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Biomedical subjects

T Kuroda

Publications and source records attributed to T Kuroda.

At least 271 records · Page 15Linked to original sources

[Characteristics of blood pressure regulating endocrinological factors in elderly essential hypertensives].

Plasma renin activity (PRA) was lower in elderly normotensive subjects and essential hypertensives (EHT), and a significant negative correlation was found between PRA and age in both groups. In EHT, the proportion of the low renin group to total EHT increased with aging. There was a significantly positive correlation between plasma norepinephrine (PNE) and age in NT, but not in EHT. The mean value of PNE in young subjects was significantly higher in EHT than in NT, but not in the middle-aged and elderly groups, suggesting the important role of PNE in young EHT. Power spectral analysis revealed a significant reduction of both sympathetic and parasympathetic activity with aging in NT and EHT, indicating much caution may be required if sympathetic nerve activity is evaluated only by PNE levels in elderly EHT. The expanded plasma volume was another characteristic in elderly EHT, and suppressed activity of renal kallikrein-kinin, prostaglandin and dopamine may be involved with its mechanisms. Regarding insulin sensitivity in elderly EHT, it was shown that 1) the reduction of insulin sensitivity plays some role in age related acceleration of hypertension and glucose intolerance, 2) selective insulin resistance with respect to glucose metabolism already exists at lower ages in EHT, and 3) both Na retention and pressor system activation via insulin action might be a cause of blood pressure elevation in EHT.

Adult↗

Effects of lysosomal protease inhibitors on the degradation of acetylated low density lipoprotein in cultured rat peritoneal macrophages.

The effect of protease inhibitors, leupeptin and pepstatin A, on the metabolism of acetylated low density lipoprotein (acetyl-LDL) was investigated in cultured rat peritoneal macrophages and compared with that of chloroquine. While both leupeptin and pepstatin inhibited the proteolytic degradation of 125I-acetyl-LDL, a combination of both showed an additive effect. Similar to chloroquine, both protease inhibitors diminished [3H] oleate incorporation into cellular cholesteryl[3H] oleate and increased cholesterol content of macrophages. These results suggest that both thiol protease and cathepsin D participate in the physiological degradation of apolipoprotein in macrophages. The inhibition of apolipoprotein degradation seemed to have an effect on cholesterol metabolism in macrophages cultured with acetyl-LDL.

Acetylation↗

Direct transfer of copper from metallothionein to superoxide dismutase: a possible mechanism for differential supply of Cu to SOD and ceruloplasmin in LEC rats.

Copper (Cu) and zinc (Zn)-binding superoxide dismutase (Cu,Zn-SOD) is synthesized always in a form of holo-protein in the liver of LEC rats, a genetically disordered mutant strain in Cu metabolism which accumulates Cu in a form bound to metallothionein (MT). On the other hand, ceruloplasmin (Cp) is synthesized in the liver and excreted into the blood plasma mostly as an apo-protein before the onset of acute hepatitis, and then holoform at the onset of jaundice. Thus, Cu is supplied differentially between Cp and SOD, and at different times, i.e., before and at the onset of acute hepatitis. Availability of Cu to apo-SOD was examined to explain the mechanisms for the differential supply of Cu among three different Cu forms; i) cuprous ion bound to glutathione, ii) free cupric ion, and iii) cuprous ion bound to MT. Cu was transferred to SOD from the three Cu complexes though MT-bound Cu was a less efficient Cu source to apo-SOD. The results indicate that SOD is always present in a holo-form in LEC rats because even MT-bound Cu can be supplied to SOD, while Cp is present in an apo-form because Cu is sequestered to MT and not available in free ionic forms in LEC rats before the onset of acute hepatitis.

Animals↗

Protective effect of the thromboxane A2 receptor antagonist ONO 3708 on ischemia-reperfusion injury in the dog liver.

