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Biomedical subjects

K Yasuda

Publications and source records attributed to K Yasuda.

At least 127 records · Page 7Linked to original sources
PubMed2001

Polyhydroxylated alkaloids isolated from mulberry trees (Morusalba L.) and silkworms (Bombyx mori L.).

New polyhydroxylated alkaloids, (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine-N-propionamide from the root bark of Morus alba L., and 4-O-alpha-D-galactopyranosyl-calystegine B(2) and 3 beta,6 beta-dihydroxynortropane from the fruits, were isolated by column chromatography using a variety of ion-exchange resins. Fifteen other polyhydroxylated alkaloids were also isolated. 1-Deoxynojirimycin, a potent alpha-glucosidase inhibitor, was concentrated 2.7-fold by silkworms feeding on mulberry leaves. Some alkaloids contained in mulberry leaves were potent inhibitors of mammalian digestive glycosidases but not inhibitors of silkworm midgut glycosidases, suggesting that the silkworm has enzymes specially adapted to enable it to feed on mulberry leaves. The possibility of preventing the onset of diabetes and obesity using natural dietary supplements containing 1-deoxynojirimycin and other alpha-glucosidase inhibitors in high concentration is of great potential interest.

Alkaloids↗
PubMed2001

Seven single nucleotide substitutions in human Fc(gamma) receptor IIB gene.

Variation screening for the immunoglobulin G Fc receptor IIB (Fc(gamma)RIIB) gene was performed with the genomic DNA from 100 healthy Japanese subjects. We identified 3 non-synonymous and 2 synonymous substitutions and 2 single-nucleotide polymorphisms in an intron region. These substitutions were found to be located in the ligand-binding domain and the intron, which might alter the function of Fc(gamma)RIIb.

Amino Acid Motifs↗
PubMed2001

Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.

Variation in the CYP3A enzymes, which act in drug metabolism, influences circulating steroid levels and responses to half of all oxidatively metabolized drugs. CYP3A activity is the sum activity of the family of CYP3A genes, including CYP3A5, which is polymorphically expressed at high levels in a minority of Americans of European descent and Europeans (hereafter collectively referred to as 'Caucasians'). Only people with at least one CYP3A5*1 allele express large amounts of CYP3A5. Our findings show that single-nucleotide polymorphisms (SNPs) in CYP3A5*3 and CYP3A5*6 that cause alternative splicing and protein truncation result in the absence of CYP3A5 from tissues of some people. CYP3A5 was more frequently expressed in livers of African Americans (60%) than in those of Caucasians (33%). Because CYP3A5 represents at least 50% of the total hepatic CYP3A content in people polymorphically expressing CYP3A5, CYP3A5 may be the most important genetic contributor to interindividual and interracial differences in CYP3A-dependent drug clearance and in responses to many medicines.

Alleles↗
PubMed2001

Synergistic effect of polymorphisms of uncoupling protein 1 and beta3-adrenergic receptor genes on autonomic nervous system activity.

OBJECTIVE: To investigate the association of the promoter region -3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the beta3 adrenergic receptor (beta3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4+/-2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or beta3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of beta3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203.2+/-50.3 vs 462.2+/-83.6 ms(2); mean+/-s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with beta3AR polymorphism in decreasing sympathetic nervous system activity.

Adult↗
PubMed2001

Risk factors for complications following resection of large gastric cancer.

BACKGROUND: Although there is a low mortality rate after gastrectomy in Japan, most studies include many early gastric cancers. There have been few studies on the morbidity after gastrectomy for advanced gastric cancer. The aim of this study was to clarify the characteristics and risk factors for postoperative complications after resection of large gastric cancers based on three clinical factors: patient, operation and tumour. METHODS: A retrospective study was carried out on 97 patients with a gastric tumour measuring 10 cm or more in diameter. Postoperative complications were recorded and the patients were divided into two groups: 38 with complications and 59 without. Patient, operative and tumour findings were compared between the two groups. RESULTS: Overall morbidity and mortality rates were 39 and 7 per cent respectively. The most frequent complication was pleural effusion (17 per cent), followed by anastomotic leakage (14 per cent), abdominal abscess (12 per cent), wound infection (12 per cent), pancreatic leakage (8 per cent) and peritonitis (6 per cent). Risk factors associated with postoperative complications were operating time (400 versus 337 min, P < 0.01), blood loss (1338 versus 782 ml, P < 0.01), pancreatic invasion (26 versus 8 per cent, P < 0.05) and raised serum carcinoembryonic antigen (CEA) level (5 ng/ml or greater) (36 versus 17 per cent, P < 0.05), independent of patient age, nutritional status, type of gastrectomy, splenectomy or pancreatectomy, extent of lymph node dissection, tumour location, size and stage of disease. CONCLUSION: Even in Japan, the morbidity of gastrectomy for large gastric cancer is high and associated with operating time, blood loss, pancreatic invasion and serum CEA level.

