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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 361 records · Page 20Linked to original sources
PubMed1988

The urokinase type of plasminogen activator in cancer of digestive tracts.

The amounts of urokinase (UK) antigen and tissue plasminogen activator (t-PA) antigen were determined in plasma, urine and tissues of patients with cancer of digestive tracts. Urinary levels of UK, but not those of t-PA increased in patients with cancer, and generally decreased after the removal of cancer by operation. Urinary UK levels kept increasing in patients with recurrence of cancer or with metastasis into liver or peritoneum. Plasma levels of t-PA, but not those of UK decreased in patients with cancer. When the amounts of UK were compared in cancer tissues and their adjacent normal mucosal layer, cancer tissues always had higher levels of UK, but t-PA levels were same between tumor tissues and normal mucosa. The results suggest that the type of plasminogen activator was UK-type in cancer of digestive tracts.

Adenocarcinoma↗
PubMed1988

Degradation of Glu- and Lys-plasminogen by elastase in the presence or absence of tranexamic acid.

Glu-plasminogen (Glu-plg) was degraded by elastase in the presence or absence of tranexamic acid. Glu-plg was degraded faster in the presence of tranexamic acid. Increase in the concentration of tranexamic acid resulted in increase in the appearance of degradation products, reaching a plateau level at 1 mM of tranexamic acid. Fifty percent increase in the concentration of one of degradation products was obtained at 0.22 mM of tranexamic acid, which is similar to a dissociation constant (Kd) of low affinity lysine binding sites (LBS) with tranexamic acid. As to the degradation rate of two isozymes of Glu-plg (Glu-plg I and II), Glu-plg II containing one carbohydrate chain was degraded faster than Glu-plg I containing two carbohydrate chains. Comparison of the degradation rates of Glu-plg and Lys-plg indicated that Lys-plg was degraded faster.

Cyclohexanecarboxylic Acids↗
PubMed1988

Autoradiographic and immunoblotting analyses of the activation pathways of plasminogen by urokinase and tissue plasminogen activator in the plasma or clotted plasma.

The activation pathway of Glu-plasminogen (Glu-plg) was analyzed by using immunoblotting and autoradiography. Glu-plg was slowly activated to Glu-plasmin by urokinase (UK) and tissue plasminogen activator (t-PA) in the plasma. Significant amounts of a complex of alpha 2AP with plasmin were found. On the other hand, UK and t-PA rapidly activated Glu-plg in the clotted plasma. The major form of plasmin was Lys-form, and significant amounts of alpha 2M complexed with plasmin were found. A complex of alpha 2AP with plasmin was not so significantly formed in the clot, confirming ineffective inhibition of plasmin by alpha 2AP in the presence of fibrin. Glu-plg was directly activated by UK or t-PA to Glu-plasmin and further to Lys-plasmin in the plasma or clotted plasma.

Autoradiography↗
PubMed1988

Activation of Val442-plasminogen (mini-plasminogen) by urokinase, streptokinase and tissue plasminogen activator.

Glu-plasminogen (Glu-plg), Lys-plg and Val442-plg (mini-plg) were activated by urokinase (UK), streptokinase (SK) or tissue plasminogen activator (t-PA). Their activation rates were kinetically analyzed. UK activated Lys-plg with smaller Km and nearly identical Vmax as Glu-plg. Mini-plg was activated by UK with higher Vmax but with the same Km as Glu-plg. On the other hand, t-PA activated Glu-plg, Lys-plg and mini-plg with the same Vmax, but Km was in the order of Glu-plg greater than mini-plg greater than Lys-plg. Fibrin hardly enhanced the UK activation of mini-plg, and fibrinogen, fragment D or E did not enhance the activation of mini-plg by UK. Only D domain, but not E domain, complexed with K5 of mini-plg and SK hydrolysed S-2251 faster than a dimolecular complex of mini-plg and SK, thus a trimolecular mixture of D, SK and mini-plg having a better activator activity than SK-mini-plg complex. In the t-PA activation of mini-plg, fibrin and fibrinogen enhanced the activation, but fragment D or E was ineffective, suggesting that a molecule containing more than one domain was required for the enhanced activation of mini-plg by t-PA.