BACKGROUND: Prostaglandins are widely known to have cytoprotective effects in a variety of conditions. Thromboxane A2 has the opposite effect of prostaglandins. In this study the effects of the thromboxane A2 receptor antagonist ONO 3708 on ischemia and subsequent reperfusion in the dog liver was evaluated. METHODS: Mongrel dogs weighing from 10 to 15 kg were divided into three groups: a control group, a group with induced liver ischemia and subsequent reperfusion, and a group that received ONO 3708 and then underwent induced liver ischemia and subsequent reperfusion. Liver ischemia was induced by the Pringle procedure for 60 minutes. The concentrations of total free amino acids, aromatic amino acids, and branched-chain amino acids in blood taken from the portal and hepatic veins were examined before and after the Pringle procedure in the latter two groups and at the corresponding points in the control group. RESULTS: Disturbances in amino acid metabolism in the liver occurred 5 minutes after the declamping in the ischemic group, and prostaglandin I2 and thromboxane A2 levels and lipid peroxide production, were increased. In contrast, hepatic amino acid metabolism was unchanged, and prostaglandin I2 and thromboxane A2, and lipid peroxide production, were normalized in the group that was treated with ONO 3708. CONCLUSIONS: ONO 3708 appears to protects hepatic tissue from ischemia-reperfusion injury through free-radical scavenging, by increasing prostaglandin I2 levels, and by decreasing thromboxane A2 production.

6-Ketoprostaglandin F1 alpha↗

[A clinicopathological study of renal hemodynamics in patients with systemic lupus erythematosus].

We evaluated the clinical value of the glomerular filtration rate (GFR) and renal plasma flow (RPF) in patients with systemic lupus erythematosus (SLE). All of the patients fulfilled the criteria for SLE of the American Rheumatism Association and were divided into two groups by the criteria for disease activity. GFR and RPF were simultaneously measured by the standard clearance technique using sodium thiosulfate and sodium paraaminohippurate, respectively. Ninety-six clinically active patients and 60 inactive patients underwent one clearance study. In 36 other patients, repeated clearance studies were undertaken on two occasions during the period from the active to inactive phase. The mean RPF was 590.3 +/- 213.7 ml/min in 132 active patients and 485.7 +/- 184.0 ml/min in 96 patients without disease activity (p < 0.01), whereas the mean GFR was comparable between the two groups. In active SLE, the mean GFR in 76 patients with proteinuria was 76.0 +/- 38.2 ml/min as compared with 104.8 +/- 34.3 ml/min in 56 patients without proteinuria (p < 0.01); however, there was no significant difference in the mean RPF between the two groups. A fall in GFR was frequently observed in patients with class IV lupus nephritis. In contrast, there was no significant difference in the mean RPF between class IV patients and the patients in the other classes. As a result, a marked decrease in the filtration fraction (FF) was frequently observed in class IV lupus nephritis, irrespective of the use of diuretics or antihypertensive agents. Semiquantitative histological analyses revealed that mesangial proliferative changes were more responsible than glomerular sclerotic changes for these hemodynamic features.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[A clinical study of renal hemodynamics in patients with lupus nephritis].

This study was designed to evaluate the clinical significance of glomerular filtration rate (GFR) and renal plasma flow (RPF) in 122 patients with lupus nephritis. All patients had definite clinical evidence of active lupus nephritis, including urinary and immunological abnormalities. The average RPF was 634.5 +/- 171.4 ml/min in systemic lupus erythematosus patients and 537.4 +/- 141.9 ml/min in 37 age-and sex-matched patients with primary glomerular disease (PGD) (p < 0.01). A fall in GFR, accompanied by massive proteinuria and hypocomplementemia, was observed frequently in patients with class IV lupus nephritis (diffuse proliferative GN). In contrast, RPF did not change in most patients except in some with increased RPF. No correlation was noticed between RPF and proteinuria or immunological abnormalities. As a result, a marked fall in filtration fraction (FF) was observed frequently in class IV lupus nephritis, and was correlated significantly with urinary and immunological abnormalities. Follow-up data during treatment in the active to inactive phases (average 7.8 months) were available for 39 patients. The average GFR increased significantly from 56.9 +/- 31.4 ml/min in the pre-treatment stage to 74.5 +/- 26.9 ml/min in the post-treatment stage, accompanied by an improvement in proteinuria and hypocomplementemia. On the other hand, RPF decreased significantly from 521.3 +/- 217.1 to 437.6 +/- 156.2 ml/min, so that FF increased significantly as the renal and immunological parameters normalized. Additionally, the renal function was evaluated in 11 patients during the exacerbation of lupus nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

