Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
2000
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Zsfassung in dt. Sprache. - Würzburg, Univ., Diss., 2000 |
| Beschreibung: | IV, 112 Bl. Ill., graph. Darst. |
Internformat
MARC
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| 245 | 1 | 0 | |a Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis |c von Maria Margarida Souto-Carneiro |
| 264 | 1 | |c 2000 | |
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Datensatz im Suchindex
| _version_ | 1812460858918305792 |
|---|---|
| adam_text |
1. INTRODUCTION
5
1.1. AIMS OF THE PRESENT STUDY.
6
1.1.1. CHARACTERISATION OF THE ANTIGEN-DRIVEN B-LYMPHOCYTE MATURATION
AND
RECIRCULATION IN RHEUMATOID ARTHRITIS.6
1.1.2. CHARACTERISATION OF ARTHRITOGENIC ANTIGENS.6
1.2. HISTORICAL BACKGROUND.
7
1.3. SYNOVIAL MEMBRANE AS THE PRIMARY INFLAMMATION SPOT.9
1.4. THE ROLE OF T-CELLS AND HLA-DRB1 GENES IN RHEUMATOID ARTHRITIS.10
1.4.1. HLA-DRB1 MOLECULES MAY SHAPE THE T-CELL REPERTOIRE IN RA.11
1.4.2. T-CELL STIMULATION LEADING TO JOINT DESTRUCTION.12
1.5. SYNOVIAL B-LYMPHOCYTES IN RHEUMATOID ARTHRITIS.13
1.5.1 THE ORGANISATION OF SYNOVIAL B-LYMPHOCYTES.15
1.5.2. THE REPERTOIRE OF SYNOVIAL B-LYMPHOCYTE SPECIFICITIES.20
1.5.2.1. SYNOVIAL B-LYMPHOCYTES WITH SPECIFICITY FOR "SELF ANTIGENS"
.20
1.5.2.2. POLYREACTIVE ANTIBODIES FROM SYNOVIAL B-LYMPHOCYTES
.21
1.5.2.3 MONOREACTIVE ANTIBODIES FROM SYNOVIAL B-LYMPHOCYTES
.22
1.5.2.4. SYNOVIAL B-LYMPHOCYTES SPECIFIC FOR "NON-SELF ANTIGENS".
.25
2
. MATERIALS AND METHODS.26
2.1. PATIENTS.26
2.1.1. PATIENT, DISEASE ACTIVITY, AND TISSUE SAMPLES (IGVH GENE
ANALYSIS).26
2.1.2. PATIENTS, TISSUE AND BLOOD SAMPLES, AND HISTOPATHOLOGICAL
ANALYSIS (ELB
13/3-56 STUDY).
26
2.2. IMMUNOHISTOCHEMISTRY:.27
2.3. IMMUNOHISTOCHEMISTRY OF HUMAN CARTILAGE WITH ELB 13/3-56.28
2.4. HISTOPATHOLOGICAL SCORE OF INFLAMMATORY INFILTRATION:.29
2.5. PCR AMPLIFICATIONS.30
2.5.1. RNA-ISOLATION FROM CRYOSECTIONS WITH RNEASY-KIT AND CDNA
SYNTHESIS.30
L
BIBLIOGRAFISCHE INFORMATIONEN
HTTP://D-NB.INFO/961487704
2.5.2. PCR AMPLIFICATION OF CDNA.31
2.5.3. DNA EXTRACTION AND AMPLIFICATION OF LGV
H GENES BY NESTED PCR.31
2.5.4. PCR-AMPLIFICATION WITH ELB 13/3-56 SPECIFIC PRIMERS.33
2.6. LIGATION OF THE PCR PRODUCTS TO THE PLASMID VECTORS.33
2.7. PREPARATION OF COMPETENT DH5A
E. COLI
.34
2.8. TRANSFORMATION OF COMPETENT BACTERIA.34
2.9. MINI-PLASMID ISOLATION.35
2.10. RESTRICTION ANALYSES.35
2.11. IGVH GENE SEQUENCE ANALYSES.35
2.12. ANTIBODY PURIFICATION.36
2.13. IMMUNOBLOTTING.36
2.14. IMMUNOPERCIPITATION.37
2.15. SILVER-STAINING OF THE SDS-PAGE GEL.37
2.16. PROTEIN IDENTIFICATION.38
2.17. COMP PURIFICATION.39
2.18. PHAGE DISPLAY.40
2.19. EPITOPE-ELISA:.41
2.20. PHOTOGRAPHIC MATERIAL.43
3. RESULTS. 44
3.1. CHARACTERISATION OF THE ANTIGEN-DRIVEN B-LYMPHOCYTE MATURATION AND
RECIRCULATION IN RHEUMATOID ARTHRITIS.44
3.1.1. LOCAL DISEASE ACTIVITY AND DURATION OF LOCAL DISEASE (TABLE 3).44
3.1.2. HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY OF SYNOVIAL TISSUE.45
3.1.3. COMPARISON OF THE MUTATED VH SEGMENTS WITH THE GERMLINE GENES.46
2
3.1.3.1. PRESENCE OF PSEUDOGENES (TABLE 4)
.46
3.1.3.2. DELETIONS AND MIXED MOLECULES
.48
3.1.3.3. LOCAL OVERALL R/S RATIOS RAISE WITH TIME OF DISEASE DURATBN
(FIG 8)
.51
3.1.3.4. HETEROGENITY AMONG THE CDR3
.52
3.1.4. COMPARISON OF THE SEQUENCES FROM THE SAME VH FAMILY AMPLIFIED
FROM EACH
LOCATION.52
3.1.4.1. VH1 FAMILY
.52
3.1.4.2. VH4 FAMILY
. 56
3.2. CHARACTERISATION OF ARTHRITOGENIC ANTIGENS.58
3.2.1. ELB13/3-56 IS EXPRESSED IN THE SYNOVIAL MEMBRANE OF RA
PATIENTS.58
3.2.2. ELB13/3-56 SHOWS IMMUNEREACTIVITY TO HUMAN HYALINE CARTILAGE.59
3.2.3. SPECIFIC BANDS IN THE IMMUNOBLOT OF ELB13/3-56 WITH CARTILAGE
EXTRACTS.60
3.2.4. ELB13/3-56 SPECIFICALLY BINDS TO COMP .61
3.2.5. POTENTIAL EPITOPE FOR ELB13/3-56 LOCATED AT THE C-TERMINAL REGION
OF COMP
.63
