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S Terukina

Publications and source records attributed to S Terukina.

At least 19 recordsLinked to original sources
PubMed1990

Delayed intermolecular gamma-chain cross-linking by factor XIIIa in fibrinogen Asahi characterized by a gamma-Met-310 to Thr substitution with an N-glycosylated gamma-Asn-308.

In an abnormal fibrinogen with gamma-Met-310 to Thr substitution accompanied by an extra oligosaccharide attached to gamma-Asn-308, factor-XIIIa-mediated intermolecular gamma-dimer formation of fibrin was found to be markedly delayed. The delayed gamma-dimer formation was not due to impaired fibrin polymerization because the fibrinogen gamma-chain also failed to be efficiently cross-linked by factor XIIIa. Since fluorescent amine was normally incorporated into the abnormal gamma-chain by factor XIIIa, we conclude that the abnormal molecules were unable to align their gamma-chains in an anti-parallel fashion because of inaccessibility of the molecules with a profoundly perturbed conformation near the carboxyl terminal region of the gamma-chain included in the D domain.

Fibrinogen↗
PubMed1989

A monoclonal antibody that triggers deacylation of an intermediate thrombin-antithrombin III complex.

Upon incubation of antithrombin III with thrombin in the presence of a monoclonal antibody recognizing an epitope exposed on the heavy chain part of thrombin-cleaved two-chain antithrombin III, antithrombin III was preferentially cleaved by the enzyme as a substrate, rather than covalently complexed with the enzyme to form an equimolar, stable acyl complex. Once the stable acyl complex was formed between the enzyme and antithrombin III, however, no further liberation of two-chain antithrombin III was observed. Kinetic studies showed that heparin does not affect this reaction, although generation of thrombin-cleaved two-chain antithrombin III is apparently accelerated in accordance with the rate constant for heparin-enhanced thrombin-antithrombin III complex formation. Here we propose the term "switching antibody" for an antibody that triggers deacylation of an intermediate enzyme-inhibitor complex by switching the enzyme-inhibitor reaction from the major pathway of stable acyl complex formation to an alternative pathway of cleavage of the inhibitor as a substrate.

Antibodies, Monoclonal↗
PubMed1989

A gamma methionine-310 to threonine substitution and consequent N-glycosylation at gamma asparagine-308 identified in a congenital dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen Asahi.

In an abnormal fibrinogen with severely impaired polymerization of fibrin monomers, we identified a methionine-to-threonine substitution at position 310 of the gamma chain. Furthermore, asparagine at position 308 was found to be N-glycosylated due to a newly formed consensus sequence, asparagine(308)-glycine(309)-threonine(310). The two structural defects in the mutant gamma chain may well perturb the conformation required for fibrin monomer polymerization that is specifically assigned to the D domain of fibrinogen. This alteration also seems to affect the intermolecular gamma chain cross-linking of fibrin and fibrinogen, although the amine acceptor gamma glutamine-398 was found to function normally. These functional abnormalities may well be related to posttraumatic hemorrhage as observed in a 33-yr-old man with moderate hemorrhagic diathesis related to injuries since his early adolescence. The structure of the extra carbohydrate moiety attached to asparagine-308 was found to be identical with those derived from the normal B beta and gamma chains as evidenced by HPLC.

Adult↗
PubMed1989

Fibrinogen Sapporo: dysfibrinogenemia characterized by the replacement of A alpha arginine-16 by histidine resulting in the delayed release of fibrinopeptide A by thrombin.

Congenital dysfibrinogenemia was found in a 60-year-old asymptomatic female and her daughter. Purified fibrinogen derived from the propositus, apparently a heterozygote for the abnormality, characteristically showed delayed but complete release of fibrinopeptide A upon digestion with thrombin but its defective release by Ancrod, a snake venom enzyme, from half of her fibrinogen molecules. This congenital dysfibrinogenemia with an A alpha arginine (Arg) to histidine (His) substitution was tentatively designated as fibrinogen Sapporo. Although this type of abnormal fibrinogen had been identified among Caucasians, no such cases have so far been reported in Japan.

Female↗
PubMed1989

Fibrinogen Kyoto III: a congenital dysfibrinogen with a gamma aspartic acid-330 to tyrosine substitution manifesting impaired fibrin monomer polymerization.

