Practice/education , Germany
2.
Z Evid Fortbild Qual Gesundhwes ; 168: 88-95, 2022 Feb.
Article in German | MEDLINE | ID: mdl-35144910

ABSTRACT

BACKGROUND: The Competence Centre for Residency Training in Family Medicine Bavaria (CCRTB) was established to improve the quality of postgraduate medical training by offering additional seminars and mentoring programmes as well as regular 'train-the-trainer' courses for educating physicians. In addition, residents have the opportunity to participate in a regional training network. OBJECTIVE: The aim was to assess the burden of burnout and the importance of the learning environment in the clinical training phase. METHODS: We conducted a cross-sectional study. Burnout was assessed using the Maslach Burnout Inventory (MBI), which comprises the scales "Emotional Exhaustion", "Depersonalisation" and "Personal Accomplishment". The quality of the learning environment was recorded using the German version of the Dutch Residency Educational Climate Test (D-RECT German). In addition, multivariable linear regressions were performed to estimate the impact of learning environment, year of training and participation in a regional network on the level of burnout. RESULTS: 129 clinical residents enrolled in the CCRTB were invited to participate in the study, 78 (61%) of whom submitted a response. 76 (59%) of these residents were included in the analyses. The present study discloses an increased burden of burnout among residents in the clinical training phase, with approx. 40% reaching a critical burnout score. A higher quality of the learning environment was associated with significantly milder burnout symptoms on the majority of the D-RECT scales. CONCLUSION: Family medicine residents in the clinical training phase show a high burden of burnout. Therefore, increasing the quality of the learning environment appears to be an effective key element in achieving a reduction of burnout in clinical training. This might contribute to an increase in professional satisfaction, which finally may also prevent migration from the medical profession.


Subject(s)
Family Practice , Internship and Residency , Burnout, Psychological , Cross-Sectional Studies , Germany , Humans
3.
ZFA (Stuttgart) ; 98(12): 416-421, 2022.
Article in German | MEDLINE | ID: mdl-37274626

ABSTRACT

Background: Since 2019, the competence center for specialist training in family medicine Bavaria (KWAB) offers an individual mentoring program to accompany specialist training in family medicine. The mentors are confidants for matters of specialist training, private practice, career development and compatibility of work and family life. The training takes place after registration via an online portal. Methods: The evaluation was conducted 24 months after the start of KWAB mentoring (06/30/2021-08/01/2021). All active participants were interviewed via online survey. In each case, separate questionnaires were developed, which inquire on the one hand about the content-related aspects of the mentoring, such as topics discussed, and on the other hand about the individual mentoring relationship, such as the interpersonal relationship. The mentees received 39 questions (34 closed, 5 open) and the mentors received 26 questions (21 closed, 5 open), which were subsequently analyzed using descriptive statistics. Results: N = 30 mentors and N = 72 mentees were invited to participate in the evaluation (25 (83 %) mentors and 32 (44 %) mentees participated). More than half of the participants met each other at least twice. The main methods of communication were telephone, face-to-face meetings, and email contacts. The individual time commitment in each case was judged to be appropriate. According to the mentors, the mentees showed interest in the content of the program and demonstrated availability and commitment. All respondents indicated a high level of satisfaction with one-on-one mentoring and would recommend it to others. Conclusions: Mentors and mentees in family medicine residency reported a great benefit from the one-on-one mentoring offered and a will to continue their mentoring relationships even after the project period.

