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Biomedical subjects

M Sato

Publications and source records attributed to M Sato.

At least 523 records · Page 29Linked to original sources
PubMed2000

Dopamine D1 receptor gene polymorphism is associated with essential hypertension.

Dopamine has been shown to influence renal sodium excretion through a direct interaction with the dopamine receptor (DR). The dopamine D1 receptor (DRD1) has been localized to the proximal tubules and is known to increase sodium excretion by inhibiting Na-H exchanger and Na,K-ATPase activity. Defective renal dopamine production and/or DR function have been reported in essential hypertension (EH) as well as in genetic models of animal hypertension. With a restriction fragment length polymorphism of the DRD1 gene, we performed an association study in patients with EH. One hundred thirty-one subjects with EH and 136 age-matched normotensive (NT) controls were studied. Polymerase chain reaction was used to amplify the A-48G polymorphic site in the DRD1 gene, and restriction analysis of the polymerase chain reaction product was used to score the A and G alleles. The allele frequencies in the EH group and NT group were then compared. The G allele was observed more frequently in the EH group than in the NT group, and the allele frequencies in the 2 groups differed significantly (chi(2)=6.5, P=0.01). Multiple logistic linear regression analysis revealed that the genotype frequencies of A/A, A/G, and G/G differed significantly (odds ratio=2.1; 95% CI=1.19 to 3.66) between the EH and NT groups. EH patients who possess the G allele had a higher diastolic blood pressure than those lacking the G allele (P<0.01). Thus, the alleles detected by this restriction fragment length polymorphism in the DRD1 gene are associated with EH, and they appear to influence the diastolic blood pressure of Japanese EH patients.

Adult↗
PubMed2000

Urokinase cisternal irrigation therapy for prevention of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage: a study of urokinase concentration and the fibrinolytic system.

BACKGROUND AND PURPOSE: Cisternal irrigation therapy with urokinase (UK) was performed in multiple institutions to prevent symptomatic vasospasm. The efficacy and safety of this therapy were evaluated, and the optimal concentration of UK was estimated. METHODS: This therapy was performed in 28 patients who underwent surgery within 72 hours of the onset of severe subarachnoid hemorrhage (Fisher's group 3, CT number [Hounsfield units] >60). After the aneurysm was clipped, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally and in the prepontine or chiasmatic cistern (outlet). Lactated Ringer's solution with UK (30, 60, or 120 IU/mL) was infused at a rate of 30 mL/h. The presence of symptomatic vasospasm was evaluated by changes in the clinical symptoms and the presence of a new low-density area on CT scan. Drained irrigation fluid and peripheral blood were examined chronologically to evaluate the fibrinolytic system. RESULTS: Symptomatic vasospasm was observed transiently in 3 cases (10.7%) without any low-density area on CT scan. In the 120-IU/mL group, no symptomatic vasospasm occurred. Analysis of drainage fluid suggested that UK 120 IU/mL is effective. The mean values of total drained blood volume for the respective groups were as follows: 58 mL in 30 IU/mL, 106 mL in 60 IU/mL, and 143 mL in 120 IU/mL. No abnormal changes were observed in the coagulative and fibrinolytic systems after UK irrigation. CONCLUSIONS: These results suggest that cisternal irrigation therapy with UK is safe and effective for the prevention of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.

Biomarkers↗
PubMed2000

On-line EM algorithm for the normalized gaussian network.

A normalized gaussian network (NGnet) (Moody & Darken, 1989) is a network of local linear regression units. The model softly partitions the input space by normalized gaussian functions, and each local unit linearly approximates the output within the partition. In this article, we propose a new on-line EMalgorithm for the NGnet, which is derived from the batch EMalgorithm (Xu, Jordan, &Hinton 1995), by introducing a discount factor. We show that the on-line EM algorithm is equivalent to the batch EM algorithm if a specific scheduling of the discount factor is employed. In addition, we show that the on-line EM algorithm can be considered as a stochastic approximation method to find the maximum likelihood estimator. A new regularization method is proposed in order to deal with a singular input distribution. In order to manage dynamic environments, where the input-output distribution of data changes over time, unit manipulation mechanisms such as unit production, unit deletion, and unit division are also introduced based on probabilistic interpretation. Experimental results show that our approach is suitable for function approximation problems in dynamic environments. We also apply our on-line EM algorithm to robot dynamics problems and compare our algorithm with the mixtures-of-experts family.

Algorithms↗
PubMed2000

Expression of menin in parathyroid tumors.

