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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 199 records · Page 11Linked to original sources
PubMed1994

Genetic heterogeneity of dominantly inherited olivopontocerebellar atrophy (OPCA) in the Japanese: linkage study of two pedigrees and evidence for the disease locus on chromosome 12q (SCA2).

We did a linkage study of 2 multigenerational pedigrees with dominant olivopontocerebellar atrophy (OPCA) other than SCA1, with chromosome 12q microsatellites. Multipoint linkage analysis led to the conclusion that the disease locus locates within the 6.2 cM interval between IGF1 and D12S84/D12S105. This result coincides with that of Cuban ataxia pedigrees designated as SCA2. Our study provides genetic evidence that dominant OPCA in the Japanese consists of at least two genetically different disorders; SCA1 and SCA2.

Adolescent↗
PubMed1994

Genetic polymorphisms of cytochrome P4502E1 related to the development of alcoholic liver disease.

BACKGROUND/AIMS: Because heavy drinkers do not always develop alcoholic liver disease (ALD), genetic factors may be involved. Cytochrome P4502E1 is the main enzyme that oxidizes ethanol in the non-alcohol dehydrogenase pathway. Recently, the presence of genetic polymorphisms of this enzyme was confirmed. In the present study, the genotypes of P4502E1 were analyzed in patients with or without ALD. METHODS: After extraction of DNA from white blood cells, genotypes of P4502E1 were determined by restriction fragment length polymorphisms using two endonucleases. The genotypes were separated into three types: type A, type C (homozygous for the c1 or c2 gene), and type B (heterozygous for both genes). RESULTS: In 50 patients with ALD, the prevalence of type A was 16% and that of the c2 gene was 84%. The genotypes in 10 heavy drinkers without ALD were all type A. In 34 patients with non-alcoholic liver disease and in 88 patients without hepatobiliary disease, the prevalence of type A was 65% and 71%, respectively, indicating a significantly higher prevalence of the c2 gene in ALD. In healthy nonalcoholics, the prevalence of type A was 62%-68%. CONCLUSIONS: These results suggest that polymorphisms of P4502E1 may be related to the development of ALD.

Acetaminophen↗
PubMed1994

Relationships between serum lipids, serotonin, platelet aggregation and some fibrinolytic parameters in humans.

We have studied relationships between serum lipids, plasma serotonin (5-hydroxytryptamine, 5-HT), platelet aggregation in the platelet-rich plasma (PRP), and some fibrinolytic parameters in healthy volunteers. LDL was positively related to 5-HT-induced platelet aggregation. Higher serum HDL levels were related to higher fibrinolytic activity expressed by shorter euglobulin clot lysis time (ECLT). No correlation existed between serum lipids and plasma 5-HT. Plasma 5-HT was found to be related to tissue plasminogen activator (t-PA), suggesting some link between plasma serotonin and the release of t-PA from endothelial cells. There were mutual relations among fibrinolytic parameters such as tissue plasminogen activator (t-PA) antigens, total plasminogen activator inhibitor-1 (PAI-1), t-PA-PAI-1 complex, free PAI-1, and ECLT. In conclusion higher LDL may be more thrombogenic due to enhanced 5-HT induced platelet aggregation whereas high HDL may be more protective against thrombosis due to enhancement of fibrinolysis.

Adult↗
PubMed1994

Stress-dependent changes in fibrinolysis, serotonin and platelet aggregation in rats.

The effects of different kinds of acute stress on collagen-induced whole blood platelet aggregation and fibrinolysis in relation to blood serotonergic measures were studied. In rats water-immersion restraint stress resulted in a shortening of euglobulin clot lysis time (ECLT), an increase in tissue plasminogen activator (tPA) activity with a concurrent fall in its inhibitor activity. Footshock caused rather a suppression in fibrinolysis with a prolongation of ECLT and a decline in tPA activity as well as a reduction in whole blood platelet aggregation induced by collagen. Serotonin (5-HT) level, a marker of a severity of stress, increased after footshock application with a concomitant rise in its major metabolite-5-hydroxyindoleacetic acid (5-HIAA). This indicates an enhanced 5-HT metabolism. Following water-immersion restraint stress 5-HT and 5-HIAA levels did not differ from controls. In both groups of stressed animals an inverse correlation between tPA activity and blood serotonin was observed. Our data indicate that these types of stress may influence either fibrinolysis or peripheral serotonergic mechanism in different ways. Acute and severe stress such as footshock by causing an impairment in fibrinolysis and a rise in 5-HT may contribute to the pathogenesis of thrombosis and henceforth to the development of atherosclerosis.

