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| 2. |
- Larsson, K, et al.
(författare)
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A Western blot and molecular genetic investigation of the estrogen receptor beta in giant cell arteritis.
- 2006
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Ingår i: Clinical and experimental rheumatology. - 0392-856X. ; 24:2 Suppl 41
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The epidemiology of giant cell arteritis (GCA) may indicate a pathogenetic relationship between GCA and female sex hormone metabolism; GCA is two to four times more common in women compared with men. Our previous analyses gave no support for the hypothesis that the pathogenesis of GCA should be related to somatic mutations in the estrogen receptor alpha (ERalpha) gene. The object of the present study was to investigate the size of the estrogen receptor beta (ERBeta), and the size and nucleotide sequence of the ERBeta gene in temporal arteries in GCA. METHODS: The ERBeta protein was analyzed by Western blot technique and the ERBeta gene by RT-PCR and direct sequencing of the PCR product. RESULTS: Western blot analysis revealed an ERBeta of normal size. There were no aberrations in size or nucleotide sequence in the ERBeta gene in the GCA patients. CONCLUSION: The present observations gave no support for the hypothesis that somatic mutations in the ERBeta gene should be involved in the pathogenesis of GCA.
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| 3. |
- Larsson, K, et al.
(författare)
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Early menopause, low body mass index, and smoking are independent risk factors for developing giant cell arteritis.
- 2006
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 65:4, s. 529-32
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess female sex hormone related variables in a group of women with biopsy positive giant cell arteritis and a control group. METHODS: 49 women with biopsy positive giant cell arteritis, aged 50 to 69 years at the time of diagnosis, answered a questionnaire on hormonal and reproductive factors. The same questions were answered by a large population of women from the same geographical area in connection with routine mammograms. The results were tested statistically, using logistic regression analysis of each variable adjusted for age, and a multivariate logistic regression analysis including age and the variables which differed significantly between giant cell arteritis and controls. RESULTS: From the multivariate logistic regression analysis, three independent variables were associated with an increased risk of having giant cell arteritis: smoking and being an ex-smoker (odds ratio (OR) = 6.324 (95% confidence interval (CI), 3.503 to 11.418), p<0.0001); body mass index (a reduction of 1.0 kg/m2 increased the risk by 10% (OR = 0.898 (0.846 to 0.952), p = 0.0003); and menopause before the age of 43 (OR = 3.521 (1.717 to 7.220), p = 0.0006). CONCLUSIONS: There was a significant association between hormonal and reproduction related factors and the risk of developing giant cell arteritis in women given the diagnosis before the age of 70. The results suggest a possible role of oestrogen deficiency in the pathogenesis of giant cell arteritis. To confirm the results, an extended study will be needed, including women older than 70.
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| 4. |
- Nordborg, Claes, 1946, et al.
(författare)
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Cell-type-specific expression of p53 and p21 in giant cell arteritis.
- 2005
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0903-4641. ; 113:9, s. 594-9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the expression of TP53 (p53) and CDKN1A (CIP1; p21) in the arterial wall in giant cell arteritis (GCA). Cross-sections from 18 temporal artery biopsies displaying GCA and 8 control arteries were double-stained with monoclonal antibody directed at p53 or p21 on the one hand and alpha-smooth muscle actin, CD68 (macrophage) or CD3 (T-cell) on the other. Nuclear p53 was expressed in CD68-positive cells and smooth muscle cells in 16 of the 18 inflamed arteries. P21-positive nuclei were found in CD68-positive cells in 14 biopsies and in smooth muscle cells in all the specimens. All p53-positive giant cells also contained p21-positive nuclei. In the giant cells, immunopositive nuclei were mixed with negative ones. CD3-positive T-cells did not express p53 or p21. Only one p53-positive smooth muscle cell nucleus was found in the non-GCA controls and, compared with GCA, p21 expression was noted in few smooth muscle nuclei. The presence of p53 and p21 in the same types of cell in GCA indicates that the former protein is functional; p21 expression is induced by wild-type, functional p53 but not by its mutant form. The current observations suggest cellular stress in GCA, the nature of which requires further investigation.
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| 5. |
- Nordborg, Claes, 1946, et al.
(författare)
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Expression of the class I interferon-related MxA protein in temporal arteries in polymyalgia rheumatica and temporal arteritis.
- 2009
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Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 38:2, s. 144-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to assess the expression of the interferon type I (IFN-I)-associated MxA protein in polymyalgia rheumatica (PMR) and temporal arteritis (TA). METHODS: Non-inflamed temporal artery biopsies from 11 PMR patients were compared with biopsies from 13 patients given other diagnoses. Coded sections were screened immunocytochemically for MxA protein, CD83, CD68, CD3, and S100 protein. Inflamed temporal artery biopsies from four patients with TA were also investigated. RESULTS: Focal MxA expression was seen in non-inflamed arteries, more frequently in PMR than in controls (p = 0.0124). MxA expression was also more common in adventitial dendritic cells (DCs) in PMR (p = 0.0124). Activated adventitial DCs were detected in PMR. Focal MxA expression in the inflamed biopsies from the patients with TA was not related spatially to the inflammation. CONCLUSIONS: The expression of MxA protein in arteries from patients with PMR and TA shows that non-inflamed and inflamed vessel walls are influenced by IFN-I. Further studies are required to elucidate whether IFN-I plays a role in the initiation of PMR and/or TA, serving as a link between the innate and the adaptive immune responses, as in some other autoimmune disorders.
