ABSTRACT
BACKGROUND: A genetic component is thought to contribute to 30-40% of the expression of rheumatoid arthritis (RA) with the HLA-DR4, w4 (B1*0401), w14 (B1*0404) genes (and associated shared rheumatoid epitope) constituting a substantial portion of this risk. AIM: Our objective was to determine the presence of these risk factors in a group of patients with RA and to correlate presence with disease outcome. METHOD: Forty-three RA patients who had been regularly assessed up to a ten year period since their initial entry into two gold treatment trials were studied. DR4, w4, w14 and shared rheumatoid epitope were determined on peripheral blood lymphocytes using flow cytometry and specific monoclonal antibodies. Disease outcome was measured by Health Assessment Questionnaire (HAQ) score and C-Reactive Protein (CRP) as a serological measure of joint inflammation. RESULTS: To confirm accuracy of the flow cytometric technique, DR typing and epitope status was compared with results obtained by genotyping in a subset of 14 patients. There was complete concordance between these two techniques for the rheumatoid epitope. However, concordance was not complete (both false positives and false negatives) for DR4, w4 and w14. Hence the presence of rheumatoid epitope was only evaluated further in the larger group. The presence of the shared rheumatoid epitope correlated positively with poorer outcome on serological assessment (p < 0.05). No significant correlation between HAQ score and rheumatoid epitope status was observed although a weak trend was noted. CONCLUSION: These studies suggest that determination of rheumatoid epitope status by flow cytometry may provide useful data concerning the long term outcome of patients with RA.
Subject(s)
Arthritis, Rheumatoid/genetics , Epitopes , HLA-DR4 Antigen/genetics , Aged , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/immunology , C-Reactive Protein/analysis , Cohort Studies , Factor Analysis, Statistical , Female , Flow Cytometry , Humans , Male , Prognosis , Risk FactorsABSTRACT
We have identified, in the rabbit medulla and pons, neurons which project to the C1-region of the rostral ventrolateral medulla. By combining tyrosine hydroxylase immunohistochemistry with retrograde transport of Fluoro-Gold we determined whether any of the retrogradely labelled neurons synthesize catecholamines. The only doubly labelled cells were located in the area postrema. No other group of catecholamine-synthesizing neurons in either the medulla or the pons was found to project to the C1-area of the rostral ventrolateral medulla. Pharmacological agents which lower arterial pressure by stimulating adrenoceptors in the rostral ventrolateral medulla may act on receptors which are not innervated by catecholamine-synthesizing perikarya located outside the C1-region.
Subject(s)
Catecholamines/analysis , Medulla Oblongata/anatomy & histology , Pons/anatomy & histology , Stilbamidines , Animals , Fluorescent Antibody Technique , Fluorescent Dyes , Histocytochemistry , Male , Medulla Oblongata/cytology , Medulla Oblongata/enzymology , Neural Pathways/anatomy & histology , Neural Pathways/cytology , Pons/cytology , Pons/enzymology , Rabbits , Tyrosine 3-Monooxygenase/analysisABSTRACT
When Fast blue is injected into the rabbit spinal cord it is retrogradely transported into nerve cell bodies located in the medial and the descending vestibular nuclei. Approximately 50% of the Fast blue-positive cells also contain glutamic acid decarboxylase-like immunoreactivity. These neurons presumably synthesize gamma-aminobutyric acid (GABA) and the rabbit vestibulospinal pathway therefore contains a substantial inhibitory component.
