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Biomedical subjects

T Nakane

Publications and source records attributed to T Nakane.

At least 37 records · Page 2Linked to original sources

Increased peroxisomal fatty acid beta-oxidation and enhanced expression of peroxisome proliferator-activated receptor-alpha in diabetic rat liver.

To determine whether the increased fatty acid beta-oxidation in the peroxisomes of diabetic rat liver is mediated by a common peroxisome proliferation mechanism, we measured the activation of long-chain (LC) and very long chain (VLC) fatty acids catalyzed by palmitoyl CoA ligase (PAL) and lignoceryl CoA ligase and oxidation of LC (palmitic acid) and VLC (lignoceric acid) fatty acids by isotopic methods. Immunoblot analysis of acyl-CoA oxidase (ACO), and Northern blot analysis of peroxisome proliferator-activated receptor (PPAR-alpha), ACO, and PAL were also performed. The PAL activity increased in peroxisomes and mitochondria from the liver of diabetic rats by 2.6-fold and 2.1 -fold, respectively. The lignoceroyl-CoA ligase activity increased by 2.6-fold in diabetic peroxisomes. Palmitic acid oxidation increased in the diabetic peroxisomes and mitochondria by 2.5-fold and 2.7-fold, respectively, while lignoceric acid oxidation increased by 2.0-fold in the peroxisomes. Immunoreactive ACO protein increased by 2-fold in the diabetic group. The mRNA levels for PPAR-alpha, ACO and PAL increased 2.9-, 2.8- and 1.6-fold, respectively, in the diabetic group. These results suggest that the increased supply of fatty acids to liver in diabetic state stimulates the expression of PPAR-alpha and its target genes responsible for the metabolism of fatty acids.

ATP-Binding Cassette Transporters↗

Decreased activity of plasma cholesteryl ester transfer protein in children and adolescents with insulin-dependent diabetes mellitus.

The aims of the present study were to determine whether the activity of cholesteryl ester transfer protein (CETP) is altered in the plasma of children and adolescents with insulin-dependent diabetes mellitus (IDDM), and whether high-density lipoprotein-cholesterol (HDL-C) levels reflect CETP activity. Plasma CETP activity was measured by a micromethod for radioisotopic assay, using exogenous lipoproteins as donor and acceptors. The study subjects were 22 Japanese children and adolescents with IDDM (8M, 14F) with a mean age of 13.0 y. They were non-obese and did not suffer from any significant nephropathy. The age-matched control group consisted of 20 children (10M, 10F) with a mean age of 12.7y. Serum triglycerides were significantly decreased, while the levels of HDL-C and apolipoprotein (apo) A1 were markedly increased, in the IDDM patients. Plasma CETP activity was significantly lower in the IDDM patients than in the control children. None of the anthropometric indices nor the biochemical data correlated significantly with CETP activity in the IDDM patients. Suppression of CETP along with the putative activation of lipoprotein lipase due to peripheral hyperinsulinism appears to induce synergistically the increase in HDL-C in IDDM children.

Adolescent↗

Effect of peroxisome proliferator on extracellular glutathione peroxidase in rat.

Glutathione peroxidase (GPX) activity measured using tert-butyl hydroperoxide as a substrate detects solely cellular/classical GPX (cGPX) in rat liver and kidney, and extracellular/plasma glutathione peroxidase (EC-GPX) in rat serum. To investigate the effect of peroxisome proliferator on EC-GPX, we measured activities of GPX and catalase in rat liver, kidney and serum, and then we performed immunoblot and Northern blot analyses in the kidney. Rats were fed on a diet containing either 2% (w/w) di-2-ethylhexyl phthalate (DEHP) or 0.25% (w/w) clofibrate for two or three weeks, respectively. Catalase activity was increased 1.4-fold (p < 0.001) in the treated liver, but not in the kidney. GPX activity was decreased to 59.2% (DEHP) and 70.4% (clofibrate) of the control (p < 0.001) in the serum but was unaltered in the liver and kidney. The immunoreactivity for EC-GPX was also significantly decreased in the DEHP-treated kidney compared with the control. The mRNA levels of EC-GPX and cGPX were unaltered. The immunostaining for 4-hydroxy-2-nonenal, a maker of lipid peroxide, was more intense in the treated kidney compared with the control. These results suggest that EC-GPX is post-transcriptionally decreased by peroxisome proliferator through the oxidative stress in the renal tubules. This may be a new deleterious effect of an endocrine disruptor DEHP.

