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Biomedical subjects

T Krieg

Publications and source records attributed to T Krieg.

At least 271 records · Page 15Linked to original sources
PubMed1982

Immunofluorescent localization of type IV collagen and laminin in human skin and its application in junctional zone pathology.

Purified antibodies against type IV collagen and laminin were used ot localize basement membranes by indirect immunofluorescence in various anatomical regions of normal and diseased human skin. The two proteins showed extensive codistribution. A continuous linear staining was found along the epidermal-dermal junction and around hair follicles, sebaceous gland acini and small capillaries. The same proteins also surrounded individual cells such as those found in vessels, hair erector muscles and subcutaneous tissue. Blister formation in bullous pemphigoi left type IV collagen and laminin on the floor of the blister, while the bullous pemphigoid antigen as detected by human autoantibodies was found on both sides of the blister. In solid basal cell carcinoma a strong staining was found around all tumour islands as well as focally within the cell clusters. This suggests that the tumour cells produce these basement membrane proteins but have lost, at least in part, control of polar deposition.

Adolescent↗
PubMed1982

Molecular defects in inborn disorders of collagen metabolism.

Disturbances of collagen metabolism may result in the manifestation of clinical symptoms. The collagen disorders that best characterized are genetically inherited and are known to vary at the clinical and molecular levels. Defective posttranslational modifications of collagen chains due to mutant enzymes have been found in patients with the Ehlers-Danlos syndrome and cutis laxa. Altered selection of collagen types and defective primary structure of the molecules themselves are prominent features in osteogenesis imperfecta. In other pathological conditions, such as Marfan syndrome, no clear molecular defect has been identified as yet.

Collagen↗
PubMed1981

Some aspects of the modulation and regulation of collagen synthesis in vitro.

We reviewed here a number of publications containing data on the quantitative aspects of collagen synthesis in vitro. In one section we discussed the factors which modulate the amount of collagen synthesized in various culture systems and in another section we presented experimental evidence for regulatory mechanisms operating in collagen synthesis on the transcriptional and/or translational levels. We believe that growing knowledge of the mechanisms controlling collagen synthesis will help us to understand and deal with fibrotic processes better.

Animals↗
PubMed1981

Case report and study of collagen metabolism in Marfan's syndrome.

The case report on a 33 year old woman with prominent features of Marfan's syndrome is presented. Characteristic signs were seen in the bones, the eyes, the cardiovascular system, and the lungs. Due to regurgitation of both the aortic and mitral valves and an aneurysm of the ascending aorta a double valve replacement was made, including a prosthesis of the aorta. The problems of early diagnosis and therapy of the life-threatening cardiovascular complications are discussed. Tissue specimens from the aorta were analysed histochemically and biochemically. Histology showed a typical necrosis of the media with cyst formation. Biochemical analysis by in vitro labeling of collagen in tissue explants and by electron microscopical evaluation showed proportions of type I and type III collagen which were significantly different from controls. In both the media and the adventitia the amount of type I collagen was drastically reduced as shown by quantitation of collagen and procollagen. Fibroblasts derived from the skin of the patient showed a normal content of type I and type III collagen. It is conceivable that the reduced content of type I collagen in the aortic wall is responsible for the weakness of the vessel wall causing formation of aneurysm and its sequelae.

Adult↗
PubMed1981

Osteogenesis imperfecta: biochemical and clinical evaluation of 13 cases.

Skin fibroblasts were cultured from 13 patients with Osteogenesis imperfecta and collagen biosynthesis was investigated in vitro. In those patients characterised by only mild manifestations of the disease, the ratio of collagen types I and III was disturbed. By contrast, fibroblasts obtained from patients with Osteogenesis imperfecta of a more severe type synthesised collagen types I/III in a normal ratio.

Adolescent↗
PubMed1981

Scleroderma fibroblasts: some aspects of in vitro assessment of collagen synthesis.

Fibroblasts were cultured from skin biopsies of patients with systemic sclerosis in different stages of the disease. In vitro synthesis of collagen was checked after a pulse with tritiated proline. The ratio between type I and type III collagen was normal in all patients. Six of seven cultures derived from patients in the active state showed an increased synthesis of collagen relative to other proteins. Addition of serum (normal and diseased) to the culture medium did not stimulate synthesis of collagen in any culture with normal collagen synthesis.

Adult↗
PubMed1981

[Defective type I collagen in a woman patient with juvenile idiopathic scoliosis (author's transl)].

The molecular causes of idiopathic scoliosis have not yet been clarified to any appreciable extent and are probably heterogeneous. The occurrence of scolioses in congenital diseases of the connective tissue points to changes in connective tissue metabolism. Collagen is the most essential structural connective tissue component of bone. It was the aim of our investigations to examine the synthesis of collagen of Types I and II in order to identify a possible molecular defect. In the woman patient examined by the authors, a pathologically changed alpha-chain of the collagen of Type I was found as the probable cause of this particular case of idiopathic scoliosis.

Adolescent↗
PubMed1981

Variability in collagen and fibronectin synthesis by scleroderma fibroblasts in primary culture.

Primary cultures of fibroblasts obtained from the papillary, reticular and subcutaneous layer of scleroderma skin were analyzed for protein synthesis by metabolic labeling and radioimmunoassays. Several of these cultures showed a 10- to 20-fold increase in the production of total protein and collagen as well as of fibronectin and type III procollagen as compared to cells from unaffected individuals. Most of the increases were noted in the reticular and subcutaneous layers. With cells from other patients increased synthesis was found in some of the explants or for only some of the products. The heterogeneity observed here could represent heterogeneity in the disease, in the cells studied or in the state of the disease at the time the cells were obtained.