Acute Disease↗
PubMed1994

Stress and/or tranylcypromine treatment affects serotonergic measures in blood and brain in rats.

Since stress can alter serotonin (5-hydroxytryptamine, 5-HT) turnover in the brain and the periphery, the effects of different types of acute stress on serotonin and related substances in the whole blood and various brain areas in rats pretreated with tranylcypromine (TCP) were studied. TCP administered alone caused a rise in 5-HT, a fall in its metabolite (5-hydroxyindoleacetic acid, 5-HIAA) in the whole blood and in every part of the brain analyzed relative to controls. In rats given TCP and subjected to footshock or water-immersion restraint stress similar changes, but to a different extent, were observed. 5-HT level remained essentially constant except in the blood and the limbic system, whereas 5-HIAA level was found to be increased in the blood and the brain, mainly in the limbic system and the brainstem following footshock. Water-immersion restraint stress caused an increase in 5-HT only in the limbic system without any changes in 5-HT and 5-HIAA in the blood. Relative to controls, an increase in total tryptophan concentration in the whole blood and in every part of the brain was found only after footshock application with or without pretreatment with TCP. In conclusion, responses to stress in rats may depend upon the type of stimulus applied as well as of a concurrent administration of TCP. Some regional differences may account for an altered in vivo efficacy of this drug.

Animals↗
PubMed1994

Effect of hypothalamic 5,7-dihydroxytryptamine lesion on the anterograde transport of serotonin as measured with labeled alpha-methyl serotonin.

The anterograde axonal transport of serotonin along the medial forebrain bundle (MFB) 5 days after unilateral dorsal hypothalamic 5,7-dihydroxytryptamine (5,7-DHT) lesion was examined in rat brain. Measurements were done using in vivo synthesized radioactively labeled alpha-methyl serotonin (used here as a serotonin tracer), from i.v. injected labeled alpha-methyl-L-tryptophan, a substitute neurotransmitter and analog of serotonin. Data indicated that after destruction of the presynaptic terminals with 5,7-DHT, the rate of axonal transport of serotonin and/or the rate of serotonin synthesis in the spared and/or damaged neurons was increased. The rate of serotonin anterograde transport on the lesioned side was above 25 mm/d compared to 12.31 +/- 0.49 mm/d on the contralateral side and 12.13 +/- 0.44 mm/d in control (sham injected) rats. The difference in rate between the lesioned and control rats was highly significant; P < 0.005 (two-tailed t-test). The amount of neurotransmitter anterogradely transported along the medial forebrain bundle and/or synthesized in the neurons was 18.8 +/- 4.1 times greater on the side of the 5,7-DHT hypothalamic lesion than that on the contralateral sides or that found in the saline-injected rats. There was no difference in the radioactivity found on the left or right side of the medial forebrain bundle in the rats 5 days after lesion in the rostal midbrain with 5,7-DHT. Five days after the lesion there was also no difference in the anterograde protein transport measured by stereotaxic injection of [3H]proline into the dorsal raphe.

5,7-Dihydroxytryptamine↗
PubMed1994

Serotonergic systems in brain and blood under stress and tranylcypromine treatment in rats.