Blood Loss, Surgical↗
PubMed2001

IgG1 anti-P2 as a marker of response to interferon in patients with chronic hepatitis C.

To study the relations of antibody production to long-term outcomes after interferon (IFN) treatment in patients with chronic hepatitis C (CH-C), we used ELISA to measure the levels of antibodies against HCV core protein and peptides. Samples from 21 complete responders and 36 non-responders were collected before IFN therapy, soon after the end of IFN therapy and 6 months later. Using a set of 19 synthesized HCV core peptide antigens, we found that anti-P2 (11-25a.a.) was the most prevalent of all IgG antibodies (93%: 39/42). Among complete responders, IgG1 anti-P2 levels had fallen by the end of IFN therapy (from 79.8 +/- 60.4-46.1 +/- 44.2: P < 0.01), and were lower still 6 months after the end of IFN therapy (31.0 +/- 35.2: P < 0.001); this change was the greatest of all antibodies studied. Among the non-responders, there was no change within the follow-up period. Soon after the end of IFN therapy, IgG1 anti-P2 levels were more than 30% lower than the initial value in more than two-thirds of the complete responders, but in only one-third of the non-responders (14/20 vs. 8/25: P < 0.05). Six months after the end of IFN therapy, IgG1 anti-P2 levels were more than 30% lower than the initial value in more than 85% of the complete responders, but in only 12% of the non-responders (17/20 vs. 3/25: P < 0.001). In conclusion, the changes in levels of IgG1 anti-P2 paralleled the activity of chronic hepatitis C after IFN therapy, and IgG1 anti-P2 levels may be markers of the efficacy of IFN therapy.

Adult↗
PubMed2001

Dehydroepiandrosterone sulphate is increased and dehydroepiandrosterone-response to corticotrophin-releasing hormone is decreased in the hyperthyroid state compared with the euthyroid state.

OBJECTIVE: Dehydroepiandrosterone (DHEA) and DHEA-sulphate (S) have been suggested to play protective roles in many pathological states, some of which are observed in hyperthyroidism. If DHEA and DHEA-S levels change in hyperthyroidism, they might participate as a possible causative link with such pathophysiological changes in hyperthyroidism. However, the CRH-ACTH-DHEA system in hyperthyroidism has not been clearly defined. We examined plasma levels of DHEA and DHEA-S together with ACTH and cortisol in both hyperthyroid (Hyper) and euthyroid states (Eu). METHODS: Eighteen patients (5 men and 13 women, aged 46.9 +/- 2.8 years) with Graves' disease were studied before treatment and again in the euthyroid state following treatment with methimazole. A 100 microg hCRH stimulation test and a low-dose (0.5 microg) 1-24 ACTH stimulation test were performed on separate days. Basal levels and A area under the response curve (AUC) were compared between Hyper and Eu. RESULTS: DHEA-S was higher in Hyper than in Eu. However, basal DHEA did not differ between Hyper and Eu. The ratio of DHEA to DHEA-S was lower in Hyper than in Eu. AAUC of DHEA during a CRH test was lower in Hyper than in Eu. However, AAUC of DHEA during an ACTH test was similar in both Hyper and Eu. Basal ACTH was higher in Hyper than in Eu. In both CRH and ACTH tests, AAUC of cortisol response was lower in Hyper than in Eu, although the basal cortisol level was not different. CONCLUSION: The balance of the conversion between DHEA-S and DHEA in the hyperthyroid state favoured DHEA-S. Similar to cortisol, the DHEA response in the CRH test in hyperthyroidism seemed to be insufficiently compensated for by increased ACTH, although the DHEA response to low-dose ACTH was similar in the hyperthyroid and euthyroid states. Increased DHEA-S might play some role in the pathological states in many organs in hyperthyroidism.

Adrenocorticotropic Hormone↗
PubMed2001

Novel alpha-L-fucosidase inhibitors from the bark of Angylocalyx pynaertii (Leguminosae).

