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Biomedical subjects

T Urano

Publications and source records attributed to T Urano.

At least 163 records · Page 9Linked to original sources

Correlations between platelet aggregation, fibrinolysis, peripheral and central serotonergic measures in subhuman primates.

We have studied the relationships between whole blood and plasma serotonin (5-hydroxytryptamine, 5-HT), its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) and serum lipids, platelet aggregation in the whole blood and in the platelet-rich plasma (PRP), and some fibrinolytic parameters in monkeys. Plasma 5-HT was found to be positively related to 5-HT- and ADP-induced platelet aggregation, tissue plasminogen activator (tPA) activity, serum cholesterol and LDL-cholesterol, whereas 5-HT in cerebrospinal fluid correlated inversely with serum cholesterol. Plasminogen activator inhibitor (PAI) activity was positively related to LDL. Euglobulin clot lysis time was related to both tPA and PAI activities. The significance of these findings and the possible role of 5-HT in atherogenesis and hemostasis are discussed.

Animals↗

Daily variations of platelet aggregation in relation to blood and plasma serotonin in diabetes.

The circadian rhythms of platelet aggregation in the whole blood and platelet rich plasma-PRP and plasma serotonin were studied in healthy volunteers (n = 10) and diabetic patients (type II diabetes mellitus n = 12). Platelet aggregation in the whole blood induced by collagen (2 micrograms/ml), ADP (10 microM), arachidonic acid (0.5 mM) and epinephrine (10 microM), and in PRP induced by collagen (2 micrograms/ml), ADP (5 microM), arachidonic acid (250 microM), epinephrine (10 microM) and serotonin-5-HT (1 microM) was measured at 7:30, 11:30, 17:00, 23:00, 4:00 and 7:00. In healthy subjects collagen- and ADP-induced platelet aggregation in the whole blood was significantly lower at 23:00 and 4:00 when compared to values at 7:30. In PRP normal and diabetic platelet response was the lowest during the night. Diabetic platelets exhibited an enhanced response to 5-HT starting from 17:00 until 4:00 when compared to 7:30. 5-HT-induced platelet aggregation was found to be significantly higher throughout the study in DM patients over controls in parallel to plasma 5-HT. In healthy volunteers plasma 5-HT was higher at 17:00 when compared to baseline values, whereas in DM patients plasma 5-HT was elevated starting from 17:00 until 4:00. An enhanced response of diabetic platelets to 5-HT together with elevated plasma 5-HT levels may contribute, at least partly, to the pathogenesis of diabetic vasculopathy and 5HT2 receptor blockers may be of value in DM patients.

Adenosine Diphosphate↗

Isolation of human nm23 genomes and analysis of loss of heterozygosity in primary colorectal carcinomas using a specific genomic probe.

Genomic clones of nm23-H1 and -H2 were isolated. The nm23-H1 and -H2 genes were located in a tandem array 4 kilobases apart. Each genome contained 5 exons and most of the splicing sites in the exon-intron junctions of two isotypes were essentially identical. A probe derived from intron 4 of nm23-H1 was used to examine the loss of heterozygosity (LOH) in primary colorectal carcinomas. Twenty-nine of 42 samples were informative and LOH was found in 3 of these 29. In all three samples with LOH, cancer tissues expressed lower levels of nm23-H1 mRNA when compared with those without LOH.

Amino Acid Sequence↗

Electric-foot-shock induced the suppression of fibrinolytic activity in rats.

Electric-foot-shock was given to rats to initiate constant mental stress and its effect on fibrinolytic activity was analyzed. After the termination of electric-foot-shock which was given for an hour, euglobulin clot lysis time in the stressed group significantly prolonged than those in the control group. tissue plasminogen activator activity was also significantly lower in the stressed group. These effects lasted at least for an hour and returned to the control values 24 hours after the stress. Whole blood serotonin levels, which mainly show serotonin contents in platelets, were higher in the stressed group. A negative correlation between whole blood serotonin and tPA activity in the stressed group was obtained. These results suggest that prolonged mental stress impairs fibrinolysis by decreasing tPA activity with a concomitant increase of serotonin contents in platelets.

Animals↗

Expression of human nm23-H1 and nm23-H2 proteins in hepatocellular carcinoma.

