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Biomedical subjects

E Nordborg

Publications and source records attributed to E Nordborg.

36 records · Page 2Linked to original sources
PubMed1993

Bone mineral content of the third lumbar vertebra during 18 months of prednisolone treatment for giant cell arteritis.

Altogether forty-four patients with giant cell arteritis (GCA) were randomly allocated to either daily morning or alternate-day administration of prednisolone. The BMC of the third lumbar vertebra was determined using dual photon absorptiometry. At least ten measurements were performed in each patient during a period of 18 months. During the course of treatment there was no significant change of the mean BMC in either group compared to the pre-treatment value. The changes of BMC were independent of such potentially explanatory variables as cumulative dose of prednisolone, initial BMC, sex and body weight. Corticosteroid treatment in patients with GCA, in the doses used by us, does not appear to cause excessive bone loss.

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PubMed1993

Plasma viscosity in giant cell arteritis as a predictor of disease activity.

Thirty one patients with giant cell arteritis (GCA) receiving standardised prednisolone treatment were followed up for one year with analyses of plasma viscosity, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and fibrinogen concentration. On the day of diagnosis all patients had an increased plasma viscosity and ESR, whereas the concentration of CRP was normal in three patients and fibrinogen concentration and haptoglobin values were normal in one patient. IgG levels were increased in two patients. Plasma viscosity correlated significantly with the ESR, IgG level, and fibrinogen concentration. Laboratory variables in subgroups of patients with GCA proved by biopsy were not different from the whole group of patients with GCA. The follow up showed that CRP normalised faster than the ESR, plasma viscosity, and fibrinogen concentration. Plasma viscosity and the ESR paralleled clinical findings more closely and predicted flare ups better than the other variables. Plasma viscosity had advantages over the ESR for predicting flare ups and in the clinical monitoring of treatment with glucocorticoids.

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PubMed1992

Giant cell arteritis.

Giant cell arteritis is a generalized inflammatory disorder involving large and medium-sized arteries. The etiology is unknown, although an autoimmune pathogenesis seems probable. In view of the clinical similarities between patients with positive biopsy findings for polymyalgia rheumatica and those with negative biopsy findings, many authors favor the concept that polymyalgia rheumatica is an expression of an underlying giant cell arteritis. There is, however, still controversy as to whether polymyalgia rheumatica and temporal arteritis are different expressions of one and the same disease or two separate, partly overlapping types of giant cell arteritis. A single etiologic factor may be responsible for the two conditions, sometimes expressing itself as polymyalgia rheumatica and sometimes as giant cell arteritis. Recent findings of morphologic similarities in terms of arterial wall atrophy, calcifications, and inflammatory reactions may indicate that polymyalgia rheumatica and temporal arteritis represent different degrees or stages of the same disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1991

Temporal artery morphology and morphometry in giant cell arteritis.

Paraffin sections and more than 7,000 plastic cross-sections of temporal arteries from 27 patients with a clinical diagnosis of polymyalgia rheumatica (PMR), 16 patients with a clinical diagnosis of temporal arteritis (TA) and 18 age- and sex-matched postmortem controls were studied using light microscopy. A new method was developed to permit a morphometric comparison between biopsies and autopsy specimens. Two stages of inflammation were discerned in TA. In atrophic arterial segments there was a focal, foreign-body, giant-cell reaction to the calcified internal elastic membrane (IEM) with a spatially correlated, mononuclear cell infiltration. Isolated giant cells were also found to attack the IEM in these cases. The majority of the biopsies displayed a different picture with a diffuse macrophage attack on media and intima with numerous and apparently macrophage-derived giant cells, which did not attack calcifications. The latter arteries were significantly widened (p less than 0.02), which indicates that this phase is the later one. Non-inflamed segments of PMR vessels displayed a significant, non-reactive media atrophy compared with controls (p less than 0.03) and their IEM calcifications were significantly larger (p less than 0.02). The circumference was smaller in atrophic PMR arteries than in inflamed TA arteries (p less than 0.006), which contradicts post-inflammatory scarring.

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PubMed1991

von Willebrand factor antigen and plasminogen activator inhibitor in giant cell arteritis.