Aldehydes↗

Treatment of xerostomia with the bile secretion-stimulating drug anethole trithione: a clinical trial.

BACKGROUND: Saliva protects the oral mucosa, inhibiting microbial overgrowth. Hyposalivation, therefore, induces multiple oral disorders, although treatment of hyposalivation is very difficult. METHODS: A cholagogue, anethole trithione (AT) was administered to patients with symptomatic hyposalivation (xerostomia) caused by senile hypofunction (4 men and 17 women; senile group), medications (6 men and 17 women; drug group), and oral cancer therapy (two men and three women; cancer group). For control groups, an artificial saliva was administered to 45 patients consisting of senile hypofunction (10 men and 16 women), drug-induced xerostomia (3 men and 10 women) and oral cancer therapy-induced xerostomia (four men and two women). RESULTS: Two weeks after administration of AT (6 tablets per day), both nonstimulated salivary flow rate (SFR) and stimulated SFR increased in a statistically significantly manner from 0.76 +/- 0.41 and 5.18 +/- 3.02 to 1.54 +/- 1.33 (P<0.05) and 9.07 +/- 4.10 mL/10 min (P<0.05), respectively. Of the three groups, the drug group showed the largest increases in both SFRs, from 0.90 +/- 0.54 and 6.29 +/- 4.12 to 1.69 +/- 1.65 and 12.09 +/- 5.10 mL/10 min (P<0.05 and P<0.02, respectively). Patients in the control group had almost constant SFRs. After AT administration, the salivary viscosity was, however, mildly decreased and concentrations of secretory-immunoglobulin A, lactoferrin, potassium, and chloride in nonstimulated saliva were almost constant. Corresponding with the increase of salivation, oral discomfort and inflammation were improved or resolved in 41 patients of the AT group within about 4 weeks, whereas improvement was observed in only nine patients of the control group. CONCLUSIONS: These results indicate that AT sufficiently stimulates salivation and improves xerostomia.

Adult↗

An epidemic of parapoxvirus infection among cattle: isolation and antibody survey.

A disease characterized by papules, nodules, vesicles and, rarely, pustules and ulcers on teats was seen among cattle on a farm in Chiba Prefecture, Japan. A virus was isolated by inoculation of fetal bovine lung cell cultures from a vesicle on a teat of an infected cow. The virus was subsequently passaged in fetal bovine lung and muscle cells in which it produced complete cytopathic changes. The virus was identified by physicochemical examinations and electromicroscopic observation as a parapoxvirus. A seroepidemiological survey was performed on antibody to the isolated virus by the agar gel immunodiffusion test. The isolated virus formed a precipitation line which cross reacted with other parapoxviruses isolated previously in Japan. The positive rate was more than 50% among cattle in the Kanto district. The positive rate increased with age. It was suggested that parapoxvirus infection might have already been prevalent among cattle in Japan.

Age Factors↗

Changes in serum leptin concentration during behavioral therapy in obese children.

To determine the pathophysiological implications of serum leptin level in obesity, we monitored the changes in serum leptin level during outpatient treatment with life style modification in children. Fifty-five obese Japanese children (34 boys and 21 girls; mean age, 9.64 years) were studied. The control children consisted of 42 nonobese subjects (27 boys and 15 girls). The serum leptin concentration was 4.35 +/- 0.46 ng/ml (mean +/- SEM) in the control girls and 2.93 +/- 0.21 ng/ml in the control boys. The serum leptin concentrations in the obese boys and girls were higher than those in their lean counterparts. The concentration in the obese boys (16.28 +/- 1.41 ng/ml) was similar to that in the obese girls (20.33 +/- 2.0 ng/ml). The logarithmic value of serum leptin concentration at the first blood sampling in obese children was correlated with percent overweight and percent body fat. In 36 obese children (24 boys and 12 girls) whose serum leptin concentrations were monitored serially during treatment of obesity, the percent overweight was significantly decreased after the initial sampling. In each individual, the changes in leptin concentration were roughly parallel to those in percent overweight. The ratio of the leptin concentration at the second blood sampling divided by the one at the first sampling in each individual was closely correlated with the respective delta percent overweight. These results suggest that the preceding course of obesity determines the serum leptin level of obese children on longitudinal basis, and that the leptin level reflects the degree of obesity on cross-sectional basis.