3.2.6. HEPTAMERIC COMP-EPITOPE BINDS EFFICIENTLY RA SERUM.64
4. DISCUSSION. 67
4.1. IGVH GENES FROM DIFFERENT ANATOMICAL REGIONS -WITH DIFFERENT
HISTOPATHOLOGICAL PATTERNS- OF A RHEUMATOID ARTHRITIS PATIENT SUGGEST
CYCLIC RE
ENTRY OF MATURE SYNOVIAL B-CELLS IN THE HYPERMUTATION PROCESS.67
4.1.1. AMINO ACID DELETIONS AND MIXED MOLECULES: A NOVEL PATHWAY TO
GENERATE
ANTIBODY SPECIFICITIES?.67
4.1.2. APPARENT MUTATIONAL PATTERN AMONG THE 19 AMINO ACID VH1
SEGMENTS.69
4.1.3. CYCLIC RE-ENTRY OF MUTATED RHEUMATOID ARTHRITIS SYNOVIAL B-CELLS
IN THE
HYPERMUTATION PROCESS.70
4.2. HUMAN RHEUMATOID SYNOVIAL B-CELL HYBRID,OMA WITH A NEW DISEASE
RELATED
SPECIFICITY FOR CARTILAGE OLIGOMERIC MATRIX PROTEIN (COMP).71
4.2.1. FINE-SPECIFICITY OF THE COMP SPECIFIC B-CELL HYBRIDOMA.72
4.2.2. LOCAL GENERATION OF A RHEUMATOID ARTHRITIS ASSOCIATED COMP
SPECIFIC
AUTOANTIBODY.73
4.2.3. ARTHRITOGENIC IMMUNE RESPONSE TO COMP SUGGESTS A FAILURE IN
TOLERANCE
INDUCTION.74
4.2.4. SYNOVIAL AUTOANTIBODY WITH A PERPETUATING FUNCTION IN JOINT
DESTRUCTION.76
3
4.3. CONCLUSION AND FUTURE PRESPECTIVES
77
5.
LITERATURE. 80
6. ABSTRACT/ ZUSAMMENFASSUNG.96
6.1. ENGLISH.96
6.2. DEUTSCH.99
7. ABREVIATIONS.103
8. ACKNOWLEDGMENTS.106
9.
CURRICULUM VIT/E/ LEBENSLAUF.107
10. PUBLICATIONS LIST/ VEROFFENTLICHUNGEN.108
10.1. ORIGINAL ARTICLES/ ORIGINALARBEITEN.108
10.2. PUBLISHED ABSTRACTS/VEROFFENTLICHTEN ABSTRACTS.109
10.3. PRIZES/ PREISE.110
10.4. COMMUNICATIONS/ VORTRDGE.110
11. EIDESSTATTLICHEN ERKLARUNGEN.112
4 |
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| spelling | Souto-Carneiro, Maria Margarida 1973- Verfasser (DE-588)122890698 aut Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis von Maria Margarida Souto-Carneiro 2000 IV, 112 Bl. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. Sprache. - Würzburg, Univ., Diss., 2000 Rheumatoide Arthritis (DE-588)4076708-5 gnd rswk-swf B-Lymphozyt (DE-588)4137121-5 gnd rswk-swf Molekularbiologie (DE-588)4039983-7 gnd rswk-swf Synovialmembran (DE-588)4134251-3 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Rheumatoide Arthritis (DE-588)4076708-5 s B-Lymphozyt (DE-588)4137121-5 s Synovialmembran (DE-588)4134251-3 s Molekularbiologie (DE-588)4039983-7 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009143248&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Souto-Carneiro, Maria Margarida 1973- Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis Rheumatoide Arthritis (DE-588)4076708-5 gnd B-Lymphozyt (DE-588)4137121-5 gnd Molekularbiologie (DE-588)4039983-7 gnd Synovialmembran (DE-588)4134251-3 gnd |
| subject_GND | (DE-588)4076708-5 (DE-588)4137121-5 (DE-588)4039983-7 (DE-588)4134251-3 (DE-588)4113937-9 |
| title | Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis |
| title_auth | Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis |
| title_exact_search | Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis |
| title_full | Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis von Maria Margarida Souto-Carneiro |
| title_fullStr | Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis von Maria Margarida Souto-Carneiro |
| title_full_unstemmed | Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis von Maria Margarida Souto-Carneiro |
| title_short | Molecular and functional analyses of human synovial B-lymphocytes in rheumatoid arthritis |
| title_sort | molecular and functional analyses of human synovial b lymphocytes in rheumatoid arthritis |
| topic | Rheumatoide Arthritis (DE-588)4076708-5 gnd B-Lymphozyt (DE-588)4137121-5 gnd Molekularbiologie (DE-588)4039983-7 gnd Synovialmembran (DE-588)4134251-3 gnd |
| topic_facet | Rheumatoide Arthritis B-Lymphozyt Molekularbiologie Synovialmembran Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009143248&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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