The multiple endocrine neoplasia type 1 (MEN1) gene seems to be a tumor suppressor that encodes a 610-amino acid protein termed menin and that plays an important role in the development of MEN1 syndrome. Recent reports indicate that heterozygous germline mutations of this gene are responsible for the disease onset of MEN1. In this study we examined the expression of menin in parathyroid tumors from primary hyperparathyroidism (PHP), secondary hyperparathyroidism (SHP), and MEN1 and thyroid tumors including Basedow's disease, thyroid cancer, and adrenocortical tumors. Both ribonucleic acid and protein from these tumors were applied to RT-PCR and Western blotting, respectively. Primers for RT-PCR were designed to amplify the sequence between exons 2 and 3 of the MEN1 gene. Specific antibody against menin was generated in guinea pigs immunized with the recombinant peptide from amino acid residues 443-535 of menin made by using glutathione-S-transferase (GST) gene fusion. Menin messenger ribonucleic acid was strongly expressed on RT-PCR analysis in the parathyroid tumors from both PHP and SHP. Western blotting revealed a specific band of approximately 67 kDa in parathyroid tumors from PHP and SHP, with a much weaker such band detected in thyroid tumors. Menin expression was down-regulated in MEN1 samples, including nonsense mutation and deletion mutant. These findings suggest that menin is predominantly synthesized and stored in parathyroid tumors resulting from PHP and SHP.

Actins↗
PubMed2000

Formation and specification of distal leg segments in Drosophila by dual Bar homeobox genes, BarH1 and BarH2.

Here, we show that BarH1 and BarH2, a pair of Bar homeobox genes, play essential roles in the formation and specification of the distal leg segments of Drosophila. In early third instar, juxtaposition of Bar-positive and Bar-negative tissues causes central folding that may separate future tarsal segments 2 from 3, while juxtaposition of tissues differentially expressing Bar homeobox genes at later stages gives rise to segmental boundaries of distal tarsi including the tarsus/pretarsus boundary. Tarsus/pretarsus boundary formation requires at least two different Bar functions, early antagonistic interactions with a pretarsus-specific homeobox gene, aristaless, and the subsequent induction of Fas II expression in pretarsus cells abutting tarsal segment 5. Bar homeobox genes are also required for specification of distal tarsi. Bar expression requires Distal-less but not dachshund, while early circular dachshund expression is delimited interiorly by BarH1 and BarH2.

Animals↗
PubMed2000

Growth inhibition of human leukemia HL-60 cells by an antisense phosphodiester oligonucleotide encapsulated into fusogenic liposomes.

We report here the antisense effect of phosphodiester oligodeoxynucleotide (D-ODN) using fusogenic liposomes (FL) as its carrier. FL has envelope proteins of the Sendai virus within its membrane and introduces its contents directly and efficiently into cytosol by means of the virus-cell fusion mechanism. Using antisense (AS) D-ODN 15-mer complementary to the c-myc proto-oncogene mRNA, including the translation initiation codon site, we analyzed the growth of HL-60 cells by [3H]-thymidine uptake. AS-ODNs encapsulated in FL inhibited the growth by about 70% that of the control HL-60 cells at 2.48 microM. In contrast, sense and scramble D-ODNs encapsulated in FL showed no effect of the growth of HL-60 cells at the same concentration. Even at 50 microM, free form D-ODNs did not show any effect. These results suggest that FL is potentially a useful delivery vehicle for oligonucleotide-based therapeutics, and that D-ODN may be a likely candidate for oligodeoxynucleotides when an efficient delivery system is used.

Base Sequence↗
PubMed2000

Alteration in membrane fluidity of rat liver microsomes and of liposomes by protoporphyrin and its anti-lipidperoxidative effect.

The effect of protoporphyrin (PP) on membrane fluidity was investigated by electron paramagnetic resonance spectroscopy using doxyl stearate spin probes in relation to the anti-lipidperoxidative effect of PP. PP decreased the membrane fluidity in rat liver microsomes at concentrations above 1 mM and also in phosphatidylcholine (PC)-cholesterol (Cho) (100:8, a molar basis) liposomes. The lipid peroxidation stimulated by Fe2+ and L-ascorbic acid in those membrane preparations was attenuated along with the decrease in membrane fluidity by PP. Similar results were also found in Cho-rich PC (100:30 to 100) liposomes having less fluidity. These results suggest that the decrease in the membrane fluidity caused by PP may be involved in the antioxidative action of PP.

Animals↗
PubMed2000

Hemodynamic effects of phosphodiesterase III inhibitor in patients with a large ventricular left-to-right shunt.

