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21.
Trond P. Leren Kari Solberg Olaug K. Rødningen Oddveig Røsby Serena Tonstad Leiv Ose Kåre Berg 《Human genetics》1993,92(1):6-10
DNA from 40 unrelated familial hypercholesterolemia (FH) heterozygotes were subjected to analyses of single-strand conformation polymorphisms (SSCPs) of exon 10 of the low density lipoprotein receptor (LDLR) gene. Four different SSCP patterns were observed. The underlying mutations were characterized by DNA sequencing. Three of the patterns represented the three genotypes of a recently described sense mutation in codon 450. A method based upon the polymerase chain reaction (PCR) was developed to analyze this mutation. The frequencies of the wild-type (G at nucleotide 1413) and mutant (A at nucleotide 1413) alleles were 0.56 and 0.44, respectively. The fourth pattern was found in only one FH heterozygote and was caused by heterozygosity at nucleotide 1469 (G/A). Nucleotide 1469 is the second base of codon 469Trp(TGG). The GA mutation changes this codon into the amber stop codon, and is referred to as FH469Stop. The mutant receptor consists of the amino terminal 468 amino acids. Because the truncated receptor has lost the membrane-spanning domain, it will not be anchored in the cell membrane. FH469Stop destroys an AvaII restriction site, and this characteristic was used to develop a PCR method to establish its frequency in Norwegian FH subjects. Two out of 204 (1%) unrelated FH heterozygotes possessed the mutation. 相似文献
22.
Anthony John Pastore Alvaro Montoya Manasi Kamat Kari B. Basso James S. Italia Abhishek Chatterjee Maria Drosou Dimitrios A. Pantazis Alexander Angerhofer 《Protein science : a publication of the Protein Society》2023,32(1):e4537
Oxalate decarboxylase from Bacillus subtilis is a binuclear Mn-dependent acid stress response enzyme that converts the mono-anion of oxalic acid into formate and carbon dioxide in a redox neutral unimolecular disproportionation reaction. A π-stacked tryptophan dimer, W96 and W274, at the interface between two monomer subunits facilitates long-range electron transfer between the two Mn ions and plays an important role in the catalytic mechanism. Substitution of W96 with the unnatural amino acid 5-hydroxytryptophan leads to a persistent EPR signal which can be traced back to the neutral radical of 5-hydroxytryptophan with its hydroxyl proton removed. 5-Hydroxytryptophan acts as a hole sink preventing the formation of Mn(III) at the N-terminal active site and strongly suppresses enzymatic activity. The lower boundary of the standard reduction potential for the active site Mn(II)/Mn(III) couple can therefore be estimated as 740 mV against the normal hydrogen electrode at pH 4, the pH of maximum catalytic efficiency. Our results support the catalytic importance of long-range electron transfer in oxalate decarboxylase while at the same time highlighting the utility of unnatural amino acid incorporation and specifically the use of 5-hydroxytryptophan as an energetic sink for hole hopping to probe electron transfer in redox proteins. 相似文献
23.
Maternal origin of nucleated erythrocytes in peripheral venous blood of pregnant women 总被引:3,自引:0,他引:3
Anna Slunga-Tallberg Wa'el El-Rifai Mauri Keinänen Kari Ylinen Tapio Kurki Katherine Klinger Olavi Ylikorkala Sakari Knuutila 《Human genetics》1995,96(1):53-57
We studied the origin of nucleated red blood cells (NRBC) in peripheral venous blood samples from 40 pregnant women carrying a male fetus, using a technique that allows direct chromosomal analysis by in situ hybridisation on immunologically and morphologically classified cells. Samples from ten nulligravid women were studied as controls. NRBC were enriched by negative magnetic activated cell sorting (miniMACS) using anti-CD45 monoclonal antibody. NRBC were detected by alkaline phosphatase anti-alkaline phosphatase immunostaining using a monoclonal anti-glycophorin A antibody. The origin of the NRBC was determined by fluorescence in situ hybridisation using X and Y specific probes. NRBC were found in 37 of the 40 pregnant women at a range of 1 to 230 per 20 ml of venous blood and in 6 of the 10 controls at a range of 1 to 3 per 20 ml of venous blood. All NRBC detected in the pregnant women were evidently of maternal origin, and in the pregnant women the number of NRBC was significantly higher (P < 0.05) than in the controls. Pregnancy per se seems to induce the appearance of maternal NRBC in the circulation, and it cannot therefore be assumed that NRBC isolated from the maternal blood are of fetal origin on the basis of morphology alone. Discrimination of fetal NRBC must occur for prenatal diagnosis of fetal genetic disorders. 相似文献
24.
