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Biomedical subjects

H Yamazaki

Publications and source records attributed to H Yamazaki.

At least 19 recordsLinked to original sources
PubMed2006

Plutonium isotopes derived from Nagasaki atomic bomb in the sediment of Nishiyama reservoir at Nagasaki, Japan.

The source of plutonium in sediments deposited at Nishiyama reservoir at Nagasaki was characterized by their (240)Pu/(239)Pu atom ratio. The average ratio was approximately 0.03, except in two layers. The main source of the plutonium was the Nagasaki atomic bomb. The plutonium continues to flow into the reservoir even now. The (240)Pu/(239)Pu atom ratios in two layers were higher than the average, which showed that plutonium in these layers were made of those of nuclear tests added to those of the atomic bomb.

Cesium Radioisotopes↗
PubMed2006

Reduced-intensity unrelated cord blood transplantation for treatment of metastatic renal cell carcinoma: first evidence of cord-blood-versus-solid-tumor effect.

We report a 69-year-old man with cytokine-resistant metastatic renal cell carcinoma treated with reduced-intensity unrelated cord blood transplantation. The patient achieved durable donor engraftment with minimal graft-versus-host disease. The patient showed regression of metastatic disease, providing the first evidence of a graft-versus-tumor effect on a solid tumor resulting from cord blood graft.

Aged↗
PubMed2006

Closed rupture of the flexor tendons of the little finger secondary to non-union of fractures of the hook of the hamate.

We report six patients with closed flexor tendon rupture affecting the little finger, occurring secondarily to non-union of the hook of the hamate bone. The ununited fragments were separated from the basal part of the hook by more than 1mm. The fragments were also rounded and showed marginal sclerosis. Non-union was located in the middle part of the hook in three patients, the tip in two, and the base in one. At operation, the fragments were removed in all patients. Five patients were treated by free tendon grafts using three palmaris and two plantaris grafts and one underwent tendon transfer. Postoperative total range of active motion of the little finger averaged 218 degrees (range 185-265 degrees ). All patients returned to their original employment. This series would suggest that flexor tendon rupture can occur after fracture of the hook of the hamate bone, even when the ununited fragment is small and/or rounded.

Adult↗
PubMed2006

Evaluation of a novel kit for the rapid detection of extended-spectrum beta-lactamases.

Since a method of rapidly detecting extended-spectrum beta-lactamase (ESBL) production in gram-negative isolates from patients with severe infection is urgently required, the present study of a novel commercial kit was conducted. The Cica-Beta Test I (Kanto Chemical, Tokyo, Japan) is designed for the rapid detection of ESBL in gram-negative bacteria directly from isolated colonies in a 15-min protocol. In this study, a total of 304 strains of Klebsiella spp., Escherichia coli and Proteus mirabilis were tested using the novel kit and the phenotypic confirmatory disk test using cefotaxime and ceftazidime with and without clavulanate. The kit showed 95.5 and 98.1% sensitivity and specificity, respectively, as compared to the disk test, and thus proved to be an appropriate tool for the rapid detection of ESBL.

Bacteriological Techniques↗
PubMed2006

Species differences in hydrolase activities toward OT-7100 responsible for different bioavailability in rats, dogs, monkeys and humans.

OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-a] pyrimidine) is an amide moiety-bearing pyrazolopyrimidine derivative with a potential analgesic effect. To determine the factors responsible for observed species differences in the bioavailability of this drug, human and experimental animal samples were used to investigate in vitro microsomal and cytosolic hydrolase activities in the liver and small intestine vis-à-vis the pharmacokinetics of OT-7100. The AUC(0-t) values of OT-7100 after oral administration in rats, dogs and monkeys were 0.163, 0.0383 and 0.00147 microg h ml(-1) divided by mg kg(-1), respectively. The bioavailabilities of OT-7100 after oral administration in rats, dogs and monkeys were 36, 17 and 0.3%, respectively. The plasma concentration-time profiles of intravenously administrated OT-7100 in rats, dogs and monkeys were similar. The hydrolase activities toward OT-7100 in liver microsomes or cytosol were approximately similar in rats, dogs, monkeys and humans. In contrast, hydrolase activities of small intestinal microsomes from monkeys were higher (36.1 ng mg protein(-1) min(-1)) than those of rats, dogs and humans (5.4, 1.4 and 4.3 ng mg protein(-1) min(-1), respectively). These results suggest that the primary factor influencing first-pass metabolism for the OT-7100 is enzymatic hydrolysis in the small intestine. This information provides an important index for extrapolating the pharmacokinetics of drugs in humans using studies on monkeys.