High levels of quinolinic acid in brain of epilepsy-prone E1 mice.

Quinolinic acid (QUIN) may act.as an excitotoxin when it is abundant in the brain. We have shown previously that the activity of 3-hydroxyanthranilate 3,4-dioxygenase, a QUIN-synthesizing enzyme, was abnormally high in the brains of epilepsy-prone E1 mice as compared with that of ddY mice. Here, we estimated the QUIN contents in the brains of these mice. The results showed that the basal QUIN content in the cerebral cortex of E1 mice was twice as high as that of ddY mice. Systemic injection of 400 mumol/kg body weight of L-tryptophan (L-Trp) increased the cortical levels of QUIN in both E1 mice and ddY mice by 189% and 118%, respectively. Administration of 400 mumol/kg each of L-threonine and D,L-methionine had no appreciable effect on the L-Trp-caused increase in the cortical QUIN levels. Co-administration of 5-fluorotryptophan or 5-methyltryptophan, tryptophan analogs, with L-Trp did not reduce but rather enhanced the cortical QUIN levels (by 18% and 92%, respectively). No significant change in the cortical QUIN concentrations was observed with injection of 2 mg/kg body weight of E. coli lipopolysaccharide (LPS) in E1 mice. However, injection of L-Trp in the LPS-treated E1 mice produced a more marked increase in the cortical QUIN levels than that injected with L-Trp alone. These results suggest that the brain QUIN contents of E1 mice are dependent not only on the activity of QUIN-synthesizing enzyme but also on the rate of flux of its substrate, L-Trp or its metabolite(s), in the brain.

Aging↗

Participation of oxidative stress in the process of osteoclast differentiation.

In the present paper, the involvement of active oxygen species in bone resorption has been studied. In order to compare the production of active oxygen by mouse marrow culture cells, fluorescence due to peroxides reacted with 2,7-dichlorofluorescin was measured. After marrow cells were cultured with 1,25-(OH)2D3 for 8 days, there were tartrate resistant acid phosphatase positive multinucleated cells (TRACP(+)MNCs), TRACP positive mononucleated cells, macrophage-like cells and marrow derived stromal cells. Among these cells, TRACP(+) cells could produce almost the equivalent amount of peroxides as could the macrophage-like cells. In order to examine the role of active oxygen in bone metabolism, the amount of oxidative stress was altered during the culture period in the same marrow culture system. Catalase, a catabolic enzyme of hydrogen peroxide (H2O2), significantly suppressed the formation of TRACP(+)MNCs in a dose dependent manner. This suppression was limited in the early stage of the culture period and was reduced by the addition of exogenous H2O2 to culture. Moreover, when superoxide dismutase, a converting enzyme from superoxide anion to H2O2, was added in this system, the formation of TRACP(+)MNCs was significantly increased. These results strongly suggest that active oxygen species, especially H2O2, may be involved in the regulation of osteoclast formation.

Acid Phosphatase↗

Dual actions of glucagon: direct stimulation and indirect inhibition of dog pancreatic secretion.

