Thesis (doctoral)--Lund University, 1994.

Thesis (doctoral)--Lund University, 1994.

Thesis--University of Helsinki, 1978.

Thesis--University of Helsinki, 1978.

Abstract The most threatening outcome of interstitial lung diseases is death caused by progressive pulmonary fibrosis characterised by increased collagen deposition, although the clinical course is highly variable. The aim of this study was to evaluate the role of procollagen I and III propeptides in estimating collagen metabolism and its relationship to disease activity and prognosis in patients with sarcoidosis, fibrosing alveolitis and asbestos-related lung diseases. The study included 160 patients. The levels of procollagen I carboxyterminal propeptide (PICP) and procollagen III aminoterminal propeptide (PIIINP) in serum, bronchoalveolar lavage fluid (BALF) and epithelial lining fluid (ELF) were assessed from 137 patients employing human antigens. There were 60 patients with sarcoidosis, 18 with fibrosing alveolitis and 5 with asbestosis and 17 controls. Thirty-seven patients had been exposed to asbestos, but did not show parenchymal involvement. Twenty-five of them had pleural plaques, while 12 had normal chest radiographs. Immunohistochemical stainings for procollagen I aminoterminal (PINP) and III aminoterminal propeptide were carried out on open lung biopsies of the remaining 23 of the 160 patients, of whom 13 had sarcoidosis and 10 fibrosing alveolitis. Antibodies to these procollagen peptides react with the aminoterminal domains of the corresponding propeptides intracellularly and with the respective pN-collagen in collagen fibres in the extracellular space. Procollagen III aminoterminal propeptide was elevated in the sera of the patients with sarcoidosis and fibrosing alveolitis, but not in the asbestosis or asbestos-exposed patients as compared to the controls. The level of PIIINP in BALF was highest in sarcoidosis and second highest in fibrosing alveolitis, but hardly detectable in the other groups. BALF-PICP was higher in the patients with fibrosing alveolitis, sarcoidosis and asbestosis than in the controls. PIIINP in BALF correlated with BALF-PICP, serum angiotensin-converting enzyme (S-ACE), interleukin 2-receptor, BALF-albumin and BALF-lymphocytes and BALF-PICP had a significant correlation with BALF-albumin and BALF-lymphocytes in sarcoidosis. BALF/ELF-PICP had an inverse correlation with the specific diffusion coefficient (DLCO/VA) in fibrosing alveolitis. Both PIIINP and PICP were higher in ELF than in serum in sarcoidosis and fibrosing alveolitis and PICP was higher in ELF compared to serum in asbestosis, suggesting active local synthesis in the lower respiratory tract. The levels of PIIINP in BALF were significantly elevated in sarcoidosis patients with parenchymal involvement compared to those without. Detectable PIIINP in BALF also predicted a poor outcome in fibrosing alveolitis. BALF-PIIINP reflected the disease activity based on chest radiographs in sarcoidosis and a poor prognosis in fibrosing alveolitis, whereas BALF-PICP marked the development of fibrosis. In lung biopsy specimens, type I and III pN-collagens were increased in fibrosing alveolitis and sarcoidosis. Type I pN-collagen was expressed in areas with damaged or deficient alveolar epithelium. Type III pN-collagen was present underneath regenerative, metaplastic alveolar and bronchiolar type epithelium and was accumulated both in the loose, newly formed fibrosis and in the denser old fibrosis. Type I procollagen was present in intracellular spots in newly formed fibrosis. In sarcoidosis, type I procollagen was present intracellularly in granulomas, whereas type III pN-collagen was expressed extracellularly around granulomas.

No description available.

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

This investigation was carried out to characterize and quantitate the collagen of rockfish intramusclar connective tissue. Different species ot rocktish were chosen to represent the range of product quality experienced by the fish processing industry. Species included widow, a rockfish noted tor its soft flesh, yellowtail, a rockfish possessing flesh of intermediatary texture and canary rockfish known for its firm flesh. The intramuscular connective tissue collagen was extracted from white muscle and total, salt, acid and insoluble collagen content was estimated by hydroxyproline analysis. No significant difference was observed among species with regard to all collagen fractions. Mean salt, acid and unsoluble collagen contents were 5.5 %, 8.7 % and 86 %, respectively indicating a relatively highly crosslinked and stable collagen compared to that reported for other fish collagens. The denatured acid soluble collagen traction was characterized by chromatography on CM-cellulose and the presence of three different alpha chains was established by SDS-polyacrylamide gel electrophoresis and amino acid analysis of the collagen components. The molecular weight for the alpha chains was estimated to be 96,000 based upon agarose molecular sieve chromatography. The alpha chains, designated αl, α2 and α3, had significantly different amino acid composition with the α3 chain possessing a higher level of hydroxylated lysine than αl and α2. In general, the amino acid composition of rockfish muscle collagen was similar to other reported fish collagens. Digestion of purified connective tissue and acid soluble muscle collagen with CNBr and subsequent analysis by LDS-polyacrylamide slab-gel electrophoresis showed identical peptide patterns indicating the presence of only one molecular type of collagen. This evidence along with the observed ratio of the collagen components resolved by CM-cellulose chromatography supported a molecular composition of αl-α2-α3 for rockfish muscle connective tissue collagen. Significant difference in skin thickness between species was observed. This correlated with the general quality ranking of the three species by the fish processing industry of canary>yellowtail>widow. Skin from canary rockfish was 38 % thicker than skin from widow rockfish while yellowtail had a skin of intermediatary thickness. From this observation, it was concluded that skin thickness and strength plays a more important role than intramuscular connective tissue characteristics in determining quality of product obtainable from the different rockfish species. / Graduation date: 1984

No description available.

No description available.