The extract of bark of Angylocalyx pynaertii (Leguminosae) was found to potently inhibit mammalian alpha-L-fucosidases. A thorough examination of the extract resulted in the discovery of 15 polyhydroxylated alkaloids, including the known alkaloids from seeds of this plant, 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), 1-deoxymannojirimycin (DMJ) and 2,5-imino-1,2,5-trideoxy-D-mannitol (6-deoxy-DMDP). Among them, eight sugar-mimic alkaloids showed the potent inhibitory activity towards bovine epididymis alpha-L-fucosidase and their Ki values are as follows: 6-deoxy-DMDP (83 microM), 2,5-imino-1,2,5-trideoxy-L-glucitol (0.49 microM), 2,5-dideoxy-2,5-imino-D-fucitol (17 microM), 2,5-imino-1,2,5-trideoxy-D-altritol (3.7 microM), DMJ (4.7 microM), N-methyl-DMJ (30 microM), 6-O-alpha-L-rhamnopyranosyl-DMJ (Rha-DMJ, 0.06 microM), and beta-L-homofuconojirimycin (beta-HFJ, 0.0053 microM). We definitively deduced the structural requirements of inhibitors of alpha-L-fucosidase for the piperidine alkaloids (DMJ derivatives). The minimum structural feature of alpha-L-fucosidase inhibitors is the correct configuration of the three hydroxyl groups on the piperidine ring corresponding to C2, C3 and C4 of L-fucose. Furthermore, the addition of a methyl group in the correct configuration to the ring carbon atom corresponding to C5 of L-fucose generates extremely powerful inhibition of alpha-L-fucosidase. The replacement of the methyl group of beta-HFJ by a hydroxymethyl group reduced its inhibitory potential about 80-fold. This suggests that there may be a hydrophobic region in or around the active site. The existence or configuration of a substituent group on the ring carbon atom corresponding to the anomeric position of L-fucose does not appear to be important for the inhibition. Interestingly, Rha-DMJ was a 70-fold more potent inhibitor of alpha-L-fucosidase than DMJ. This implies that the lysosomal alpha-L-fucosidase may have subsites recognizing oligosaccharyl structures in natural substrates.

1-Deoxynojirimycin↗
PubMed2001

Frequent presence of HBV in the sera of HBsAg-negative, anti-HBc-positive blood donors.

BACKGROUND: Recent studies have revealed that HBV may not be cleared even after the disappearance of serum HBsAg. The purpose of this study was to investigate whether the replication of HBV persists in HBsAg-negative blood donors who lack apparent liver disease. STUDY DESIGN AND METHODS: Serum HBV was examined by using PCR coupled with Southern blotting in 50 blood donors who were identified to be HBsAg negative but anti-HBc positive. RESULTS: HBV DNA was detected in the sera from 19 (38%) of 50 donors. In 11 of the 19, HBV existed exclusively as immune complexes, while HBV presumably did not exist as immune complexes in the remaining eight. The levels of HBV DNA were similar to those in patients who had recovered from acute HBV. Some nucleotide substitutions, which did not confer amino acid changes in the major epitope of HBsAg, were found in the preS-S regions. CONCLUSION: The replication of HBV is ongoing in a substantial proportion of healthy blood donors who have anti-HBc. Blood from such donors may contain very low levels of HBV free of immune complex formation and should be excluded for transfusion. The fact that such blood donors apparently lacked liver disease suggests no pathogenicity of such "occult" HBV.

Adult↗
PubMed2001

Comparisons of intraosseous graft healing between the doubled flexor tendon graft and the bone-patellar tendon-bone graft in anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study was to compare intraosseous graft healing between the doubled flexor tendon (FT) graft and the bone-patellar tendon-bone (BPTB) graft in anterior cruciate ligament (ACL) reconstruction. TYPE OF STUDY: Randomized trial. METHODS: A biomechanical and histologic study was conducted with 24 adult beagle dogs. Bilateral ACL reconstructions were performed in each animal. Autogenous doubled FT and BPTB grafts were used for the left and right knees, respectively. Each end of the 2 grafts was tethered with a polyester suture to a screw post with a washer. The animals were then allowed unrestricted activities in their cages. Eight animals were killed at 3, 6, and 12 weeks, respectively. RESULTS: Histologically, the FT graft was anchored to the tunnel wall with newly formed collagen fibers resembling Sharpey's fibers by 12 weeks. These fibers were more abundant in the anterior (ventral) gap than in the posterior (dorsal) gap. In the BPTB graft, the bone plug was anchored with newly formed bone at 3 weeks, although osteocytes in the plug trabeculae were necrotic for 12 weeks. Degeneration of the tendon-bone junction in the plug progressed at 6 weeks. Tensile testing showed that the weakest site was different not only between the 2 grafts but also between the observation periods. In the FT graft, the weakest site was the graft-wall interface at 3 weeks and the intraosseously grafted tendon at 6 weeks. In the BPTB graft, the weakest site was the graft-wall interface at 3 weeks and the proximal site in the bone plug at 6 weeks. The ultimate failure load of the FT graft was significantly inferior (45.8%) to that of the BPTB graft at 3 weeks (P =.021). At 6 weeks, the load of the FT graft was 85% that of the BPTB graft without a significant difference (P =.395). CONCLUSIONS: As to the clinical relevance, the fixation device chosen for soft-tissue fixation appears to be more important than comparing it to the BPTB graft, although this has yet to be conclusively proven.

