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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 289 records · Page 16Linked to original sources
PubMed1991

The activation of plasminogen by T-PA-PAI-1 complex in the absence of fibrin.

The activity of tissue plasminogen activator-plasminogen activator inhibitor-1 (t-PA-PAI-1) complex to convert plasminogen to plasmin was examined by using fibrin autography and casein zymography where plasminogen was added or removed for casein layer. Fibrin autography was more sensitive to the activity of t-PA even in the complex with PAI-1, but casein zymography was more sensitive to plasmin. The inhibitory activity of PAI-1 toward t-PA diminished when plasma was clotted, thus in the presence of fibrin. These results indicate that t-PA-PAI-1 complex has a catalytic activity even in the absence of fibrin, but the activity is enhanced in its presence.

Fibrin↗
PubMed1991

The effects of polysaccharides on plasminogen activation by single chain-and two chain-tissue plasminogen activator.

We examined the effects of polysaccharides on t-PA mediated plasminogen activation using single-chain tissue plasminogen activator (sct-PA) and two-chain tissue plasminogen activator (tct-PA). Unfractionated heparin, low molecular weight heparin (LMW heparin) and dextran sulfates enhanced the activation rate of plasminogen by sct-PA about three-fold to six-fold. Chondroitin sulfate C did not enhance the activation. The activation of plasminogen by tct-PA was slightly enhanced by unfractionated heparin, but not by other polysaccharides. Conversion of sct-PA to tct-PA was not stimulated by polysaccharides. SDS-PAGE showed no enhancement of the conversion from sct-PA to tct-PA by plasmin in the presence of polysaccharides. However, the enhancement of sct-PA mediated activation of plasminogen by unfractionated heparin, LMW heparin and dextran sulfates in the presence of aprotinin was shown with SDS-PAGE. It was suggested that unfractionated heparin, LMW heparin and dextran sulfates form complex with sct-PA and plasminogen, and stimulate the conversion of sct-PA to tct-PA.

Animals↗
PubMed1991

Stimulation of the amidolytic activity of single chain tissue-type plasminogen activator by fibrinogen degradation products: possible fibrin binding sites on single chain tissue-type plasminogen activator molecule.

The steady-state kinetics of the amidolytic activity of single chain tissue-type plasminogen activator (tPA) were analyzed in the presence or absence of different molecular forms of fibrinogen degradation products. Single chain tPA showed a Km value of 1.6 mM and kcat value of 4.9/s toward the chromogenic substrate H-D-Ile-Pro-Arg-p-nitroanilide (S-2288). In the presence of infinite concentrations of fibrinogen, kinetic constant was calculated as about 8-times higher than that in the absence of fibrinogen, mainly caused by the decrease of Km value. The dissociation constant (Ka) for this stimulation by fibrinogen was 2.9 microM. When the same assay was conducted with fragment X or fragment D of fibrinogen, the kinetic constants increased 3.2 and 2.9-times, respectively, whereas no enhancement was obtained by fragment E. Neither lysine analogues nor monoclonal antibody toward domains of finger and epidermal growth factor of tPA quench the enhancement by fibrinogen. This enhancement was not observed in the case of the two chain form of tPA. These results indicate that fibrinogen enhances the amidolytic activity of single chain tPA by binding to kringle 2 domain or light chain through D domain of fibrinogen.

Binding Sites↗
PubMed1991

Effects of N-terminal peptide of Glu-plasminogen on the activation of Glu-plasminogen and its conversion to Lys-plasminogen.