Behavior Therapy↗

Angiotensin II type 1 receptor blockade prevents up-regulation of angiotensin II type 1A receptors in rat injured artery.

We investigated the effects of the angiotensin II (Ang II) type 1 receptor (AT1) antagonist KRH-594 on levels of the mRNAs for AT1A, AT1B, platelet-derived growth factor-receptor beta (PDGF-Rbeta), and extracellular matrix (ECM)-related genes using the competitive reverse transcription-polymerase chain reaction (RT-PCR) method and on neointimal formation in the balloon-injured rat carotid artery. The mRNA levels for AT1A and PDGF-Rbeta, but not for AT1B, increased from day 3 after injury to day 14. KRH-594 administered orally at 3 and 10 mg/kg/day significantly suppressed these increases. KRH-594 (10 mg/kg/day) also suppressed the injury-induced gene expressions for transforming growth factor-beta1 and fibronectin and reduced collagen alpha1(I) and alpha1(III) mRNA levels for the first 7 days after injury. KRH-594 (10 and 30 mg/kg/day) significantly and dose-dependently reduced the neointimal area in cross sections of the artery 14 days after injury. Another AT1 antagonist, TCV-116 (candesartan cilexetil; 1 and 3 mg/kg/day p.o.), had similar effects on the morphological change and AT1A mRNA level, whereas a smooth muscle relaxant, hydralazine (10 mg/kg/day p.o.), did not. These results indicate that up-regulation of AT1A, PDGF-Rbeta, and ECM-related genes in the balloon-injured carotid artery is in part an AT1-mediated phenomenon and that prevention of receptor up-regulation may contribute to the attenuating effects of AT1 antagonists on neointimal formation after injury.

Angiotensin Receptor Antagonists↗

Effect of selenium deficiency on cellular and extracellular glutathione peroxidases: immunochemical detection and mRNA analysis in rat kidney and serum.

To determine the effect of selenium (Se) deficiency on expression of glutathione peroxidase (GSH-Px) 1 and 2, we measured GSH-Px activity in rat serum, liver and kidneys, serum immunoreactive GSH-Px 2, and the mRNAs of kidney GSH-Px 1 and 2. We purified rat GSH-Px 2 and raised polyclonal antibodies. Immunoreactive GSH-Px 2 was measured by rocket immunoelectrophoresis. GSH-Px 2 was purified 1470-fold with a specific activity of 250 units/mg. Immunoblotting detected only GSH-Px 2 in rat serum, and much less GSH-Px 2 than GSH-Px 1 in kidney. Immunoblot signal of kidney GSH-Px 1 and 2 decreased progressively in Se deficient rats. Serum GSH-Px activity in Se deficient rats at 1, 2, 3, and 4 weeks declined to 33, 20, 10, and 9% of the control, while the serum level of immunoreactive GSH-Px 2 was 58, 24, 15, and 10% of the control, suggesting the presence of an inactive protein at week 1. GSH-Px activity declined to 4 and 11% of the control in the liver and kidney at 4 weeks. The mRNAs of kidney GSH-Px 1 and 2 showed similar decreases, and were 24 and 23% of the control at 4 weeks. GSH-Px mRNA levels were better preserved than GSH-Px activity, suggesting that GSH-Px expression was regulated at both pre-translational and translational levels.

Animals↗

Relationships between an index of body fat distribution (based on waist and hip circumferences) and stature, and biochemical complications in obese children.

