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Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 397 records · Page 22Linked 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

[Age-related changes in Bruch's membrane of the senescence accelerated mouse].

We studied pathological changes in Bruch's membrane of Senescence Accelerated Mouse (SAM) P/1. Tannic acid was used to demonstrate collagen fibers and microfibrils in Bruch's membrane. With aging, thickening of Bruch's membrane, especially thickening of the basement membrane of the choriocapillaris, was remarkable. The distance between collagen fibers also became wider, and many more fine fibrils appeared around each collagen fibril with aging. These changes were observed mor in the posterior area than in the periphery.

Aging↗
PubMed1993

[Basic and clinical evaluation of EIA (pin immuno assay, PIA) kit for antithyroglobulin antibody (TGAb) and antimicrosomal (antiperoxidase) antibody (TMAb)].

Newly developed enzyme immunoassay kit (Pin Immuno Assay, PIA) for quantitative determination of serum antithyroglobulin antibody (TGAb) and antimicrosomal (-peroxidase) antibody (TMAb) was evaluated. The method utilizes the Sandwich ELISA principle with a unique micropin as solid phase coated with antigen. Reproducibilities assessed by intra- and interassay variation were less than 6.9% (CV) and 7.2% for TGAb or 4.2% and 6.0% for TMAb respectively. Changes in the first or second incubation time did not affect both TGAb and TMAb values. Upper normal limits obtained from 47 healthy subjects were 150 IU/ml for TGAb and 25 IU/ml for TMAb. Positive results in TGAb were obtained 60.0% in patients with Graves' disease and 80.0% in chronic thyroiditis and in TMAb 77.8% in Graves' disease and 66.7% in chronic thyroiditis. Patients with other autoimmune diseases such as SLE, RA were also found high incidence of positive results, 48.3% for TGAb and 65.0% for TMAb respectively. These results indicate that the nonradioisotopic assay technique for thyroid autoantibodies are useful in diagnosis of autoimmune diseases especially thyroid diseases.

Autoantibodies↗
PubMed1993

Plasma amino acid profile in relation to arterial ketone body ratio in surgical patients.

A total of 357 plasma amino acid profiles from 93 surgical patients were statistically analyzed in relation to the changes in arterial ketone body ratio, which reflects the hepatic mitochondrial redox state. When the arterial ketone body ratio was above 0.7, all plasma amino acid levels were within the normal range. When it was between 0.7 and 0.4, plasma levels of aspartate, glutamate, valine, isoleucine, leucine, ornithine, and arginine decreased, and plasma levels of tyrosine, phenylalanine, proline, and methionine increased. Furthermore, when it was below 0.4, almost all plasma amino acids markedly increased. These results indicate that arterial ketone body ratio accurately reflects the alterations in plasma amino acid profile, and can serve as an indicator for providing nutritional support by amino acid supplement in surgical patients.

Adult↗
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

Increased arterial ketone body ratio as a prerequisite for recovery after hepatectomy.

It is reported that a prompt increase in the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate), which reflects the mitochondrial redox state of the liver graft, is a decisive prerequisite for graft survival in clinical liver transplantation. To contrast the rôle of hepatic mitochondrial redox state in partial hepatectomy with that in hepatic replacement, the changes in the ketone body ratio were investigated in 107 cases of hepatectomy. The ketone body ratio in uneventful cases (n = 70) in the first three days after hepatectomy was significantly higher than that in eventful cases. In the uneventful cases, the ketone body ratios were all increased to above 1.0 within two days after hepatectomy, except in diabetics, whose preoperative values did not reach 1.0 under oral glucose load. However, 20 (22.7%) out of 88 cases whose ketone body ratios promptly increased after hepatectomy had mild to moderate complications thereafter. It is suggested that the recovery of hepatic mitochondrial redox state is also a prerequisite in partial hepatectomy, where a reduced and often damaged liver confronts systemic metabolic load.

Adenoma, Bile Duct↗
PubMed1993

Changes in energy substrates in relation to arterial ketone body ratio after human orthotopic liver transplantation.