BACKGROUND: The expression of nm23-H1 and nm23-H2 proteins in 25 hepatocellular carcinomas was studied immunohistochemically. METHODS: Tissue specimens were reacted with anti-human nm23-H1 and nm23-H2 monoclonal antibodies (MoAb) (H1-229 and H2-206, respectively) and then stained by the biotin-streptoavidin complex method. RESULTS: Adjacent nontumorous tissues were intensely stained with nm23-H1 and nm23-H2. Of the 25 hepatocellular carcinomas, 60% were positive for MoAb H1-229, and 68% were positive for MoAb H2-206. These immunoreactivities were most common in the cytoplasm of tumor cells. There was no significant correlation between the expression of nm23-H1 protein and tumor size, Edmondson's histopathologic classification, or invasion of the capsule. However, the authors observed an inverse relationship between nm23-H1 expression and intrahepatic metastases of hepatocellular carcinomas. There was no significant correlation between the expression of nm23-H2 protein and clinicopathologic findings. Only a short survival period was observed in patients with hepatocellular carcinoma with reduced nm23-H1 or nm23-H2 proteins. CONCLUSIONS: The results suggest that nm23-H1 protein plays a role in the suppression of intrahepatic metastasis of hepatocellular carcinoma and that the combined expression of nm23-H1 is associated with favorable prognosis.

Carcinoma, Hepatocellular↗

Different effect of 5,6-trans-prostaglandin E2 on plasminogen activation by urokinase and streptokinase.

We examined the effects of 5,6-trans-prostaglandin E2 (trans-PG E2) on fibrinolysis and plasminogen activation by either urokinase or streptokinase. trans-PG E2 was found to enhance fibrinolysis induced by urokinase and inhibit the one by streptokinase. These effects were also appeared in the method using synthetic chromogenic substrate S-2251, which suggested that the effects of trans-PG E2 were induced in the circumstances without coagulation factors such as fibrinogen, thrombin or fibrin. Moreover, the enhancement effect of trans-PG E2 on fibrinolysis by urokinase was investigated. The result of SDS-PAGE indicated that plasmin formation rate from plasminogen by urokinase was accelerated in the presence of trans-PG E2. As trans-PG E2 increased the hydrolyzing rate of S-2288 by urokinase, trans-PG E2 directly interacted with urokinase. Therefore, the enhancement effect of trans-PG E2 on plasminogen activation by urokinase could be explained, at least in part, as follows: at first trans-PG E2 directly exerts its effect on urokinase, then it causes the increase of generation rate of plasmin from plasminogen.

Amino Acid Sequence↗

Plasminogen activators and their inhibitors in non-small cell lung cancer. Low content of type 2 plasminogen activator inhibitor associated with tumor dissemination.

BACKGROUND: Evidence suggests that plasminogen activators and their inhibitors play an important role in tumor spread. METHODS: In this study, we measured the antigen levels of urokinase (u-PA), tissue plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and type 2 plasminogen activator inhibitor (PAI-2), and cancer tissue (19 adenocarcinomas and 19 squamous cell carcinomas) and normal lung tissue. RESULTS: u-PA, PAI-1, and PAI-2 antigen levels in cancer tissue were significantly higher than those in normal tissue (P < 0.001 in u-PA and PAI-1; P < 0.005 in PAI-2), whereas t-PA antigen levels in cancer tissue were significantly lower than those in normal tissue (P < 0.005). In case with lymph node involvement (LN+ cases), PAI-2 antigen levels were significantly lower than those in cases without lymph node involvement (LN- cases) (P < 0.02), whereas there was no difference in either u-PA or PAI-1 antigen levels between these two groups. Furthermore, u-PA antigen levels showed a significant positive correlation with PAI-2 antigen levels in LN- cases (r = 0.696; P < 0.005), although there was no correlation between these two parameters in LN+ cases. CONCLUSIONS: The antigen levels of u-PA, PAI-1, and PAI-2 in cancer tissue were significantly higher than those in normal tissue, and lower content of PAI-2 was associated with lymph node metastasis.

Adenocarcinoma↗

Effects of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA.

Effects of heparan sulfate analogue (HHS-5) and other sulfated polysaccharides on the fibrinolytic system were investigated. Activation rate of native plasminogen (Glu-plg) by tissue plasminogen activator (t-PA), urinary plasminogen activator (u-PA) and single-chain u-PA (scu-PA) was enhanced in the presence of HHS-5 dose dependently up to 10 micrograms/ml. Activation rate of Glu-plg by sct-PA was more enhanced than that by tct-PA in its presence. HHS-5 enhanced the activation of Glu-plg by t-PA or u-PA compared to the activation of Lys-plg. SDS-PAGE confirmed that the enhancement of the hydrolysis of S-2251 by the mixture of Glu-plg, sct-PA and HHS-5 was due to the facilitation of the conversion of Glu-plg to plasmin. HHS-5 only slightly enhanced the amidolytic activity of sct-PA or tct-PA. The enhancement of the activation of plasminogen by t-PA or u-PA was more significant in the presence of HHS-5 than in the presence of chondroitin sulfate C, dextran sulfate or heparin. It is possible that the enhancement of the activation of Glu-plg by activators in the presence of HHS-5 was due to the conformational change of Glu-plg upon interaction with HHS-5.

