Mast cells, extracellular matrix components, TGFbeta isoforms and TGFbeta receptor expression in labial salivary glands in systemic sclerosis.
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OBJECTIVE: To determine whether there was altered elaboration of non-collagenous extracellular matrix proteins or expression of TGFbeta isoforms and their receptors in salivary glands of patients with systemic sclerosis (SSc) and Raynaud's phenomenon (RP). Because of the possible role of mast cells in the early stages of SSc their presence was also investigated. METHODS: Sections of normal labial salivary glands (n=10) and glands from patients with SSc (n = 13) and RP (n = 5) were stained immunohistochemically and using acid toluidine blue. RESULTS: SSc glands contained more mast cells than control tissues (p<0.005) and similar numbers to those found in RP specimens. There were no differences in the pattern or amount of non-collagenous matrix proteins detected. Tenascin and elastin were predominantly found surrounding ducts whereas fibronectin had a more general distribution. TGFbeta isoforms and receptors were expressed by glandular epithelium, fibroblasts, vascular endothelium and inflammatory cells. Cell counts showed no differences in expression of TGFbeta1 or TGFbeta receptors between groups. However, the percentage of TGFbeta2 positive fibroblasts was significantly higher in SSc glands compared with controls (p<0.004). RP glands showed an intermediate level of expression. By contrast, a lower percentage of RP fibrolasts expressed TGFbeta3 compared with controls with SSc glands showing an intermediate level of expression. CONCLUSIONS: These results show that (a) there are no changes in glandular expression of tenascin, elastin and fibronectin in SSc and RP and (b) both conditions are associated with an increased salivary gland mast cell population and changes in expression of TGFbeta2 and beta3 isoforms by glandular fibroblasts. (+info)
Prevalence of Raynaud's phenomenon in a healthy Greek population.
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OBJECTIVE: Raynaud's phenomenon (RP) is comprised of repeated episodes of colour changes of the skin of digits on cold exposure or emotional stress. The prevalence of RP in the general population is variable fluctuating between 4%-15%, among surveys. The aim of this study was to estimate the prevalence of RP in a healthy working Greek population and to investigate the possible association of RP with various demographic, social and other factors. METHODS: A total of 756 employees of the University Hospital of Ioannina was included in the study. They belong to the administrative (120 subjects), nursing and technical (a representative sample of 418 and 218 subjects, respectively) personnel. Five hundred subjects (111 men and 389 women) responded in a face to face interview based on a specially conformed questionnaire. The study began in November 1997 and was completed in March 1998. RESULTS: Twenty six subjects with RP (1 man and 25 women) were found. Their mean (SD) age was 32.73 (5.77) years. The prevalence of RP was 5.2% (0.9% in men and 6.4% in women). The sex ratio, male/female, was 1/7.1. An association between RP and migraine was found. However, there were no significant correlations of RP with smoking, alcohol and coffee consumption, dietary habits, occupational history and drug exposure. No social or other demographic parameters associated to RP frequency were found. CONCLUSIONS: The prevalence of RP (5.2%) in the population studied is relatively low compared with previous studies. RP focuses on the fourth decade of life and affects mainly women. There was no evidence of any correlation of RP with social, environmental or personal parameters while an association of RP with migraine was found. Geographical or genetic factors, or both, may be responsible for these results. (+info)
Raynaud's phenomenon as a manifestation of parvovirus B19 infection: case reports and review of parvovirus B19 rheumatic and vasculitic syndromes.
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Infection with human parvovirus B19 is manifested as erythema infectiosum, transient aplastic crisis, or hydrops fetalis. Rheumatic manifestations include arthropathy and various vasculitic syndromes. Isolated Raynaud's phenomenon due to parvovirus B19 has never been described. We report on 2 previously healthy sisters with new-onset Raynaud's phenomenon accompanied by severe generalized polyarthralgia. A full workup was negative, except serology for parvovirus B19, which was positive. All symptoms gradually subsided within 3-5 months, and no recurrence has been noted during the 3 years since onset. We review all the studies in the English-language literature on parvovirus B19-induced rheumatic and vasculitic syndromes. We hypothesize that the pathogenesis of Raynaud's phenomenon in our patients involved immune-mediated endothelial damage leading to platelet activation and vasoconstriction. We recommend that in cases of unexplained Raynaud's phenomenon, serology for parvovirus B19 be included in the evaluation. (+info)
Circulating concentrations of soluble L-selectin (CD62L) in patients with primary Sjogren's syndrome.