Ecomorphological correlates in ten species of subtropical seagrass fishes: diet and microhabitat utilization 总被引:6,自引:0,他引:6
Philip J. Motta Kari B. Clifton Patricia Hernandez Bradley T. Eggold 《Environmental Biology of Fishes》1995,44(1-3):37-60
Synopsis Ecomorphological correlates were sought among ten species of distantly related subtropical seagrass fishes. Morphometric data associated with feeding and microhabitat utilization were compared by principal components analysis, cluster analysis, and canonical correspondence analysis to dietary data. Morphology was generally a poor predictor of diet except for a group of mid-water planktotrophic filter feeders. Separation of the species along morphological axes appears to be related more to microhabitat utilization resulting in three major groups: (1) a group of planktotrophic, mid-water fishes specialized for cruising and seeking out evasive prey characterized by a compressed fusiform body, forked caudal fin, long, closely spaced gill rakers, short to intermediate! length pectoral fin, pointed pectoral fin, large lateral eye, short head, and a terminal or subterminal mouth; (2) slow swimming, less maneuverable epibenthic fishes that pick or suck their prey off the substrate. They are united by more rounded caudal and pectoral fins, and short or no gill rakers; and (3) a group of more mobile and maneuverable epibenthic foragers characterized by a more compressed, sub-gibbose body, long, pointed pectoral fins, forked caudal fins, large lateral eyes, subterminal mouth, and greater jaw protrusibility. Cases of convergence in trophic and microhabitat utilization characters were apparent in some of the groups. 相似文献
25.
Albert de la Chapelle Christina Kari Markku Nurminen Sven Hernberg 《Human genetics》1977,37(2):183-194
Summary An epidemic of agranulocytosis and granulocytopenia occurred in 1975 in conjunction with clozapine treatment of mental patients in Finland. An attempt was made to assess the epidemiologic and genetic factors contributing to the adverse drug effect. The estimated incidence rate in Finland was 2.1/1000 patient-months. This figure could not be compared with rates from other countries because of the inexact nature of the figures reported so far. All 16 cases occurred in seven hospitals in southwestern Finland, whereas the overall hospital net use of the drug was geographically evenly distributed. The difference between the observed and the proportionally expected incidence of cases amongst the hospitals where clozapine was used was statistically significant. The average consumption of the drug did not differ between the hospitals where cases occurred and those where no definite cases could be diagnosed. Six-generation pedigree analyses failed to reveal significant parental consanguinity or genetic kinship between probands. Neither did the birth places of the ancestors of the probands disclose a typical isolate pattern. In conclusion, the cases appeared to be confined to a few hospitals in southwestern Finland. Although a genetic factor is not excluded, we found no evidence in support of a genetic mechanism. 相似文献
26.
We have investigated methionine adenosyltransferase activity (MAT) in extracts of a variety of normal and malignant human tissues and cultured cell lines. MAT activity assayed from 17 different cultured cell lines varied to a great extent. Ramos (human, Burkitt's lymphoma) and EL4 (mouse, T cell lymphoma) cell showed MAT activity near 300 pmol/mg per min. Daudi (human, Burkitt's lymphoma) and almost all monolayer cells had MAT activity below 100 pmol/mg per min. Human peripheral blood lymphocytes had MAT activity of 36 pmol/mg permin. The MAT activity of the cell lines can be related to doubling time: cell lines with short doubling times have much higher MAT activity than other cell lines. A large variation in MAT activity in different human tissues was observed. In autopsy samples MAT activity was highest in the brain and in the colon. Malignant tissue samples gave much higher MAT activity than normal tissues. Lung cancer (carcinoma squamocellulare pulmonis) had MAT activity of 30.7 pmol/mg per min, while in normal lung it was 2.4 pmol/mg per min. 相似文献
27.
