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B Wiman

Publications and source records attributed to B Wiman.

126 records · Page 7Linked to original sources
PubMed1975

Amino-acid sequence of the cyanogen-bromide fragment from human plasminogen that forms the linkage between the plasmin chains.

The complete amino acid sequence of a cyanogen bromide fragment (122 residues) obtained from plasminogen is described. This fragment forms the overlap between heavy (A) and light (B) chains of human plasmin. The particular arginyl-valyl bond cleaved in the second step of the activation process is shown to be Arg98-Val99 in this fragment. This site is not very similar to the one in the NH2-terminal part of the molecule (Arg68-Met69). Remarkable homologies with the 'triple loops' ('kringle structures') found in the non-thrombin part of prothrombin are demonstrated. Homologies occurred during evolution of this chain.

Amino Acid Sequence↗
PubMed1975

On the primary structure of human plasminogen and plasmin. Purification and characterization of cyanogen-bromide fragments.

Most of the cyanogen bromide fragments obtained from human plasminogen and plasmin have been purified using combinations of gel filtration and ion-exchange chromatography. The purified fragments have been characterized by molecular weight determination (dodecyl sulphate electrophoresis), amino acid analysis, carbohydrate analysis and direct NH2-terminal amino acid sequence determination. Since some of the purified fragments were compounds with uncompletely cleaved methionyl bonds it was possible to clarify the organization of most of the cyanogen bromide fragments in the plasminogen molecule. The fragment containing the arginyl-valyl bond cleaved during the second step of the activation process is further identified. It is also shown that the microheterogeneity that normally exists in human plasminogen probably has its origin in several sites. One such site is situated in the light (B) chain of plasmin, while another is situated in the carboxyterminal part of the heavy (A) chain. Neither of these sites seems to contain sialic acid.

Amino Acid Sequence↗
PubMed1975

Structural relationship between "glutamic acid" and "lysine" forms of human plasminogen and their interaction with the NH2-terminal activation peptide as studied by affinity chromatography.

Urokinase digestion of maleinated plasminogen results in cleavage of the single peptide bond Arg-68-Met-69, which is one of the bonds normally cleaved during the first step of the activation procedure. The inactive intermediate compound formed in this way was subjected to NH2-terminal amino acid sequence analysis, which clearly demonstrates the structural relationship between the forms of plasminogen with different NH2-terminal amino acids. It is thus shown that lysine-78 and valine-79 in the "glutamic acid" plasminogen actually are the NH2-terminal amino acids in "lysine" and "valine" plasminogen respectively. The forms with glutamic acid in NH2-terminal position are called plasminogen A, while all other forms lacking the NH2-terminal part of the molecule and which can be activated in a single step are called plasminogen B. By affinity chromatographic studies of the NH2-terminal activation peptide on insolubilized plasminogen B, it was demonstrated that this peptide has specific affinity for plasminogen B. It was also shown that this noncovalent interaction is broken by 6-aminohexanoic acid in two concentration. The tryptic heptapeptide (Ala-Phe-Gln-Tyr-His-Ser-Lys) which occupies the positions number 45 to 51 in the NH2-terminal activation peptide (as well as in the intact plasminogen molecule) is importance for the conformational state of the plasminogen molecule.

Amino Acid Sequence↗
PubMedDate not supplied

Secretion of plasminogen activator inhibitor-1 from cultured human umbilical vein endothelial cells is induced by very low density lipoprotein.