BACKGROUND: Changes in energy substrate metabolism, as well as those in arterial ketone body ratio (KBR; acetoacetate/3-hydroxybutyrate), were investigated to follow energy status of hepatic allograft. METHODS: Plasma concentrations of energy substrates were measured immediately after 35 orthotopic liver transplantations in 32 adult patients. RESULTS: Twenty-three patients left the intensive care unit within 1 month (group A), six patients were forced to stay in the intensive care unit longer than 1 month (group B), and the other six grafts failed within 1 month (group C). In group B the KBR was significantly lower than in group A 6 hours after reperfusion of the grafts (0.70 +/- 0.09 vs 1.21 +/- 0.10, mean +/- SEM; p < 0.05). In group C the KBR remained significantly lower than in group A at 6 hours (0.65 +/- 0.04 vs 1.21 +/- 0.10; p < 0.01), on the first postoperative day (0.64 +/- 0.03 vs 1.36 +/- 0.10; p < 0.001), and on the second postoperative day (0.65 +/- 0.02 vs 1.58 +/- 0.11; p < 0.01). Total ketone body concentration (TKB) was significantly higher in group B than in group A at 4 hours (462.9 +/- 105.0 mumol/L vs 201.6 +/- 32.6 mumol/L; p < 0.01), 6 hours (483.4 +/- 102.1 mumol/L vs 125.5 +/- 25.9 mumol/L; p < 0.001), and the first postoperative day (481.1 +/- 196.6 mumol/L vs 123.9 +/- 24.1 mumol/L; p < 0.001). No increase in TKB was observed in group C. CONCLUSIONS: It is suggested that low values in KBR accompanied with low levels of TKB should be regarded as a strong indicator of graft failure and fatty acid oxidation and ketogenic pathways are accelerated to compensate for energy deficits in patients with low values in KBR and high levels of TKB until KBR recovers immediately after orthotopic liver transplantation.

Acyl Coenzyme A↗
PubMed1992

Apolipoprotein E1 Lys-146----Glu with type III hyperlipoproteinemia.

During the screening of samples obtained from 5 individuals with type III hyperlipidemia, we identified a variant of apolipoprotein (apo) E which exhibited a discrepancy in apo E phenotype showing the E3/E1 isoform on isoelectric focusing (IEF) analysis and E3/E3 on gene analysis. Sequence analysis of the DNA of the proband that was amplified by PCR and subcloned, revealed a single substitution of one lysine (AAG) for one glutamic acid (GAG) at position 146, thereby adding two negatively charged units to apo E3. This defect had been described only for apo E1 to date (Mann et al. (1989) Clin. Res. 37, 520A (abstract)). In this case, PCR-mediated site-directed mutagenesis was used to identify the structural alterations forming the abnormal E1 genotype in the proband's family. Purified apo E1 Lys-146----Glu showed less than 10% of binding activity to apo B, E receptor on human skin fibroblasts compared with apo E3. This substitution demonstrates that Lys-146 is essential for the binding of apo E to the receptor.

Adult↗
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

Application of a novel apparatus, the quartz chemical analyzer, to the determination of endotoxin in blood.

A novel apparatus called a quartz chemical analyzer (QCA) has been developed using a quartz crystal resonator. This apparatus measures sample viscosity changes based on resonant frequency changes of the quartz crystal. The apparatus was used to determine bacterial endotoxin concentrations by monitoring the gelation reaction of Limulus amebocyte lysate. The QCA determined endotoxin concentrations with good accuracy and reproducibility in the range of 0.001-3 EU/ml for endotoxin standard (JP XII). For endotoxin determination in human whole blood and plasma samples, the inhibitory reaction was eliminated by pretreatment of a fourfold dilution at 60 degrees C and incubation for 30 min. There are many advantages of the QCA method compared with the turbidimetric and chromogenic methods. For example, QCA can measure sample viscosity changes with high sensitivity and accuracy because QCA detects minor resonant frequency changes and the frequency data give a numerical value for easy quantitation. QCA can examine turbid samples, and the required quantities of samples and reagents are small, since the quartz crystal detects sample viscosity changes directly. The endotoxin determination time may be shortened by raising the reaction temperature, and QCA can detect other types of coagulation reactions.

