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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 253 records · Page 14Linked to original sources
PubMed1993

Serotonergic measures in blood and brain and their correlations in rats treated with tranylcypromine, a monoamine oxidase inhibitor.

Tranylcypromine, a monoamine oxidase inhibitor, was administered to male Wistar rats in order to investigate its effects on blood and brain serotonin related substances after 1, 4, and 24 h following injection and possible relations between serotonergic measures in central nervous system and periphery. The dose of the drug tested was responsible for an increase in blood serotonin with a simultaneous fall in its metabolite 5-hydroxyindoleacetic acid (5-HIAA) compared to either pretreatment or control values. These changes were the most marked after 4 and 24 h following tranylcypromine injection. Almost all brain areas studied (cerebellum, medulla, hypothalamus, striatum, midbrain, hippocampus, and cortex) were to be affected by monoamine oxidase inhibitor treatment. They exhibited a rise in serotonin content starting from 1 h after drug administration and lasted in many parts of the brain up to 24 h, which was accompanied by a parallel fall in 5-HIAA level. All these changes were significant when compared to baseline and control values. Alterations in blood serotonin correlated positively with changes in brain serotonin and negatively with brain 5-HIAA, while the opposite pattern of correlations was found regarding blood 5-HIAA and the content of serotonin and 5-HIAA in various brain areas studied. This pattern of correlations speaks in favor of an existence of mutual relations between blood and brain serotonin related substances. Our results suggest that blood serotonin and 5-HIAA may serve as an index of monoamine oxidase inhibitor action on the central serotonergic system.

Animals↗
PubMed1993

The alcohol-altered liver membrane antibody and hepatitis C virus infection in the progression of alcoholic liver disease.

Progression of alcoholic liver disease is closely related to drinking habits. However, prognosis of alcoholic liver disease is not determined just by drinking habits, but also by other factors. In this study, the roles of alcohol-altered liver membrane antibody and hepatitis C virus infection were analyzed in alcoholic patients who were followed up for various lengths of time. Serial changes of liver histological appearance were analyzed in 39 patients with alcoholic liver disease who were followed for long periods (49.7 +/- 34.3 mo) and who underwent liver biopsy at least two times. Prognoses of 35 patients with alcoholic cirrhosis who were followed for more than 1 yr were also evaluated. Development of cirrhosis in alcoholic liver disease was significantly higher in the alcohol-altered liver membrane antibody-positive patients than in the patients negative for this antibody. On the other hand, hepatitis C virus markers were not related to development of cirrhosis. However, hepatocellular carcinoma developed more frequently in the hepatitis C virus marker-positive patients. In patients with cirrhosis, the cumulative rates of hepatocellular carcinoma development were significantly higher in the hepatitis C virus marker-positive patients than in the marker-negative patients. Cumulative survival rates in the hepatitis C virus marker-positive patients were significantly lower than rates in the hepatitis C virus marker-negative patients, even in noncancer patients. However, such differences were not observed in the alcohol-altered liver membrane antibody-positive and alcohol-altered liver membrane antibody-negative cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohols↗
PubMed1993

Role of ethanol-inducible cytochrome P-450 2E1 in the development of hepatocellular carcinoma by the chemical carcinogen, N-nitrosodimethylamine.

Cytochrome P-450 2E1 is a specific isozyme of cytochrome P-450 induced by ethanol. P-450 2E1 may also be the only enzyme that metabolizes N-nitrosodimethylamine at a very low concentration. Because N-nitrosodimethylamine is a procarcinogen, the possibility that induction of P-450 2E1 by alcohol abuse may accelerate the carcinogenic action of a very small dose of N-nitrosodimethylamine should be considered. To investigate this possibility, effects of ethanol on the hepatic carcinogenic action of a very small dose of N-nitrosodimethylamine were analyzed in rats. Sixty Wistar male rats were divided into two groups (ethanol and control) according to the liquid diets they were fed. After preliminary feeding, N-nitrosodimethylamine in two concentrations (1.5 ng/ml and 3.0 micrograms/ml) in drinking water was given with the diets for 40 or 60 wk. To avoid metabolic competition between ethanol and n-nitrosodimethylamine, we gave N-nitrosodimethylamine and the diets alternately. The average amount of N-nitrosodimethylamine consumed per day was 11 to 37 ng/kg body weight in the 1.5-ng group and was 27 to 37 micrograms/kg body weight in the 3.0-microgram group. Hepatic P-450 2E1 content was six times higher in the ethanol-treated groups than in the control groups throughout the experiment. Visible nodules and enzyme-altered foci were not found in rats in any group at the end of the fortieth week. These preneoplastic changes were found at the end of the sixtieth week only in rats in the groups treated with both ethanol and N-nitrosodimethylamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Genetic and epidemiologic studies on alcoholic liver diseases].