Fibrin↗
PubMed1988

HLA-DQ system and insulin-dependent diabetes mellitus in Japanese: does it contribute to the development of IDDM as it does in Caucasians?

Fifty-six unrelated Japanese patients with insulin-dependent diabetes mellitus (IDDM) were HLA-typed, and restriction fragment length polymorphism (RFLP) analysis was performed after enzyme digestion with Bam HI and Taq I by using both DR and DQ probes. As previously reported, increased frequencies of Bw54, Cw1, DR4, and DRw53, which are in strong linkage disequilibrium in the Japanese population and make the characteristic Japanese haplotype, were confirmed. DQw4, a new allele of the DQ system recognized by the monoclonal antibody HU-46 and in linkage disequilibrium with this haplotype, presented the highest IDDM association. The RFLP analysis also showed the strongest correlation to IDDM when the DQ probe was applied. These results indicate that HLA-DQ might play the most important role in the development of IDDM in Japanese as well as in Caucasians. The correlation of DQ beta amino acid sequences strongly associated with IDDM in Japanese are discussed in this study, and contrasting results were found when such sequences were compared with those of Caucasians.

Amino Acid Sequence↗
PubMed1988

Effects of malotilate treatment on the serum markers of hepatic fibrogenesis in liver cirrhosis.

Malotilate, a hepatotropic agent, was given to 39 cirrhotic patients for more than 32 weeks. The serial changes in the serum levels of hepatic fibrogenesis markers, such as procollagen type III N-terminal peptides (P-III-N-P) and immunoreactive prolyl hydroxylase beta-subunit (IR-BPH) were analyzed. Serum albumin levels, transaminase and choline esterase activities and the Normotest values were found to be significantly improved by malotilate treatment. The levels of both serum markers of hepatic fibrogenesis were also significantly reduced by malotilate. The prognoses of the decompensated liver cirrhosis patients treated with malotilate were significantly better than those who did not receive malotilate. These results indicate that the effects of malotilate on chronic liver diseases are not simply biocosmetic, but rather are related to an improvement in the basal changes of the liver, including a decrease in the fibrogenetic stimulus. These effects of malotilate improved the prognosis of liver cirrhosis.

Adult↗
PubMed1988

Measurements of the concentration of free plasminogen activator inhibitor (PAI-1) and its complex with tissue plasminogen activator in human plasma.

A new assay system to measure free plasminogen activator inhibitor (PAI-1) and its complex with tissue plasminogen activator (t-PA) was developed. A silicone piece coupled with anti-PAI-1 monoclonal antibody was incubated with human plasma or human plasma which had previously been incubated with t-PA in order to convert all the free PAI-1 to t-PA-PAI-1 complex. After incubation, the amounts of t-PA bound on each silicone piece were measured by enzyme immunoassay. The amounts of t-PA on a silicone piece incubated with plasma represent the amounts of t-PA-PAI-1 complex in the original plasma, and the amounts of t-PA on a silicone piece incubated with plasma previously added with t-PA represent total PAI-1 (the complex plus free PAI-1). Using the technique, the concentration of t-PA-PAI-1 complex seems to increase with age and there was a good correlation between the concentration of free PAI-1 and t-PA-PAI-1 complex in the plasma.

Antibodies, Monoclonal↗
PubMed1988

Changes in various parameters of fibrinolysis in persons infused with tissue plasminogen activator: special reference to plasminogen activator inhibitor.

Tissue plasminogen activator (t-PA) purified from culture of human lung cells was infused over 30 min at the dose of 7.2 mg or 14.4 mg per person into human male volunteers. T-PA declined rapidly after the cessation of infusion with T1/2, alpha of about 4 min and T1/2, beta of about 40 min. The plasma fibrinogen and plasminogen did not change during and after the infusion of t-PA. The concentration of alpha 2antiplasmin (alpha 2AP) did not change but that of alpha 2AP-plasmin complex increased to about 200 nM at the infusion of 14.4 mg/person. Fragment D was hardly found at the infusion of 7.2 mg but some increase in the concentration of D was observed at the infusion of 14.4 mg. The concentration of free plasminogen activator inhibitor (PAI-1) rapidly declined and kept low up to 150 min, and returned to normal the following day. The concentration of t-PA-PAI-1 complex increased rapidly, and slowly declined after the end of the infusion of t-PA, suggesting no significant release of PAI-1 in response to increase in plasma concentration of t-PA or t-PA-PAI-1 complex. The addition of thrombin to the blood after withdrawal resulted in the significant formation of D-dimer, even at 150 min after the infusion. There was not hyperaggregability of platelets during and after the infusion of t-PA. These results suggest that the infusion of t-PA at the dose of 7.2 mg or 14.4 mg/person for 30 min resulted in high fibrinolytic potential in the blood without the breakdown of fibrinogen or increase in PAI-1.

