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Biomedical subjects

T Sugano

Publications and source records attributed to T Sugano.

At least 37 records · Page 2Linked to original sources
PubMed1999

Changes in hepatic nitrogen metabolism in isolated perfused liver during the development of thioacetamide-induced cirrhosis in rats.

Changes in hepatic nitrogen metabolism in isolated perfused liver were studied during the induction of experimental cirrhosis by thioacetamide in female Sprague-Dawley rats. Cirrhosis of the micronodular type developed during 12-week administration of thioacetamide. Despite an increase in food consumption for 4 weeks after the end of administration, the physiological changes characteristic of cirrhosis were maintained. The rate of urea excretion per unit liver weight was significantly decreased compared with pair-fed control rats both during and after thioacetamide treatment. During 4 weeks of thioacetamide treatment, the rate of urea production in perfused liver from a combination of 0.25 mM NH4Cl and 1 mM glutamine decreased slightly, without a decrease in the maximum rate of urea production from 10 mM NH4Cl. In cirrhotic rats, the rate of urea production in perfused liver from NH4Cl and/or glutamine decreased, with a decrease in the maximum rate of urea production. The Km of ureagenesis for NH3 was unchanged in cirrhotic livers. During 4 weeks of thioacetamide treatment, glutamate dehydrogenase activity decreased, but the thioacetamide-induced cirrhotic state had no effect on glutamate dehydrogenase or glutaminase activity. Glutamine synthetase activity was decreased in rats treated with thioacetamide for 4 or 12 weeks. These results are consistent with the hypothesis that the capacity for urea production from NH3 and amino acids is decreased in the development of cirrhosis.

Alanine Transaminase↗
PubMed1999

Characteristics of nitrogen metabolism in rats with thioacetamide-induced liver cirrhosis.

Female Sprague-Dawley rats were given 0.03% thioacetamide (TAA) in their drinking water daily for 4 or 12 weeks, and were then given normal water for 4 weeks after the end of a 12-week TAA treatment to investigate amino acid metabolism. In the malnourished precirrhotic stage (stage 1) and the malnourished cirrhotic stage (stage 2), the aromatic amino acids (AAA), Glu, Asp, Orn, Arg and Cit increased, and the branched-chain amino acids (BCAA) decreased slightly. Because these changes normalized in the well-nourished cirrhotic stage (stage 3), they might have resulted from impairment of hepatocytes and malnutrition. The net uptake of BCAA into the liver increased in stage 2, but the AAA uptake did not exceed that in normal controls. Portal venous plasma AAA increased to the same level as arterial plasma AAA. These results suggest that the decrease in BCAA was partially due to liver uptake and that the increase in AAA was induced by reduction of liver uptake and overproduction in extrahepatic tissues. The liver contents of BCAA and AAA were unchanged in all stages, so were fully utilized in the impaired liver. The increases in Glu, Asp, Orn and Cit might have resulted from overproduction in the liver, because these contents of the liver increased in stage 2. In conclusion, the changes in amino acid metabolism in rats with cirrhosis induced by TAA closely resemble those seen in human liver cirrhosis.

Amino Acids↗
PubMed1999

Relationship between atrioventricular delay, QT interval and cardiac function in patients with implanted DDD pacemakers.

QT interval may change when cardiac function is improved by optimizing the atrioventricular the (AV) delay. The relationship between AV delay, QT interval and cardiac function in patients with implanted DDD pacemakers was studied in 12 patients (aged 71+/-12 SD years) with complete or high degree AV block. Cardiac output (CO) was measured using a Swan-Ganz catheter or by continuous Doppler echocardiography. The pacing rate was fixed at 70-80/min to eliminate the influence of heart rate. The AV delay was prolonged stepwise by 30 ms starting from 90 ms. All measurements were performed after 5 min of pacing. When the AV delay was prolonged, the CO and QT interval gradually increased and reached a peak, and then decreased. When the CO was increased from the minimum to the maximum value by optimizing the AV delay, the QT interval was significantly prolonged from 440+/-40 to 456+/-39 ms (P<0.002). The CO increased from 5.5+/-2.5 to 6.0+/-2.5 l x min(-1) (P<0.002) when the AV delay was changed, during which the QT interval was prolonged from the minimum to the maximum value. There was a significant positive correlation between the optimal AV delay at which CO was maximal (161+/-33 ms) and the optimal AV delay predicted from the maximum QT interval (167+/-29 ms, r=0.85, P<0.001). In conclusion, the optimal AV delay can be predicted from the QT interval.