In order to analyze the mechanism of the intramolecular binding of the N-terminal peptide of Glu-plasminogen (Glu-plg) to its kringles, which results in its tight conformation, we synthesized peptides of the N-terminal portion of Glu-plg molecules and analyzed their effects on the activation of Glu-plg and its conversion to Lys-plasminogen (Lys-plg) by plasmin. Three peptides of Ala44-Lys50, Ala44-Glu51 and Ala44-Ser49 were synthesized in order to examine the effect of lysine residue in the peptide. Ala44-Lys50 and Ala44-Glu51 enhanced the activation of Glu-plg by urokinase, whereas the activation of Lys-plasminogen (Lys-plg) was slightly inhibited. The conversion of Glu-plg to Lys-plg by plasmin was also enhanced by these peptides. The results suggest that Ala44-Lys50 and Ala44-Glu51 worked on Glu-plg in a similar manner as lysine analogues by making its conformation looser. The third peptide Ala44-Ser49 did not have any effect on the activation of Glu-plg by urokinase or the conversion of Glu-plg to Lys-plg by plasmin. Ala44-Lys50 residue of Glu-plg is, therefore, strongly implicated as a candidate for the responsible site of the intramolecular binding in Glu-plg.

Alanine↗
PubMed1991

MRI of subarachnoid dissemination of medulloblastoma.

We report two cases with subarachnoid dissemination of medulloblastoma depicted clearly by Gadolinium-DTPA enhanced MRI. We also demonstrate the superiority of Gadolinium-DTPA enhanced MRI over nonenhanced MRI, CT, myelography and postmyelographic CT for diagnosing subarachnoid dissemination and for monitoring the response to therapy.

Brain↗
PubMed1991

Hepatitis C virus RNA genome in plasma of patients with non-A, non-B hepatitis.

Recently, the assay system of anti-hepatitis C virus antibody (HCV-Ab) was developed. However, there is no clinically useful method to detect hepatitis C virus (HCV) itself. The authors recently developed a method to detect the HCV-RNA genome in plasma using polymerase chain reaction (PCR). In the present study, the specificity of this assay in detecting HCV infection was investigated. Freshly obtained 1 ml plasma specimens from 100 patients with various liver diseases and from 11 control subjects were studied. In patients with non-A, non-B (NANB) hepatitis-related liver diseases, HCV-RNA was detected in 2 out of 7 cases of acute hepatitis, in 29 out of 31 cases of chronic hepatitis, in 17 out of 21 cases of cirrhosis and in 2 out of 6 cases of hepatocellular carcinoma. On the other hand, no HCV-RNA was detected in 15 cases of various types of alcoholic liver diseases, in 12 cases of hepatitis B related liver diseases, and in 11 controls. HCV-RNA was detected in 2 of 6 drinkers with chronic hepatitis. The prevalence of HCV-RNA was not closely related to a history of blood transfusions. These results suggest that our method for HCV-RNA is specific for HCV infection and HCV infection is the likely etiology of most chronic NANB hepatitis cases. The clinical usefulness of our method is illustrated by the fact that we were able to study 100 patients and needed only 1 ml plasma per HCV-RNA assay.

Electrophoresis, Polyacrylamide Gel↗
PubMed1991

Genotyping of the aldehyde dehydrogenase 2 (ALDH2) gene using the polymerase chain reaction: evidence for single point mutation in the ALDH2 gene of ALDH2-deficiency.

About half of all Japanese lack the activity of aldehyde dehydrogenase 2 (ALDH2), and suffer a flush after alcohol intake due to the marked elevation of blood acetaldehyde concentration. The cause of ALDH2 deficiency is thought to be a single point mutation in codon 487 of the ALDH2 gene. However, this mutant ALDH2 gene has not yet been cloned and sequenced. We amplified and cloned the exon 12 of the ALDH2 gene using polymerase chain reaction (PCR), and revealed that normal GAA coding glutamic acid is replaced for AAA coding lysine in codon 487 of the mutant ALDH2 gene. Based on this finding, we performed the genotyping of the ALDH2 gene using PCR and allele-specific oligonucleotide probes. The genotypes of 13 subjects with ALDH2-active phenotype were all homozygous for the normal ALDH2 gene (ALDH2(1)), while in 9 subjects with ALDH2-deficient phenotype 2 subjects were homozygous for the mutant ALDH2 gene (ALDH2(2)) and the other 7 subjects were heterozygous for both genes, indicating that the mutant ALDH2 gene is dominant. In 20 normal control subjects, the prevalence of ALDH2(1)/ALDH2(1), ALDH2(1)/ALDH2(2) and ALDH2(2)/ALDH2(2) was 45%, 45% and 10% respectively. On the other hand, in 36 alcoholic liver disease patients, the prevalence of the genotypes was 83%, 17% and 0%. These results confirmed the previous observation that the incidence of ALDH2 deficiency is much lower in alcoholic liver disease patients than in the general population, and suggested that most of the ALDH2 deficient patients with alcoholic liver disease are heterozygous for the normal and mutant ALDH2 genes.