Polymorphic alleles of several genes such as ADH2, ALDH2, ApoB100, GST1, GST3 and ALAD were investigated from the aspect of the relationship with alcohol related diseases. DNAs were prepared from whole blood samples of 84 healthy controls (male), 70 patients (male) with alcohol related diseases and 87 patients (male) with non-alcoholic diseases. PCR technique was used for the detection of GST1 showed a good correlation to alcoholic liver diseases. The patients with alcoholic liver diseases had a higher frequency of ALDH2*1 than the healthy controls (p < 0.005). The frequencies of GST1 gene deletion in the samples were as follows: Healthy controls; 47.6%, alcoholic liver diseases (fibrosis: 75%, cirrhosis: 65.5%, hepatoma: 75%) and non-alcoholic liver diseases: 54%. The data indicated that the patients with alcoholic liver diseases had a significantly higher frequency of gene deletion than the healthy controls (p < 0.005). In addition, homozygote of ALAD1 allele detected by MpsI-RFLP showed a good correlation to alcoholic liver diseases. Thus, the genetic polymorphism of ALDH2, GST1 gene deletion and ALAD can be applied widely for the study of genetic association with alcoholic liver diseases.

Alcohol Dehydrogenase↗
PubMed1993

Serotonin as a factor involved in pathophysiology of thromboangiitis obliterans.

Whole blood and plasma levels of serotonin (5-hydroxy-tryptamine, 5-HT) as well as its uptake and spontaneous release from blood platelets were studied in 20 patients suffering from thromboangiitis obliterans (TAO, Buerger's disease) and 20 healthy subjects matched in pairs for age. Results of patients suffering from thromboangiitis obliterans differed in several ways from those of controls. Whole blood 5-HT content was significantly lower in the group of patients compared to that of the control group. It was established that patients with Buerger's disease have significantly greater plasma concentrations of free serotonin. In Buerger's disease patients, maximal platelet serotonin uptake velocity (Vmax) was significantly decreased. It was associated with the enhanced spontaneous release of 5-HT from blood platelets. We conclude that impaired platelet serotonin uptake and increased local concentration of serotonin in the vicinity of platelets in Buerger's disease may lead to platelet activation via 5-HT2 receptors, and it could be involved in the pathogenesis of thromboembolic complications.

Adult↗
PubMed1993

Changes in type IV collagen content in livers of patients with alcoholic liver disease.

An increase of serum type IV collagen levels in patients with liver disease has been reported; however, the mechanisms of this increase are not yet well known. We recently developed an assay system for type IV collagen content in liver biopsy specimens. In this study, type IV collagen content in the livers and sera of patients with alcoholic liver disease and nonalcoholic liver disease was determined. Serum and hepatic type IV collagen contents were measured with a one-step sandwich enzyme immunoassay system using monoclonal antibodies for human type IV collagen. Hepatic type IV collagen content increased significantly in liver disease. In alcoholic liver disease, type IV collagen content in patients with mild fibrosis was lower than that in advanced types of alcoholic liver disease. In nonalcoholic liver disease, hepatic type IV collagen content tended to increase with the progression of fibrosis. Type IV collagen content in alcoholic liver disease was significantly higher than that in the corresponding type of nonalcoholic liver disease. Hepatic total collagen content increased significantly in parallel with the progression of fibrosis in both alcoholic liver disease and nonalcoholic liver disease. The total collagen content in each type of alcoholic liver disease was significantly lower than that in the corresponding type of nonalcoholic liver disease. The ratio of type IV collagen to total collagen content was the highest in livers showing mild fibrosis, both in alcoholic liver disease and nonalcoholic liver disease, and decreased in parallel with the progression of fibrosis. The ratio in patients with alcoholic liver disease was significantly higher than that in those with the corresponding nonalcoholic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen↗
PubMed1992

Autoradiographic study of peripheral benzodiazepine receptors in animal brain tumor models and human gliomas.

In vitro binding of [3H]PK-11195 (1-(2-chlorophenyl)-N-methyl-(1- methylpropyl)-3-isoquinoline carboxamide) in rodent AA ascites and C6 glioma as well as in human gliomas was investigated. The Bmax (mean +/- S.D.) of AA ascites tumor and C6 glioma is 1.39 +/- 0.15 pmol/mg tissue and 4.50 +/- 0.76 pmol/mg tissue, respectively. This Bmax is 9 and 30 times, respectively, higher than the one found in the rat cortex (0.15 +/- 0.03 pmol/mg tissue). A Bmax of 1.26 +/- 0.24 pmol/mg tissue and 0.64 +/- 0.08 pmol/mg tissue was found in human malignant and low grade gliomas respectively. This Bmax value should be compared to 0.35 +/- 0.04 pmol/mg tissue found in the normal human cortex. There are significant (P less than 0.05) differences between Bmax in tumors and normal cortex. There was no significant difference in KD between the malignant and low grade gliomas. C6 glioma has a KD significantly greater than rat cortex. In some cases of human low grade gliomas, kinetic measurements suggested the presence of two affinity receptor sites. However, at this time, heterogeneity of the tissue cannot be excluded as being at least in part a source of this.