4.
Med Educ Online ; 26(1): 1959284, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34323662

ABSTRACT

The competence centre for Residency Training in Family Medicine Bavaria (CCRTB) was established to improve the quality of postgraduate medical education by offering training and mentoring programmes for residents, and by providing train-the-trainer and mentoring courses for supervisors. Beyond that, regional Residency Training Networks (RTN) on avoluntary basis were developed to facilitate structured and efficient clinical rotation programs. Primary aim was to investigate the burden of burnout and the development of professionalism among CCRTB-residencies within a cross-sectional study. Secondary aim was to evaluate differences between CCRTB-residents with and without participation in aregional RTN. Burnout was determined with the Maslach Burnout Inventory (MBI), comprising the scales emotional exhaustion, depersonalization, and personal accomplishment. Ambulatory professionalization was evaluated using the German Professional Scale (Pro-D), comprising the scales professionalism towards the patient, towards other professionals, towards society, and towards oneself. Statistical significance of group differences was calculated by nonparametric tests. Multivariable linear regression modelling was performed to estimate the independent impact of professionalization and RTN participation on burnout scores. 347 CRRTB residents in ambulatory postgraduate training were invited, 212 (61.1%) participated, and 197 (92.9%) were included in our analyses. Lower emotional exhaustion and depersonalization, and increased personal accomplishment was associated with increased professionalisation, which was significant for nearly all Pro-D scales (p ≤ 0.05). RTN residents showed higher professionalism towards the patient (p = 0.031), other professionals (p = 0.012), and towards the society (p = 0.007) than residents of unstructured programs, and higher levels of personal accomplishment (p < 0.05). Early and efficient professionalization might be akey to reduce burnout and to establish asatisfying career in family medicine. Train-the-trainer and mentoring concepts should be implemented regularly for the training of residents. Thus, increased engagement in medical didactics should be aprerequisite for accreditation as atraining practice for residents.


Subject(s)
Burnout, Professional , Internship and Residency , Burnout, Professional/epidemiology , Cross-Sectional Studies , Emotions , Humans , Surveys and Questionnaires
5.
Med Decis Making ; 41(3): 329-339, 2021 04.
Article in English | MEDLINE | ID: mdl-33629614

ABSTRACT

OBJECTIVE: Dealing with uncertainty is a core competence for physicians. To evaluate the impact of an educational intervention on family medicine residents' (FMRs') intention to request diagnostic tests and their attitudes toward uncertainty. METHODS: Nonrandomized controlled trial. Intervention group (IG) FMRs participated in interactive "dealing with uncertainty" seminars comprising statistical lessons and diagnostic reasoning. Control group (CG) FMRs participated in seminars without in-depth diagnostic lessons. FMRs completed the Dealing with Uncertainty Questionnaire (DUQ), comprising the Diagnostic Action and Diagnostic Reasoning scales. The Physicians' Reaction to Uncertainty (PRU) questionnaire, comprising 4 scales (Anxiety Due to Uncertainty, Concern about Bad Outcomes, Reluctance to Disclose Uncertainty to Patients, and Reluctance to Disclose Mistakes to Physicians) was also completed. Follow-up was performed 3 months later. Differences were calculated with repeated-measures analysis of variance. RESULTS: In total, 107 FMRs of the IG and 102 FMRs of the CG participated at baseline and follow-up. The mean (SD) Diagnostic Action scale score decreased from 24.0 (4.8) to 22.9 (5.1) in the IG and increased in the CG from 23.7 (5.4) to 24.1 (5.4), showing significant group difference (P = 0.006). The Diagnostic Reasoning scale increased significantly (P = 0.025) without a significant group difference (P = 0.616), from 19.2 (2.6) to 19.7 (2.4) in the IG and from 18.1 (3.3) to 18.8 (3.2) in the CG. The PRU scale Anxiety Due to Uncertainty decreased significantly (P = 0.029) without a significant group difference (P = 0.116), from 20.5 (4.8) to 18.5 (5.5) in the IG and from 19.9 (5.5) to 19.0 (6.0) in the CG. CONCLUSION: The structured seminar reduced self-rated diagnostic test requisition. The change in Anxiety Due to Uncertainty and Diagnostic Reasoning might be due to an unspecific accompanying effect of the extra-occupational seminars for residents.


Subject(s)
Family Practice , Internship and Residency , Physicians , Anxiety , Family Practice/education , Humans , Intention , Uncertainty
6.
Gesundheitswesen ; 82(4): 306-312, 2020 Apr.
Article in German | MEDLINE | ID: mdl-30901774

ABSTRACT

BACKGROUND: There is an increasing demand for physicians in Germany. At the same time, there are many licensed doctors who are not actively working as physicians. To win them back to their original field of expertise would be a policy to bring doctors into the health care system in a timely manner. The aims of this study were therefore, on the one hand, to explore individual reasons for leaving the medical profession and for deciding to return to the medical profession. Furthermore, the value of participating in a re-entry seminar was assessed in this process. METHODOLOGY: As part of a qualitative study, 28 semi-structured interviews were conducted with former participants in a re-entry seminar of the Bavarian Medical Association. These were recorded with a dictaphone, pseudonymised, transcribed and evaluated according to Mayring's qualitative content analysis. RESULTS: Reasons that led to a career break were the family situation, unappealing working conditions, a change of residence as well as the mediocre job situation at the time of the so-called "doctor flood". The reasons for the resumption of medical work were decreased familial demands, financial necessity, the fear of missing one's professional connection, being under-challenged in the current job and the desire for approval. The re-entry seminar was evaluated by the majority as being "decisive" on the way back to the medical profession. Positive aspects were the exchange with like-minded people and the regained self-confidence in one's own abilities. CONCLUSION: Making it possible to combine family and career is a central task in preventing the loss of highly qualified workers. Re-entry seminars should specifically address the aspects of compatibility of family and career, individual fears and peer exchange.