Turnover of prolyl hydroxylase tetramers and the monomer-size protein in chick-embryo cartilaginous bone and lung in vivo 总被引:1,自引:0,他引:1
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Kari Majamaa Eeva-Riitta Kuutti-Savolainen Leena Tuderman Kari I. Kivirikko 《The Biochemical journal》1979,178(2):313-322
The turnover of prolyl hydroxylase and an immunoreactive protein that corresponds in size to the smaller subunit of the enzyme was studied in vivo after injection of [(3)H]leucine into 11-day chick embryos. The specific radioactivity and total radioactivity of the monomer-size protein were much higher than those of the enzyme tetramers in the cartilaginous bone at 3h and 12h after the radioisotope injection, indicating that the monomer-size protein represents precursors rather than degradation products of the enzyme tetramers. Between 24 and 144h after the injection the specific radioactivity and total radioactivity of the two forms of the enzyme protein showed essentially identical decay rates, the observed specific radioactivity of the monomer-size protein being about 120-130% and total radioactivity about 80% of that of the enzyme tetramers. The true half-life, when corrected for dilution caused by tissue growth and re-utilization of the [(3)H]leucine, was 37.9h for the monomer-size protein and 39.0h for the tetramers. The results obtained in the lung were less reliable owing to high blank radioactivity values in the immunoprecipitation, but even so some definite differences were found between this tissue and the cartilaginous bone. The specific radioactivity of both forms of the enzyme protein at 24h was only about 20-25% of that in the cartilaginous bone. The total radioactivity of the monomer-size protein in the lung remained about 5 times that of the enzyme tetramers, whereas it was only about 0.8 times that of the tetramers in the cartilaginous bone. As in the cartilaginous bone, the decay rates of both forms of the enzyme protein were essentially identical in the lung, with a true half-life of about 46h. The results suggest that the rate of prolyl hydroxylase synthesis is slower in the lung than in the cartilaginous bone, whereas the degradation rates are fairly similar in these two tissues. The data further suggest that, in the lung at least, a large part of the monomer-size protein became degraded without being converted into enzyme tetramers. 相似文献
28.
Kari Hemminki 《Molecular and cellular biochemistry》1975,8(2):123-128
Kinetics of incorporation of (3H) uridine into cytoplasmic RNA fractions of rat liver is investigated. The fractions include free and membrane bound polysomes, rough membranes sedimenting with mitochondria and free cytoplasmic RNA particles. (1) Poly(A) containing RNA, isolated by oligo-dT cellulose, amounts to 0.4% of the total RNA in the homogenate, 0.5% in bound polysomes, 3.4% in free polysomes and 16% in free cytoplasmic RNA particles. (2) The rate of (3H) uridine incorporation into RNA lacking poly(A) proceeds uniformly in all subcellular fractions except for free cytoplasmic RNA particles, which accumulate negligible amounts of radioactivity. (3) The initial labelling of RNA containing poly(A) is most active in free cytoplasmic RNA particles supporting their identity as mRNA en route to polysomes. The initial specific radioactivities decrease in the following order: homogenate, bound polysomes, rough membranes sedimenting with mitochondria, free polysomes. The data suggest that mRNA is supplied to free and membrane-bound polysomes via different routes. The kinetic analysis indicates that free cytoplasmic RNA particles may be a precursor of mRNA of free polysomes rather than that of bound polysomes. (4) The kinetic differences of free and membrane bound polysomes are also demonstrated by comparing the radioactivity of RNA containing poly(A) to the total radioactivity at various incorporation times. In bound polysomes this decreases from 31% at 1 h to 10% at 25 h, whereas in free polysomes the corresponding ratio increases from 10 to 13%. RNA containing poly(A) of free cytoplasmic RNA particles represents 64% of the total radioactivity throughout the experiment. 相似文献
29.
30.
Saharinen P Eklund L Miettinen J Wirkkala R Anisimov A Winderlich M Nottebaum A Vestweber D Deutsch U Koh GY Olsen BR Alitalo K 《Nature cell biology》2008,10(5):527-537
The receptor tyrosine kinase Tie2, and its activating ligand Angiopoietin-1 (Ang1), are required for vascular remodelling and vessel integrity, whereas Ang2 may counteract these functions. However, it is not known how Tie2 transduces these different signals. Here, we show that Ang1 induces unique Tie2 complexes in mobile and confluent endothelial cells. Matrix-bound Ang1 induced cell adhesion, motility and Tie2 activation in cell-matrix contacts that became translocated to the trailing edge in migrating endothelial cells. In contrast, in contacting cells Ang1 induced Tie2 translocation to cell-cell contacts and the formation of homotypic Tie2-Tie2 trans-associated complexes that included the vascular endothelial phosphotyrosine phosphatase, leading to inhibition of paracellular permeability. Distinct signalling proteins were preferentially activated by Tie2 in the cell-matrix and cell-cell contacts, where Ang2 inhibited Ang1-induced Tie2 activation. This novel type of cellular microenvironment-dependent receptor tyrosine kinase activation may explain some of the effects of angiopoietins in angiogenesis and vessel stabilization. 相似文献