Aldehyde Dehydrogenase↗
PubMed1991

Alcohol-induced depression: involvement of serotonin.

We examined tryptophan and serotonin (5-hydroxytryptamine) levels in the blood after consumption of alcohol. Forty-five minutes after drinking, whole blood serotonin concentration was significantly reduced, whereas no changes were observed in tryptophan level. The diurnal rhythm of 5-HT in subjects who the day before had drunk alcohol was quite different from the control group, but very similar to that of patients with depression. The results strongly suggest that the mechanism of depression after alcohol drinking may be related to serotonin.

Adult↗
PubMed1991

Lymphoproliferative lesion of the hypoglossal nerve: case report.

A rare case of a lymphoproliferative lesion in the hypoglossal nerve is reported. The patient, a 52-year-old woman, had symptoms identical with those of hypoglossal neurinoma. Computed tomography and magnetic resonance imaging revealed a lesion at the left cerebellomedullary angle. The tumor was removed, and histopathological studies revealed that the tumor consisted predominantly of lymphocytes.

Cranial Nerve Diseases↗
PubMed1991

Typing of hepatitis C virus genomes by restriction fragment length polymorphism.

Recently, we reported that hepatitis C virus (HCV) can be classified genetically into two types, HCV-K1 and HCV-K2, which show 67% and 71% identity at the nucleotide and amino acid sequence levels in a 340 bp region which encodes the NS5 gene Gly-Asp-Asp motif. To develop a rapid method to classify the genomes of HCV isolates, we identified restriction fragment length polymorphisms (RFLPs) in reverse transcriptase-polymerase chain reaction products encoding a portion of the NS5 gene. AluI and AccII enabled HCV to be classified into the K1 and K2 types, and Sau96I enabled classification into the K1 type, and the K2a and K2b subtypes. These RFLPs also generally allow Japanese isolates to be distinguished from the prototype (PT, an isolate from the U.S.A.), which is a K1 type. Sequence analysis of the 5'-untranslated regions of Japanese isolates revealed near identity between the K1 type and PT, and 93 to 94% identity between the K1 and K2 types, indicating that there are type K1- and K2-specific RFLPs in this region. Our results suggest that the nucleotide sequences of the K1 and K2 types are different throughout the HCV genome. The incidence of HCV types K1, K2a and K2b, and PT in 50 samples was 74%, 16%, 8% and 2%, respectively.

Base Sequence↗
PubMed1991

Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes.

In order to clarify the relationships between acetaldehyde (Ac-CHO) metabolism and low Km (mitochondrial) aldehyde dehydrogenase (ALDH2) genotypes, hepatic ALDH2 activity was determined and serial changes of blood Ac-CHO levels after ethanol administration were analyzed in the individuals homozygous for the normal ALDH2 genes, heterozygous for the normal and mutant ALDH2 genes, and homozygous for the mutant ALDH2 genes. Genomic DNA was extracted from white blood cells and genotyping of ALDH2 was performed using the polymerase chain reaction technique and slot blot hybridization with synthesized oligonucleotide probes specific to the normal and mutant ALDH2 genes. ALDH2 activity was not detectable in the liver in two cases of the mutant homozygote. In four out of eight cases of the heterozygote, hepatic ALDH2 activity was measurable, although the activity was lower compared with that in the normal homozygote. Blood ethanol levels after alcohol administration were not different among the three different ALDH2 genotypes. Blood Ac-CHO levels after drinking of alcohol were significantly higher in the heterozygotes and the mutant homozygotes than in the normal homozygotes. The levels after a moderate amount of ethanol (0.8 g/kg of body weight) in a case of the mutant homozygote were not different from those of the heterozygotes. However, the levels after a small amount of ethanol (0.1 g/kg of body weight) were significantly higher in the mutant homozygotes than in the heterozygotes. These results indicate that hepatic ALDH2 activity is lacking completely, and metabolism of Ac-CHO in the liver is severely impaired in the homozygotes of the mutant ALDH2 genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1991