Clinical studies have demonstrated an impaired fibrinolytic function in patients with angiographically ascertained coronary artery disease or previous myocardial infarction. This decreased fibrinolytic function is to a major extent explained by the presence of high plasma levels of plasminogen activator inhibitor-1 (PAI-1) and is most common in patients with hyperlipoproteinemias type IIB and IV. To further investigate the association between hypertriglyceridemia and elevated plasma levels of PAI-1, cultured human umbilical vein endothelial cells were exposed to purified lipoproteins isolated from normo- and hypertriglyceridemic (NTG and HTG) individuals. We found that very low density lipoprotein (VLDL) from both NTG and HTG subjects stimulated the secretion of PAI-1 from endothelial cells in a dose-dependent manner. HTG-VLDL at a concentration of 100 micrograms/ml gave rise to a 73% increase in PAI-1 secretion as compared to control cultures, whereas NTG-VLDL only gave rise to a 30% increase (p less than 0.05), indicating that HTG-VLDL is a more potent stimulus to PAI-1 secretion than is NTG-VLDL. Experiments in which endothelial cells were exposed to VLDL subfractions indicated that large VLDL particles, in particular, induce PAI-1 release. Binding experiments demonstrated a specific cellular binding of both NTG- and HTG-VLDL to the cells, but HTG-VLDL bound about four times more effectively than NTG-VLDL. Exposure of the endothelial cells to an LDL receptor antibody was found to block 75% (p less than 0.005) of the VLDL-induced secretion of PAI-1 from the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMedDate not supplied

Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity.

Plasminogen activator inhibitor-1 (PAI-1), a rapid inhibitor of tissue-type plasminogen activator, has been shown to be an independent risk factor for recurrent myocardial infarction (MI) at a young age. To investigate whether genetic variation in the PAI-1 gene is affecting plasma PAI-1 levels, a sample of 145 patients with an MI before the age of 45 years was genotyped for two polymorphisms at the PAI-1 locus, together with a sample of 95 healthy individuals of a similar age. All individuals were measured for plasma PAI-1 levels as well as for other fibrinolytic and metabolic risk indicators. A HindIII restriction fragment length polymorphism (RFLP) was used in this study in conjunction with a previously unreported eight-allele dinucleotide repeat polymorphism at the PAI-1 locus. The dinucleotide repeat polymorphism and HindIII RFLP were in strong linkage disequilibrium. There was no difference in the frequency of alleles of either polymorphism between patient and control groups. However, the smaller dinucleotide repeat alleles were significantly associated (p = 0.03) with higher plasma PAI-1 levels in the patient sample. This association was also apparent in the control sample but not at significant levels. Differences in regression coefficients for the effect of triglycerides on plasma PAI-1 levels suggest that triglyceride regulation of PAI-1 is genotype specific. Our data suggest that genetic variation at this locus contributes to between-individual differences in the level of plasma PAI-1, which is important in fibrinolysis and the pathogenesis of MI.

Adult↗
PubMedDate not supplied

Angiostatin fragments in urine from patients with malignant disease.

Angiostatin, a family of fragments originating from the NH2-terminal portion of plasminogen, has been described as a potent inhibitor of angiogenesis. In order to examine to what extent angiostatin can be detected in cancer patients, urine was collected from 117 patients with different types of malignancies and subjected to Western blot analysis, utilizing antibodies raised against "kringles" 1-3 in plasminogen. A heterogeneous mixture of fragments was observed, with patterns that also varied between patients. Angiostatin fragments were quantified by densitometric scanning. The concentrations were 27 +/- 75 (SD) micrograms L-1 (range, 1-565 micrograms L-1) in urine from cancer patients, as compared to 3 +/- 2 (SD) micrograms L-1 (range, 1-10 micrograms L-1) in urine from healthy individuals. Thirty-three patients (28%) had elevated levels using a cut off level at 15 micrograms L-1 (clearly above the highest level obtained among control subjects). NH2-terminal amino acid sequence analysis of purified angiostatin fragments from one patient showed a heterogeneous pattern, but were consistent with the region between the preactivation peptide in plasminogen and "kringle" 1, as expected. Several of the patients with urinary angiostatin showed signs of poor kidney function. We conclude that angiostatin can be detected in urine from cancer patients, but at present, the clinical significance of this finding is unclear.

Albuminuria↗