A congenital dysfibrinogen characterized by impaired fibrin monomer polymerization was found in an asymptomatic 50-year-old woman and her two sons. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) run according to the method of Laemmli, we noticed two gamma chain species in fibrinogen and its plasmic fragments D1 and D2, consisting of a normal species and an apparently lower molecular weight (mol wt) variant in respective fractions. However, in fragment D3 only a single gamma chain remnant was observed. By chromatofocusing of the plasmic-CaCl2 digests of the abnormal fibrinogen, we separately isolated the normal and abnormal D1 species, the latter having been eluted in a slightly higher pH range. As expected, the abnormal D1 species failed to interfere with thrombin clotting of normal fibrinogen and normal fibrin monomer polymerization, whereas the normal D1 species inhibited them markedly. By analyzing the lysyl endopeptidase digests of the isolated gamma chain, we identified a replacement of aspartic acid by tyrosine at position 330 of the mutant gamma chain. The point mutation from an aspartic acid (pK for the beta-carboxyl = 3.86) to a tyrosine (pK for the aromatic hydroxyl = 10.07) may have perturbed the folding gamma chain structure in the D domain of fibrinogen specifically required for polymerization.

Amino Acid Sequence↗
PubMed1988

Normal plasmic cleavage of the gamma-chain variant of "fibrinogen Saga" with an Arg-275 to His substitution.

We have identified a gamma-Arg-275 to His substitution in an abnormal fibrinogen designated as "fibrinogen Saga" characterized by impaired fibrin monomer polymerization. By chromatofocusing chromatography, we isolated normal and abnormal fragment D1 populations separately from the plasmic-calcium digests of fibrinogen derived from the propositus, a heterozygote for the abnormality. We found that both normal and abnormal fragment D1's were similarly protected from digestion by plasmin in the presence of calcium ions and further degraded to fragments D2 and D3 due to cleavage of the gamma-chain remnant when calcium ions were replaced by chelating agents. Abnormal fragment D1 failed to inhibit both thrombin-clotting of normal fibrinogen and polymerization of normal fibrin monomer, while normal D1 exhibited marked inhibitory activities. In an aberrant peptide comprising residues gamma-274-302 isolated by HPLC from the lysyl endopeptidase-digests of abnormal fragment D1, we identified a His substituting for an Arg at position 2, which corresponds to position 275 of the mutant gamma-chain.

Adolescent↗
PubMed1988

Substitution of gamma Arg-275 by Cys in an abnormal fibrinogen, "fibrinogen Osaka II". Evidence for a unique solitary cystine structure at the mutation site.

In an abnormal fibrinogen with impaired fibrin monomer polymerization designed as fibrinogen Osaka II, we have identified substitution of Arg by Cys at position 275 of the gamma chain. This Cys is linked to a free cysteine molecule by a disulfide link as evidenced by fast atom bombardment mass spectrometry. This finding was supported by identification of a single cysteine released from isolated abnormal fragment D1 upon reduction. This unique cystine structure at the mutation site has not been reported heretofore in any abnormal protein including fibrinogen. The substitution may well perturb the structure required for fibrin monomer polymerization, specifically that assigned to the carboxyl-terminal D domain of fibrinogen. Indeed, isolated fragment D1 with the Cys substitution failed to inhibit thrombin-mediated clotting of normal fibrinogen and normal fibrin monomer polymerization, while normal fragment D1 inhibited them markedly. Our data seem to provide supporting evidence that the putative polymerization site(s) assigned to the D domain of fibrinogen may be structure-dependent, including the carboxyl-terminal segment of the gamma chain as well as a contiguous region that contains the gamma 275 residue.

Adolescent↗
PubMed1988

Characterization of an apparently lower molecular weight gamma-chain variant in fibrinogen Kyoto I. The replacement of gamma-asparagine 308 by lysine which causes accelerated cleavage of fragment D1 by plasmin and the generation of a new plasmin cleavage site.

Congenitally abnormal fibrinogen Kyoto I with impaired fibrin monomer polymerization contains a normal gamma-chain and a gamma-chain variant (gamma Kyoto I) that has an apparently lower Mr on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the Laemmli system (Laemmli, U. K. (1970) Nature 227, 680-685) but migrates with apparently normal Mr in the Weber and Osborn system (Weber, K., and Osborn, M. (1969) J. Biol. Chem. 244, 4406-4412). Reverse-phase high performance liquid chromatographic analyses of the cyanogen bromide or lysyl endopeptidase cleavage fragments of the purified gamma-chains of fibrinogen Kyoto I showed the presence of peptides not seen from normal fibrinogen. Amino acid sequence analysis of these peptides indicated that gamma Asn308 of the gamma-chain variant is replaced by lysine. Purified fragment D1 of fibrinogen Kyoto I also contains two types of D1 gamma-remnants: normal and apparently lower Mr types. Abnormal fragment D1 is cleaved faster to fragments D2 and D3 by plasmin in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) than normal fragment D1, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by immunoblotting using anti-gamma-chain monoclonal antibody. Analysis of peptides released from fragment D1 by plasmin in the presence of EGTA demonstrated the cleavage of the gamma Lys308-Gly309 bond. Fragment D1 of fibrinogen Kyoto I has normal calcium binding properties. The data suggest that a region or conformation containing gamma Asn308 affects the polymerization of fibrin monomers and that the gamma Asn308----Lys replacement causes a conformational change in the gamma-chain which results in the accelerated cleavage of gamma Lys356-Ala357 and gamma Lys302-Phe303 bonds by plasmin and also results in the generation of a new plasmin cleavage site between Lys308 and Gly309 in the presence of EGTA. During these studies, we found that part of the gamma Lys212-Glu213 bond in fragment D1 is cleaved by plasmin in the presence of EGTA.