Subject(s)
Career Choice , Medicine , Physicians , Germany , Humans , Qualitative Research
7.
GMS J Med Educ ; 34(5): Doc60, 2017.
Article in English | MEDLINE | ID: mdl-29226228

ABSTRACT

Introduction: In different German regions, seminar programs have been conducted for General practice residents. In each region, selection and teaching of learning content is conducted in a different manner. So far, no structured, standardized curriculum has been implemented nationwide. We have investigated, if the development of a common 5-year program of learning topics is conceivable between the different university departments of General practice in Germany. Method: The seminar program working group of the DEGAM (German College of General Practitioners and Family Physicians) has conducted an online survey based on information gathered via preliminary telephone conference (n=7; physicians with postgraduate teaching experience) among all German university departments of General Practice and two non-university teaching institutions, identified via the internet. 884 topics were extracted from 14 Seminar programs. The topics were entered in a database, discussed and categorized: Practice management/practice work flow/standardized documentation forms/quality management (n=33 topics), common acute and chronic diseases, including disease management programs (n=29 topics), communication, neurological, psychological and psychiatric consultations (n=24 topics), common medical problems, including eye, ear, nose, throat, skin and pediatric problems (n=99 Topics) family physicians general approach, including epidemiology, shared decision making, test of time (n=42 Topics). These topics have been rated for priority and desirable number of teaching-units. Results: A catalogue of 111 topics was designed, encompassing 160 teaching units. There is a suggestion of wide topics collections plus an add-on catalogue. Conclusion: A proposal for a 5-year-thematic catalogue for postgraduate training of general practice residents in Germany has been developed. This newly developed curriculum has the potential to improve knowledge and skills that have not been covered during in-house and ambulatory general practice residencies.


Subject(s)
General Practice/economics , Internship and Residency , Curriculum , Family Practice , Germany , Humans , Pediatrics
8.
Z Evid Fortbild Qual Gesundhwes ; 115-116: 79-84, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27837964

ABSTRACT

BACKGROUND: Undergraduate training aims to enable medical students to become fully qualified physicians. The aim of the study was to explore the competences that newly graduated doctors (beginners) bring along from medical school into their postgraduate training. In this way areas can be identified that need to be better addressed during either under- or postgraduate training. METHODS: Competencies were assessed using a paper-based questionnaire that was sent out to 405 physicians in Bavaria being in the possession of a postgraduate training license in internal medicine, surgery and anaesthesiology. The questionnaire included items exploring the fields of competencies outlined in the CanMeds role descriptions. The results were analyzed using descriptive and exploratory methods. RESULTS: 190 of 405 questionnaires (47 %) were returned. 96 % of the participants were male, the average age was 54 years. The results indicated that most young medical professionals had the necessary theoretical knowledge to take up postgraduate training. However, putting theory into practice does not work well enough from the physician's point of view. DISCUSSION: An approach to further support the transfer of enormous amounts of theoretical knowledge acquired during years of study into medical expertise is needed. In this respect, recently published competence-based curricula for under- and postgraduate training might prove useful.


Subject(s)
Clinical Competence , Education, Nursing, Continuing , Curriculum , Female , Germany , Humans , Male , Middle Aged , Students, Medical , Surveys and Questionnaires
9.
Eur J Cell Biol ; 90(6-7): 553-9, 2011.
Article in English | MEDLINE | ID: mdl-21185106