Animals↗
PubMed1992

Endothelins inhibit serotonin-induced platelet aggregation via a mechanism involving protein kinase C.

Endothelins are a family of three peptides that act as local hormones released by the endothelium. They were found to inhibit rabbit and dog platelet aggregation in vivo, but no effect was observed in vitro. In order to investigate the possible interaction between endothelins and human platelet serotonin receptors, their effects on platelet aggregation induced by serotonin was studied. Endothelin-1, -2 and -3 had a dual action, on platelet aggregation and calcium mobilization induced by serotonin. When added at the same time as serotonin, endothelin potentiated the response to the amine. On the contrary, preincubation of platelet suspension with endothelin resulted in a concentration-dependent inhibition of the serotonin-mediated platelet response. Moreover, endothelin-1 inhibited serotonergic amplification of epinephrine-induced aggregation of platelets. We hypothesize that endothelins can bind to the platelet membrane and interact with serotonin receptors. The diverse effect of endothelins on serotonin-induced aggregation and calcium mobilization may be due to stimulation of protein kinase C.

Adult↗
PubMed1992

Blood serotonergic mechanisms in type 2 (non-insulin-dependent) diabetes mellitus.

Serotonin (5-hydroxytryptamine, 5HT) is believed to play a role in vasospasm and increased platelet aggregability that in turn could contribute to atherosclerosis. The present study was designed to evaluate a possible participation of serotonin in the development of vascular complications in diabetes mellitus. Whole blood and plasma serotonin, the platelet uptake and release of the amine and serotonin- induced platelet aggregation were studied in 32 patients with Type 2 diabetes. The patients were divided into three groups according to the presence and advancement of retinopathy. Mean levels of blood serotonin content were significantly lower in diabetic patients. The concentration of the amine in the plasma was markedly increased in diabetes. It was correlated with vascular changes of the retina. We established that platelets from diabetic patients took up less serotonin when compared to the control group. Concomitantly enhanced spontaneous release of 5HT from platelets was observed. The platelets of diabetic patients showed increased response to serotonin. There was a relation between serotonin-induced aggregation and the presence of retinopathy. These results suggest that serotonin may be involved in the pathogenesis of diabetic vasculopathy.

Adult↗
PubMed1992

Plasminogen activators and plasminogen activator inhibitor 1 before and after venous occlusion of the upper limb in thromboangiitis obliterans (Buerger's disease).

Plasma levels of plasminogen activators (t-PA, u-PA) and their inhibitor (PAI-1) were studied in patients suffering from Buerger's disease and healthy volunteers before and after 15 minutes of venous occlusion test. The baseline levels of t-PA in group of patients did not differ from those of controls. On the contrary patients with Burger's disease showed a marked increase in u-PA antigen concentrations with concomitant decrease in PAI-1 antigen levels. During venous stasis t-PA antigen concentrations increased in all subjects, however it was much pronounced in controls. Venous occlusion resulted in significant decrease in free PAI-1 levels in the group of patients only. In conclusion, Buerger's disease is associated with the endothelial derangement with increased u-PA release and decreased PAI-1 release, which does not influence the function of fibrinolytic system. The fact that the reduced response of the endothelium to release t-PA after venous stasis goes in parallel with marked decrease in PAI-1 antigen levels seems to suggest that patients suffering from Buerger's disease are not at high risk of intravascular fibrin deposition.

Arm↗
PubMed1992

Possible role of plasminogen activator inhibitor 2 in the prevention of the metastasis of gastric cancer tissues.

The concentrations of urinary type plasminogen activator (u-PA), plasminogen activator inhibitor 1 (PAI-1), and PAI-2 were measured in gastric cancer tissues and adjacent healthy mucosal tissues. Levels of u-PA, PAI-1 and PAI-2 were higher in cancer than in control tissues. PAI-1 levels were higher together with the progression of cancer however there were no differences in u-PA or PAI-2 levels. Tumors with higher PAI-1 and lower PAI-2 levels tend to metastasize to remote lymph nodes. When the numbers of involved lymph nodes were analyzed, tumors with the large number of metastatic lymph nodes showed higher PAI-1 and lower PAI-2 level. No difference was shown in u-PA levels among these groups. These tendencies were more significant in patients with progressed gastric cancer. These results suggest that tumor with higher PAI-2 levels tend to localize or have less tendency to metastasize to lymph nodes. On the other hand PAI-1 was generally higher in tumor with invasion into nearby tissue or with nodal metastasis.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Plasminogen activator system in human breast cancer.

