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Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Receiver operating characteristic (ROC) analysis of the ability of arterial ketone body ratio to predict graft outcome after liver transplantation--its sensitivity and specificity.

To evaluate the ability of arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate) to predict graft prognosis after liver transplantation, the diagnostic value as a predictive index was compared between AKBR and conventional liver function tests using receiver operating characteristic (ROC) analysis. The ROC curves were determined for AKBR, GOT, GPT, total bilirubin, serum lactate level, and prothrombin time, all of which were measured on the 1st and 2nd postoperative days in 88 cases of liver transplantation. Comparisons of the areas under the ROC curves between AKBR and other tests revealed the significant superiority of AKBR to other tests in predicting graft death within 1 month after transplantation. The present study suggests that AKBR can be used as an accurate index to predict graft prognosis after liver transplantation.

Adolescent↗
PubMed1992

Kasabach-Merritt syndrome in two neonates.

Two neonates with a giant hemangioma associated with thrombocytopenia (Kasabach-Marritt syndrome) have been managed at Kure National Hospital. The first case was initially difficult to distinguish from overwhelming infection or other tumors but improved after radiotherapy. The second case was resistant to radiation and steroid therapy. Magnetic resonance imaging determined a tumor extending into the surrounding soft tissues better than did enhanced computed tomography. Subtotal excision of the tumor and various drugs were effective only transiently and 51Cr-labeled platelets sequestrated into the residual hemangioma. Severe thrombocytopenia persisted for approximately 15 months requiring extra care for head and body contusions, but finally improved by treatment with platelet-active drugs such as acetylsalicylic acid, dipyridamole, and pentoxifylline.

Disseminated Intravascular Coagulation↗
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↗
PubMed1992

A simple method to assess osteoclast-mediated bone resorption using unfractionated bone cells.

To determine osteoclastic bone resorption we established a simple assay system in which unfractionated cells obtained from femora of 13-day-old mice were cultured on a dentine slice and the number of osteoclasts and their induced pit area on the slices were measured. When the bone cells (1 x 10(5) cells/dentine slice) were cultured in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or human parathyroid hormone (hPTH) for 4 days, at which time newly-formed osteoclasts were not detected, the pit area was dose-dependently increased, being a 4.3- or 4.1-fold respective increase over the control at a 10(-8) M concentration of hormones. Chick calcitonin (cCT) inhibited the osteoclastic bone resorption induced by either of these hormones. cCT alone also suppressed the bone resorption by the cells (3 x 10(5) cells/dentine slice). These findings indicate that 1,25(OH)2D3 or hPTH may mainly activate pre-existing osteoclasts, resulting in increased bone resorption, and that cCT may suppress this osteoclastic activity. When 1,25(OH)2D3 or hPTH was added to the cells pre-cultured in factor-free medium for 6 days, at which time pre-existing osteoclasts had almost degenerated, new osteoclasts were formed, resulting in an increase in pit formation. Thus this system is a useful method which could more sensitively evaluate the effects of hormones or factors on osteoclast formation and activation than other previous systems.

Animals↗
PubMed1992

A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to fibronectin and invasin but not recruitment to adhesion plaques.

A point mutation in a highly conserved region of the beta 1 subunit, Asp130 to Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of alpha 5 beta 1 to fibronectin (FN) without disrupting gross structure or heterodimer assembly. The D130A mutation also interferes with binding to invasin, a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding by alpha 5 beta 1(D130A), it was recruited to adhesion plaques formed on FN by endogenous hamster receptors. Thus, intact ligand binding function is not required for recruitment of alpha 5 beta 1 to adhesion plaques. Overexpression of beta 1(D130A) partially interfered with endogenous alpha 5 beta 1 function, thus defining a dominant negative beta 1 integrin mutation.

Adhesins, Bacterial↗
PubMed1992

A mixture of nucleosides and a nucleotide alters hepatic energy metabolism 24 hours after hepatectomy in rabbits.

The effect of administering a nucleoside-nucleotide mixture on hepatic energy metabolism was evaluated at 24 h after hepatectomy in rabbits that had had 70% of their livers removed. After hepatectomy, animals were administered continuous intravenous infusion of 2 mL/(kg body wt-h) of 9 g/L NaCl (Group S), 5.99 mmol/L nucleoside-nucleotide mixture (Group N1) or 11.98 mmol/L nucleoside-nucleotide mixture (Group N2). At 24 h after hepatectomy, the hepatic adenylate energy charge in Group S (0.83 +/- 0.01, mean +/- SEM) was significantly lower than that before hepatectomy (0.90 +/- 0.01). By contrast, the values in Groups N1 and N2 after hepatectomy (0.74 +/- 0.04 and 0.73 +/- 0.04, respectively) were significantly lower than that in Group S. The hepatic mitochondrial phosphorylation rate before hepatectomy was 46.40 +/- 4.88 nmol ATP/(mg mitochondrial protein-min). After hepatectomy, significantly greater values were observed in Groups N1 and N2 (69.53 +/- 7.20 and 63.31 +/- 6.11, respectively), yet those values were less than observed in Group S (109.14 +/- 4.80). These results suggest that the nucleoside-nucleotide mixture suppressed the enhancement of hepatic mitochondrial phosphorylative activity at a time when hepatic adenylate energy charge is compromised. Such enhancement is needed to compensate for the increased energy expenditure due to surgical intervention.

Adenosine Diphosphate↗
PubMed1992

The introduction of microvascular surgery to hepatic artery reconstruction in living-donor liver transplantation--its surgical advantages compared with conventional procedures.

Microvascular surgery for the reconstruction of the graft artery has been used since the 8th case in our series of 14 liver transplantations using living-related donors, and the clinical results have been compared between the first seven cases (the Loupe group) and the last seven cases (the Micro group). Seven arteries in 7 grafts were reconstructed with the use of loupe magnification in the Loupe group, while 8 arteries in 7 grafts were anastomosed with microscopic techniques in the Micro group. Statistically, there was no difference between the two groups in general background, including age, body weight and primary disease of the recipient, and in medical and surgical factors possibly relating to postoperative thrombosis of the hepatic artery. In two cases in the Loupe group, one or two additional reconstructions were necessary to obtain sufficient blood flow, while 8 arteries were anastomosed in the Micro group without any arterial complication in the postoperative period. There was no difference in time required for completing the arterial reconstruction (45.1 +/- 18.1 min in the Loupe versus 44.4 +/- 6.9 min in the Micro [mean +/- SEM]). Postoperative ultrasonic Doppler duplex study demonstrated a temporary decrease in the arterial flow in 2 cases of the Loupe group, and partial thrombosis of the artery was suspected. Additionally there were two episodes of hepatic artery thrombosis in 1 case of the Loupe group, in which emergent revision for thrombectomy and reanastomosis was performed at the first episode. This illustrated the higher incidence of arterial complications in the Loupe group compared with the Micro group (4 episodes/7 arteries in the Loupe versus 0/8 arteries in the Micro, P less than 0.05). In the present series there were no graft failures or arterial complications in the three deaths in the series. The clinical improvements achieved by microvascular surgery in living-donor liver transplantation suggest an alternative technical strategy for dealing with problematic arterial reconstruction in adult liver transplantation.

Child↗