Sixty three patients (51 women, 12 men) with giant cell arteritis were studied by serial analyses of von Willebrand factor antigen (vWF: Ag) concentration and plasminogen activator inhibitor activity. Their mean age at the time of diagnosis was 71 years. Two hundred and one randomly selected subjects from the general population, aged 75 years, served as controls. The mean concentration of vWF:Ag in the patients with giant cell arteritis before the start of corticosteroid treatment was 2.63 (SD 1.35) IU/ml compared with 1.71 (0.69) IU/ml in the general population. The vWF:Ag concentration slowly decreased and reached the control range about 18 months after the diagnosis. The vWF:Ag did not correlate with the clinical group of giant cell arteritis nor with the results of temporal artery biopsy. Flare ups and vascular complications were not indicated by the vWF:Ag. Plasminogen activator inhibitor activity in the patients was not significantly different from that of the general population at any time. It was concluded that the determination of vWF:Ag and plasminogen activator inhibitor activity is of limited clinical value in the diagnosis, prognosis, and monitoring of steroid treatment in patients with giant cell arteritis.

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PubMed1990

Epidemiology of biopsy-proven giant cell arteritis (GCA).

During a 10-year period from 1st January 1977 to 31st December 1986, a temporal artery biopsy was performed in 2307 patients in the city of Göteborg. The biopsy revealed giant cell arteritis (GCA) in 284 (12.5%) of patients. The average annual incidence of biopsy-proven GCA was 6.7 per 100,000 inhabitants. For women and men it was 9.9 and 3.5 per 100,000 inhabitants, respectively. In individuals aged 50 years or older, the average incidence was 18.3 per 100,000 inhabitants, with values of 25 and 9.4 for women and men, respectively. The annual incidence rate increased significantly (P less than 0.01) for women, but not for men; this result was not explained by demographic changes in the population.

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PubMed1988

HLA-DR expression in the vascular lesion and circulating T lymphocytes of patients with giant cell arteritis.

Giant cell arteritis (GCA) is a vascular inflammatory disease characterized by accumulations of T lymphocytes and macrophages in the arterial wall. In order to characterize the immune response in GCA, we have analysed temporal artery biopsies using a double-staining immunofluorescence method and studied T lymphocytes in peripheral blood with a fluorescence-activated cell sorter (FACS). HLA-DR was expressed on 28% (range 16-42%) of all T lymphocytes in the wall of the inflamed temporal artery, but only on average on 6% of peripheral blood T lymphocytes, indicating a high degree of local T cell activation in the inflammatory lesion. The proportions of T lymphocytes, T helper/inducer and T suppressor/cytotoxic cells in the blood of GCA patients before treatment with prednisolone did not deviate from those in normal individuals, but there was a minor increase in T helper cells after initiation of steroid therapy. The number of T helper cells expressing HLA-DR antigen and IL-2 receptor was not altered after 6-10 days of treatment with prednisolone. We found no evidence of HLA-DR expression by arterial smooth muscle cells in the GCA lesions, suggesting that these cells do not serve as antigen-presenting cells in GCA.

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PubMedDate not supplied

Estrogen receptors in giant cell arteritis. An immunocytochemical, western blot and RT-PCR study.

OBJECTIVE: Giant cell arteritis (GCA) is a chronic form of vasculitis which predominantly affects women over 50 years of age. The aim of this study was to analyse the presence of estrogen receptor alpha (ER) in the temporal arteries of patients with GCA. METHODS: Inflamed temporal artery biopsies from 43 GCA patients were stained with monoclonal antibodies to two different segments of the ER and compared with non-inflamed arteries from age- and sex-matched controls who had not received a clinical diagnosis of GCA. The protein that was extracted from 4 GCA-positive biopsies and 4 non-GCA controls was analysed using the Western blot method with a monoclonal antibody to ER. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis using primer pairs specific to ER-cDNA was performed on the total RNA from 4 GCA-positive biopsies and 4 non-GCA controls. RESULTS: The inflamed arteries expressed distinct cytoplasmic immunoreactivity to ER in activated mononuclear inflammatory cells and in giant cells. Biopsies from GCA patients and controls displayed cytoplasmic ER positivity in smooth muscle cells. Western blot analysis revealed two bands corresponding to approximately 64 and 54 kDa, respectively, in the inflamed arteries and controls. In the inflamed biopsies and non-GCA controls, RT-PCR analysis revealed a strong band corresponding to approximately 670 bp, as expected, and a weaker band corresponding to approximately 440 bp. CONCLUSION: In inflamed arteries from GCA patients, smooth muscle cells, activated mononuclear inflammatory cells and giant cells express cytoplasmic ER. Non-inflamed control arteries also express cytoplasmic ER in smooth muscle cells. The accumulation of cytoplasmic ER may suggest the involvement of estrogen not only in GCA but also in normal vascular aging. The results justify further investigations into the pathogenetic roles of estrogen metabolism in GCA.

