Evidence for the formation of a trimolecular complex between streptokinase, plasminogen and fibrinogen.
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Electrophoresis, Polyacrylamide Gel↗
Biomedical subjects
A Takada
Publications and source records attributed to A Takada.
Hepatic aldehyde dehydrogenase activity in liver diseases, with particular emphasis on alcoholic liver disease.
Hepatic aldehyde dehydrogenase isozyme activity was measured in 51 patients with various types of liver diseases, including 24 patients with alcoholic liver disease, to elucidate the relationship between hepatic aldehyde dehydrogenase activity and liver disease, especially alcoholic liver disease. The levels of low-Km and total aldehyde dehydrogenase activity in the liver decreased both in alcoholic and nonalcoholic liver disease patients, who showed an isoelectric focusing pattern of the usual type. There was no significant difference in the aldehyde dehydrogenase activity between alcoholic and nonalcoholic liver disease. In alcoholic liver disease, the decrease in the activity was significantly correlated with the progression of liver histology. The activity in liver cirrhosis was significantly lower than that in the other types of alcoholic liver disease. In nonalcoholic liver disease patients, the unusual type of hepatic aldehyde dehydrogenase activity observed was not different from the unusual type observed in nonhepatobiliary disease patients. These results indicate that the reduction of hepatic low-Km aldehyde dehydrogenase activity is a change that occurs subsequent to liver damage. Genetic abnormality in aldehyde dehydrogenase may not be important in the pathogenesis of alcoholic liver injury.
Aldehyde Dehydrogenase↗
The T-cell receptor alpha, beta and gamma polymorphism in Japanese.
Polymorphism in the genes encoding the alpha (alpha), beta (beta) and gamma (gamma) chains of the human T-cell receptors was analyzed both in population and family studies. Against twelve unrelated Japanese, several out of the 15 restriction endonucleases tested, revealed restriction fragment length polymorphism. The segregation of the polymorphic fragments were confirmed among 15 members of three families. In most of the cases paternal and/or maternal haplotypes could be assigned. By testing the polymorphic enzymes among the random healthy Japanese, the frequency of each polymorphic fragment was then determined. Although the polymorphism found in this study was similar to that reported in Caucasians, some differences were observed. Such differences are discussed. The restriction fragment length polymorphism in both population and family studies, derived from alpha, beta and gamma chains of the T-cell receptor found in this report, might be useful markers for genetic analysis of the T-cell function in relation to immunological disorders.
Humans↗
The association of esophageal hiatus hernia with Mallory-Weiss syndrome.
The incidence of esophageal hiatus hernia in Mallory-Weiss syndrome was analyzed from endoscopic findings in order to clarify the association with Mallory-Weiss syndrome. Hiatus hernia was diagnosed from findings of both esophagoscopy and gastroscopy. In 23 patients with Mallory-Weiss syndrome confirmed by endoscopy, hiatus hernia was found 21 cases (91.3%), in which 9 (39.1%) were definite hernias and 12 (52.2%) were minor hernias. In 80 control cases of various gastrointestinal diseases, definite hernia was found in 7 cases (8.8%), and minor hernia was found in 13 cases (16.2%). The incidence of hiatus hernia in Mallory-Weiss syndrome was thus significantly higher than that in the control group. The incidence of hiatus hernia evaluated only by esophageal findings was lower than that evaluated by combined findings from the gastric and esophageal directions. These results indicate that evaluation from the gastric direction is an essential procedure for the diagnosis of esophageal hiatus hernia and that hiatus hernia is one of the predisposing factors for the development of Mallory-Weiss syndrome.
Alcoholic Intoxication↗
Subcellular localization of aldehyde dehydrogenase isozymes in human liver.