Amino Acid Sequence↗
PubMed1987

Fibrinogens Kawaguchi and Osaka: an amino acid substitution of A alpha arginine-16 to cysteine which forms an extra interchain disulfide bridge between the two A alpha chains.

Structural analyses of fibrinogens from patients with congenital dysfibrinogenemia, designated as fibrinogens Kawaguchi and Osaka, have been performed to identify the difference responsible for the lack of fibrinopeptide A release. For the structural studies, a new strategy was employed. Amino acid sequence analysis of one of the lysyl endopeptidase-peptides isolated from the abnormal fibrinogens indicated that in both fibrinogens, arginine-16 of the A alpha chain had been replaced by cysteine. To characterize the chemical nature of the sulfhydryl group of cysteine-16, a tryptic peptide containing cysteine-16 of the A alpha chain was prepared from intact fibrinogen Kawaguchi. The amino acid composition and the molecular weight determination of this aberrant peptide revealed that it was a dimeric NH2-terminal peptide corresponding to residues 1-19 derived from the abnormal A alpha chain. These results indicate that the half-cystine at position 16 in the abnormal A alpha chain forms an intramolecular disulfide bridge with the same residue in the other abnormal A alpha chain and that fibrinogen Kawaguchi is a homo dimer composed of two identical abnormal halves.

Amino Acid Sequence↗
PubMed1985

Fibronectin and deposits of fibrinolytic components in glomerular capillary walls.

The distribution of fibronectin (FN) and the depositions of fibrinolytic components in human renal glomeruli with a variety of pathologic disorders were examined on biopsy specimens by immunofluorescence and immunoenzymatic methods. In a majority of the cases with thickening of capillary walls and/or with fibrin deposits in the capillary walls, staining for FN along the walls of the capillary loops (capillary pattern) was noted in addition to the staining in the mesangial area. In the capillary pattern with fibrin deposition, deposits of alpha 2-plasmin inhibitor and plasminogen, which are major components of the fibrinolytic system, were also seen along the capillary walls with a high frequency of occurrence. Plasminogen deposits, however, were found only in the glomeruli with deposits of alpha 2-plasmin inhibitor. There was no direct relationship between the degree of proteinuria and the appearance of the capillary pattern of FN or the deposition of the fibrinolytic components. These findings suggest that the appearance of FN in the walls of the capillary loops has some causal relationship with the local activation of blood coagulation factors which is frequently followed by activation of the fibrinolytic enzyme system.

Adult↗
PubMed1985

[Clinical studies on SM-4300, a new intravenous human gamma-globulin].

With the recent development of new potential antibiotics, it has become easier to treat patients with common bacterial infections. However, we find it difficult to handle severe infections due to opportunistic pathogens, developed in the so-called immunocompromised patients. SM-4300 is a newly developed intravenous human gamma-globulin, which is said to be intact without conventional enzyme-treatment and sulfonization. SM-4300 is also free from large molecules of aggregated gamma-globulin. SM-4300 was administered in combination with antibiotics to 2 patients of severe respiratory infections, having refractory underlying diseases. Case No. 1 was a 65-year-old female with bronchopneumonia, who had been suffering from pulmonary fibrosis, chronic bronchitis, chronic congestive heart failure and tricuspid insufficiency for several years. During her hospitalization because of these diseases, she developed cough with slight sputum and exertional dyspnea accompanied by high body temperature of 38 degrees C on January 1983. Chest X-ray revealed infiltration in the right lung field which was compatible with bronchopneumonia. SM-4300 of 5 g was added intravenously on 5th day after 4 day-cefotiam treatment with no improvement. High body temperature subsided and laboratory data became normal around 3 days after single SM-4300 injection. Case No. 2 was a 68-year-old male patient of chronic bronchitis with chronic pulmonary emphysema and bronchial asthma. Around the end of May 1983, he complained of dyspnea on exertion and had mucopurulent sputum, more than 100 ml daily, from which Pseudomonas aeruginosa was cultured in large number. He was afebrile.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