Animals↗
PubMed2006

Prediction of in vivo drug clearance from in vitro data. II: potential inter-ethnic differences.

Potential differences in drug clearance between Japanese and Caucasians were investigated by integrating data on demography, liver size, the abundance of the major cytochromes P450 and in vitro metabolic parameters. Eleven drugs (alprazolam, caffeine, chlorzoxazone, cyclosporine, midazolam, omeprazole, sildenafil, tolbutamide, triazolam, S-warfarin and zolpidem) fulfilled the entry criteria of the study (i.e. the necessary in vitro metabolism data were available and clearance values had been reported both in Caucasians and Japanese). Values of relevant biological variables were obtained from the literature, and clearance predictions were made using the Simcyp Population-Based ADME Simulator. The ratios of observed oral clearance (CLp.o.) values in Caucasians compared with Japanese ranged from 0.6 to 2.8 (integrating data from 82 sources). The CLp.o. values for alprazolam, caffeine and zolpidem were not statistically different between Caucasian and Japanese (p>0.05), whereas those for chorzoxazone, cyclosporine, omeprazole, tolbutamide and triazolam were higher in Caucasians (p<0.05), and those for midazolam, sildenafil and S-warfarin were higher in Japanese (p<0.05). CLp.o. values, predicted from in vitro data, were within 3-fold of observed in vivo values for seven of the 11 drugs in Japanese. Values for the predicted ratios ranged from 1.6 to 4.9. The predicted ratios were not significantly different from observed ratios for cyclosporine, omeprazole, tolbutamide and triazolam. Only partial success in predicting ethnic differences in clearance indicates the need for larger and more reliable databases on relevant variables. With such information, in silico predictions might be used with more confidence to decrease the need for repeating pharmacokinetic studies in different ethnic groups.

Asian People↗
PubMed2006

Inter-individual variation of cytochrome P4502J2 expression and catalytic activities in liver microsomes from Japanese and Caucasian populations.

The aim of this study was to investigate the inter-individual variations in cytochrome P4502J2 (CYP2J2) and its typical drug oxidation activities in human liver microsomes in both Japanese and Caucasian populations. CYP2J2 contents were determined immunochemically in liver microsomes from 20 Japanese and 29 Caucasian samples using recombinant CYP2J2 commercially available as a standard. Ebastine hydroxylation and astemizole O-demethylation activities were compared. The CYP2J2 genotype was determined by direct sequencing of liver genomic DNA. The mean expression levels of CYP2J2 determined immunochemically in liver microsomes from Japanese and Caucasian samples were 2.0 +/- 1.5 and 1.2 +/- 2.1 pmol CYP2J2 mg-1 protein (mean +/- standard deviation), respectively, accounting for 1.8 +/- 1.1% and 0.52 +/- 0.65% of the total hepatic P450 content (0.15 +/- 0.19 and 0.27 +/- 0.14 nmol P450 mg-1 protein, respectively). The individual variation of the two marker drug oxidation activities could not be fully accounted for by the CYP2J2 contents or currently known CYP2J2 genotypes. The amounts of CYP2J2 in liver microsomes with the CYP2J2*7 allele (-76G>T) were decreased to 39% compared with those of liver microsomes from other individuals. The results indicate that CYP2J2 accounts for approximately 1-2% of total P450 in human liver microsomes. The information about large inter-individual variation of the CYP2J2 suggests that this enzyme plays a significant role in the metabolism of xenobiotics and may be useful in in-silico simulations of drug disposition.

Adolescent↗
PubMed2005

Ethnic differences between Japanese and Caucasians in the expression levels of mRNAs for CYP3A4, CYP3A5 and CYP3A7: lack of co-regulation of the expression of CYP3A in Japanese livers.