The secretory actions of glucagon on the exocrine pancreas were examined using two kinds of canine preparations. In the isolated and blood-perfused dog pancreas with venous drainage, i.a. injection of glucagon did not inhibit secretin/cholecystokinin-octapeptide (CCK-8)-stimulated pancreatic secretion, but instead dose dependently enhanced both basal and stimulated pancreatic secretion. Glucagon-induced increase of pancreatic secretion was potentiated by 3-isobutyl-1-methylxanthine. In contrast, i.v. bolus injection of glucagon (3 and 10 nmol/kg) first augmented transiently then suppressed secretin/CCK-8-stimulated pancreatic secretion while simultaneously increasing circulating plasma somatostatin immunoreactivity from 14.2 to 214 fmol/ml in anesthetized intact dogs. The inhibition of secretin/CCK-8-stimulated pancreatic secretion and elevation of plasma somatostatin immunoreactivity induced by glucagon were comparable with those due to somatostatin-14. Thus, these results indicate that glucagon stimulates pancreatic secretion directly; the inhibitory action of glucagon is indirect and appears to be related to a rise in the circulating level of somatostatin immunoreactivity.

1-Methyl-3-isobutylxanthine↗

Quinolone antimicrobial agents substituted with morpholines at the 7-position. Syntheses and structure-activity relationships.

A series of novel 7-substituted 1-cyclopropyl-6,8-difluoro-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids have been prepared and tested for antibacterial activities and for convulsive activities in combination with nonsteroidal antiinflammatory drug. Structure-activity relationships revealed that 7-(2-(aminomethyl)morpholino) derivative 28 had a better Gram-positive activity than the reference quinolones, such as ciprofloxacin, norfloxacin, and ofloxacin. Its Gram-negative activity was equipotent with those of norfloxacin and ofloxacin but was inferior to that of ciprofloxacin. In mouse systemic infection models, 28 showed an excellent therapeutic efficacy which might result from the potent antibacterial activity and suitable physicochemical properties. Convulsive activities of 7-morpholino derivatives in combination with nonsteroidal antiinflammatory drug fenbufen or its metabolite biphenylacetic acid markedly diminished as compared to those of 7-piperazino derivatives in the electrophysiological, biochemical, and behavioral experiments. These results suggest that 28 (Y-26611) is a novel quinolone with reduced neurotoxic excitatory adverse reaction.

4-Quinolones↗

Bending properties and transformation temperatures of heat treated Ni-Ti alloy wire for orthodontic appliances.

The effect of heat treatment temperature on bending properties and transformation temperatures of a Ni-Ti alloy wire, 1.0 mm in diameter, was investigated so that superelasticity could be used in orthodontic appliances needing shape memory processes. The heat treatment process was at 713 K for 1.8 ks and between 673 K and 813 K for 1.8 ks. A three-point bending test and differential scanning calorimetry were performed. The transformation temperatures of the wires were lowered with increasing heat treatment temperature. The reverse transformation finishing temperature was below the body temperature with the treatment above 753 K. Residual deflection of the Ni-Ti wire after bending was small with the secondary heat treatment above 733 K. The load in the unloading process was less changeable and increased with the treatment temperature between 733-813 K. Secondary heat treatment in this range was suitable for using superelasticity in expansion arch appliances.

Dental Alloys↗

Molecular cloning and characterization of a human carboxylesterase gene.

A cDNA encoding human liver carboxylesterase and its gene were isolated. Nucleotide sequence analyses of the cDNA revealed that the predicted enzyme protein consists of 567 amino acids, including 18 amino acids of a putative signal peptide. Comparison of the deduced amino acid sequences of this enzyme with those of seven other carboxylesterases in various mammalian species, together with experimental data from several other laboratories, showed that these enzymes can be classified into three groups depending on the sequences at their carboxyl terminals and the presence or absence of one exon. A human carboxylesterase gene was found to span approximately 30 kb and to have 14 small exons. Alignments of this gene with those of human cholinesterase and rat cholesterol esterase indicated insertional sites at some introns and homologous amino acid sequences around them, although these genes have different numbers of exons. Thus the results supported the conclusion that these esterases evolved from a common ancestral gene.

Amino Acid Sequence↗

Gas-forming liver abscess after transcatheter arterial embolization for hepatocellular carcinoma: report of a case.