The subcellular distribution of aldehyde dehydrogenase (ALDH) isozymes in human liver was studied by isoelectric focusing and biochemical procedures in biopsied liver specimens obtained during surgical procedures. Four types of ALDH isozymes (ALDH I, II, III and IV) were identified in human liver by isoelectric focusing. In 6 of the 13 livers examined, ALDH I was not detected, indicating that about half of the Japanese people may be classified as the unusual type. ALDH I, which exhibits a low Km with respect to acetaldehyde (Ac-CHO), was located mainly in the mitochondrial and cytosolic fractions. ALDH II (high Km for Ac-CHO) was found to be localized mainly in the microsomal and cytosolic fractions. ALDH III and IV (very high Km for Ac-CHO) were localized in all fractions, except for ALDH III in the microsomal fraction. Biochemical analysis indicates that low Km ALDH activity was localized in the mitochondrial and cytosolic fractions, while high Km and whole ALDH activities were detected in all 3 fractions. More than 80% of the low Km, high Km and whole ALDH activity was found in the cytosolic fraction. These distribution patterns were quite different from those in rats. These results indicate that the results obtained in animal experiments cannot be directly applied to humans and that the main site of Ac-CHO oxidation in the human liver is in the cytosol.
Aldehyde Dehydrogenase↗
Changes in liver and spleen volumes in alcoholic liver disease.
Liver and spleen volumes were determined using computed tomography in 57 subjects with alcoholic liver disease and 76 subjects with nonalcoholic liver disease, in order to clarify the clinical characteristics and pathogenetic mechanisms of portal hypertension in alcoholic liver disease. The liver volumes in alcoholic liver disease were significantly larger than those in nonalcoholic liver disease, except in cases of decompensated liver cirrhosis. The increase in liver volume in alcoholic liver disease showed a significant correlation with the degree of hepatocytic ballooning. Overlapping of values for liver volume between alcoholic and nonalcoholic liver disease was quite small, suggesting that determination of liver volumes could be helpful for making etiological diagnoses in chronic liver disease. Spleen volumes were increased in the advanced cases of both alcoholic and nonalcoholic liver disease. The correlations between liver and spleen volumes were quite different between alcoholic and nonalcoholic liver disease. In nonalcoholic liver disease, a negative correlation was obtained, while, on the other hand, it was significantly positive in alcoholic liver disease. This appears to suggest that the pathogenetic mechanism of portal hypertension may differ between the diseases. After abstinence from alcohol, the decrease in liver and spleen volumes showed a statistically significant correlation, suggesting that ballooning of the hepatocytes may play a role in the augmentation of portal hypertension in alcoholic liver disease.
Humans↗
Studies on aldehyde dehydrogenase type V-A isozymes in liver disease.
Aldehyde dehydrogenase (ALDH) V-A isozymes in saliva were detected in 96 patients with or without liver disease in order to clarify the relationships of the presence or absence of ALDH V-A isozymes to the metabolism of acetaldehyde (Ac-CHO) and alcoholic liver disease. The incidence of ALDH V-A deficiency was not different between the patients with alcoholic liver disease and those with non-alcoholic liver disease, nor between the patients with liver disease and without liver disease in no relation to alcohol misuse. Ac-CHO metabolism was not different between ALDH V-A deficient and non-deficient patients even in the ALDH I-deficient patients. These results indicated that ALDH V-A isozymes play virtually no role in the metabolism of Ac-CHO and its deficiency is not related to the development of alcoholic liver disease.
Acetaldehyde↗
The role of the fibrinolytic system in acute myocardial infarction after a normal exercise test.
A 67-year-old man had an acute myocardial infarction with thrombosis in the left anterior descending artery shortly after normal exercise. We were able to measure the fibrinolytic components in this patient just prior to his developing acute myocardial infarction as well as during convalescence. In this case, marked increase in total plasminogen activator inhibitor-1 (PAI-1) antigen, mainly due to free PAI-1 antigen, was observed in basal conditions before the onset of acute myocardial infarction. On the appearance of ischaemia, plasminogen activator activity was suppressed, probably due to decreased tissue plasminogen activator antigen release and increased PAI activity, compared with that during convalescence. This suggests that some patients with coronary artery disease who have a high level of free PAI-1 antigen in basal conditions may have a strong tendency to develop acute myocardial infarction, due to further impaired fibrinolysis on the induction of ischaemia.