OBJECTIVE: To determine the clinical utility of a new age-adjusted measure of body fat distribution (based on waist and hip circumferences) and stature, in relation to biochemical complications in obese children. DESIGN: Cross-sectional, clinical study. The formula to calculate the common standard deviation score (SDS) of waist-to-hip ratio/height (WHR/Ht) was obtained from the data of control children. The relationship between WHR/Ht SDS, as the age-adjusted measure, in obese children and their clinical laboratory data was evaluated. SUBJECTS: Outpatient obese Japanese children (102 boys and 75 girls) and control children (508 boys and 549 girls), ranging in age from 6-15 y. MEASUREMENTS: Height, body weight, waist girth, hip girth, triceps and subscapular skinfold thicknesses, as anthropometric measures. Percent overweight, percent body fat, waist girth, WHR and WHR/Ht SDS as criteria for obesity. Clinical laboratory analyses for fasting blood samples of obese children. RESULTS: The WHR/Ht SDS closely correlated with age in obese children, thus reflecting the progress of abdominal obesity during growth. The obese boys were more hyperlipidaemic than the girls were, although the percent overweight was similar in both genders. The percent overweight, percent body fat, waist girth and WHR/Ht SDS all correlated well with triglyceride (TG), alanine aminotransferase (ALT) and insulin in boys, whereas only waist girth and WHR/Ht SDS showed a close correlation with TG and insulin in girls. The obese subjects were subdivided according to the number of abnormal values observed in TG, ALT and insulin. For obese boys, all five indices of obesity were higher in the groups with complications than in the group without. In the girls, only the WHR/Ht SDS constantly differed between subgroups. WHR/Ht SDS most obviously distinguished the groups with complications from the other group with a wide margin of difference (2-fold in boys and > 2-fold in girls) in the mean values. CONCLUSION: The WHR/Ht SDS can serve as an index predicting the occurrence of biochemical complications in obese children ranging from the age of 6-15 y.

Adipose Tissue↗

Detection of bovine viral diarrhea virus (BVDV) using reverse transcription polymerase chain reaction assay.

The reverse transcription polymerase chain reaction (RT-PCR) was applied to detect bovine viral diarrhea virus (BVDV) for the rapid diagnosis. The primers were selected from the p80 region of BVDV gene. The RT-PCR assay detected all of the 17 BVDV strains tested including cytopathogenic and non-cytopathogenic strains, while specific amplification was not observed from 17 bovine viruses other than BVDV. Detection limit of the assay was 10(1.5) TCID50/ml. Sera and organ samples were collected from four field bovine viral diarrhea-mucosal disease (BVD-MD) cases; mucosal disease, abortion, diarrhea and persistent infection. The RT-PCR assay detected BVDV from those samples more than conventional virus isolation method.

Abortion, Veterinary↗

[Two cases of subarachnoid hemorrhage associated with neurofibromatosis type I: a case of multiple cerebral aneurysms and arteriovenous malformation, and another case of an anterior communicating artery aneurysm].

Two cases of subarachnoid hemorrhage associated with neurofibromatosis type I (von Recklinghausen's disease) are reported. A 30-year-old male patient (case 1) had been diagnosed as having neurofibromatosis type I due to neurofibroma and café-au-lait spot. He suffered from subarachnoid hemorrhage and angiography showed multiple aneurysms in the right and left middle cerebral arteries and left internal carotid artery. He also had arteriovenous malformation in the left temporal lobe. Case 2 was that of a 62-year-old female patient with neurofibroma and café-au-lait spot. She suffered from subarachnoid hemorrhage and angiography showed an aneurysm in the anterior communicating artery. Both patients were discharged with no deficits after neck clipping, however they both suffered from large-sized hematoma in the punctured site of the femoral artery after angiography. The cerebral aneurysms associated with neurofibromatosis type I are often multiple and may coexist with arteriovenous malformation.

Adult↗

Pharmacological analysis of responses to ATP in the isolated and perfused canine coronary artery.

Vascular responses of the isolated and perfused canine coronary artery to adenosine 5'-triphosphate (ATP) were analyzed pharmacologically. At basal perfusion pressure, ATP induced a vasoconstriction followed by a vasodilation dose-dependently. The potency order for vasoconstriction was alpha,beta-methylene ATP > 2-methylthio ATP > UTP > ATP. That for vasodilation was ATP > 2-methylthio ATP > alpha,beta-methylene ATP >> UTP in the preparations precontracted by 20 mM KCl. Aminophylline inhibited the vasodilation induced by adenosine, but not that induced by ATP. Alpha,beta-methylene ATP and suramin inhibited the vasoconstriction induced by ATP. Reactive blue 2 inhibited the vasodilation induced by ATP, but not the vasoconstriction. Removal of the endothelium by saponin and L-N(G)-nitroarginine inhibited the vasodilation induced by ATP, but indomethacin did not. The results suggest that ATP induces vasoconstriction via P2X purinoceptors on the smooth muscle and vasodilation via P2Y purinoceptors on the endothelium through mainly the release of nitric oxide in the canine coronary artery, respectively.