Effect of mental stress on platelet aggregation: possible link to catecholamine levels.

The present study was aimed at testing the hypothesis about the relation between mental stress and platelet function. Plasma samples were obtained from 100 students immediately before, and 30 min and 7 h after undergoing a bleeding time test, which was used as mental stressor. Platelet responses to serotonin, ADP and collagen, as well as plasma catecholamine levels were assayed. Plasma serotonin levels had a high negative correlation with the bleeding time. Stress resulted in an increase in platelet responses to serotonin, ADP and to the elevation of catecholamine levels. Furthermore, a significant negative correlation between the platelet aggregation induced by ADP and collagen and the bleeding time was demonstrated. It is concluded that mental stress had a significant effect on platelet aggregation. This study provides evidence of increased platelet aggregability in association with elevated plasma catecholamine levels.

Adenosine Diphosphate↗
PubMed1991

Subcutaneous leiomyosarcoma developing in a radiation dermatitis.

A case of subcutaneous leiomyosarcoma developing in a skin affected by radiation dermatitis is presented. A 59-year-old patient had been suffering from radiation dermatitis induced by radiotherapy for a mediastinal tumor diagnosed at 24 years of age. Thirty-four years later, slow growing nodules developed in this lesion. Light and electron microscopic studies revealed that the tumor was a subcutaneous leiomyosarcoma. There is no previous report of a subcutaneous leiomyosarcoma developing in radiation dermatitis.

Dermatitis↗
PubMed1991

Microvascular decompression for hemifacial spasm. Patterns of vascular compression in unsuccessfully operated patients.

To determine the causative factors of unsuccessful microvascular decompression for hemifacial spasm, the follow-up results in 53 patients were assessed retrospectively. The mean follow-up period was 36 months. There were 32 patients who had compression of the seventh cranial nerve ventrocaudally by an anterior inferior cerebellar artery (AICA) or a posterior inferior cerebellar artery. Of these 32 patients, 30 (94%) had excellent postoperative results. Of 14 patients with more severe compression by the vertebral artery, nine (64%) had excellent results, three (21%) had good results, and two (14%) had poor results; in this group, three patients with excellent results experienced transient spasm recurrence. There were seven patients in whom the meatal branch of the AICA coursed between the seventh and eighth cranial nerves and compressed the dorsal aspect of the seventh nerve; this was usually associated with another artery compressing the ventral aspect of the nerve ("sandwich-type" compression). Of these seven patients, five (71%) had poor results including operative failure in one and recurrence of spasm in four. The authors conclude that the clinical outcome was closely related to the patterns of vascular compression.

Adult↗
PubMed1991

Different types of chronic hepatitis in alcoholic patients: does chronic hepatitis induced by alcohol exist?