Adult↗
PubMed1988

Effects of malotilate on alcoholic liver injury in rats.

Malotilate (diisopropyl 1,3-dithio-2-yldenemalonate), a hepatotrophic drug, was administered to rats with alcohol-pyrazole hepatitis, which is considered to be a suitable experimental model for alcoholic liver injury, in order to elucidate the effects of malotilate on alcoholic liver injury. The number of ballooned hepatocytes and necrotic hepatocytes were smaller in the alcohol-pyrazole hepatitis rats treated with malotilate for 12 weeks (Al-Py Mal group) than for those without malotilate treatment (Al-Py group). Immunohistochemically, the retention of transferrin, one of the secretory proteins from the liver, in the ballooned hepatocytes was inhibited by malotilate. Biochemically, transferrin content in the Golgi fraction of the hepatocytes was significantly lower in the Al-Py Mal group than in the Al-Py group. Hepatic acetaldehyde levels in the Al-Py Mal group were significantly lower than those in the Al-Py group, even though ethanol metabolic rates were not different between the two groups. These results indicated that malotilate prevented the development of hepatocytic injury in alcohol-pyrazole hepatitis by decreasing hepatic acetaldehyde levels and preventing the retention of transferrin in the hepatocytes.

Acetaldehyde↗
PubMed1988

Enhanced activator activity of the mixture of streptokinase and a modified form of plasminogen (Lys-plasminogen) in the presence of fibrin: role of conformational change of plasminogen.

Equimolar concentrations of Lys-plasminogen (Lys-PLG) and streptokinase (SK) were mixed with various concentrations of fibrin, fibrinogen, fragment D or E (potentiating agents). The activity of the mixture was measured by the hydrolysis of S-2251. Kinetic analyses indicated that catalytic rate constant (kcat) of the hydrolysis of S-2251 increased in the presence of increasing amounts of potentiating agents. Km did not change in their presence. Effectiveness of the enhancement of the hydrolysis of S-2251 was in the order of fibrin greater than fibrinogen greater than E greater than D. It could be concluded that a complex of SK, Lys-PLG and potentiating agent is a better enzyme, thus activator, than a complex of SK and Lys-PLG. Since Lys-PLG does not change its conformation and its activation rate upon interaction with fibrin, the enhanced activator activity of complex of SK, Lys-PLG and potentiating agent may not be due to the conformational change of Lys-PLG.

Chromogenic Compounds↗
PubMed1988

Comparison of kinetic parameters of the activation of Glu-plasminogen by tissue plasminogen activator obtained from various sources.

Kinetic analyses were made for the activation of Glu-plasminogen (Glu-Plg) by tissue plasminogen activator (t-PA) obtained from various sources. We compared kinetic parameters for three t-PA preparations. t-PA(M) was obtained from cultured melanoma cell line, and t-PA(W) and t-PA(TD) were obtained from cells with recombinant DNA. t-PA(W) had two chains whereas t-PA(TD) had one chain. Although values of kinetic parameters were different in the three t-PA preparations, there were following general tendencies. The presence of catalytic amounts of fibrin resulted in a decrease in Km, whereas the presence of larger amounts of fibrin resulted in an increase in kcat with a slight decrease in Km. The presence of fibrinogen also enhanced the activation of Glu-Plg by t-PA with an increase in kcat and without change in Km. When the effects of fragment D or E were compared, the presence of increasing amounts of E resulted in an increase in kcat, but the presence of increasing amounts of D resulted in an increase in kcat and a decrease in Km. The results suggest that roles of D and E domains of fibrin may be different in the enhanced activation of plasminogen by t-PA.