ABSTRACT

Wnt proteins are secreted, palmitoylated glycoproteins with multiple functions in cell proliferation and migration as well as tissue organization. They are best known for their role in embryonic development and tissue homeostasis. In the last years, Wnt signaling was also shown to be involved in the regulation of inflammatory processes: Wnt5a is induced in human macrophages in response to mycobacteria and conserved bacterial structures and contributes to the regulation of pro-inflammatory cytokines via its receptor Frizzled (Fzd) 5. Wnt5a is also induced in other infectious and inflammatory diseases such as tuberculosis, sepsis, psoriasis, rheumatoid arthritis and atherosclerosis. In contrast, Wnt3a, a ligand of Fzd1, is constitutively expressed by bronchial epithelial cells and mediates anti-inflammatory effects on mycobacteria-infected macrophages via the Wnt/beta-Catenin signaling pathway. This pathway suppresses the activity of GSK3beta, a well known regulator of NF-kappaB-dependent gene transcription. Here we review recent data on immunomodulatory activities of Wnt proteins. Additional experiments using exogenous Wnt homologs further support the notion that TLR/NF-kappaB and Wnt signaling are functionally interconnected.


Subject(s)
Macrophages/metabolism , Mycobacterium Infections/metabolism , Mycobacterium/metabolism , Wnt Proteins/metabolism , Animals , Humans , Macrophages/immunology , Mice , Mycobacterium Infections/blood , Mycobacterium Infections/immunology , Signal Transduction , Wnt Proteins/immunology
10.
J Investig Dermatol Symp Proc ; 12(1): 26-33, 2007 May.
Article in English | MEDLINE | ID: mdl-17502866

ABSTRACT

Differential induction of cell death in mycobacteria-infected monocytes and macrophages has been invoked as one possible mechanism by which some tumor necrosis factor (TNF)-targeted biologicals reactivate tuberculosis more frequently than others. We infected primary human monocytes and monocyte-derived macrophages with the virulent Mycobacterium tuberculosis strain H37Rv and followed the rate of cell death in the absence or presence of a wide concentration range of four different TNF-targeted biologicals: infliximab and adalimumab (both monoclonal antibodies to human TNF) and etanercept and polyethylene-glycols TNFR1 (fusion constructs of human TNFR2 and TNFR1, respectively). None of the TNF-targeted biologicals used modulated the death rate of monocytes/macrophages induced by infection with M. tuberculosis alone. Our data support the view that mycobacteria-induced cell death is largely independent of TNF and that the primary target for differential modulation by TNF-targeted biologicals during tuberculosis is not a recently recruited monocyte or freshly differentiated macrophage.


Subject(s)
Macrophages/microbiology , Monocytes/microbiology , Mycobacterium tuberculosis/pathogenicity , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized , Cell Death , Cells, Cultured , Etanercept , Humans , Immunoglobulin G/pharmacology , Infliximab , Macrophages/immunology , Macrophages/pathology , Monocytes/immunology , Monocytes/pathology , Mycobacterium tuberculosis/immunology , Polyethylene Glycols/pharmacology , Receptors, Tumor Necrosis Factor , Receptors, Tumor Necrosis Factor, Type I/pharmacology
11.
J Neuroimmunol ; 162(1-2): 28-42, 2005 May.
Article in English | MEDLINE | ID: mdl-15833357

ABSTRACT

CD40, a TNF-R-related cell surface receptor, is shown here to be expressed by glioma cells in vitro and in vivo. Glioma cell lines expressing low levels of CD40 at the cell surface resist cytotoxic effects of CD40L. CD40 gene transfer sensitizes glioma cells to CD40L. Inhibition of protein synthesis potentiates cell death which involves CD40 clustering and caspases 8 and 3 processing. CD40-transfected LN-18 cells acquire resistance to CD95L. In contrast, subtoxic concentrations of CD40L strongly sensitize these cells for TNF-alpha-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling.


Subject(s)
Apoptosis/physiology , CD40 Antigens/physiology , CD40 Ligand/physiology , Glioma/metabolism , Amino Acid Chloromethyl Ketones/pharmacology , Antibodies/pharmacology , Antineoplastic Agents/pharmacology , Blotting, Northern/methods , Blotting, Western/methods , CD40 Antigens/immunology , CD40 Antigens/pharmacology , CD40 Ligand/pharmacology , Caspases/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Collagen Type XI/metabolism , Dose-Response Relationship, Drug , Drug Interactions , Fas Ligand Protein , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Glioma/pathology , Humans , Immunohistochemistry/methods , Immunoprecipitation/methods , Leupeptins/pharmacology , Membrane Glycoproteins/pharmacology , Neuroprotective Agents/pharmacology , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerases , RNA Interference/physiology , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction/methods , Time Factors , Transfection/methods , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology , fas Receptor/immunology , fas Receptor/metabolism
12.
Glia ; 44(3): 296-301, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14603470