To verify the existence of chronic hepatitis induced by alcohol, the clinicopathological features of chronic hepatitis in heavy drinkers were studied using various viral markers. Histological features of chronic active hepatitis were seen in 27 heavy drinkers. These patients were divided into four groups. The AL group (seven cases) consisted of alcoholics who were negative for both hepatitis C antibody and HBsAg; the HB group (four cases) was positive for HBsAg; the HC1 group (seven cases) was positive for hepatitis C antibody but negative for hepatitis C virus-RNA genome; and the HC2 group (nine cases) was positive both for hepatitis C antibody and hepatitis C virus-RNA genome. Serum AST and ALT activity declined during 4 wk of abstinence in most patients in the AL group and in the HC1 group. The response of serum AST and ALT to abstinence was poor in most patients in the HB group and the HC2 group. Serum desialo-transferrin and alcohol liver membrane antibodies were detected more frequently in the sera of patients in the AL group and HC1 group. A trend toward increased frequency of centrilobular ballooning existed in the AL group, but this did not reach statistical significance. These results suggest that chronic active hepatitis in patients in the AL group, in whom markers of HBV and hepatitis C virus were absent, may be caused by alcohol. Patients in the HC1 group who had hepatitis C antibody but not hepatitis C virus-RNA may represent cases where both alcohol and hepatitis C virus are involved.

Adult↗
PubMed1991

[Serum cholesterol levels in normal subjects taking into consideration the accuracy of the measuring system].

Serum cholesterol levels were determined in 5,843 normal subjects aged zero to seventy years. The accuracy of our assay method was checked by Standard Reference Material 909 and Certified Reference Serum, both of which were supplied by the National Bureau of Standards. Reference values of serum cholesterol were confirmed for each age group. That of male subjects in the 15-20 year age group was within a range of 109-203 mg/dl, and that of female subjects in the 20-25 year age group was within a range of 133-215 mg/dl. Therefore, among normal subjects, the above-mentioned age groups had the lowest serum cholesterol levels. Serum cholesterol levels increased with age in both male and female subjects. The upper limit of cholesterol levels was 248 mg/dl for males in the 50-60 year age group and 284 mg/dl for females in the same age group. We observed the necessity of paying consideration those changes which occur with aging, in the determination of reference values of serum cholesterol. Our findings also showed that serum cholesterol levels remained nearly constant in male subjects of all age groups over a period of 25 years. However, we found mean levels in female subjects in the 50-70 year age groups to be significantly elevated, when compared with those observed in persons in the same age group of 25 years previous. We also found that the mean cholesterol level in girls aged 12 years was higher than that of boys the same age.

Adolescent↗
PubMed1991

Alcoholic liver disease in heterozygotes of mutant and normal aldehyde dehydrogenase-2 genes.

To clarify the pathogenetic role of acetaldehyde in the development of alcoholic liver disease, genotyping of aldehyde dehydrogenase-2 genes was performed and the clinical features of the alcoholic liver disease patients with different genotypes were compared. Genotyping of aldehyde dehydrogenase-2 was performed in 47 patients with alcoholic liver disease using the polymerase chain reaction and slot-blot hybridization. Of the 47 patients with alcoholic liver disease, 40 were homozygous for the normal aldehyde dehydrogenase-2 gene and the remaining seven cases were heterozygous for the normal and mutant aldehyde dehydrogenase-2 genes. No homozygote was found for the mutant aldehyde dehydrogenase-2 genes. Daily alcohol intake was less than 100 gm in all heterozygotes without relation to the type of alcoholic liver disease. On the other hand, all but four patients homozygotic for the normal aldehyde dehydrogenase-2 gene drank more than 100 gm alcohol/day. The mean daily alcohol intake in the heterozygotes was significantly lower than that in the normal homozygotes. The incidence of alcoholic fibrosis tended to be lower in the heterozygotes than in the normal homozygotes (14.2% vs. 52.5%). On the other hand, the incidence of alcoholic hepatitis and/or cirrhosis tended to be higher in the heterozygotes than in the normal homozygotes. These results indicate that alcoholic liver disease develops even with moderate amounts of alcohol intake in heterozygotes of the aldehyde dehydrogenase-2 genes, in which acetaldehyde metabolism in the liver is impaired and liver damage in the heterozygotes is more severe than that in the normal homozygotes, suggesting that habitual drinkers who are heterozygotes of the aldehyde dehydrogenase-2 genes may be at high risk for alcoholic liver disease.

Alcohol Drinking↗