The effects of stress on serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), and/or tryptophan in whole blood and various brain areas of rats pretreated with tranylcypromine were studied. In the whole blood, tranylcypromine given alone caused a rise in levels of 5-HT and a fall in levels of its metabolite (5-HIAA) and the ratio of 5-HIAA:5-HT, whereas in stressed rats pretreated with tranylcypromine only the last two findings were observed. We found that animals given tranylcypromine and subjected to water-immersion restraint stress exhibited the greatest rise in 5-HT levels in midbrain, hippocampus, and hypothalamus, together with the lowest 5-HIAA:5-HT ratio relative to controls, whereas in cortex, cerebellum, medulla, and striatum the highest levels of 5-HT together with the lowest ratio of 5-HIAA:5-HT were observed after the administration of tranylcypromine alone. 5-HT levels were found to be higher in medulla and striatum in rats given tranylcypromine alone relative to stressed rats pretreated with this drug. We concluded that regional differences account for variable effects of tranylcypromine on blood and brain serotonergic systems in vivo.

Animals↗
PubMed1994

Full-length sequence of the genome of hepatitis C virus type 3a: comparative study with different genotypes.

Hepatitis C virus (HCV) type K3a (type 3a), which represents a minor genotype in Europe, the U.S.A. and Asia, appears to be significantly distributed throughout Australia and Brazil. We amplified the HCV-K3a/650 genome by reverse transcription polymerase chain reaction in ten overlapping fragments and determined the nucleotide sequences. The total sequence was 9454 bases in length and contained an open reading frame of 3021 amino acids, which is 10 or 11 amino acids longer than in HCV type 1 and 12 amino acids shorter than the sequence of type 2. These differences were due to the different lengths of both the putative envelope protein E2 and the NS5A regions, whose nucleotide lengths differ between types 1 and 2 also. Phylogenetic analysis of the putative core region and a portion of NS5B encoding the Gly-Asp-Asp motif indicated that HCV-K3a closely matched the corresponding type 3a group. The deletion and addition of amino acids in both E2 and NS5A may be associated with their pathobiological features.

Amino Acid Sequence↗
PubMed1994

Growth-promoting effect of bacterial products from Clostridium perfringens on human keratinocytes.

Wound healing substance (WHS) from cultured Clostridium perfringens has been reported to be effective in the treatment of wounds. The effects of WHS, now named SNK-863, on proliferation and differentiation of human keratinocytes were examined. The characteristics of WHS are as follows: 1) WHS stimulates human keratinocyte growth and DNA synthesis; 2) WHS and EGF show some additive effects on human keratinocyte growth; 3) WHS does not interfere with the binding of EGF to its receptor; 4) WHS does not counteract the growth inhibitory effects of TGF-beta or vitamin D3 on human keratinocytes; 5) WHS has no significant effect on human keratinocyte differentiation. These results indicate that the growth-promoting effect of WHS on keratinocytes may contribute to the treatment of wound healing.

Cell Division↗
PubMed1994

Microheterogeneity of serum glycoproteins in alcoholics: is desialo-transferrin the marker of chronic alcohol drinking or alcoholic liver injury?

The appearance of desialo-transferrin (De-TF) in serum has been reported to be a biochemical marker of chronic alcoholism. However, conclusive evidence of whether De-TF is a marker for chronic alcohol drinking or for alcoholic liver disease (ALD) has not yet been obtained. Glycoproteins can be divided into two groups, a transferrin (TF) group and an alpha 1-acid glycoprotein (A1-AG) group, based on the characteristics of microheterogeneity (M-HTG) of each protein. In the present study, the appearance of M-HTG in serum TF and A1-AG in alcohol drinkers was compared. In 96 patients with ALD, M-HTG of TF was found in 66 patients (68.8%), and M-HTG of A1-AG was found in 61 patients (63.5%). In 20 patients with alcoholic pancreatitis, the detection rate of M-HTG of A1-AG was significantly higher than that of TF. In six patients with pancreatitis but not liver disease, M-HTG of TF was not detected. In 14 alcoholics without liver or pancreas disease, M-HTG of TF was not detected, whereas M-HTG of A1-AG was detected in 6 cases--a significant difference. The amount of alcohol consumed was not different in patients with and without liver disease. In non-ALD, M-HTG of both proteins was detected only in patients with decompensated liver cirrhosis. The detection rate of M-HTG in TF was significantly higher than in A1-AG. These results suggest that M-HTG of serum TF is a marker of ALD and that of serum A1-AG is a marker of chronic alcohol drinking.