The hemodynamic effects of olprinone, a newly synthesized phosphodiesterase (PDE) III inhibitor, were assessed in patients with a large cardiac left-to-right shunt. Ten patients with a large ventricular septal defect (VSD) were evaluated during cardiac catheterization. Olprinone was administered as a bolus, 20 microg/kg body weight, and hemodynamic data were obtained before and after the administration. Heart rate and systemic flow increased significantly after administration. On the other hand, olprinone significantly reduced left and right atrial pressure, the systolic pulmonary/arterial pressure ratio, and systemic vascular resistance. However, pulmonary flow and pulmonary vascular resistance were not changed. These results suggested that olprinone had a positive inotropic effect and selective vasodilator effect on patients with a large ventricular left-to-right shunt. Thus, PDE inhibitors may be beneficial for the treatment of patients with a large VSD.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Prevalence and clinical characteristics of patients with atrial fibrillation: analysis of 20,000 cases in Japan.

In Japan, data on the epidemiological and clinical features of atrial fibrillation (AF) are rather sparse; even less data are available on the risk of thromboembolism in nonvalvular AF. The present study enrolled 19,825 patients who visited the cardiovascular clinics of the 13 hospitals in Hokkaido, Japan, between March and July 1995. The prevalence of AF, the clinical characteristics of AF patients, and the occurrence of ischemic events were examined during the 2 year follow-up period. The prevalence of AF increased with age, and the overall prevalence was 14%. Antithrombotic therapy was used in 57% of AF patients and the incidence of ischemic events during the follow-up period was 4.6% in all AF patients. Warfarin reduced the risk of ischemic events in both the valvular and nonvalvular AF groups. A history of cerebrovascular accidents, advanced age, and the presence of underlying heart disease were each associated with a significantly increased risk of ischemic events in the nonvalvular AF group. These results show a lower incidence of ischemic events and more frequent use of antiplatelet drugs in the nonvalvular AF group. Further prospective studies are needed to determine the best preventive methods for thromboembolic complications in Japanese patients with nonvalvular AF.

Adult↗
PubMed2000

Application of the random arbitrary primed polymerase chain reaction differential display method to isolate genes of cholesterol metabolism-related proteins from rat liver.

The random arbitrary primed (RAP) polymerase chain reaction (PCR) differential display (DD) method was applied to isolate genes related to cholesterol metabolism from exogenously hypercholesterolemic (ExHC) rats and the progenitor, SD rats. Forty-seven trials of RAP-PCR DD resulted in the isolation of 37 clones differing in strain, cholesterol supplementation or their interaction. Among their fingerprints, five clones gave reproducible patterns by a Northern blotting analysis. The sequence of two clones with lower mRNA abundance in ExHC rats than in SD rats was homologous to that of fatty acid synthase and oxalyl-CoA decarboxylase. Two other clones with higher mRNA on the n-cholesterol diet were matrin F/G protein and the NMDA receptor glutamate-binding subunit. The other clone with higher mRNA abundance in ExHC rats on the cholesterol diet was myelodysplasia/myeloid leukemia factor 2. Fifteen trials of reverse transcriptase (RT)-PCR DD yielded 10 clones, but none of the fingerprints were reproduced by the Northern blotting analysis. These results indicate that RAP-PCR DD is an appropriate alternative to RT-PCR DD for isolating the genes involved in hypercholesterolemia.

Animals↗
PubMed2000

Superiority of dietary safflower oil over olive oil in lowering serum cholesterol and increasing hepatic mRnas for the LDL receptor and cholesterol 7alpha-hydroxylase in exogenously hypercholesterolemic (exHC) rats.