Animals↗
PubMed2001

The adenosine triphosphate-sensitive potassium channel opener nicorandil protects the ischemic rabbit spinal cord.

OBJECTIVE: We investigated the protective effects of an adenosine triphosphate-sensitive potassium channel opener nicorandil in the rabbit model of spinal cord ischemia. METHODS: Rabbits were randomized into 4 groups (each n = 6): the nicorandil group (100 microg/kg intravenous nicorandil 10 minutes before ischemia); the glibenclamide plus nicorandil group (3 mg/kg intravenous glibenclamide, an antagonist of adenosine triphosphate-sensitive potassium channels, 10 minutes before nicorandil administration); the vehicle group (vehicle alone); and the sham operation group (without spinal cord ischemia). Spinal cord ischemia was induced by balloon occlusion of the infrarenal abdominal aorta for 15 minutes at 39 degrees C. Neurologic function was graded into Johnson's score at 8 hours, 1 day, and 2 days. Histopathologic examination was performed at 2 days, and the number of intact motor neuron cells was compared. RESULTS: Johnson scores of the glibenclamide plus nicorandil and vehicle groups were significantly lower than those of the sham operation and nicorandil groups at each time point, and no statistically significant difference was observed between the glibenclamide plus nicorandil and vehicle groups. Histopathologic examination revealed that motor neurons were almost normal in the nicorandil group, whereas about 55% of motor neurons were lost in the vehicle and glibenclamide plus nicorandil groups. CONCLUSIONS: Nicorandil has a protective effect on the ischemic rabbit spinal cord, and the beneficial effect seems mediated through the activation of adenosine triphosphate-sensitive potassium channels.

Animals↗
PubMed2001

Platelet protein kinase C isoform content in type 2 diabetes complicated with retinopathy and nephropathy.

It has been reported that platelet aggregation in diabetic patients with microangiopathy is increased compared with healthy subjects. Chronic hyperglycemia is known to cause an increase in diacylglycerol level in various tissues. We examine whether protein kinase C (PKC) isoform content in platelets from diabetic patients is increased compared with healthy subjects, as previously described in the retina, aorta, and heart of diabetic rats. Platelet PKCalpha, beta and zeta immunoreactivity in cytosol, membrane and cytoskeleton (CS) fractions were analyzed by immunoblotting in 20 type 2 diabetic patients (who had been treated with diet alone, sulphonylureas or insulin, and whose condition was complicated with retinopathy, nephropathy, neuropathy and/or macroangiopathy) and in five healthy subjects. PKCalpha, beta and zeta immunoreactivity in cytosol, membrane and CS fractions in platelets from diabetic subjects were not significantly higher than those from healthy subjects. However, platelet PKCbeta immunoreactivity in cytosol fraction was significantly higher in diabetic patients with normal serum creatinine (Cr) level than in diabetic patients with abnormal Cr level (Cr > or =1.5 mg/dl) or in healthy subjects. Moreover, significant negative correlation between PKCbeta immunoreactivity in cytosol fraction of platelets and serum Cr level was found in diabetic patients (P < 0.05). To clarify the effect of treatment for diabetes, PKC isoform immunoreactivity in platelets was measured in type 2 diabetic patients treated with diet alone, sulphonylurea or insulin treatment. Serum creatinine level in diabetic patients with insulin treatment was significantly higher than in diabetic patients with sulphonylurea treatment and diet alone. In addition, PKCbeta immunoreactivity in diabetic patients with insulin treatment was significantly suppressed compared with that in patients treated by sulphonylurea treatment. These results suggest that chronic hyperglycemia may activate platelet PKCbeta isoform, and that insulin treatment may decrease platelet PKCbeta activity. Finally, not only PKCbeta antagonists, but also glycemic control by insulin may prevent development of diabetic microangiopathy.

Adult↗
PubMed2001

Increased platelet aggregation in diabetic patients with microangiopathy despite good glycemic control.