Acute Disease↗
Enhancement of the activation of Glu-plasminogen by urokinase in the simultaneous presence of tranexamic acid or fibrin.
The activation rate of Glu-plasminogen (Glu-plg) by urokinase (UK) was enhanced in the presence of either tranexamic acid or fibrin with an increase in the catalytic rate constant (kcat). The maximum increase in kcat was obtained at 0.5 mM of tranexamic acid and 0.1 microM of fibrin. Km did not change. The addition of fibrin to 1 mM tranexamic acid resulted in a further increase in kcat of the UK activation of Glu-plg. On the other hand, the addition of tranexamic acid to 0.1 microM fibrin further increased kcat of the UK activation of Glu-plg. Thus, stimulatory effects were observed on the activation of Glu-plg by UK in the simultaneous presence of tranexamic acid and fibrin. Fibrin-binding sites on the kringle 5 of Glu-plg may be involved in the further increase in the activation rate of Glu-plg by UK in the presence of both fibrin and tranexamic acid in comparison to that in the presence of tranexamic acid alone. Possibly, the Glu-plg binding with both tranexamic acid and fibrin (at kringle 5) may be most effectively activated by UK. It is also suggested that two molecules of Glu-plg bind to one molecule of fibrin monomer.
Cyclohexanecarboxylic Acids↗
Measurement of urinary trypsin inhibitor in urine, plasma and cancer tissues of patients with stomach cancer.
Antiserum was obtained from rabbits immunized with a highly purified preparation of urinary trypsin inhibitor (UTI) conjugated with rabbit serum albumin. Anti-UTI antibody did not cross-react with antibody against inter-alpha-trypsin inhibitor (I alpha I) as determined by immunodiffusion against human plasma. A highly sensitive enzyme immunoassay was developed for the determination of UTI-related antigens (UTIR) in plasma, urine and cancer tissues. The level of UTIR correlated with UTI activity in urine. UTIR levels in urine and plasma did not change with age, but UTIR levels were higher in the stomach cancer tissue than in the surrounding stomach mucosa. UTIR levels did not correlate with I alpha I levels in the plasma of patients with stomach cancer, thus the increase was not considered due to the contamination of circulating I alpha I in the cancer tissues.
Adolescent↗
Plasminogen activators: possible roles in cell proliferation.
Plasminogen activators (PAs) convert plasminogen to plasmin by the cleavage of the Arg-Val bond. There are two distinct types of PA, tissue type (t-PA) released from the endothelial cells of the blood vessels and urinary type (u-PA) released from urinary tubules. u-PA was found to be released from activated macrophages and virally transformed cells. t-PA was also found to be released from breast cancer cells induced by carcinogens or melanoma cells. In structure, t-PA has a finger domain homologous to fibrin-binding domain of fibronectin and a growth factor domain homologous to the epidermal growth factor. u-PA has no finger domain but has a growth factor domain. It is proposed that PA may be important in tumor growth due to the stimulation of tumor cells through binding of growth factor domain to its receptor of tumor cells. Another hypothesis is that PA may activate procollagenase to collagenase, which digests collagen to facilitate tumor growth. We have measured the concentrations of t-PA and u-PA in plasma, urine and tumor tissues of patients with cancer of the digestive tract and patients with uterine or ovarian tumors. The results indicate that the concentrations of u-PA increased in urine, plasma and cancer tissues of patients with cancer of the digestive tracts whereas no increase was observed in t-PA levels. On the other hand, the concentration of t-PA increased mostly in plasma of patients with uterine and ovarian cancers, but t-PA levels in tissues did not increase in patients with uterine and ovarian cancer.