Adult↗
PubMed1981

Disorder of collagen metabolism in a patient with osteogenesis imperfecta (lethal type): increased degree of hydroxylation of lysine in collagen types I and III.

Types I, II and III collagen were isolated from calvarium, skin and cartilage from a patient with recessive lethal osteogenesis imperfecta. the distribution of the various collagen types was normal in all three tissues. The alpha-chains were purified by molecular sieve and ion-exchange chromatography and were found to differ from the corresponding alpha-chains of age-matched controls only in that the alpha 1(I), alpha 2 and alpha 1(III) chains contained higher amounts of hydroxylysine with proportionally less lysine. alpha 1(II) was normal. The excess hydroxylysine residues were all glycosylated in the case of alpha 1(I) chains, but only partly so for the alpha 2 chains. Similar observations were made with collagen from fetuses at various stages of development. In these fetuses, however, the increase in the degree of hydroxylation of lysine in alpha 1(I), alpha 2 and alpha 1(III) varied with age, being highest in the youngest fetus. Seen in the context of embryonic development, the collagen of the patient would correspond to that of a fetus younger than 18 weeks, and one could speculate that the defect seen in this patient is the result of a disturbed process of maturation of connective tissue.

Autopsy↗
PubMed1980

Biochemical and immunological studies of fibroblasts derived from a patient with Ehlers-Danlos syndrome type IV. Demonstrate reduced type III collagen synthesis.

Fibroblasts derived from a skin biopsy of a patient with the Ehlers-Danlos syndrome (EDS) type IV were cultured in monolayer. The amount of collagen synthesized during a 24-h pulse was not different from that found with normal fibroblasts. Chromatographic procedures and immunofluorescence staining showed a normal synthesis of type I procollagen and collagen but a deficiency in synthesis of type III procollagen and collagen. This could be corroborated by radioimmuno assays showing a reduction in type III procollagen by about 90%. The secretion and degradation of collagens was not altered. The results demonstrate that the molecular defect in this particular patient is due to an impairment of the mechanism controlling the gene expression for type III procollagen.

Cells, Cultured↗
PubMed1980

Immunofluorescence analysis of collagen, fibronectin, and basement membrane protein in scleroderma skin.

Scleroderma skin and the subcutaneous tissue was studied by indirect immunofluorescence with specific antibodies against interstitial collagens and procollagens, against fibronectin and against the basement membrane proteins Type IV collagen and laminin. Staining for Type I procollagen and fibronectin was distinctly increased in the lower dermis and subcutaneous tissue. When compared with normal skin the data suggests that fibrosis may start around capillaries and in close proximity to adipose cells. Additional changes in the distribution to Type IV collagen and laminin were found in some patients and probably reflect the alterations in small blood vessels.

Adult↗
PubMed1980

Biosynthesis of two subunits of type IV procollagen and of other basement membrane proteins by a human tumor cell line.

The major collagenous component secreted into the medium of cultured HT-1080 tumor cells was identified as type IV procollagen by specific antibodies and characteristic ratios of incorporated labeled 3-hydroxyproline and 4-hydroxyproline. The disulfide-bonded molecules consisted of two subunits, pro-alpha 1(IV) and pro-alpha 2(IV) chains with apparent molecular weights of 180 000 and 165 000. No conversion of the procollagen to collagen or to procollagen intermediates was detected in the cell cultures. The two subunits apparently represent different gene products, since enzymatic digestion of the separated chains produced quite different peptide maps. Pepsin degraded native type IV procollagen successively into several fragments, some still disulfide-linked, giving rise to a complex set of polypeptide chains (Mr = 30 000-140 000). This agrees with similar diverse patterns produced by pepsin from authentic type IV collagens. The ratio between the pro-alpha 1(IV) and pro-alpha 2(IV) chains varied in several experiments between 1.3 and 1.8, suggesting that the two chains belong to different triple-helical molecules. The cells also produced distinct amounts of fibronectin (subunit Mr = 230 000) and of the basement membrane glycoprotein laminin. The latter showed three subunits with Mr = 220 000, 210 000, and 400 000. A further disulfide-bonded, non-collagenous polypeptide (Mr = 160 000) was detected but not yet identified. Immunofluorescence demonstrated these proteins within the cells but not in a pericellular matrix. The production of basement membrane components by HT-1080 cells and lack of interstitial collagens disagree with the original classification of the cell line as a fibrosarcoma.

Amino Acids↗
PubMed1980

[Influence of p-amino-benzoic acid on the hexachlorobenzene induced porphyria in the rat (author's transl)].

The effect of p-amino-benzoic (PAB) acid on the experimental hexachlorobenzene (HCB) induced hepatic porphyria of female Wistar rats was determined under different conditions: Neither a simultaneous HCB-PAB application (prophylactic administration) nor the PAB application after manifestation of the HCB-porphyria (therapeutic administration) influenced significantly the excretin of urinary porphyrins or precursors (porphobilinogen or 5-amino-levulinic acid). PAB application decreased the cytochrome P-450 content in the liver of the rats whereas HCB incuded enzymatic activity of this monooxygenase measured by the O-dealkylation of 7-ethoxycoumarin was not diminished by PAB application. The glycine concentration and the glycine content of rat livers were not decreased by the simultaneous HCB-PAB treatment in contrast to PAB controls. These findings are discussed and the conclusion is drawn that there might be different types of human porphyria cutanea tarda. The predominently exogenously induced PCT in men and the HCB induced porphyria in rats cannot be influenced by PAB application.

4-Aminobenzoic Acid↗