Adult↗
PubMed1999

Expression of hepatocyte growth factor in cultured human endometrial stromal cells is induced through a protein kinase C-dependent pathway.

To examine the production of hepatocyte growth factor (HGF) by human endometrial stromal cells (ESC) in vitro, concentrations of HGF in the culture media of ESC were measured after the addition of various amounts of 12-O-tetradecanoylphorbol 13-acetate (TPA), forskolin, lipopolysaccharide (LPS), interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNFalpha), interferon-gamma (IFNgamma), or ethynylestradiol-17alpha using an ELISA. The expression of HGF mRNA was also assayed by a reverse transcription-polymerase chain reaction. The concentration of HGF in the culture media of unstimulated ESC was below the detection level of the assay. TPA stimulated the secretion of HGF by ESC in a dose-dependent manner. TPA also induced the transcription of HGF mRNA by ESC. Forskolin, LPS, IL-1beta, IL-6, IL-8, TNFalpha, IFNgamma, or ethynylestradiol-17alpha did not alter HGF mRNA or protein levels. TPA-stimulated production of HGF was partially inhibited by the addition of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine or sphingosine. These results suggest that a protein kinase C-dependent pathway may play an important role in the regulation of HGF production by ESC. HGF secreted by ESC may be involved in the regeneration of the endometrium during the normal menstrual cycle.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Detection of two novel mutations (nt2762, exon 2, CAG to TAG, and nt2483 or 2484, exon 2, +A) in individuals with congenital type I antithrombin deficiencies.

Genetic analyses were performed on two Japanese kindreds with congenital type I antithrombin deficiency causing recurrent thrombosis. The seven exons and flanking intron regions of the antithrombin gene were amplified by polymerase chain reaction followed by direct nucleotide sequencing. In case 1, one novel nonsense mutation, CAG to TAG at codon 100, nucleotide 2762, in exon 2, was detected. In case 2, one novel minor insertion, AT to AAT at codon 7, nucleotide 2483 or 2484, in exon 2, was detected, leading to a frameshift which resulted in a stop codon TGA at codon 32.

Adolescent↗
PubMed1999

Prediction of optimal atrioventricular delay in patients with implanted DDD pacemakers.

In patients with an implanted DDD pacemaker (PM), the atrial contribution may be interrupted by too short an atrioventricular (AV) delay, and filling time may be shortened by too long an AV delay. The AV delay at which the end of the A wave on transmitral flow coincides with complete closure of the mitral valve may be optimal. The subjects were 15 patients [70.3+/-12.3 (SD) years old] with an implanted DDD PM. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter. Transmitral flow was recorded by pulsed Doppler echocardiography. AV delay was prolonged stepwise by 25 msc. When the AV delay was set at 155+/-26 ms, the end of the A wave coincided with complete closure of the mitral valve. When the AV delay was prolonged 25, 50, 75, and 100 ms from this AV delay, the interval between the end of the A wave and complete closure of mitral the valve was prolonged 16+/-5, 39+/-6, 65+/-4 and 88+/-5 ms, respectively (r = 0.97, P<0.0001) and diastolic mitral regurgitation was observed during this period. Thus, the optimal AV delay may be predicted as follows: the slightly prolonged AV delay minus the interval between the end of the A wave and complete closure of the mitral valve. When the AV delay was set at 215 ms, there was a significant positive correlation between the predicted optimal AV delay (166+/-23 ms) and the optimal AV delay (CO: 161+/-26 msec, r = 0.93, P<0.0001, PCWP: 161+/-28 msec, r = 0.95, P<0.0001). In conclusion, optimal AV delay can be predicted by this simple formula: slightly prolonged AV delay minus the interval between end of A wave and complete closure of mitral valve at the AV delay setting.

Aged↗
PubMed1999

Natriuretic peptides regulate the expression of tissue factor and PAI-1 in endothelial cells.

In the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay. Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.

