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K Tryggvason

Publications and source records attributed to K Tryggvason.

227 records · Page 13Linked to original sources
PubMed1978

Heterogeneity of pepsin-solubilized human glomerular basement membrane collagen.

The collagen component of isolated glomerular basement membrane ws solubilized by limited pepsin digestion and further purified. The amino acid and carbohydrate composition of the final material was very similar to that described for the alpha1-chains of type IV collagen. However, the presence of several components was detected when the material was analyzed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis either without or after reduction. The molecular weights of the major components in the reduced material were about 140,000, 100,000, 80,000 and less than 65,000 (in the case of five components). The data thus do not support the previous suggestion that the human glomerular basement membrane contains only one type of collagen polypeptide chain. However, part of the heterogeneity may be due to the presence of more than one collagenous part in a procollagen-type polypeptide chain, and an additional reason may lie in a partial degradation of collagenous portions during pepsin digestion.

Adolescent↗
PubMed1978

Morphometric studies on glomeruli in the congenital nephrotic syndrome.

Morphometric studies were performed on glomeruli in two kidneys of a 13-month-old patient with congenital nephrotic syndrome of the Finnish type (CNF) and two control kidneys from an 11-month-old child. The mean diameter of the glomeruli in the diseased kidneys was abnormally large for the patient's age and the mean glomerular volume about twice the normal. The number of glomeruli, counted using a statistico-geometrical method, was 74% higher than in the control kidneys, a finding which is in accordance with a previous result obtained using a different counting method. The total glomerular volume per kidney in the CNF patient was about 3 times the normal for that age, almost equalling that in a 7-year-old individual.

Finland↗
PubMed1977

Prolyl 3-hydroxylase: partial characterization of the enzyme from rat kidney cortex.

The formation of 3-hydroxyproline was studied with crude rat kidney cortex extract as a source of enzyme and chick embryo tendon protocollagen and procollagen or cartilage protocollagen as a substrate. Synthesis of 3-hydroxyproline was observed with all these substrates and the formation of 3-hydroxyproline ranged up to seven residues per pro-alpha-chain. The highest rate of 3-hydroxylation took place at 20 degrees C and the reaction required Fe2+, O2,2-oxoglutarate and ascorbate. The formation of 3-hydroxyproline was affected by chain length and the conformation of the substrate, in that longer polypeptide chains proved better substrates, while the native triple-helical conformation of protocollagen or procollagen completely prevented the reaction. Formation of 3-hydroxyproline with tendon procollagen as a substrate was not inhibited by antiserum to prolyl 4-hydroxylase or by poly(L-proline) when these substances were used in concentrations which clearly inhibited 4-hydroxyproline formation with tendon protocollagen as a substrate. Furthermore, pure prolyl 4-hydroxylase did not synthesize any 3-hydroxyproline under conditions in which the crude rat kidney cortex enzyme would readily do so. The data thus strongly suggest that prolyl 3-hydroxylase and prolyl 4-hydroxylase are separate enzymes.

Animals↗
PubMed1977

Composition of the glomerular basement membrane in the congenital nephrotic syndrome of the Finnish type.

The composition of the glomerular basement membrane (GBM) was studied in three patients with the congenital nephrotic syndrome of the Finnish type (CNF). A decrease was found in the relative amounts of amino acids characteristic of collagen, i.e. 3-hydroxyproline, 4-hydroxyproline, hydroxylysine and glycine. The decrease of hydroxyproline was also apparent in the ratio of 4-hydroxyproline to proline and in direct assays of 4-hydroxyproline in whole glomeruli. The ratio of 3-hydroxyproline to 4-hydroxyproline was decreased by about 40%. Slight increases were found in the amounts of some amino acids. No significant change was found in the glucose content of the GBM whereas the galactose content was slightly decreased. The results suggest a decrease in the relative amount of the collagen component in the GBM of CNF patients, but a decrease in the relative amount of 3-hydroxyproline indicates that other changes also exist.

Amino Acids↗
PubMed1975

Number of nephrons in normal human kidneys and kidneys of patients with the congenital nephrotic syndrome. A study using a sieving method for counting of glomeruli.

A method of graded sieving for counting of glomeruli in removed kidneys is described. The number of nephrons (glomeruli) in six normal kidneys deriving from sutopsies of three children 22-73 months of age was 1.82 plus or minus 0.35 times 10-6. The results give a little higher number than most previous studies with which they are compared. In the kidneys of two 10- and 15-month-old patients with the congenital nephrotic syndrome of the Finnish type the mean number of nephrons was 3.17 plus or minus 0.52 times 10-6 which is on the average 73% higher than in the normal kidneys studied. The number of nephrons in kidneys of five other patients showed an average of at least 3.42 plus or minus 0.30 times 10-6 the counting method being a little different. The unusually high number of nephrons in CNF kidneys seems to be fully evident.