ABSTRACT

Human glioblastoma is a highly lethal tumor known for its capability of interfering with effective antitumor immune responses. Costimulatory signals are of critical relevance in both the inductive and effector phases of immune responses. Inducible costimulator-ligand (ICOSL), a member of the B7 family of costimulatory molecules related to CD80/CD86, regulates CD4 as well as CD8 T-cell responses via interaction with its receptor, ICOS, on activated T cells. We report the expression of ICOSL by glioma cells in vitro and in vivo. In contrast to CD80 (B7.1) and CD86 (B7.2), ICOSL protein and mRNA was expressed in 7 of 12 glioma cell lines. ICOSL expression is upregulated by the inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), whereas interferon-gamma (IFN-gamma) has no such effect. Further, immunohistochemical analysis of human brain tumors demonstrates the expression of ICOSL in three of four tissue samples. ICOSL expression is functional in that a neutralizing ICOSL antibody (HIL-131) reduces Th1 and Th2 cytokine levels in cocultures of peripheral blood lymphocytes or T-cell subsets (CD4 and CD8) with glioma cells. However, ICOSL gene transfer into glioma cells does not alter their immunogenicity under primary or secondary alloreactive coculture assays.


Subject(s)
Brain Neoplasms/immunology , Brain Neoplasms/physiopathology , Carrier Proteins/genetics , Glioblastoma/immunology , Glioblastoma/physiopathology , Proteins , Adult , Aged , Aged, 80 and over , Antigens, CD , Antineoplastic Agents/pharmacology , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/physiology , Cell Line, Tumor , Cells, Cultured , Coculture Techniques , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/immunology , Humans , Inducible T-Cell Co-Stimulator Ligand , Middle Aged , Signal Transduction/immunology , Tumor Necrosis Factor-alpha/pharmacology
13.
Cancer Res ; 63(21): 7462-7, 2003 Nov 01.
Article in English | MEDLINE | ID: mdl-14612546

ABSTRACT

Human glioblastoma is a highly lethal tumor that is known for its immune inhibitory capabilities. B7-homologue 1 (B7-H1), a recently identified homologue of B7.1/2 (CD80/86), has been described to exert costimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H1 in human glioma cells in vitro and in vivo. Although lacking B7.1/2 (CD80/86), all 12 glioma cell lines constitutively expressed B7-H1 mRNA and protein. Exposure to IFN-gamma strongly enhanced B7-H1 expression. Immunohistochemical analysis of malignant glioma specimens revealed strong B7-H1 expression in all 10 samples examined, whereas no B7-H1 expression could be detected on normal brain tissues. To elucidate the functional significance of glioma cell-related B7-H1 expression, we performed coculture experiments of glioma cells with alloreactive CD4+ and CD8+ T cells. Glioma-related B7-H1 was identified as a strong inhibitor of CD4+ as well as CD8+ T-cell activation as assessed by increased cytokine production (IFN-gamma, interleukin-2, and interleukin-10) and expression levels of the T-cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (mAb 5H1). B7-H1 expression may thus significantly influence the outcome of T-cell tumor cell interactions and represents a novel mechanism by which glioma cells evade immune recognition and destruction.


Subject(s)
B7-1 Antigen/biosynthesis , Blood Proteins , Glioma/immunology , Peptides , Antigens, CD , B7-1 Antigen/genetics , B7-1 Antigen/immunology , B7-H1 Antigen , Cell Line, Tumor , Cytokines/antagonists & inhibitors , Cytokines/biosynthesis , Cytokines/immunology , Glioma/genetics , Glioma/metabolism , Humans , Lymphocyte Activation , Membrane Glycoproteins , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
14.
FASEB J ; 17(13): 1892-4, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12923066