Animals↗
PubMed1988

Physiology of plasminogen: with special reference to activation and degradation.

Plasminogen is said to be synthesized in many organs, but the major source of its production is considered to be the liver. The production of plasminogen is observed in fetal life, but its plasma level is low in new born infants, rising rapidly to attain adult levels in about 13 weeks. The plasma levels do not change much with age. Although the fibrinolytic enzyme system is influenced by many factors such as hormones, exercise, emotion, age, sex, nutritional states etc., the plasma levels of plasminogen are relatively stable. In this presentation we would like to discuss three important subjects related to the physiology of plasminogen. The first subject is the activation pathway of the native form of plasminogen (Glu-plg) by various activators in the plasma or clotted plasma. Glu-plg was not easily activated by activators such as urokinase (UK) or tissue plasminogen activator (t-PA), but activated very easily in the presence of fibrin clot. In the presence of purified clot, Glu-plg was partly activated by activators to Glu-plasmin, but also converted to Lys-plg by preformed plasmin, subsequently being activated to plasmin. Glu-plg I (containing two carbohydrate chains) changed conformation more easily upon interaction with fibrin than Glu-plg II (containing one carbohydrate chain) and Glu-plg I was also more easily activated by activators than Glu-plg II. Although Glu-plg was hardly activated by activators in the plasma, Glu-plg was activated easily in the presence of plasma clot. Results of immunoblotting experiments indicated that Glu-plg was mainly activated by activators directly to plasmin, not via Lys-plg in contrast to purified systems. The second subject is the degradation of plasminogen by elastase. Plasminogen may be degraded by proteolytic enzymes such as cathepsin or elastase. The degradation of plasminogen by elastase is shown to give rise to K1 to K3, K4, and mini-plg (containing K5). We have shown that the degradation rate to Glu-plg by elastase increased in the presence of tranexamic acid, indicating that the conformational change of Glu-plg in the presence of tranexamic acid resulted in the exposure of the hydrophobic regions connecting K3, K4 and K5, thus making them accessible to elastase. Consequently, Lys-plg or conformationally altered Glu-plg (possibly bound to fibrin or FDP) is more easily degraded in vivo. The last subject is relationship between plasma plasminogen levels and fibrinolytic activity in various ages. Although plasma plasminogen levels do not change with age, the fibrinolytic activity lowers.(ABSTRACT TRUNCATED AT 400 WORDS)

Enzyme Activation↗
PubMed1988

Connective tissue components in cultured parenchymal and nonparenchymal cells of rat liver. Immunohistochemical studies.

Connective tissue components were detected immunohistochemically in cultured rat hepatocytes and sinusoidal lining cells. In the Ito and endothelial cells, the staining reactions to prolyl hydroxylase were strong. The reaction in the hepatocytes, however, was weaker, and there was no staining reaction to prolyl hydroxylase in the Kupffer cells. In the Ito cells, types III and IV collagen were clearly positive, whereas reactions to type I collagen were very weak. In the endothelial cells, type IV collagen stained clearly, whereas the reaction for type I collagen was very weak, and there was no reaction for III. Laminin was clearly positive in the Ito and endothelial cells. Connective tissue components were not detectable in the Kupffer cells. The hepatocytes were positive for types I, III, and IV collagen, but the staining reactions to type IV collagen were weak. Laminin staining was almost negative. These results suggest that type IV collagen is produced mainly by nonparenchymal cells and that types I and III collagen are produced by both parenchymal and nonparenchymal liver cells.

Animals↗
PubMed1987

Relationship between age and plasma t-PA, PA-inhibitor, and PA activity.

A positive correlation between age and the occurrence of thrombosis has been suggested. We studied the relationship between age and fibrinolytic activities; namely levels of tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PA inhibitor) activity, and plasminogen activator activity (PA activity). A dramatic increase in both t-PA antigen and PA inhibitor was shown in persons with increasing age. PA activity decreased with age. Therefore it is suggested that the tendency of decreased PA activity with increasing age may be related to the high incidence of thrombosis in older persons.

Adolescent↗