We measured antigen levels of 2 kinds of plasminogen activator, tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (UK), as well as those of their primary inhibitors, type-I plasminogen activator inhibitor (PAI-1) and type-2 plasminogen activator inhibitor (PAI-2), in tissue extracts from benign and malignant breast tumors. Tumor tissue samples from 40 fibroadenomas and 40 breast cancers were examined. t-PA antigen levels were the same in the 2 groups. Malignant tumors contained higher levels of UK antigen than did benign tumors. In the case of breast cancer, UK antigen levels of tumors with axillary lymph-node involvement were significantly higher than those of tumors without lymph-node involvement. PAI-1 and PAI-2 antigen levels of breast-cancer tissue samples were higher than those of fibroadenoma samples. PAI-1 antigen levels of carcinomas with lymph-node involvement were also significantly higher than those of carcinomas without node involvement. PAI-2 antigen levels, on the contrary, were higher in carcinomas without node involvement. UK, PAI-1 and PAI-2 antigen levels are potentially excellent independent factors for prediction of the metastatic potential of breast cancers.

Breast Neoplasms↗
PubMed1992

Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.

Base Sequence↗
PubMed1992

Changes in the markers related to collagen synthesis in the liver of chronically alcohol treated rats.

In order to clarify the roles of Ito cells in the development of alcoholic fibrosis, markers related to collagen synthesis in the liver were analyzed in chronically alcohol treated rats. The livers were obtained from rats fed a diet containing alcohol (alcohol group) and those fed a control diet (control group) for 4 weeks. Prolyl hydroxylase (PH) activity in the whole liver tissue did not differ in the alcohol and control groups. However, the activity in the isolated Ito cells was significantly higher in the alcohol group than in the control group. Immunoreactive PH beta-subunit contents in the liver and serum were significantly higher in the alcohol group than in the control group. Hydroxyproline contents in the liver did not differ in either groups. Immunohistochemically, type IV collagen and laminin were clearly stained along with the sinusoid in the livers of the alcohol group. However, the staining reactions were very weak in the control group. Staining reactions to types I and III collagen were very weak or almost absent in the livers of both groups. Desmin-positive cells, along with the sinusoid, increased significantly in the alcohol group, especially at the centrilobular area, suggesting that the number of Ito cell increase in the centrilobular areas of the alcohol treated rats. These results suggest that type IV collagen and laminin synthesis increase in the Ito cells of chronically alcohol treated rats, although clear evidence of hepatic fibrosis was not obtained. This increase may be related to capillarization of the sinusoids and finally to the development of perisinusoidal fibrosis in alcoholics.

Animals↗
PubMed1992

Effects of vitamin A on collagen metabolism by cultured rat liver cells.

Conflicting results have been reported concerning the phenotypes of collagen produced by cultured Ito cells. These variations may be attributed to differences in pretreatment, i.e., with or without vitamin A to facilitate the separation of Ito cells. In the present study, the effects of vitamin A on collagen metabolism by Ito cells and hepatocytes of rats were analyzed. In cultured Ito cells, staining reactions to type I collagen increased, and those to type IV collagen and laminin decreased after pretreatment with vitamin A. The rate of collagen synthesis by Ito cells decreases significantly by treatment with vitamin A. The decrease was clearer in degraded collagen than in intact collagen. The synthesis of type I collagen increased and that of type IV collagen significantly decreased in Ito cells by treatment with vitamin A. In the hepatocytes, the staining reaction to type I collagen increased with vitamin A pretreatment. The net collagen and type III collagen synthesis in hepatocytes decreased by treatment with vitamin A. These results indicate that vitamin A modifies collagen metabolism in different cell types in different ways.

Animals↗
PubMed1992

Relationship between serotonergic measures in periphery and the brain of mouse.

Circadian rhythm and the relationship between the concentration of serotonin (5HT) and related substances (5-hydroxyindoleacetic acid; 5HIAA and tryptophan; Trp) in mouse brain, stomach and blood have been studied. All factors underwent circadian changes in the brain and blood. 5HT and 5HIAA levels in the stomach showed no circadian fluctuation. The concentrations of 5HT in the brain and blood did not correlate. Significant correlations were found between other serotonergic parameters analyzed in brain, stomach and blood. A significant negative correlation was observed between brain 5HIAA and blood 5HIAA. The concentration of tryptophan in the brain was correlated with the plasma total tryptophan level. There was fairly significant correlation (p less than 0.06) between brain serotonin and plasma tryptophan levels. The brain serotonin and tryptophan levels were strongly correlated (R = 0.410, p less than 0.03). Significant negative correlation was found between serotonin in the blood and serotonin in the stomach as well as between its level in the brain and in the stomach. The significance of these findings and their relationship to the use of peripheral serotonergic system as a model of neurons are discussed.

Animals↗