Cell Division↗
[Comparison of structures and functions of urokinase (u-PA) and tissue plasminogen activator (t-PA)].
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Fibrin↗
[Analysis of VH genes which encode the variable region of monoclonal antibodies directed to cancer-associated carbohydrate antigens].
Immune responses against cancer-associated, carbohydrate antigens are investigated by studying idiotypic determinants of specific antibodies with monoclonal anti-idiotypic antibodies, and by analyzing the structure of VH genes which encode the V region of the anti-carbohydrate antibodies. Four syngenic anti-idiotypic antibodies towards monoclonal antibodies which are specific to the sialyl Lewis A antigen and two kinds of SSEA-1 related antigens (sialyl SSEA-1 and fucosul SSEA-1) were obtained. Antibodies directed to carbohydrate antigens were mostly of IgM isotype, indicating these antigens are T-independent antigens, while anti-idiotypic monoclonal antibodies directed to those antibodies were mostly of IgG isotype, suggesting that T cells participate actively in the anti-idiotypic response. The Northern blotting analysis of VH genes of monoclonal antibodies directed to negatively-charged carbohydrate antigens such as gangliosides or sulfated glycolipids expressed the VH gene family J558 (group 1), followed by J606 (group 6) and Q52 (group 2) families. On the other hand, monoclonal antibodies directed to SSEA-1 related neutral carbohydrate antigens expressed VH genes of a minor family such as X24 (group 4), V31 (group 9), or 7183 (group 5). The same VH family as expressed in anti-SSEA-1 antibody (x24) was also expressed in the antibodies such as anti-i and anti-I antibodies, which are directed to the synthetic precursors of the SSEA-1 antigen. In either case, the antibodies directed to one particular carbohydrate antigen tended to express the VH gene of one particular family exclusively. This suggests idiotypic homogeneity of the anti-carbohydrate antibodies.
Animals↗
[Clinical application of cancer-associated carbohydrate antigens in the diagnosis and therapy of human cancers].
Cell surface carbohydrates are important cancer-associated antigens. The carbohydrate antigens which have been proved to be useful for the serum diagnosis of human cancers are classified from their biochemical primary structure into three categories; the type 1 chain antigens, type 2 chain antigens, and core structure-associated antigens. The SPan-1 antigen, the newly-introduced tumor marker for human pancreas cancers, seems to be a type 1 chain antigen, judging from its distribution pattern among human cancers and its good correlation with other type 1 chain antigens. Another newly-introduced tumor marker, the CA54/61 antigen, which is specific for ovarian cancers, seems to belong to the family of the core-structure-associated antigens, since both antibodies (MA54 and MA61) used for the detection of the CA54/61 antigen are shown to recognize the antigen molecule which is closely related to sialyl Tn antigen, the well-known carbohydrate core structure of mucins. There are two approaches for the therapy of human cancers employing carbohydrate antigens as target molecules. One is the direct application of the specific monoclonal antibodies (alone, or in the drug-conjugated forms) in cancer patients. In this case, special attention is paid to the use of murine antibodies in human patients. The other approach is to induce specifically an effective immune response against the cancer-associated carbohydrate antigens. For this approach, further methodological development is necessary to determine how to obtain an effective immune response to carbohydrate antigens, since they have long been known as very poor immunogens which are T-independent.
Antigens, Tumor-Associated, Carbohydrate↗
[Standardization of the method of gastric emptying analysis].
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Adult↗
[Diagnosis of the bleeding site in gastrointestinal hemorrhage by the determination of the serum urea and creatinine ratios].