Child, Preschool↗
PubMedDate not supplied

Laminin-5 gamma 2 chain as an invasivity marker for uni- and multifocal lesions in the lower anogenital tract.

During recent decades it has become apparent that there are two types of vulvar disease: the classic type found in elderly women with unicentric and unifocal lesions, and the type found in younger women, in which precancerous and invasive changes develop in the anogenital lower tract in a multicentric and multifocal fashion, often over a long period of observation. The laminin-5 gamma 2 chain is an extracellular protein that is a component of the basement membrane. Recently its expression has been recognized as a marker in cervical cancer that permits identification of invasive capacity. The aim of our study was to determine if laminin-5 gamma 2 chain antibody can act as a sensitivity marker of invasive capacity in precancerous and invasive carcinoma in women with uni- and multifocal changes in the anogenital tract. The result showed that all patients in the older group of women with invasive carcinoma of the vulva had moderate to high positive expression of the laminin-5 gamma 2 chain. In the group of younger patients with multifocal precancerous changes observed over long periods, most of the patients with vulva intraepithelial neoplasia (VIN) 3 showed laminin-5 gamma 2 chain positivity already in the precancerous changes, and all of them developed invasivity during the period of observation. Normal epithelium without atypia was mostly negative or of low immunoreactivity of laminin-5. In conclusion, positive laminin-5 gamma 2 chain expression seems to indicate the invasiveness potential of precancerous lesions and is also expressed in all investigated invasive carcinomas of the anogenital tract.

Adult↗
PubMedDate not supplied

Gain of chromosome 3q is an early and consistent genetic aberration in carcinomas of the vulva.

The aim was to determine whether specific gains of chromosome 3q and laminin-5gamma2-chain expression can improve early detection of invasive capacity in precancerous and squamous cell carcinoma of the vulva (VSCC). Six VSCC and three precancerous lesions were studied. Multicolor fluorescence in situ hybridization (FISH) probe sets were applied to nuclei suspensions prepared from archival material using the Hedley method. The probe panel consists of the centromers of chromosome 7, chromosome 3, and the TERC gene residing on the long arm of chromosome 3. Laminin-5gamma2-chain immunohistochemical analysis was performed on corresponding specimens and was expressed only in the VSCC. The genome-specific FISH analysis revealed 3q amplification in 43% of the nuclei analyzed for the VSCC and 22% of the nuclei for the precancerous lesions. Low-level 3q amplifications were found in precancerous lesions with an average fold increase of 1.15 for 3q. The invasive lesions showed higher average fold increases for 3q, averaging 1.32. Laminin-5gamma2-chain protein was expressed only in VSCC, whereas 3q gains were observed both in precancerous lesions and in VSCC, indicating that gain of chromosome 3q is an early and consistent event during carcinogenesis of VSCC.

Adult↗
PubMedDate not supplied

Animal models of Alport syndrome: advancing the prospects for effective human gene therapy.

Several animal models for Alport syndrome have been described. These are available for studies on the pathogenetic mechanisms of the disease, as well as for the development of new technologies for gene therapy in this progressive hereditary kidney disease. This review summarizes current knowledge on the molecular basis of Alport syndrome, and on the animal models which all remarkably well resemble the human disease. Recent work aimed at the development of gene therapy, including hurdles and progress are discussed.

Animals↗
PubMedDate not supplied

Plasminogen activators and steroid receptor concentrations in normal, benign, and malignant breast and ovarian tissues.

The plasminogen activator (PA) activity and oestrogen and progestin receptor concentrations were determined in normal, benign and malignant tissues of human breast and ovary. The geometric mean of PA activity was significantly higher (p less than 0.05) in malignant than in normal breast tissue specimens. PA activity was also higher in benign breast tumours than in normal tissue, but lower than in malignant tumours. The geometric means of PA activity in normal, benign and malignant ovarian tissue specimens differed even more clearly (analysis of variance: p less than 0.001). There was no significant correlation between PA activity and cytosol oestrogen or progestin receptor concentrations in either breast or ovarian cancer tissues. Our data confirm the finding that increased tissue PA activity is associated with human malignant breast tumours, compared with normal tissue and benign mammary lesions, and show that a similar situation prevails in human ovarian tissues. In addition, they show that the possible female sex steroid dependency of PA activity in human breast and ovarian malignancies cannot be demonstrated by cytosol receptor assays alone.

Breast Neoplasms↗