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OBJECTIVE: Serum concentrations of soluble (s) L-selectin (CD62L) were measured in patients with primary Sjogren's syndrome (SS) to relate these concentrations to clinical and immunological features of SS. METHODS: The study included 40 consecutive patients (38 women and two men) with a mean age of 61 years (range 24-78) who fulfilled four or more of the preliminary diagnostic criteria for SS proposed by the European Community Study Group in 1993, and 33 healthy blood donors from the hospital blood bank. A sandwich enzyme linked immunosorbent assay (ELISA) was used to detect the soluble form of human sL-selectin (CD62L). RESULTS: The mean (SEM) values of sL-selectin (CD62L) were 861 (66) microg/ml for patients with SS and 986 (180) microg/ml for healthy blood donors, but there was no significant difference. In patients with primary SS, serum sL-selectin (CD62L) concentrations were significantly higher in patients with Raynaud's phenomenon (1275 (112) microg/ml versus 789 (69) microg/ml, p=0.007), autoimmune thyroiditis (1162 (113) microg/ml versus 787 (69) microg/ml, p=0.02) and rheumatoid factor (993 (95) microg/ml versus 684 (70) microg/ml, p=0.01) when compared with patients without these features. CONCLUSION: The presence of Raynaud's phenomenon, autoimmune thyroiditis and rheumatoid factor is associated with higher concentrations of circulating sL-selectin (CD62L) in the sera of patients with primary SS. (+info)
Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries.
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Cold constricts cutaneous blood vessels by increasing the reactivity of smooth muscle alpha(2)-adrenergic receptors (alpha(2)-ARs). Experiments were performed to determine the role of alpha(2)-AR subtypes (alpha(2A)-, alpha(2B)-, alpha(2C)-ARs) in this response. Stimulation of alpha(1)-ARs by phenylephrine or alpha(2)-ARs by UK-14,304 caused constriction of isolated mouse tail arteries mounted in a pressurized myograph system. Compared with proximal arteries, distal arteries were more responsive to alpha(2)-AR activation but less responsive to activation of alpha(1)-ARs. Cold augmented constriction to alpha(2)-AR activation in distal arteries but did not affect the response to alpha(1)-AR stimulation or the level of myogenic tone. Western blot analysis demonstrated expression of alpha(2A)- and alpha(2C)-ARs in tail arteries: expression of alpha(2C)-ARs decreased in distal compared with proximal arteries, whereas expression of the glycosylated form of the alpha(2A)-AR increased in distal arteries. At 37 degrees C, alpha(2)-AR-induced vasoconstriction in distal arteries was inhibited by selective blockade of alpha(2A)-ARs (BRL-44408) but not by selective inhibition of alpha(2B)-ARs (ARC-239) or alpha(2C)-ARs (MK-912). In contrast, during cold exposure (28 degrees C), the augmented response to UK-14,304 was inhibited by the alpha(2C)-AR antagonist MK-912, which selectively abolished cold-induced amplification of the response. These experiments indicate that cold-induced amplification of alpha(2)-ARs is mediated by alpha(2C)-ARs that are normally silent in these cutaneous arteries. Blockade of alpha(2C)-ARs may prove an effective treatment for Raynaud's Phenomenon. (+info)
Autoantibody recognition of distinctly modified forms of the U1-70-kd antigen is associated with different clinical disease manifestations.