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| 7. |
- Nordborg, Claes, 1946, et al.
(författare)
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Stereological study of neovascularization in temporal arteritis.
- 2006
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Ingår i: The Journal of rheumatology. - 0315-162X. ; 33:10, s. 2020-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: As giant cell arteritis (GCA) progresses, newly formed microvessels are one of the main sites of leukocyte-endothelial cell interaction. Our aim was to stereologically map the distribution of microvessels in the temporal arterial wall and to assess their relationship to the degree of inflammation in GCA. METHODS: Inflamed temporal arteries from 21 patients who fulfilled the American College of Rheumatology criteria for GCA were analyzed. Paraffin sections, stained with an antibody directed at vascular endothelium, were analyzed stereologically. The degree of inflammation and the surface of microvascular endothelium per volume (microm2/microm3) were assessed in 4 different layers of the arterial wall. RESULTS: The degree of inflammation and of vascularization was greatest in the adventitia, smaller in the media, and smallest in the intima. A significant positive relationship was observed between the degree of inflammation and the degree of vascularization in the media and in the outer and inner layers of the intima. In 8 biopsies, the microvessels formed a prominent plexus in the intima without apparent connection with microvessels in the adventitia/media, and there were no signs of endothelial budding from the arterial lumen. CONCLUSION: Our results confirm that inflammation is a major determinant in neovascularization in GCA. Some new microvessels are formed by the budding of the adventitial vasa vasorum. The presence of intimal microvascular networks without apparent connection with microvessels in the media might indicate additional influence on neovascularization.
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| 8. |
- Nordborg, Elisabeth, 1948, et al.
(författare)
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Giant cell arteritis: strategies in diagnosis and treatment.
- 2004
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Ingår i: Current opinion in rheumatology. - 1040-8711. ; 16:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: This review summarizes current diagnostic assessments and therapeutic strategies in giant cell arteritis. Giant cell arteritis or temporal arteritis is a chronic vasculitis of large and medium-size vessels. Concurrent symptoms of proximal muscular ache and morning stiffness, polymyalgia rheumatica, are commonly seen. Recent investigations support the contention that polymyalgia rheumatica and temporal arteritis are two different expressions of the same underlying vasculitic disorder. RECENT FINDINGS: The symptomatology of giant cell arteritis is quite varying. Recently a frequent occurrence of audiovestibular manifestations was demonstrated, which should be actively searched for in the clinical investigation. Although color Doppler ultrasound, MRI, and positron emission tomography have illustrated the widespread nature of giant cell arteritis, none of these techniques may currently replace temporal artery biopsy. Biopsy of the superficial temporal artery is a safe and simple procedure, and remains the gold standard for the diagnosis of giant cell arteritis. The importance of long biopsies and meticulous histologic examination using sub-serial sectioning is emphasized. Numerous recent publications confirm the low diagnostic yield of a second, contralateral biopsy. Corticosteroids remain the cornerstone in the treatment of giant cell arteritis. Although steroid treatment promptly eliminates symptoms of systemic inflammation, its effect on inflammatory morphology is delayed. Consequently, there is a need for new therapeutic strategies. The potential role of aspirin has recently been implicated.
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| 9. |
- Forsblad d'Elia, Helena, 1961, et al.
(författare)
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Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456]
- 2004
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Ingår i: Arthritis Res Ther. - : Springer Science and Business Media LLC. - 1478-6362 .- 1465-9905 .- 1478-6354. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.
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| 10. |
- Forsblad d'Elia, Helena, 1961, et al.
(författare)
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Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1.
- 2003
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Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1465-9905 .- 1478-6354. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Hormone replacement therapy (HRT) modulates the imbalance in bone remodeling, thereby decreasing bone loss. Sex hormones are known to influence rheumatic diseases. The aim of this study was to investigate the effects of HRT on the serum levels of hormones and cytokines regulating bone turnover in 88 postmenopausal women with active rheumatoid arthritis (RA) randomly allocated to receive HRT plus calcium and vitamin D3 or calcium and vitamin D3 alone for 2 years. An increase in estradiol (E2) correlated strongly with improvement of bone mineral density in the hip (P < 0.001) and lumbar spine (P < 0.001). Both baseline levels and changes during the study of IL-6 and erythrocyte sedimentation rate were correlated positively (P < 0.001). HRT for 2 years resulted in an increase of the bone anabolic factor, insulin-like growth factor 1 (IGF-1) (P < 0.05) and a decrease of serum levels of soluble IL-6 receptor (sIL-6R) (P < 0.05), which is known to enhance the biological activity of IL-6, an osteoclast-stimulating and proinflammatory cytokine. Baseline levels of IL-6 and IGF-1 were inversely associated (P < 0.05), and elevation of IGF-1 was connected with decrease in erythrocyte sedimentation rate (P < 0.05) after 2 years. Interestingly, increase in serum levels of E2 was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05). The latter association was however not significant after adjusting for the effect of E2 (P = 0.075). The influences of IGF-1 and the IL-6/sIL-6R pathways suggest possible mechanisms whereby HRT may exert beneficial effects in RA. However, to confirm this hypothesis future and larger studies are needed.
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