The exogenously hypercholesterolemic (ExHC) rat is a strain segregated from SD rats with a high response to dietary cholesterol. To understand the underlying mechanism(s) for this hypercholesterolemia, the interactive effects of dietary fatty acid and the susceptibility of rats to dietary cholesterol on the serum cholesterol concentration and hepatic mRNA abundance of the low-density lipoprotein (LDL) receptor, cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) and 3-hydroxyl-3methylglutaryl (HMG) CoA reductase were examined. Both strains were fed on a diet supplemented with 10% each of olive, safflower or coconut oil with or without the addition of 1% cholesterol for one week. The ExHC rats fed on olive, safflower and coconut oil in combination with cholesterol respectively resulted in a 3.5-, 2.0- and 2.1-fold higher serum cholesterol concentration than that in the animals fed on the corresponding dietary fats without any supplementation of cholesterol (p < 0.01 by dietary cholesterol or type of fat). The dietary cholesterol dependent-elevation of serum cholesterol in the SD rats was less than 1.5-fold (p<0.01) and there was no dietary fat effect. The ExHC rats fed on the safflower oil-containing diet supplemented with cholesterol resulted in a higher mRNA abundance of the LDL receptor and 7alpha-hydroxylase than in the corresponding fat-fed rats without cholesterol (p<0.05). There was no dietary cholesterol-dependent change of mRNA abundance in either strain fed on olive or coconut oil, except for a decreased abundance of HMG CoA reductase mRNA in the olive oil-fed ExHC rats and coconut oil-fed Sprague-Dawley (SD) rats (p<0.05). These results indicate that the hepatic mRNA abundance of the LDL receptor and of 7alpha-hydroxylase depended on the dietary combination of cholesterol and a fatty acid and suggest that a linoleic acid-rich diet may alleviate exogenous hypercholesterolemia by activating the process involved in the hepatic uptake and biliary excretion of serum cholesterol.

Animals↗
PubMed2000

Purification and characterization of a novel alpha-L-arabinofuranosidase from Pichia capsulata X91.

An intracellular alpha-L-arabinofuranosidase from Pichia capsulata X91 was purified and characterized. The enzyme was purified to homogeneity from a cell-free extract by ammonium sulfate treatment, Concanavalin A-Sepharose, ion-exchange chromatography with DEAE Bio-Gel A agarose, arabinose-Sepharose 6B affinity chromatography, and hydroxyapatite column chromatography. The apparent molecular mass of the enzyme was estimated to be 250 kDa by native-PAGE. The enzyme molecule was suggested to be a tetramer with a subunit molecular mass of 72 kDa by SDS-PAGE. The enzyme had an isoelectric point at 5.1, and was most active at pH 6.0 and at around 50 degrees C. The alpha-L-arabinofuranosidase was active at ethanol concentrations of wine. The enzyme was inhibited by Cu2+, Hg2+, and p-chloromercuribenzoate. The enzyme hydrolyzed beet arabinan and arabinogalactan, and efficiently released monoterpenols from an aroma precursor extracted from Muscat grape juice. A considerable amount of monoterpenols was produced in the Muscat wine coupled with the enzyme addition.

Enzyme Stability↗
PubMed2000

Purification and characterization of an alpha-L-rhamnosidase from Pichia angusta X349.

An intracellular alpha-L-rhamnosidase from Pichia angusta X349 was purified to homogeneity through four chromatographic steps. The alpha-L-rhamnosidase appeared to be a monomeric protein with a molecular mass of 90 kDa. The enzyme had an isoelectric point at 4.9, and was optimally active at pH 6.0 and at around 40 degrees C. The Ki for L-rhamnose inhibition was 25 mM. The enzyme was inhibited by Cu2+, Hg2+, and p-chloromercuribenzoate. The alpha-L-rhamnosidase was highly specific for alpha-L-rhamnopyranoside and liberated rhamnose from naringin, rutin, hesperidin, and 3-quercitrin. The alpha-L-rhamnosidase was active at the ethanol concentrations of wine. It efficiently released monoterpenols, such as linalool and geraniol, from an aroma precursor extracted from Muscat grape juice.

Amino Acid Sequence↗
PubMed2000

Time-dependent structure and activity changes of alpha-chymotrypsin in water/alcohol mixed solvents.

Secondary structure of alpha-chymotrypsin in water/ethanol was investigated by circular dichroic (CD) spectroscopy. The changes in catalytic activity were discussed in terms of structural changes of the enzyme. Alpha-chymotrypsin formed beta-sheet structure in water/ethanol (50/50 by volume), but it was substantially less active as compared to that in water. At water/ethanol 10/90, alpha-chymotrypsin took on a native-like structure, which gradually changed to beta conformation with concomitant loss of activity. Change of solvent composition from water/ethanol 50/50 to 90/10 or 10/90 by dilution with water or ethanol, respectively, led to partial recovery of native or native-like structure and activity. In water/methanol, alpha-chymotrypsin tended to form stable beta-sheet structure at water/methanol ratios lower than 50/50, but the catalytic activity decreased with time. Change to alpha-helix structure with substantial loss in catalytic activity was observed when alpha-chymotrypsin was dissolved in water/2,2,2-trifluoroethanol with water contents lower than 50%. In water/2,2,2-trifluoroethanol 90/10, alpha-chymotrypsin initially had the CD spectrum of native structure, but it changed with time to that characteristic of beta-sheet structure.