A case of a gas-forming liver abscess developing after transcatheter arterial embolization for recurrent hepatocellular carcinoma (HCC) in a 65-year-old man is presented herein. He was admitted to hospital with fever and jaundice, following which ultrasonography (US) and computed tomography revealed a gas-containing abscess in the posterior segment of the hepatic lobe with multiple HCC. Percutaneous transhepatic drainage was performed using US. Antibiotics which were sensitive to the Escherichia coli bacteria detected in the abscess were administered both intravenously and through the drainage tube into the abscess. Four months later, the abscess had diminished and the patient was discharged after receiving percutaneous ultrasonographically guided ethanol injection therapy for the recurrent HCC.

Carcinoma, Hepatocellular↗

Preventive therapy against delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: trials of thromboxane A2 synthetase inhibitor and hyperdynamic therapy.

The effects of thromboxane A2 synthetase inhibitor and hyperdynamic therapy on delayed cerebral ischaemia following aneurysmal subarachnoid haemorrhage were evaluated in a series of twenty eight patients, who underwent aneurysmal clipping with 72 hours after subarachnoid haemorrhage. Postoperatively, 13 patients were treated with thromboxane A2 synthetase inhibitor, Xanbon [sodium (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoate]. Hyperdynamic therapy with dobutamine was given to the remaining 15 patients. Of the 13 patients treated with Xanbon, nine patients (69%) developed delayed cerebral ischaemia and cerebral infarcts occurred in eight patients (62%). On the other hand, of the 15 patients treated with hyperdynamic therapy, only three patients (20%) manifested delayed cerebral ischaemia and two patients (13%) developed cerebral infarcts. In the present study, the patients treated with hyperdynamic therapy met an expected incidence of ischaemic events after subarachnoid haemorrhage by today's standards, while those treated with thromboxane A2 synthetase inhibitor did not.

Adult↗

Müllerian inhibiting substance is present in embryonic testes of dogs with persistent müllerian duct syndrome.

Müllerian Inhibiting Substance (MIS) causes regression of the Müllerian ducts during a critical period in embryonic development in male mammals. In Persistent Müllerian Duct Syndrome (PMDS), an autosomal recessive trait in humans and dogs, the Müllerian ducts fail to regress in otherwise normal males. Previously we reported that PMDS-affected dogs produce bioactive testicular MIS postnatally. The purpose of the present study was to determine whether PMDS-affected canine embryos appropriately express MIS mRNA and protein during the critical period for Müllerian duct regression. Homozygous (PMDS-affected) and normal canine embryos were removed from timed pregnancies. Gonadal sex and the degree of Müllerian duct regression were determined from histologic sections. Positive immunohistochemical staining for MIS was found in testis sections of PMDS-affected and normal male embryos. A 1.8-kb MIS mRNA transcript was detected in testes of PMDS-affected males and normal male embryos and neonates. Furthermore, equal amounts of MIS mRNA transcript were detected in testes of PMDS-affected embryos and normal male littermates during the critical period for Müllerian duct regression. These data support a hypothesis of target organ resistance, such as an abnormality in the putative MIS receptor, as the etiology of the defect in this dog model.

Animals↗

Absence of hepatic uptake of Tc-99m phytate in a man with chronic toluene hepatotoxicity.

The case reported here is of a 28-year-old man diagnosed as having toluene hepatotoxicity. He had a 5-year history of exposure to toluene and was admitted to hospital complaining of two episodes of loss of consciousness. The high total bilirubin and the low prothrombin time suggested serious liver dysfunction. Based on histologic examination of a liver biopsy specimen, the diagnosis of toxic liver dysfunction caused by toluene poisoning was made. Hepatic images were not present in Tc-99m phytate scintigrams, but they were present in hepatobiliary scintigrams done with the Tc-99m N-pyridoxyl-5-methyltryptophan. The diagnosis of hepatic reticuloendothelial failure was made.

Adult↗