Angiotensin II↗
PubMed1999

The effects of angiotensin metabolites on the regulation of coagulation and fibrinolysis in cultured rat aortic endothelial cells.

Not only angiotensin II (Ang II) but also other angiotensin metabolites such as angiotensin I (Ang I), angiotensin III (Ang III), angiotensin IV, or angiotensin 1-7 have recently been reported to have various activities. Few data, however, are available on the regulation of thrombus formation. In this study, we investigated the effects of angiotensin metabolites on the mRNA expression of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue type plasminogen activator (TPA) in cultured rat aortic endothelial cells. None of the used angiotensin metabolites altered TFPI or TPA mRNA expression levels. Ang I, Ang II, and Ang III made TF and PAI-1 mRNA inductions which were inhibited by an selective antagonist of angiotensin II type 1 receptors. These metabolites made TF predominant to TFPI or PAI-1 to TPA, and could render endothelial cells thrombogenic.

Angiotensin I↗
PubMed1998

Endotoxin modulates arachidonic acid-induced glycogenolysis in the perfused rat liver.

Effects of endotoxin on arachidonic acid (AA)-induced hepatic glycogenolysis were examined in perfused rat liver. In normal rat liver, infusion of AA increased oxygen consumption and glucose production concurrently. In rats injected with lipopolysaccharide (LPS) 6 h before, AA increased glucose production but suppressed oxygen consumption. The changes in LPS-injected rat were abolished by a thromboxane (Tx) A2 receptor antagonist. The release of Tx B2 by AA increased after LPS-injection. These results suggest that priming of hepatic macrophage by endotoxin in vivo enhances Tx synthesis, resulting in modulating hepatic glycogenolysis.

Animals↗
PubMed1998

Modulation of platelet activating factor-induced glycogenolysis in the perfused rat liver after administration of endotoxin in vivo.

The effect of endotoxin treatment in vivo on platelet activating factor (PAF)-induced glycogenolysis was studied in the perfused rat liver. The addition of PAF (20 nM) to the perfusate increased glucose production concomitant with suppression of oxygen consumption in control rats without endotoxin treatment. At 6 h after endotoxin administration, PAF caused severe suppression of oxygen consumption, but glucose production was greatly inhibited. At 24 h after endotoxin treatment, PAF caused less suppression of oxygen consumption than the control, and glucose production was partially restored. The metabolic responses in the control rat were abolished by the simultaneous presence of cyclooxygenase- and lipoxygenase-inhibitors. Combined use of leukotriene (LT) D4- and thromboxane (Tx) A2-receptor antagonists inhibited the metabolic responses in the rat given endotoxin 6 h before. The efflux of Tx B2 during PAF-infusion decreased 24 h after endotoxin treatment, and Tx A2 receptor antagonist, but not LT D4 receptor antagonist, prevented the suppression of oxygen consumption. These results suggest that different eicosanoids are involved in PAF-induced glycogenolysis in different stages of endotoxemia, and that LT D1 may also play a role in PAF-induced glycogenolysis.

Animals↗
PubMed1998

Plasminogen activator inhibitor-1 promoter 4G/5G genotype is not a risk factor for myocardial infarction in a Japanese population.

There is little question that the blood clotting process is triggered and causes the vascular occlusion associated with myocardial infarction. Although it is less clear what part blood coagulation events might play in the etiology of coronary artery disease, impaired regulation of anticoagulation or fibrinolysis might be involved. Among anticoagulant and fibrinolytic factors, an elevated plasma plasminogen activator inhibitor-1 (PAI-1) concentration has been identified as a risk factor for the development of myocardial infarction. An association between one polymorphism of the PAI-1 promoter (4G/5G single nucleotide deletion/ insertion at position -675) and plasma PAI-1 levels was described in 1995. However, most recent studies seem to point to the lack of such an association. This is the first report on the frequency of this polymorphism in the Japanese population with respect to the risk of myocardial infarction. Sixty-six patients with myocardial infarction and sixty-two healthy control patients were chosen for the analysis of the PAI-1 promoter 4G/5G genotype with polymerase chain reaction-single strand conformation polymorphism. Five myocardial infarction patients and six in the control group were homozygous for the 4G/4G genotype. Twenty-eight and 27 4G/5G and 33 and 29 5G/5G genotypes were found in myocardial infarction and control groups, respectively. The total frequencies of the 4G and 5G alleles were approximately 30% and 70% in both control and myocardial infarction groups. In conclusion, the PAI-1 promoter genotype is not a risk factor for myocardial infarction in the Japanese population. This is in contrast to the first report in Caucasians, suggesting an interaction with other genetic or environmental factors which influences the risk of myocardial infarction.