Chondroitin Sulfates↗

Postoperative changes in plasma tissue-type plasminogen activator and type 1 plasminogen activator inhibitor.

To clarify the changes which occur postoperatively in intravascular fibrinolysis, plasma levels of tissue-type plasminogen activator (t-PA) antigen, the total plasminogen activator inhibitor type-1 (PAI-1) antigen, and the t-PA-PAI-1 complexes were assayed in this study. Blood samples were taken the morning before surgery, then at 0, 12, 24, 36, 60, 108, and 156 h postoperatively in ten patients who underwent radical surgery for thoracic esophageal cancer. The plasma levels of the t-PA and total PAI-1 antigens, and the t-PA-PAI-1 complexes were then measured by enzyme immunoassay. The plasma t-PA and total PAI-1 levels increased significantly in the immediate postoperative period, the percent increase of the latter being much greater than that of the former. Moreover, the calculated free t-PA antigen level was decreased throughout the postoperative period, suggesting postoperative hypofibrinolysis. The platelet count and neutrophil elastase level were significantly correlated with the free t-PA antigen level at r = 0.630, P < 0.001, and r = -0.447, P < 0.01, respectively. The results of this study indicated that post-operative hypofibrinolysis caused by the increased synthesis of PAI-1 may enhance postoperative hypercoagulability, and this may lead to the development of organ damage. Thus, the concentration of the PAI-1 antigen may be a potentially important index for the prediction of postoperative illness.

Aged↗

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↗

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↗

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↗

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↗

Failure of protection against endotoxin hepatotoxicity by selenium.

The present study was undertaken in rats to test the ability of selenium to prevent endotoxin hepatotoxicity. There were no significant morphological changes in the liver and no abnormalities of liver function in rats given 0, 6.25 or 12.5 mumol of selenium. Endotoxin administration to these rats induced focal hepatocellular coagulative necrosis and increased serum transaminase activities. However, endotoxin hepatotoxicity and mortality of the rats given endotoxin after treatment with 6.25 or 12.5 mumol of selenium were not significantly lower than in those given endotoxin alone. These facts suggest that selenium does not prevent endotoxin hepatotoxicity.

Animals↗

Regional lung hematocrit variation and assessment of acute lung injury.

Estimating blood content in the lung remains a key step in calculating lung water volume and microvascular permeability. We studied the effect of regional lung hematocrit (Hct) variation on assessment of acute lung injury. Escherichia coli endotoxin was administered in guinea pigs intravenously. Lung injury was evaluated by measuring the wet-to-dry weight ratio (W/D) and transvascular 125I-labeled albumin leakage for 3 h [tissue-to-plasma 125I-albumin ratio (T/P)] in five tissue samples from each animal. Residual blood content was corrected using either 51Cr-red blood cells as a blood cell marker, 99mTc-albumin as a plasma marker, or both, injected 10 min before the guinea pigs were killed. Lung Hct, estimated from the marker counts of lung and peripheral blood samples, was lower than peripheral blood Hct; intraindividual variation, represented by the standard deviation in each subject, was 0.024 +/- 0.015 for the control group (coefficient of variation 8.0 +/- 5.1%) and 0.026 +/- 0.013 for the endotoxin group (coefficient of variation 8.5 +/- 4.1%). Uncorrected W/D for residual blood content was greater than the corrected W/D. 99mTc-albumin correction gave values closer to the W/D corrected by both markers. T/P corrected by 99mTc-albumin showed smaller data variations than the values obtained with 51Cr-red blood cell correction, which was affected by variations in lung Hct. We recommend using a plasma marker to correct for blood content in assessing acute lung injury by W/D and T/P.

Animals↗

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↗

Elevated levels of interleukin-8 and leukotriene B4 in pulmonary edema fluid of a patient with reexpansion pulmonary edema.

We experienced a case of reexpansion pulmonary edema (RPE) after surgical treatment of pneumothorax. In this case, protein leakage and polymorphonuclear leukocyte (PMN) accumulation were observed in the reexpanded lung. Interleukin-8 and leukotriene B4 in edema fluid were increased at the onset of RPE. PMN elastase was also increased, though its peak was delayed. The plasma level of P-selectin, which mediates adhesion between PMN and endothelium, was elevated. We speculate that some of these fluid mediators may play important roles in chemotaxis and activation of PMN in the development of RPE.

Adult↗