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PubMedDate not supplied

Epidemiology of biopsy-positive giant cell arteritis: an overview.

Giant cell arteritis (GCA) is reported world-wide. However, the incidence varies greatly in different geographic regions with the highest incidence rates from Scandinavian countries and North American populations of the same descent. The etiopathogenesis of GCA is incompletely understood. Although data on a positive correlation between the occurrence of infection and the onset of GCA as well as rhythmic fluctuations in disease incidence have been reported, no statistically significant periodicity has so far been found regarding the annual incidence of GCA. Seasonal variations may indicate a role of infection or other environmental factors in the pathogenesis of GCA.

Biopsy↗
PubMedDate not supplied

The pathogenesis of giant cell arteritis: morphological aspects.

The light-microscopic, electron-microscopic and immunocytochemical characteristics of giant cell arteritis (GCA) have been investigated in a number of studies on temporal arteries. Arterial atrophy and calcification of the internal elastic membrane appear to be prerequisites for the evolution of the inflammatory process. Foreign body giant cells form close to calcifications, apparently without connection with other inflammatory cells and probably by the fusion of modified vascular smooth muscle cells. The foreign body giant cells attack the calcifications. Lymphocytes accumulate around them and may be found in pockets in their cell surface. This focal reaction is found in atrophic, calcified arterial segments in a minority of inflamed temporal artery biopsies. More commonly seen is a diffuse mononuclear attack of the vessel wall in atrophic as well as non-atrophic segments which leads to severe arterial dilatation. Langhans giant cells form by the fusion of macrophages in the diffuse inflammatory infiltrate. The fact that the diffusely inflamed arteries are markedly widened compared to the focally inflamed vessels suggests that the inflammatory process starts as a focal foreign body giant cell reaction directed at calcifications which in turn initiates a more diffuse and widespread inflammation.

Aorta↗
PubMedDate not supplied

Estrogen receptor alpha in giant cell arteritis: a molecular genetic study.

OBJECTIVE: Giant cell arteritis (GCA) predominantly affects postmenopausal women. Estrogen receptor alpha (ER alpha) accumulates in the cytoplasm of smooth muscle cells, activated mononuclear inflammatory cells and giant cells in the temporal arteries of GCA patients, as well as in smooth muscle cells in arteries from non-GCA controls. The aim of this study was to analyse whether this accumulation is related to structural aberrations in the ER alpha mRNA leading to a change in protein structure. METHODS: Total RNA was extracted from inflamed temporal artery tissue in two GCA patients and from non-inflamed arteries in two non-GCA controls. Products from the nested RT-PCR of the cDNA were cloned and plasmid inserts of 20 different clones from each case were investigated using nucleotide sequence analysis. RESULTS: A total of eight different types of transcripts lacking parts of the ER alpha mRNA were detected. Seven of these could be explained by alternative splicing. There were no significant differences between the GCA patients and the non-GCA controls in terms of the number of transcript variants. CONCLUSION: The accumulated cytoplasmic ER alpha in temporal arterial tissue from elderly persons appears mainly to be of wild type. The main structural changes in the ER alpha mRNA may be due to alternative splicing. Somatic mutations of the ER alpha gene appear to be rare and it is therefore unlikely that they are involved in the pathogenesis of GCA.

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PubMedDate not supplied

Calcification of the internal elastic membrane in temporal arteries: its relation to age and gender.