Alcohols↗
PubMed2000

Structured triacylglycerol containing medium-chain fatty acids in sn-1(3) facilitates the absorption of dietary long-chain fatty acids in rats.

A study was carried out to examine if the positional distribution of medium chain fatty acids (MCF) in triacylglycerol influences dietary fat absorption in rats. Two types of structure-specific fats, one predominantly composed of MCF in sn-1(3) and iinoleic acid in sn-2 [sn1(3)MCF-structured] and the others of MCF in sn-2 and linoleic acid in sn-1(3) [sn-2MCF-structured], were initially prepared, and the two structure-specific fats were interesterified and designated as sn-1(3)MCF-interesterified and sn-2MCF-interesterified. Synthetic fat was mixed with an equal amount of cocoa butter (103 g/kg of diet) and was supplemented to the AIN93G-based diet. Rats were fed on the diets for 4 wk. Long-chain saturated fatty acids were the predominant fatty acids excreted into the feces, and the positional distribution of MCF resulted in an altered fat absorption rate (%) of 81.8, 82.5, 84.2 and 86.3 for the rats fed on the diets containing sn-2MCF-structured, sn-1(3)MCF-interesterified, sn-2MCF-interesterified and sn-1(3)MCF-structured fats, respectively. The proportion of MCF in the serum, liver and adipose tissue triacylglycerols was not affected by the MCF distribution of the dietary fats. These results indicate that the distribution of MCF in dietary triacylglycerol is a determinant of intestinal fat absorption.

Absorption↗
PubMed2000

An insertion/deletion polymorphism in intron 18 of the type B human natriuretic peptide receptor gene is not associated with cerebral infarction.

The natriuretic peptide (NP) system may play a crucial role in the development of cardiovascular and renal diseases. C-type NP dilates arteries and lowers blood pressure, and it inhibits the proliferation of vascular smooth muscle cells via the type B NP receptor (NPRB). We determined and analyzed the structure of the NPRB gene and found an insertion/deletion (I/D) polymorphism in intron 18. In this experiment, we studied this I/D polymorphism in the NPRB gene in 241 subjects, including 118 patients with cerebral infarction (the CI group) and 123 control subjects (the non-CI group). Our goal was evaluate the association of this polymorphism with cerebral infarction. Our findings showed that genotype frequencies of the I/D polymorphism were in Hardy-Weinberg equilibrium. The frequencies for the II, ID, and DD alleles were 0.569, 0.374, and 0.057, respectively, in the non-CI group and 0.576, 0.356, and 0.068, respectively, in the CI group. No association was found between this polymorphism and cerebral infarction. These results suggest that this polymorphism in the NPRB gene is not linked to a pathogenic CI gene.

Aged↗
PubMed2000

Serum progesterone and estradiol-17beta concentrations in captive and free-ranging adult female japanese black bears (Ursus thibetanus japonicus).

Progesterone (P4) and estradiol-17beta (E2) concentrations were measured in serum samples obtained from 23 captive and 23 free-ranging adult female Japanese black bears. We then determined the relationship between changes in these sex steroid hormones and pregnancy. In all captive bears, which included animals of both known and unknown reproductive status, serum P4 concentrations were low from April to July, then tended to become higher after August. The levels then became much higher still in November and December, but returned to low levels in March. Serum P4 concentrations in eight captive pregnant bears, which had parturitions the following spring, increased gradually from August (0.5-2.4 ng/ml) to October (0.9-3.6 ng/ml), and achieved significantly higher maximum levels in December (7.2-18.0 ng/ml). Thereafter, serum P4 concentrations tended to decrease (3.5-6.4 ng/ml in January and 0.3-0.7 ng/ml in March). In all captive bears, serum E2 concentrations varied from April to October but showed low levels in November and December, and became high in January. Serum E2 concentrations in the eight pregnant bears were high in May (95.6-191.4 pg/ml) and varied from August to October (35.6-143.3 pg/ml). Subsequently, serum E2 concentrations in December dropped to significantly lower minimum levels (5.3-11.9 pg/ml) and increased again in January (67.6-153.1 pg/ml). Among the free-ranging bears, the data on serum P4 concentrations in eight bears led to expectations of pregnancy, whereas serum E2 concentrations showed no distinct evidence related to pregnancy. These results, particularly in captive pregnant bears, indicate that a marked increase of P4 in December might be accompanied by reactivation of the corpus luteum preceding implantation. Furthermore, changes in E2 concentrations suggested the possibility that a decline in December and an increase in January are associated with implantation and parturition, respectively.

Animals↗