Aged↗
PubMed1998

[DNA and RNA contents of megakaryocytes using acridine orange staining].

We developed a new microfluorometric method to measure the DNA and RNA contents of individual megakaryocytes using acridine orange (AO) staining in human bone marrow smears. Some bone marrow smears were fixed with ethanol and treated with pretreatment solution and then stained with an AO staining solution. The DNA content was assayed by measuring the green fluorescence and the RNA content was assayed by measuring the red fluorescence under B excitation with microfluorometer using peripheral lymphocytes as the control. The ploidy peak was shown to be 16N in all of 5 normal controls, but it was 8N in the patient with refractory anemia with excess of blasts in transformation (RAEB-T). There was not difference in the RNA content/DNA content ratios (RI) between each ploidy in the normal controls. The RI of the patient with RAEB-T was lower than that of the normal controls. The measurement of the DNA-RNA contents may be useful as a new megakaryocytic parameter.

Acridine Orange↗
PubMed1998

Atrial natriuretic peptide inhibits the expression of tissue factor and plasminogen activator inhibitor 1 induced by angiotensin II in cultured rat aortic endothelial cells.

The pharmacological characteristics of atrial natriuretic peptide (ANP), such as natriuresis, vasodilation, or suppression of smooth muscle cell proliferation, are well investigated. However, this is the first study to report its role on blood coagulation and fibrinolysis mediated by vascular endothelial cells. In this study, the effects of ANP on the enhanced expression of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) by angiotensin II (Ang II) in cultured rat aortic endothelial cells (RAECs) were examined. The expressions of TF and PAI-1 mRNA were detected by northern blotting methods. The activities of TF on the surface of RAECs and PAI-1 in the culture media were measured by chromogenic assay. ANP suppressed mRNA expressions of TF and PAI-1 induced by Ang II in a concentration-dependent manner. This suppression was accompanied by the decreased activities of TF and PAI-1.

Angiotensin II↗
PubMed1997

Comparison of the DNA content of megakaryocytes identified immunologically with that identified morphologically.

We devised a new microfluorometric method for determining the ploidy of megakaryocytes identified immunologically in bone marrow smears. The smears were immunostained by incubation with mouse monoclonal anti-glycoproteins (GP) IIb antibodies, followed by fluorescein isothiocyanate-conjugated goat antimouse IgG antibodies. They were then stained with 4',6-diamidino-2-phenylindole (DAPI). Megakaryocytes were identified by their GPIIb immunofluorescence using a microfluorometer and, after the filters were changed, their DNA content was assayed by measuring the intensity of DAPI fluorescence. This intensity was shown to be proportional to the DNA content when the aperture of the objective lens was reduced. We compared these results with those obtained when megakaryocytes were identified morphologically, using DAPI staining after Wright-Giemsa destaining. In all 12 normal controls, the ploidy peaks were shown to be 16N by both methods, and the mean ploidy detected by the immunological method was only reduced 0.961 times relative to the estimate from the morphological method. In contrast, in eight myelodysplastic syndrome (MDS) patients, the ploidy peaks were either 8N or 4N and the mean was reduced by 0.906 times (P = 0.018). Thus we could immunologically identify small megakaryocytes which we could not identify morphologically. Therefore, this method is useful for measuring megakaryocytic ploidy, especially in the pathological megakaryocytes of MDS patients.

Bone Marrow Examination↗
PubMed1997

Acute effect of troglitazone on glucose metabolism in the absence or presence of insulin in perfused rat hindlimb.

