Biomedical subjects

C Nordborg

Publications and source records attributed to C Nordborg.

114 records · Page 7Linked to original sources

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.

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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.

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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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