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OBJECTIVE: To examine whether autoantibody recognition of modified forms of the U1-70-kd RNP antigen correlates with manifestations of rheumatic disease. METHODS: Blinded to clinical disease manifestations, sera from 27 rheumatic disease patients with U1-70-kd antibodies were used to immunoblot control, apoptotic, and oxidatively modified HeLa cell lysates. Using densitometry, recognition of antigen fragments was quantitated. The presence or absence of 1) lupus skin disease and 2) Raynaud's phenomenon (RP) was determined for each patient by chart review. The ability of patient sera to recognize the different fragments was compared for patients with and without skin disease and with and without RP. RESULTS: Patients with lupus skin disease had higher recognition of apoptotic U1-70 kd than did patients without skin disease (mean +/- SD fragment recognition index [FRI] 1.35 +/- 0.57 versus 0.95 +/- 0.25; P < 0.024, by Student's t-test). Patients with RP had higher recognition of oxidatively modified U1-70 kd than did patients without RP (mean +/- SD FRI 0.95 +/- 0.80 versus 0.24 +/- 0.22; P < 0.048). CONCLUSION: Recognition of apoptotically and oxidatively modified forms of the U1-70-kd autoantigen are associated with distinct clinical rheumatic disease manifestations. This finding provides in vivo evidence for the hypothesis that immune recognition of modified forms of self antigens may be relevant to the pathogenesis of systemic rheumatic diseases. Understanding the antigenic modifications to which patients react may help predict the expression of rheumatic syndromes. (+info)
Vibration exposure, smoking, and vascular dysfunction.
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OBJECTIVES: Vibration white finger (VWF), also known as "occupational Raynaud's phenomenon", is marked by arterial hyperresponsiveness and vasoconstriction during cold stimulation. The impact of tobacco use, and by extension stopping smoking, on the long term course of the disease has been inconclusively characterised. The objectives of this study included assessment of the impact of tobacco use on symptoms and on objective tests in shipyard workers exposed to vibration, and in gauging the natural history of the disorder after stopping exposure and changing smoking patterns. METHODS: In a cross sectional investigation, 601 current and former users of pneumatic tools were evaluated subjectively for cold related vascular symptoms, and tested by cold challenge plethysmography. There was follow up and subsequent testing of 199 members of the severely effected subgroup of smokers and non-smokers, many of whom had stopped smoking in the interval between tests. Effects of smoking and stopping smoking on symptoms and plethsymographic results were assessed. RESULTS: Symptoms and measured abnormal vascular responses related to cold were more severe in smokers than in non-smokers. Follow up of 199 severely effected members of the cohort, all removed from exposure for 2 years, indicated that smokers were almost twice as likely to have more severe vasospasm (test finger/control finger systolic blood pressure% (FSBP%) <30) than were non-smokers (-32.2% v 17.4%). 53 Subjects who stopped smoking during the interval between tests improved, and were indistinguishable from non-smokers similarly exposed to vibration. Additional physiological benefits of stopping smoking were still apparent at further follow up examination, 1 year later. Improvements evident on plethysmography were not accompanied by improvements in symptoms, which were unaffected by smoking. CONCLUSIONS: Smoking seems to delay physiological improvement in response to cold challenge in workers with VWF, after the end of exposure to vibration. Symptoms were less likely to improve over time than digital blood pressure, and were less affected by smoking. (+info)
Prevalence of migraine and Raynaud's phenomenon in Japanese patients with vasospastic angina.
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The prevalence of migraine and Raynaud's phenomenon in Japanese patients with vasospastic angina (group I) were compared with those in 2 control groups: one with effort angina (group II) and the other group without known ischemic heart disease (group III). There were no significant differences among the 3 groups with respect to age and sex. The prevalence of migraine in group I was 23 of 100, as compared with 4 of 100 in group II (p<0.01) and 11 of 100 in group III (p<0.05). The prevalence of Raynaud's phenomenon in group I was 9 of 100, as compared with 3 of 100 in group II and 4 of 100 in group III. Thus, in Japan, the prevalence of migraine in patients with vasospastic angina was higher than those in the 2 control groups, whereas the prevalence of Raynaud's phenomenon did not differ significantly among the 3 groups. The prevalence of Raynaud's phenomenon in Japanese patients with vasospastic angina was different from that reported from North America, although the prevalence of migraine was the same. This may be partially explained by racial differences. (+info)