Antithrombin III↗
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

Rapid high-affinity transport of a chemotherapeutic amino acid across the blood-brain barrier.

The therapeutic efficacy of many anticancer drugs against intracerebral tumors is limited by poor uptake into the central nervous system. One way to enhance brain delivery is to design agents that are transported into the brain by the saturable nutrient carriers of the blood-brain barrier. In this paper, we describe a nitrogen mustard amino acid, DL-2-amino-7-bis[(2-chloroethyl)amino/bd-1,2,3,4-tetrahydro-2-napthoi c acid, that is taken up into brain with high affinity by the large neutral amino acid carrier of the blood-brain barrier. Brain transport of DL-2-amino-7-bis[(2-chloroethyl)aminol-1,2,3,4-tetrahydro-2-naphth oic acid in the rat was found to be rapid (cerebrovascular permeability-surface area product approximately 2 x 10(-2) ml/s/g), saturable and inhibitable by large neutral amino acids. Maximal influx rate (Vmax) and half-saturation (Km) constants equaled 0.26 nmol/min/g and 0.19 microM, respectively, in the parietal cortex. Regional brain uptake of acid exceeded that of the clinical analogue, melphalan, by greater than 20-fold. The results demonstrate that drug modification to produce high-affinity ligands for the cerebrovascular nutrient carriers is a viable means to enhance drug delivery to brain for the treatment of brain tumors and other central nervous system disorders.

2-Naphthylamine↗
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

Suppressive effect of carbachol on forskolin-stimulated neurite outgrowth in human neuroblastoma NB-OK1 cells.

We have used human neuroblastoma NB-OK1 cells to investigate the regulation of neurite outgrowth. Carbachol suppressed forskolin-stimulated neurite outgrowth in NB-OK1 cells although forskolin-stimulated cAMP levels were enhanced. The dose-response curve for this suppression was very similar to that for stimulation of inositol monophosphate (IP1) formation and for stimulation of the initial rise of [Ca2+]i elicited by carbachol. Carbachol-mediated changes in neurite outgrowth, IP1 formation and [Ca2+]i displayed high sensitivity for pirenzepine but low sensitivity for AF-DX116. Inhibition of intracellular calcium release with TMB-8 prevented the suppressive effect of carbachol on forskolin-stimulated neurite outgrowth. Hence we describe for the first time a relationship between neurite outgrowth and inositol triphosphate-triggered calcium release mediated by carbachol in the human neuron-derived cell line.

Atropine↗
PubMed1992

Administration of slow-release nifedipine does not affect lactate threshold, hormone release during exercise, and quality of life in normal subjects.

In a double-blind crossover study of 10 normal healthy subjects, we examined the effects of slow-release nifedipine (nifedipine-SR, 10 mg b.i.d) administration on exercise capacity, hormone levels during exercise, and quality of life (QOL) after a 2-week treatment. Two exercise tests, a progressive exercise test and a constant work-rate exercise test, were performed. Maximal oxygen uptake (VO2max) and blood lactate concentration were measured during the progressive exercise test and the exercise intensity corresponding to half lactate threshold (LT), LT, and 4 mmol/l of lactate concentration was determined. Subjects underwent 20 minutes of constant work-rate exercise at each work load, and blood lactate, plasma epinephrine, plasma norepinephrine, plasma renin activity, plasma aldosterone, atrial natriuretic peptide, plasma beta-endorphin, and met-enkephalin were measured. Taking nifedipine-SR had no effect on the responses of blood pressure, heart rate, VO2max, maximal work load, and LT compared to taking placebo. Blood lactate, plasma catecholamine, plasma renin activity, aldosterone, atrial natriuretic peptide, and beta-endorphin levels increased during exercise, and there was no difference between nifedipine-SR and placebo. Met-enkephalin did not increase with either treatment. In the QOL questionnaires, no differences were noted between the two treatments. These findings suggest nifedipine-SR to be a potentially useful drug in view of the lack of effect on exercise capacity, hormone release, and QOL.

Adolescent↗