Changes in von Willebrand factor antigen levels in venous occlusion.
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Antigens↗
Biomedical subjects
A Blann
Publications and source records attributed to A Blann.
Takayasu's arteritis: a pathogenetic role for cytotoxic T lymphocytes?
Takayasu's arteritis is an inflammatory panarteritis of unknown aetiology affecting large elastic arteries. We examined a segment of abnormal common carotid artery removed at by-pass surgery from a 23-year-old man with typical angiographic features of Takayasu's arteritis. Using monoclonal antibodies we were able to demonstrate marked infiltration of the arterial wall with OKT8 positive lymphocytes (suppressor/cytotoxic cells) but not with OKT4 positive lymphocytes (helper cells). Studies of circulating lymphocytes showed increased numbers of "activated" cells and increased in vitro cytotoxicity against cultured human umbilical cord endothelial cells, compared to normal lymphocytes. Cellular immunological mechanisms may play an important role in the pathogenesis of Takayasu's arteritis, possibly through the direct action of cytotoxic T cells on large elastic arteries.
Adult↗
Endothelial cell cytotoxicity in inflammatory vascular diseases--the possible role of oxidised lipoproteins.
One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. The nature of this serum factor is unclear, but has been suggested to be a lipoprotein. Sera from patients with (1) systemic necrotising arteritis (polyarteritis nodosa, Wegener's granulomatosis, and necrotising arteritis associated with rheumatoid synovitis), (2) systemic or joint restricted rheumatoid disease, and (3) large vessel/giant cell arteritis have been examined for cytotoxicity to human cultured endothelial cells and azide-resistant ferroxidase-like activity (indicative of the oxidised lipoprotein content). Stored sera from patients with necrotising arteritis showed a significantly enhanced tendency to develop oxidised lipoprotein, which correlated closely with human endothelial cell cytotoxicity. Fresh sera also contained this factor, but to a lesser extent. It is argued that the cytotoxic factor detected in previous clinical studies is in part an in-vitro artefact, although its accelerated development in certain patient groups might suggest an excess of pro-oxidants that have developed in vivo.
Arteritis↗
Lymphocyte sub-populations and NSAIDs. Methodological aspects.
Activated lymphocytes can be enumerated as the less dense lymphocyte population (LDL) on a Ficoll density gradient column. The numbers of LDL are higher in rheumatoid arthritis (RA) but fall with successful second-line therapy; they correlate with active synovitis rather than with extra-articular disease. A cytospin technique has been developed which uses fewer cells than conventional suspension techniques and which allows further characterization of LDL using monoclonal antibodies. This confirms that these cells are relatively T-depleted but enriched in IA bearing cells, which may relate to homing patterns to the RA synovium. Using this technique, RA patients with active synovitis were shown to have more LDL and IA bearing cells, as were the active disease controls, including patients with other autoimmune disease (vasculitis) and with non-immune disease (sepsis). There were no differences between the ratios of T-suppressor to T-helper cells within these patient groups.
Anti-Inflammatory Agents↗
Ferroxidase and ascorbate oxidase activities of caeruloplasmin in synovial fluid from rheumatoid patients.
1. The protein caeruloplasmin inhibits certain free radical reactions, in part probably due to its ability to oxidize Fe2+ into Fe3+ (ferroxidase activity). Since caeruloplasmin is present in synovial fluid from rheumatoid patients, we investigated its properties in relation to protection of the joint from damage by oxygen radicals produced by activated phagocytes. 2. The ferroxidase and ascorbate oxidase activities of serum from both normal and rheumatoid patients could be accounted for by the caeruloplasmin present, as determined immunologically. More caeruloplasmin is present in the serum of rheumatoid patients than in normal serum. 3. Synovial fluid from rheumatoid patients contains caeruloplasmin protein but its ferroxidase and ascorbate oxidase activities are abnormally low. It is suggested that ferroxidase deficiency contributes to radical damage in the rheumatoid joint.
Arthritis, Rheumatoid↗
H-2-associated differences in replicated strains of mice divergently selected for body weight.
A random-bred strain (Q) was established and divided into six replicates. Each replicate was divergently selected for 6-week weight (for over 30 generations) and each had an unselected control. We have investigated the H-2 haplotype of individual mice of the 18 selected Q strains to determine whether selection for size had also selected for H-2 or H-2-linked genes. From the results it appeared that only the H2b and H-2q haplotypes were present in the foundation stock. A large number of individuals of the six small sublines were of H-2b haplotype, while the majority of those of the six large sublines were of the H-2q haplotype. Individuals in the six control strains were H-2b, H-2q or both (i.e., H-2 heterozygotes and/or H-2 recombinants). These results suggest that control of body size is associated with H-2 or an H-2-linked gene(s).
Animals↗
A double-blind placebo-controlled trial of antioxidant therapy in limited cutaneous systemic sclerosis.
OBJECTIVE: To evaluate the effects of a combination of micronutrient antioxidants (selenium, beta-carotene, vitamin C, vitamin E and methionine) with allopurinol in patients with limited cutaneous systemic sclerosis (SSc). METHODS: The study was designed as a placebo-controlled double-blind crossover study. A carryover effect was detected retrospectively for some of the prescribed antioxidants, and so the data were analysed as: (a) a between group comparison of the first 10 week treatment period; and (b) a within group comparison of the first and second 10-week periods in those who received placebo treatment first. Study end-points were plasma von Willebrand factor (vWF), thermographic response to a standard cold challenge, frequency and duration of Raynaud's attacks, patient opinion, and specialised biochemical parameters (fatty acid profiles, antioxidants and markers of free radical injury). RESULTS: Thirty-three patients were recruited. The median duration of Raynaud's phenomenon was 10 years (range 2 to 50 years) in the active-first group and 10 years (range 4 to 53 years) in the placebo-first group. In the 10-week study, there were no differences between the active and placebo groups in the change from baseline for vWF, for the parameters of the rewarming curve, or for patients' symptoms. Despite a rise in circulating antioxidant levels, there was no fall in markers of free radical mediated injury. In the 20-week cross-over study, patients did not experience any clinical benefit from active treatment compared to placebo. CONCLUSION: No clinical benefit could be demonstrated from active treatment. There are several possible explanations for this negative result, including the short duration of therapy. It is possible that antioxidant therapy, to be effective, needs to be given early in the SSc disease process, before the onset of irreversible tissue damage.
Adult↗
Soluble markers of endothelial cell function.
Damage to the endothelium is believed to be important in the development and progression of atherosclerosis. Consequently, vascular biologists are seeking good markers of endothelial cell function which hope to provide tools to dissect the role of these cells in disease. This review will examine a number of endothelial cell products (thrombomodulin, von Willebrand factor and soluble E-selectin) and discuss their value as markers of vascular integrity.
Biomarkers↗