Troglitazone (CS-045) is a new type of antidiabetic agent that decreases plasma glucose by enhancing insulin action in insulin-resistant diabetic animals and non-insulin-dependent diabetes mellitus (NIDDM) patients. To examine the direct effect of troglitazone on glucose metabolism and insulin action in skeletal muscle, we infused troglitazone solution into perfused rat hindlimbs in the presence of 6 mmol/L glucose and in the absence or presence of insulin. In the absence of insulin, even 50 mumol/L troglitazone did not elicit glucose uptake. Troglitazone did increase lactate and pyruvate release at concentrations of 20 mumol/L and higher; however, it decreased the ratio of lactate to pyruvate (L/P ratio) and increased oxygen consumption at concentrations higher than 5 and 20 mumol/L, respectively. In hindlimb muscle, 20 mumol/L troglitazone decreased glycogen content without changing fructose 2,6-bisphosphate (F2,6P2) content in the absence of insulin. Insulin infusion with 250 microU/mL obtained half-maximal effects, causing a 2.8-fold increase in glucose uptake and a 1.5-fold increase in lactate and pyruvate release. When 20 mumol/L troglitazone was infused for 30 minutes together with 250 microU/mL insulin, insulin-induced glucose uptake significantly increased 30 minutes after troglitazone infusion, and this increase was further augmented after withdrawal of troglitazone. In insulin plus troglitazone infusion at 30 minutes after troglitazone removal, glycogen content in hindlimb muscle was significantly decreased compared with that obtained with insulin infusion alone. In summary, in the absence of insulin, troglitazone does not elicit glucose uptake, but causes an increase in glycolysis accompanied by a decrease in muscle glycogen content and L/P ratio and an increase in oxygen consumption. In the presence of insulin, troglitazone increases insulin-induced glucose uptake, and this increase is further augmented after troglitazone removal. Addition of troglitazone to insulin infusion decreased the glycogen content in hindlimb muscle. This decrease in muscle glycogen content may trigger an enhancement of insulin-induced glucose uptake similar to that observed during muscle contraction or epinephrine treatment.

Animals↗
PubMed1997

Microdialysis study of modification of hypothalamic neurotransmitters in streptozotocin-diabetic rats.

Neurochemical changes in the ventromedial hypothalamus (VMH) after a single intravenous injection of streptozotocin were examined, using in vivo brain microdialysis under free-moving conditions. Although streptozotocin-induced diabetes produced significant decreases in extracellular concentrations of noradrenaline (NA), serotonin (5-HT), and their metabolites in the VMH, the ratios of 3-methoxy-4-hydroxyphenylglycol/NA and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT were increased. Experimental diabetes led to a pronounced increase in extracellular GABA, which correlated strongly with the decrease in dialysate levels of NA, and to a smaller extent with that of 5-HT. A modification of dopamine (DA) metabolism was induced in the VMH of diabetic rats, whereas there was no change in dialysate DA levels. Daily injections of insulin were able to restore their levels to normal in the areas tested in the microdialysis study. The equal increases in dialysate 5-HT and 5-HIAA and the better restoration of the 5-HIAA/5-HT ratio after insulin therapy indicate that serotonergic activity may depend on the levels of circulating insulin more than on noradrenergic activity. Circulating NA was reduced in streptozotocin-diabetic rats, suggesting that the diabetes-induced reduction in sympathetic activity is accompanied by decreases in NA, or 5-HT, or both, in the VMH.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Change from beta- to alpha-adrenergic glycogenolysis induced by corticosteroids in female rat liver.

The conversion of beta- to alpha-adrenergic glycogenolysis by corticosteroids was studied in perfused livers of mature female rats. Isoproterenol stimulated glucose production more effectively in female rats than in male rats, but the difference in its stimulatory effect disappeared in adrenalectomized (ADX) rats, whereas it remained in adrenodemedulated rats. When ADX female rats were treated with dexamethasone sulfate, alpha-responses increased and beta-responses decreased, depending on the concentration of dexamethasone sulfate. The treatment of female rats with 1.5 mg/kg dexamethasone sulfate changed the levels of the alpha- and beta-responses to those observed in male rats, and the changes were associated with changes in the number of receptors. Although periodicity of changes in plasma corticosterone levels was observed in both male and female rats, the extent of circadian variations was significantly lower in female rats during the estrous cycle than in male rats. The variations in plasma corticosterone levels and in both alpha- and beta-responses after ovariectomy approached those in male rats. The results suggest that the level of plasma corticosterone might play an important role in the regulation of the relative levels of alpha- and beta-adrenergic responses in female rats.

Adrenal Medulla↗