Using a newly developed real-time reverse transcriptase-polymerase chain reaction method, mRNAs were quantitated for CYP3A4, CYP3A5 and CYP3A7 in adult livers from 24 Japanese and 24 Caucasian subjects to elucidate the potential ethnic differences in the expression levels of human cytochrome P450 (CYP) 3As. The expression level of CYP3A4 mRNA in Japanese livers (n = 24) was approximately three times higher than that in Caucasian livers (n = 24, p < 0.001). The mean level of CYP3A5 mRNA was approximately twice higher in Japanese (n = 9) than in Caucasians (n = 5) heterozygous for the CYP3A5 *1 allele (p = 0.057). The CYP3A7 mRNA level was twice higher in Japanese (n = 24) than in Caucasians (n = 22) carrying the CYP3A7 *1A/ *1A genotype (p = 0.042). The level of CYP3A4 mRNA did not correlate with those of CYP3A5 (r = 0.044, n = 24) or CYP3A7 (r = 0.21, n = 24) mRNAs in Japanese livers in contrast to co-regulatory expression of CYP3A4, CYP3A5 and CYP3A7 in Caucasian livers. The results indicate that there are ethnic differences in the expression levels of adult liver CYP3A mRNAs between Japanese and Caucasians, and that the mechanism(s) regulating the hepatic CYP3A expression may be different between these ethnic groups.

Aryl Hydrocarbon Hydroxylases↗
PubMed2005

Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells.

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.

Alkaline Phosphatase↗
PubMed2005

Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation.

Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16(high)CCR2(-) subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16(high)CCR2(-) monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16(low)CCR2(+) subpopulation produced little. These results were contrary to the generally accepted notion that the CD16(high)CCR2(-) monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16(high)CCR2(-) subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16(high)CCR2(-) subpopulations are of a distinct lineage from CD16(low)CCR2(+) monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo.

Acute Disease↗
PubMed2005

Glia maturation factor-beta is produced by thymoma and may promote intratumoral T-cell differentiation.

AIMS: To investigate whether Glia maturation factor-beta (GMFB) is expressed in thymomas and is associated with T-cell development. METHODS AND RESULTS: We investigated the expression of GMFB by immunohistochemistry in 86 cases of thymoma classified into five type A, 35 type AB, 11 type B1, 26 type B2, and nine type B3 thymomas according to the World Health Organization classification system. Immunoblotting and in situ hybridization (ISH) studies were also performed in selected cases. The results of the immunoblot analysis were in accordance with those of immunohistochemical scoring. The ISH study ascertained the tumour cells producing the protein. Immunohistochemically, GMFB expression was observed in one (20%) of type A, 32 (80%) of type AB, all (100%) of type B1 and B2, and eight (89%) of type B3 thymoma with statistically significant differences between type A and type AB, type B1, or type B2 thymoma, and between type B3 and type AB or type B2 thymoma. There was a significant correlation between GMFB expression and the amount of accompanying non-neoplastic T cells. GMFB promoted T-cell differentiation into CD4-/CD8+ cells when analysed by two-colour flow cytometry. CONCLUSIONS: The present study suggests that T-cell development in thymoma may be maintained partly by GMFB produced by the tumour cells.

Adult↗
PubMed2004

Effect of pitavastatin on apolipoprotein A-I production in HepG2 cell.

There are few reports describing the mechanism of HDL-elevating action of HMG-CoA reductase inhibitors (statins). As it is considered that the key step of HDL production is the secretion of apolipoprotein A-I (apoA-I), we investigated the effect of statins on apoA-I synthesis and secretion by HepG2 cell to elucidate the mechanism of the action. Each statin induced apoA-I expression (mRNA and protein) dose-dependently: the rank order of the apoA-I induction pitavastatin (3 microM)>simvastatin (10 microM)>atorvastatin (30 microM). The induction of apoA-I by statins disappeared with addition of mevalonate, which indicates that the effect is HMG-CoA reductase inhibition-dependent. Based on HMG-CoA reductase inhibition, pitavastatin-induced apoA-I more efficiently than simvastatin and atorvastatin. Further study revealed that pitavastatin increased ABCA1 mRNA in HMG-CoA reductase-dependent manner and that Rho and Rho kinase inhibitor (C3T and Y27632) increased apoA-I production in the HepG2 cells. These results suggest that pitavastatin efficiently increases apoA-I in the culture medium of HepG2 cells by promoting apoA-I production through inhibition of HMG-CoA reductase and suppression of Rho activity and by protecting apoA-I from catabolism through ABCA1 induction and lipidation of apoA-I.