Adenosine Triphosphate↗

Different contributions of ATP and noradrenaline to neurotransmission in the isolated canine intermediate auricular artery.

Vasoconstrictor responses elicited by periarterial electrical nerve stimulation were analyzed pharmacologically in the canine isolated, perfused intermediate auricular artery. Phentolamine (10 microM) significantly inhibited the vasoconstrictor responses to stimulation at 5 Hz and over but not those to stimulation at frequencies below 5 Hz. Additionally administered alpha, beta-methylene ATP (1 microM) abolished the phentolamine-resistant vasoconstrictions at all frequencies used in this study. In contrast, suramin (100 microM) inhibited the vasoconstrictor responses to stimulation at 5 Hz and below but not those to stimulation at frequencies higher than 5 Hz. Phentolamine abolished the suramin-resistant vasoconstriction at all frequencies. Phentolamine and alpha, beta-methylene ATP selectively abolished the vasoconstrictor responses to exogenous noradrenaline and ATP, respectively. These results show that the co-transmission of noradrenaline and ATP exists at sympathetic nerve terminals in the canine intermediate auricular artery, and that purinergic transmission is mainly involved in the vasoconstrictor responses to low-frequency nerve stimulation.

Adenosine Triphosphate↗

Increased plasma cholesteryl ester transfer activity in obese children.

To determine whether enhanced activity of cholesteryl ester transfer protein (CETP) contributes to the development of atherogenic lipoprotein profiles in obese children, plasma CETP activity was assayed according to a micro-method, by co-incubating lipoprotein-deficient samples with exogenous donor and acceptor lipoproteins. The study subjects were 31 obese children (14 males and 17 females). Serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC:high-density lipoprotein (HDL)-C, LDL-C:HDL-C, apolipoprotein (apo) B, and apo B:apo Al were increased in obese children. Thus they appeared to exhibit an atherogenic lipoprotein profile, with a relative decrease in cholesterol carried by HDL compared with the cholesterol in the other lipoprotein fractions. The mean fasting plasma insulin level was also increased. CETP activity was significantly higher in the obese children than in nonobese control children, and was correlated with LDL-C, TC:HDL-C, LDL-C:HDL-C, and apo B:apo Al. These results suggest that an increase in plasma CETP activity results in atherogenic change in lipoprotein metabolism in obese children. The increase in CETP may be due to the adiposity or insulin resistance. Alternatively, dyslipidemia per se, physical inactivity or excessive fat intake, that are commonly found in obese children, may contribute to the increase in CETP activity.

Adolescent↗

UTP induces vascular responses in the isolated and perfused canine epicardial coronary artery via UTP-preferring P2Y receptors.

1. Vasoconstrictor responses of the isolated and perfused canine epicardial coronary artery to uridine 5'-triphosphate (UTP) were analysed pharmacologically. 2. At basal perfusion pressure, UTP induced vasoconstriction in a dose-related manner and the vasoconstriction was sometimes followed by a slight vasodilatation at large doses (more than 10 nmol). The rank order of potency for vasoconstriction was UTP = UDP > ATP > TTP > or = ITP >> UMP. At raised perfusion pressure by 20 mM KCl, the vasoconstriction was not changed and a small vasodilatation was induced at large doses. The rank order of potency for vasodilatation was induced at large doses. The rank order of potency for vasodilatation was ATP >> ITP > or = UDP > UTP > or = TTP. The maximal vasodilator response to UTP was much less than that to ATP. UMP did not induce vasodilatation. 3. The P2X receptor agonist and desensitizing agent alpha, beta-methylene ATP (1 microM) and the P2 receptor antagonist suramin (100 microM) inhibited the vasoconstrictor responses to ATP but not those to UTP and UDP. The P2 receptor antagonist reactive blue 2 (30 microM) did not inhibit the vascular responses to UTP. 4. UTP (200 microM) desensitized the vasoconstrictor responses to UTP, but not either the vasodilator responses to UTP or the vasoconstrictor responses to ATP and UDP. UDP (200 microM) did not desensitize the vascular responses to UTP. 5. Preincubating the UDP stock solution and arterial preparation with hexokinase (10 and 1 uml-1, respectively) did not change the vasoconstrictor responses to UDP. 6. The Ca channel blocker diltiazem (1 microM) inhibited the vasoconstrictor responses to UTP but not those to ATP and UDP. Incubation in a Ca(2+)-free solution containing 1 mM EGTA inhibited the vascular responses to ATP, UTP and UDP. 7. Removal of the endothelium by an intraluminal injection of saponin (1 mg) inhibited the vasodilator responses to UTP. Indomethacin, a cyclo-oxygenase inhibitor (1 microM), inhibited the vasodilator responses to UTP, but NG-nitro-L-arginine, a nitric oxide synthase inhibitor (300 microM), did not have an inhibitory effect. 8. The results suggest that (1) UTP induces vasoconstriction via UTP-preferring P2Y receptors on the smooth muscle and vasodilatation via receptors different from those mediating the vasoconstriction induced by UTP and mediating the vasodilatation by ATP on the endothelium, through mainly the release of prostacyclin in the canine epicardial coronary artery; (2) UDP induces vasoconstriction via UDP-preferring P2Y receptors; and (3) L-type Ca ion channels are involved in the vasoconstriction induced by UTP, but not in that induced by UDP.