ABSTRACT

B7-H1 is a novel B7 family protein attributed to costimulatory and immune regulatory functions. Here we report that human myoblasts cultured from control subjects and patients with inflammatory myopathies as well as TE671 muscle rhabdomyosarcoma cells express high levels of B7-H1 after stimulation with the inflammatory cytokine IFN-gamma. Coculture experiments of MHC class I/II-positive myoblasts with CD4 and CD8 T cells in the presence of antigen demonstrated the functional consequences of muscle-related B7-H1 expression: production of inflammatory cytokines, IFN-gamma and IL-2, by CD4 as well CD8 T cells was markedly enhanced in the presence of a neutralizing anti-B7-H1 antibody. This observation was paralleled by an augmented expression of the T cell activation markers CD25, ICOS, and CD69, thus showing B7-H1-mediated inhibition of T cell activation. Further, we investigated 23 muscle biopsy specimens from patients with polymyositis (PM), inclusion body myositis (IBM), dermatomyositis (DM), and nonmyopathic controls for B7-H1 expression by immunohistochemistry: B7-H1 was expressed in PM, IBM, and DM specimens but not in noninflammatory and nonmyopathic controls. Staining was predominantly localized to areas of strong inflammation and to muscle cells as well as mononuclear cells. These data highlight the immune regulatory properties of muscle cells and suggest that B7-H1 expression represents an inhibitory mechanism induced upon inflammatory stimuli and aimed at protecting muscle fibers from immune aggression.


Subject(s)
B7-1 Antigen/metabolism , B7-1 Antigen/physiology , Blood Proteins , Muscle, Skeletal/immunology , Myositis/immunology , Peptides , Antigens, CD , B7-H1 Antigen , Cells, Cultured , Humans , Interferon-gamma/pharmacology , Lymphocyte Activation , Membrane Glycoproteins , Models, Immunological , Myoblasts/drug effects , Myoblasts/metabolism , Rhabdomyosarcoma , T-Lymphocytes/immunology , Tumor Cells, Cultured
15.
Brain ; 126(Pt 5): 1026-35, 2003 May.
Article in English | MEDLINE | ID: mdl-12690043

ABSTRACT

Inducible co-stimulator ligand (ICOSL), a member of the B7 family of co-stimulatory molecules related to B7.1/2, regulates CD4 as well as CD8 T-cell responses via interaction with its receptor ICOS on activated T cells. Here we examined the expression and the functional relevance of ICOSL in human muscle cells in vivo and in vitro. We investigated 25 muscle biopsy specimens from patients with polymyositis, dermatomyositis, inclusion body myositis, Duchenne muscular dystrophy and non-myopathic controls for ICOSL expression by immunohistochemistry. Normal muscle fibres constitutively express low levels of ICOSL. However, ICOSL expression is markedly increased in muscle fibres in inflammatory myopathies. Cell surface staining was most prominent in the contact areas between muscle fibres and inflammatory cells, which in turn show expression of ICOS as a marker of T-cell activation. Muscle endothelial cells show constitutive expression of ICOSL under normal and pathological conditions. We also detected mRNA and cell surface protein expression of ICOSL on myoblasts cultured from control subjects and patients as well as in TE671 muscle rhabdomyosarcoma cells. ICOSL expression was upregulated by tumour necrosis factor-alpha (TNF-alpha), whereas interferon-gamma (IFN-gamma) had no such effect. Co-culture experiments of major histocompatibility complex (MHC) class II-positive myoblasts with CD4 T cells together with superantigen demonstrated that the expression of muscle-related ICOSL has functional consequences: the production of Th1 (IFN-gamma) and Th2 cytokines [interleukin (IL)-4 and IL-10] by CD4 T cells was markedly reduced in the presence of a neutralizing anti-ICOSL monoclonal antibody (mAb HIL-131), thus showing the importance of ICOSL co-stimulation for T-cell activation. Taken together, our results demonstrate that human muscle cells express ICOSL, a functional co-stimulatory molecule distinct from B7.1 and B7.2. ICOSL-ICOS interactions may play an important role in inflammatory myopathies, providing further evidence for the antigen-presenting capacity of muscle cells.


Subject(s)
Carrier Proteins/analysis , Muscle Fibers, Skeletal/immunology , Myositis/immunology , Proteins , Adult , Aged , Aged, 80 and over , Antigens, CD , Carrier Proteins/genetics , Case-Control Studies , Cells, Cultured , Coculture Techniques , Dermatomyositis/immunology , Humans , Immunohistochemistry/methods , Inducible T-Cell Co-Stimulator Ligand , Interferon-gamma/pharmacology , Lymphocyte Activation , Middle Aged , Muscular Dystrophy, Duchenne/immunology , Myositis, Inclusion Body/immunology , Polymerase Chain Reaction/methods , RNA, Messenger/analysis , Rhabdomyosarcoma , T-Lymphocytes/immunology , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/pharmacology
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