Alcoholism↗
PubMed1994

Plasminogen activators and plasminogen activator inhibitor 1 in urinary tract cancer.

The plasminogen activation system is considered to play an important role in cancer growth and metastasis. Both plasminogen activators (PAs) and their fast-acting inhibitors are produced in tumor cells and their surrounding tissues. In order to clarify the influence of the existence of malignant tumor in urinary tract on the systemic fibrinolytic activity, we designed a study in which we compared the plasma levels of PAs and their inhibitors between before and after radical resection of tumors. Fourteen patients with renal cell carcinoma and 14 patients with transitional cell carcinoma participated in the study. In both groups, plasma levels of tissue-type plasminogen activator and urokinase-type plasminogen activator before the operation were higher than those 15 days after operation. The plasma level of plasminogen activator inhibitor 1 (PAI-1), however, did not change after the operation in the renal cell carcinoma group, and it decreased slightly in the transitional cell carcinoma group although it was not significant. When these values of the groups with or without metastasis were compared to other organs or lymph nodes, the PAI-1 level before operation was significantly higher in the group with metastasis than that without metastasis. In the three groups divided by the degree of atypia, PAI-1 level in the most atypical group was the highest. These results suggest that the fibrinolytic system in the plasma of cancer patients may play an important role in tumor growth and metastasis.

Carcinoma, Renal Cell↗
PubMed1994

Protection of mice against Aujeszky's disease virus infection by intranasal vaccination with inactivated virus.

Intranasal vaccination of mice with inactivated Aujeszky's disease virus (ADV) induced IgA and IgG antibody responses to the virus in the secretion of the respiratory tract, resulting in complete protection of the animals against intranasal challenge with virulent ADV. The immune response was enhanced by the use of the cholera toxin B subunit (CTB) as an adjuvant. On the other hand, subcutaneous vaccination of mice with inactivated ADV, even together with CTB, scarcely stimulated secretory antibody responses, resulting in only partial protection. The present results suggest that development of a vaccination procedure to stimulate the mucosal immune response should improve the protective effects of the inactivated herpesvirus vaccines, and thereby make it possible to control the infections by prohibiting virus replication at the site where primary infection takes place, as well as inhibiting subsequent latency and reactivation of the virus.

Administration, Intranasal↗
PubMed1994

Foot shock-induced changes in blood and brain serotonin and related substances in rats.

The effects of electric foot shock on peripheral and central serotonergic systems in rats have been studied. We have focused on the time course alterations with particular attention being paid to changes in 5-HT, 5-HIAA, tryptophan concentrations and 5-HIAA/5-HT ratios in blood and various parts of the brain, observed within 1 h following stress application. Blood and brain (7 regions) samples were taken immediately after electric foot shock, 30 min, 1 and 24 h later. In the blood stress induced a rise in tryptophan level as well as rises in 5-HT, 5-HIAA levels and 5-HIAA/5-HT ratio within 1 h following stressful treatment. Tryptophan concentration was found to be increased in every part of the brain within 1 h after electric foot shock application. In striatum it remained higher even after 24 h. 5-HT level showed a significant rise only in medulla, while hypothalamus was the sole region where a fall in 5-HT was found. In other parts of the brain 5-HT level remained unaffected by stress. 5-HIAA content increased in almost every brain area studied except cerebellum and striatum. 5-HIAA/5-HT ratios shared the same pattern of changes. Briefly, foot shock altered 5-HT turnover in various brain regions, in particular within the first hour following stress application, whereas delayed response to stress was rarely observed. Increased brain tryptophan level seems to be necessary to cope with the enhanced 5-HT metabolism caused by stress, reflecting as a rise in 5-HIAA concentration and 5-HIAA/5-HT ratio.

Animals↗
PubMed1994

Fenestration of the middle cerebral artery associated with an aneurysm--case report.

A 36-year-old female suddenly developed a severe headache. Computed tomography demonstrated subarachnoid hemorrhage in the left Sylvian fissure. Left carotid angiography revealed a fenestration at the distal portion of the M1 portion of the left middle cerebral artery, and an aneurysm arising from the proximal end of the fenestration. These findings were confirmed when the aneurysm neck was clipped. The embryonic origin of this lesion indicates that congenital factors may result in aneurysm formation.