Apolipoprotein A-I↗
PubMed2004

De novo formation characteristics of dioxins in the dry zone of an iron ore sintering bed.

The objectives of this work are to understand the details of the mechanism of dioxin formation in the part of a sintering bed termed the dry zone, and to obtain ideas on how to prevent their formation. Sinter mixtures of various composition types were heated in a packed bed reactor, and dioxins in the outlet gas and in the sinter mixture residue were measured. The dioxin formation potential of a simple sinter mixture composed of iron ore, coke and limestone was markedly lower than that of fly ash from a municipal solid waste incinerator (MSWI). In consideration of this result, a series of experiments were conducted using a sinter mixture impregnated with CuCl2. Experimental results showed that dioxin formation was temperature-dependent in the range of 300-550 degrees C, with the maximum observed at around 300 degrees C, which was quite similar to that of fly ash from the MSWI. The homologue distribution of PCDD/Fs in gas and solid reflected the possible difference in carbonaceous materials in coke and activated coke. Gaseous hydrogen chloride acted as a chlorinating reagent for dioxin formation.

Chlorine Compounds↗
PubMed2004

Novel resistin promoter polymorphisms: association with serum resistin level in Japanese obese individuals.

OBJECTIVES: Resistin, an adipocyte-secreted cytokine recently discovered in mice, has been proposed as a link between obesity and diabetes. We analyzed resistin gene polymorphisms and examined their association with serum resistin level and obesity phenotypes in humans. SUBJECTS AND METHODS: Sixty young, obese, non-diabetic subjects taking no medication were studied. DNA sequencing and genotyping of identified single nucleotide polymorphisms were performed. Associations between polymorphisms and serum resistin level, BMI, body composition, fat distribution, and several indices of insulin sensitivity were examined. Moreover, single nucleotide polymorphisms in the promoter region were examined for their influence on resistin gene transcriptional activity using luciferase reporter vectors. RESULTS: Ten non-coding single nucleotide polymorphisms were found. The -638G>A, -420C>G, and -358G>A polymorphisms in the promoter region showed marked linkage disequilibrium with each other, and were associated with serum resistin level; however, there was no association between these polymorphisms and parameters related to adiposity or insulin resistance. The results of luciferase assay revealed that -638G>A together with the -420C>G polymorphism influenced resistin gene transcriptional activity. CONCLUSION: We found that variability in the serum resistin level might be related to polymorphic variants of the promoter region of the gene.

Adenine↗
PubMed2004

Comparative effects of amino acids and glucose on insulin secretion from isolated rat or mouse islets.

Glucose and the combination of leucine and glutamine were used to stimulate insulin secretion from rat islets during a dynamic perifusion and the responses obtained were compared with those elicited from mouse islets under identical conditions. In rat islets, glucose (15 mM) or the amino acid combination of 10 mM glutamine plus 20 mM leucine were most efficacious and peak second-phase insulin release responses were 20- to 30-fold above prestimulatory rates. In contrast to rat islet responses, sustained second-phase insulin secretory responses to the same agonists were minimally increased 1- to 2-fold from mouse islets. Parallel studies demonstrated that phospholipase C (PLC) was markedly activated in rat, but not mouse, islets by both high glucose concentrations and the amino acid combination. Additional studies documented that glucose and amino acid responses of both rat and mouse islets were amplified by carbachol or forskolin. However, wortmannin, a phosphatidylinositol 3-kinase inhibitor, amplified only the responses to glucose leaving the responses to the amino acid mixture unaltered. These observations support the concept that mitochondrial metabolism alone is minimally effective in stimulating insulin secretion from islets. The activation of the supplementary second messenger systems (PLC and/or cAMP) appears essential for the emergence of their full secretory potential. The mechanism regulating the potency and specificity of wortmannin's impact on glucose-induced secretion remains to be identified; however a unique mechanism is supported by these findings.

Adenylyl Cyclases↗