Adenosine Triphosphate↗

New age-adjusted measure of body fat distribution in children and adolescents: standardization of waist-hip ratio using multivariate analysis.

OBJECTIVE: To explore a new anthropometric index of body fat distribution adjusted for ages ranging from 6-15 y in both boys and girls. DESIGN: Sex, age, and 11 anthropometric variables were subjected to principal component analysis. Based on these results, we developed a new anthropometric index, namely an age-adjusted measure of body-fat distribution. This index was evaluated statistically for suitability of use in epidemiological surveys. SUBJECTS: Japanese children, including obese and nonobese subjects, in one elementary and one junior high school in Yamanashi Prefecture, Japan: 508 boys and 549 girls whos ages ranged from 6 y 1 mon-15 y. MEASUREMENTS: Measurements included the height (Ht), body weight, circumference of the waist, hip and thigh. Body mass index, the ratios of the waist, hip or thigh to the Ht, waist-hip ratio (WHR) and waist-thigh ration were calculated. RESULTS: The first principal component (PC 1) accounted for 49.8% of the total variation, and was interpreted as an indicator of the general size on an individual. PC 2 accounted for 25.9%, and was interpreted as a shape measure that indicates body fat distribution. Calculation of WHR/Ht, a parameter that represented PC 2 adjusted by PC 1, gave an highly robust linear regression equation for age by gender. The residuals from the regression line for WHR/Ht deviated from normal distribution only in the boys, whereas the mean residual was nearly zero and distribution of the residuals was similar in three age subgroups by gender, supporting the use of the common standard deviation score in all age groups as an indicator of body fat distribution. CONCLUSION: The common standard deviation score of WHR/Ht can serve as an epidemiological index of body fat distribution adjusted for ages between 6 and 15 y.

Adipose Tissue↗

Gene expression of MASH-1, MATH-1, neuroD and NSCL-2, basic helix-loop-helix proteins, during neural differentiation in P19 embryonal carcinoma cells.

We examined the gene expression of MASH-1, MATH-1, neuroD and NSCL-2 during neural differentiation of P19 embryonal carcinoma cells using reverse transcription-polymerase chain reaction and high performance liquid chromatography. These proteins are members of basic helix-loop-helix transcription factor family and their expressions are reported to be transient and restricted in the nervous system during early neurogenesis. Retinoic acid (RA-, 1 microM)-treatment and aggregation for 4 days induced and greatly increased MASH-1, neuroD and NSCL-2 mRNA in P19 cells. The increases peaked at day 3, 4 and 5, respectively. RA-treatment increased MATH-1 mRNA slightly. mRNA of MAP2, a neural differentiation marker, were increased by RA-treatment and the increases reached to the plateau at day 5. The results indicate that the gene expression of MASH-1, MATH-1, neuroD and NSCL-2 during neural differentiation in P19 cells is transient and the order is similar to that in the mouse embryo nervous system as previously reported.

Actins↗