Adult↗
PubMed1994

Detection of antigens related to hepatitis C virus RNA encoding the NS5 region in the livers of patients with chronic type C hepatitis.

Hepatitis C virus is a positive single-strand RNA virus distantly related to flaviviruses. Therefore RNA replicase, an RNA-dependent RNA polymerase, may be essential for the replication of hepatitis C virus, as well as other RNA viruses. In this study we synthesized the recombinant polypeptide (HCV-NS5 antigen) with a 576 bp cDNA encoding a part of the NS5 region of the HCV genome that has the Gly-Asp-Asp motif. The antibody against this polypeptide was obtained from rabbit serum. In Western-blot analysis with NS5 IgG HCV antibody, an 84-kD protein was clearly detected as a single band in the microsomal fraction but not in the nuclear and mitochondrial fractions or in the cytosol fraction. Immunohistochemically, HCV-NS5 antigen was clearly stained in the cytoplasm of hepatocytes but not in the nucleus or cell membrane. Moreover, as determined on immunoelectron microscopy, HCV-NS5 antigen was demonstrated with fine granular distribution along the endoplasmic reticulum but not in other organelles, including the nucleus and mitochondria. Immunoreaction in other cell types was negative. These results indicate that replication of HCV may occur only in hepatocytes and that HCV-NS5 may be produced in the endoplasmic reticulum of these cells. HCV-NS5 antigen was stained only in the livers of hepatitis C virus-positive patients but not in sections from patients with chronic type B hepatitis or alcoholic fibrosis. In chronic type C liver disease, the overall detection rate of HCV-NS5 antigen was 56% (33% in chronic persistent hepatitis, 52% in chronic active hepatitis and 86% in cirrhosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Genotypes of ALDH2 related to liver and pulmonary diseases and other genetic factors related to alcoholic liver disease.

Genetic factors related to the development of alcoholic liver and pancreatic diseases (ALD and APD) and of alcohol-induced asthma were analyzed. The development of ALD is genetically controlled and is directly associated with the polymorphisms of the genes of acetaldehyde (Ac-CHO) and ethanol-metabolizing enzymes, aldehyde dehydrogenase-2 (ALDH2) and cytochrome P4502E1. The development of ALD and APD may also be genetically linked with the induction of gamma-glutamyl transferase (GTT) by alcohol. Alcohol-induced asthma is related to the genotypes of ALDH2 and is caused by rapid elevation of blood Ac-CHO. ALDH1 plays a very important role in the oxidation of Ac-CHO in blood.

Acetaldehyde↗
PubMed1994

Acquisition of pathogenicity of a Newcastle disease virus isolated from a Japanese quail by intracerebral passage in chickens.

Newcastle disease virus (NDV) was isolated from a Japanese quail (Cotornix cotornix japonica). The effect of intracerebral and intranasal passages of the NDV in chickens on the pathogenicity was studied. Pathogenicity of the viruses of different passage levels was compared with that of the original isolate by the mean death time with the minimum lethal dose in chicken embryos, intracerebral pathogenicity index in day-old chicks, intravenous pathogenicity index with 6-week-old chickens and the mortality rates of chickens and quails inoculated intravenously or intranasally. The original isolate from the quail did not kill chickens but only embryos and some one-day-old chicks, exhibiting a mesogenic character. Pathogenicity of the virus of the 10th intranasal passage was not different from that of the original isolate. The viruses passaged intracerebrally, on the other hand, killed chickens of all ages by either route of inoculation, showing a velogenic property. Virus recovery from the blood and the brain was positive only in the chickens infected with brain-passaged viruses by any route of inoculation. Virus titers in the tissues of chickens infected with the brain-passaged viruses were higher than those with the original isolate and the virus of the 10th intranasal passage. These results indicate that the enhanced pathogenicity of the mesogenic NDV isolate from the quail for chickens was induced by acquiring the properties of neurotropism and pantropism through intracerebral passage in chickens.

Animals↗