OBJECTIVE: To investigate the age and sex distribution of calcifications of the internal elastic membrane (IEM) in temporal arteries. METHODS: Calcifications of the IEM were assessed light-microscopically in temporal arteries from 40 women and 21 men, aged 51 or more, who were known not to have giant cell arteritis (GCA). Their relation to age and the difference between women and men were tested statistically. RESULTS: The IEM calcifications differed morphologically from the calcifications in Mönckeberg's mediosclerosis and atherosclerosis. They increased significantly with age and were 2.62 times more common in women than men. CONCLUSION: Previous morphological studies indicate that the inflammatory process in GCA is initiated by a foreign-body, giant-cell attack on calcifications of the IEM. The present study showed that IEM calcifications in non-GCA controls show an age and sex distribution similar to that of GCA morbidity. The results may indicate that the presence of IEM calcifications in the general population influences the age and sex distribution of GCA. Furthermore, the findings support the hypothesis that the calcifications, although not disease specific, may play a pathogenetic role in the latter.

Age Factors↗
PubMedDate not supplied

A Western blot and molecular genetic investigation of the estrogen receptor beta in giant cell arteritis.

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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PubMedDate not supplied

Morphological aspects of giant cells in giant cell arteritis: an electron-microscopic and immunocytochemical study.

OBJECTIVES: To compare the morphology of foreign body and Langhans giant cells in the two different inflammatory phases of giant cell arteritis (GCA). METHODS: Electron microscopy was performed on 6 positive temporal arterial biopsies. Light microscopy and immunocytochemistry for macrophage-associated antigen (KP1) and alpha-smooth muscle actin (alpha-SMA) were performed on 16 positive biopsies. RESULTS: A focal granulomatous reaction with foreign body giant cells was found only in association with the internal elastic membrane (IEM) in atrophic arterial segments, which often displayed calcification of the IEM. Diffuse invasion of lymphocytes and monocytes/macrophages affected non-atrophic as well as atrophic arterial segments. Within such segments Langhans giant cells were found in all layers of the wall. Electron microscopy of biopsies displaying the focal foreign body reaction revealed that large cells devoid of lysosomes but with cytoplasmic densities, tightly packed cytoplasmic filaments and numerous micropinocytotic vesicles formed clusters close to calcified parts of the internal elastic membrane. Furthermore, foreign body giant cells were surrounded by large cells devoid of lysosomes. Lysosomes tended to concentrate in central parts of the foreign body giant cells. In the diffusely inflamed arteries, the Langhans giant cells were surrounded by mononuclear cells rich in lysosomes. The lysosomes in the Langhans giant cells were more evenly distributed than in foreign body giant cells. Immunocytochemistry of biopsies displaying the focal granulomatous reaction revealed an uneven, often central immunoreactivity for the macrophage marker (KP1) in the foreign body giant cells, and immunostaining for alpha-smooth muscle antigen (alpha-SMA) showed their poor delineation from the surrounding vascular smooth muscle cells. The Langhans giant cells in the diffusely inflamed arteries displayed a strong even cytoplasmic immunoreactivity for KP1 and a distinct delineation from the smooth muscle cells in the alpha-SMA staining. CONCLUSION: Differences in terms of distribution, light microscopy, immunocytochemistry and electron microscopy between the two types of giant cells in GCA indicate a difference in their function as well as their histogenesis.

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PubMedDate not supplied

The inflammatory reaction in giant cell arteritis: an immunohistochemical investigation.

OBJECTIVE: To assess the distribution of the inflammatory reaction in giant cell arteritis (GCA). METHODS: Semiquantitative analysis on cryostat sections stained with monoclonal antibodies against inflammatory markers. RESULTS: The inflammatory infiltration was strongest in the adventitia where it showed sharp demarcation along the outer border of the media. The endothelial immunopositivity for HLA-DR was strongest in adventitial microvessels. The immunopositivity for macrophages, B-cells, HLA-DR, ICAM-1 and IL-2 was significantly stronger in the outer than in the inner half of the intima. CONCLUSION: The distribution of immunostainings and the crowding of cells seen at the outer media border indicates that the majority of the inflammatory cells enter the arterial wall from adventitial microvessels, migrate through the media and that the cell migration and the inflammatory activity focuses on the peripheral intima/internal elastic membrane.

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