Serum urea/creatinine (Ur/Cr) ratios were determined in patients showing massive gastrointestinal (GI) bleeding in order to evaluate the bleeding site. In 36 cases of upper GI bleeding, serum Ur/Cr ratios were 119.1 +/- 4.0. The ratios were 54.1 +/- 12.1 and 58.4 +/- 10.3 in 23 cases of lower GI bleeding and 50 control cases without GI bleeding, respectively. The ratio in the upper GI bleeding cases were significantly higher than those in the lower GI bleeding and the control cases. In all cases of upper GI bleeding, except for 6 cases in which blood volume flowed into the GI tract was small, the ratios were beyond 81. On the other hand, in the lower GI bleeding and the control cases, the ratios were all below 81. Values over 81 in serum Ur/Cr ratios in upper GI bleeding cases continued until the 3rd day after bleeding. These results indicate that determination of serum Ur/Cr ratios is a simple and useful procedure for diagnosis of the bleeding site in cases showing massive GI bleeding.
Adolescent↗
Relationship between smoking and fibrinolytic system with special reference to t-PA and PA inhibitor.
Recently tissue plasminogen activator (t-PA) has been clinically applied to the thrombolytic therapy of myocardial infarction. We investigated relationship between cigarette smoking and fibrinolytic system, namely the plasma level of t-PA antigen, plasminogen activator inhibitor (PAI), and PA activity. Nineteen healthy volunteers were asked to smoke for 10 min. The plasma levels of t-PA antigen, PAI activity, PA activity and catecholamine were measured together with measurement of blood pressure and heart rate before, soon after or 30 min after cigarette smoking. Plasma t-PA antigen after cigarette smoking increased to 8.83 +/- 3.11 ng per ml, significantly higher (p less than 0.005) than 6.35 +/- 1.7 ng/ml before cigarette smoking. Plasma PAI activity after cigarette smoking was 5.52 +/- 2.03 u/ml, significantly higher (p less than 0.05) than 4.18 +/- 1.06 u/ml before smoking. Plasma PA activity after smoking was 6.28 +/- 3.85 u/ml significantly higher (p less than 0.05) than 4. 49 +/- 2.74 u/ml. Furthermore, plasma epinephrine level after smoking increased to 59.1 +/- 52.4 pg/ml (p less than 0.1), compared with 36.2 +/- 22.5 pg/ml before smoking. There was a positive correlation between the rate of increase in plasma t-PA antigen and the rate of increase in plasma epinephrine after smoking. It is suggested that plasma epinephrine was related to the mechanism of increased plasma levels of t-PA in cigarette smoking.
Adult↗
Kinetic analyses of the enhancement of the activities of t-PA induced by the presence of monoclonal antibody (C9-5).
Nine monoclonal antibodies (Mab) against two chain tissue plasminogen activator (t-PA(W] were obtained. The effects of these Mabs on the enzymatic activities of one chain t-PA (t-PA(TD] and two chain t-PA (t-PA(W] were examined by incubating t-PA and Mabs with S-2288, or with plasminogen (plg) and S-2251 in the presence or absence of fibrin. One of Mabs called C9-5 significantly enhanced the activities of t-PA, which were kinetically analyzed. The kinetic analyses of the hydrolysis of S-2288 by t-PA showed increase in kcat from 5.17/sec to 7.75/sec in the presence of 75 micrograms/ml of C9-5 without change in Km. When Glu-plg was activated by t-PA(TD) in the absence of fibrin, Km decreased from 2 microM to 0.17 microM in the presence of C9-5 without change in Vmax. The addition of fibrin resulted in further decrease in Km from 0.133 microM to 0.077 microM. When Lys-plg was activated by t-PA(TD) in the absence of fibrin, Km decreased from 0.408 microM to 0.185 microM in the presence of C9-5, and kcat increased from 0.131 sec-1 to 0.465 sec-1. The presence of fibrin further increased kcat of the activation of Lys-plg. Similar results were obtained when plasminogen was activated by t-PA(W). Mab, C9-5, was shown to bind to B-chain of t-PA by immunoblotting. These results suggest that a dimolecular complex of t-PA and C9-5 has a higher affinity to plasminogen in the presence or absence of fibrin.
Animals↗