The pathogenesis of diabetic micro- and macroangiopathy cannot be fully explained by hyperglycemia alone. To clarify diabetic complications mediated by increased platelet activity, we have studied platelet aggregation and its second messenger molecules such as protein kinase C (PKC), RhoA, and phosphatidylinositol 3-kinase (PI3- kinase), in six diabetic patients with diabetic retinopathy and other diabetic complications in spite of good glycemic control. Their HbA(1c) levels throughout the observation period had been less than 6% with diet treatment alone, despite which diabetic retinopathy developed to the pre-proliferative stage during 2-8 years observation. Low-dose thrombin (< 0.5 U/ml)-stimulated platelet aggregation in the diabetic patients was enormously elevated compared with healthy control subjects. PKC, RhoA and PI3-kinase activities in the cytosol- and membrane-associated fractions were examined in the platelets from the two patients (Cases 2 and 4). Platelet membrane-associated RhoA and PI3-kinase activity in Case 2 were increased before the stimulation. Platelet RhoA and PI 3-kinase activities in Case 4 were increased after the stimulation with low-dose thrombin (0.01 U/ml). Membrane-associated immunoreactive PKC alpha, but not PKC beta in Cases 2 and 4 was elevated. Although platelet hyperactivity in these four patients was observed, PKC and RhoA in mononuclear leukocytes from these patients were not different from healthy subjects. Membrane-associated PKC alpha and RhoA immunoreactivities also increased in the other three cases. These results suggest that hyperreactivity of PKC alpha may lead to increased RhoA and PI3-kinase activities and platelet hyperfunction in diabetic patients with good glycemic control, and that raised platelet PKC alpha may be implicated in the pathogenesis of diabetic complications.

Adult↗
PubMed2001

Differential effect of PKC isoform on insulin- and phorbol ester-stimulated glucose uptake mechanism in rat adipocytes.

Insulin stimulates glucose uptake in association with phosphatidylinositol (PI) 3-kinase activation mechanisms in rat adipocytes. Insulin stimulated glucose uptake to 6.5-fold, and 12-o-tetradecanoyl phorbol 13-acetate (TPA) also stimulated glucose uptake to 4.5-fold in rat adipocytes. We examined these differences in glucose uptake, PKCzeta activation, and PI 3-kinase activation after stimulation with insulin and TPA. TPA stimulated PI 3-kinase activity and increased the p85 subunit of PI 3-kinase immunoreactivity in anti-phosphotyrosine antibody-immunoprecipitated protein. Insulin and TPA provoked increases in membrane PKCzeta immunoreactivity. The PI 3-kinase inhibitor, wortmannin, suppressed insulin-induced increases in glucose uptake, PI 3-kinase activity, and PKCzeta activation. Wortmannin also suppressed TPA-induced PI 3-kinase activity and PKCzeta activation but suppressed TPA-induced glucose uptake to only a small extent. The PKC inhibitor, Go6976, which only inhibits conventional PKCalpha and _, suppressed TPA-induced glucose uptake, but suppressed insulin-induced glucose uptake to only a small extent. On the other hand, the PKC inhibitor, RO32-0432, which inhibits conventional, novel, and atypical PKCs, markedly suppressed both insulin- and TPA-induced glucose uptake. These results suggest that insulin-induced glucose uptake is mainly mediated by PI 3-kinase-PKCzeta signaling, whereas phorbol ester-induced glucose uptake is mainly mediated by conventional PKC despite PI 3-kinase and PKCzeta activations.

Adipocytes↗
PubMed2001

Enhancement of oxidative damage to cultured cells and Caenorhabditis elegans by mitochondrial electron transport inhibitors.

The mechanisms that lead to mitochondrial damage under oxidative stress conditions were examined in primary and cultured cells as well as in the nematode Caenorhabditis elegans (C. elegans) treated simultaneously with electron transport inhibitors and oxygen gas. Oxygen loading enhanced the damage of PC 12 cells by thenoyltrifluoroacetone (TTFA, a complex II inhibitor), but did not by rotenone (a complex I inhibitor), antimycin (a complex III inhibitor), and sodium azide (a complex IV inhibitor). In primary hepatocytes, the enhancement was observed with the addition of sodium azide and rotenone, but not by TTFA or antimycin. In the nematode, only rotenone and TTFA enhanced the sensitivity under hyperoxia. These results demonstrate that highly specific inhibitors of electron transport can induce oxygen hypersensitivity in cell levels such as PC 12 cells and primary hepatocytes, and animal level of C. elegans. In addition the cell damage is different dependent on cell type and organism.

Animals↗