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Biomedical subjects

M Murata

Publications and source records attributed to M Murata.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Surgical treatment for ruptured aneurysm of a coronary artery to pulmonary artery fistula; report of a case].

We reported a successful operative case of ruptured coronary artery aneurysm associated with coronary artery to pulmonary artery fistula. The patient was a 74-year-old woman who was admitted for syncope and chest oppression. Echocardiogram and chest CT scan revealed cardiac tamponade. Ruptured coronary aneurysm, 3 cm in diameter, was found at emergent operation. After emergent coronary angiography, which demonstrated an aneurysm arising from the left anterior descending coronary artery and draining into the pulmonary artery, orifice of draining artery to the aneurysm was closed and coronary artery fistula was ligated. She recovered smoothly and post operative angiogram revealed disappearance of the aneurysm.

Aged↗
PubMed2002

Minor histocompatibility antigens--targets of graft versus leukemia responses.

Immune-mediated elimination of tumor cells by donor T cells recognizing recipient minor H antigens contributes to the curative potential of allogeneic HCT. The importance of the allogeneic response to a successful outcome is clearly illustrated by the results of stem cell transplant for malignancy after nonmyeloablative conditioning. Remarkably little is understood about the molecular nature of minor H antigens and this has impeded efforts to determine the role of specific disparities in graft versus tumor reactions or to manipulate T cell responses to augment antitumor activity without exacerbating GVHD. The isolation of minor H antigen-specific CD8+ and CD4+ T cell clones from recipients of allogeneic HCT has provided the reagents to characterize their expression on leukemic progenitors and to identify the genes encoding these antigens. Using cDNA expression cloning, genetic polymorphisms in the human IFI-75, Uty, KIAA0020, and UGT2B17 genes have been identified to encode new minor H antigens presented by HLA A3, B8, A2, and A29 respectively. Two of these genes are preferentially expressed in hematopoietic cells including leukemic progenitors suggesting it may be possible to augment T cell responses to promote a selective graft versus leukemia effect. A third gene, UGT2B17 is highly expressed in liver and GI tract and may be a target for GVHD in these organs. The studies to identify the molecular nature of minor H antigens have provided insights into the complexities of the graft versus host response associated with allogeneic HCT, but the challenge for the future will be to develop strategies that can selectively induce durable graft versus tumor effects without GVHD. A critical issue in developing specific immunotherapy to augment GVL responses is to determine which minor H antigens are expressed on leukemic stem cells. Studies using transplantation of human AML into SCID mice have identified a putative leukemic stem cell which is contained in the CD34+ CD38- subset of the blast population and is present in very low frequency (<1/200,000) in blood or bone marrow from AML patents. We have examined the ability of minor H antigen-specific CTL to prevent engraftment of human AML in NOD/SCID mice. These studies show that engraftment of leukemias derived from individuals encoding the minor H antigen can be specifically prevented demonstrating that AML stem cells express minor H antigens and are targets for CTL. One approach to determine directly which minor H antigens can be selectively targeted to induce a GVL effect without GVHD is to adoptively transfer T cell clones of defined specificity and function to patients who relapse after HCT. Studies of this approach are now in progress in acute leukemia and have provided important insights into potential obstacles of T cell therapy for relapsed leukemia after HCT.

Animals↗
PubMed2002

Clinical implications of leptin and its potential humoral regulators in long-term low-calorie diet therapy for obese humans.

OBJECTIVE: To address the clinical implications of leptin and to re-examine the relationship between leptin and its potential humoral regulators such as insulin, nonesterified fatty acids (NEFA) and triiodothyronine (T3) in low-calorie diet (LCD) for obese humans. DESIGN: Longitudinal study. SETTING: University and foundation hospitals. SUBJECTS: Ten obese men and 10 premenopausal obese women. INTERVENTIONS: Five men and five women took 800 kcal/day LCD and another five men and five women took 1400 kcal/day balanced deficit diet (BDD) during 4 weeks. RESULTS: Plasma leptin levels in the LCD group decreased more markedly (46.2+/-14.6 to 13.2+/-3.6 ng/ml) than that expected for the decrement in percentage fat (39.0+/-1.7 to 35.9+/-1.7%) and body mass index (BMI; 35.4+/-2.4 to 33.1+/-2.2 kg/m(2)), while that in the BDD group did not decrease significantly (14.9+/-3.5 to 13.4+/-2.8 ng/ml). The ratio of the decrease in leptin levels to that of BMI during the first week was significantly greater than that during the following 3 weeks (39.5+/-2.7 vs 29.3+/-2.1%, P=0.017). The plasma insulin and T3 levels also fell substantially in the first week and continued to decrease during the entire course. Plasma leptin levels measured weekly in each subject were correlated well with insulin (r=0.586, P=0.0003) and T3 (r=0.785, P=0.0004). Multiple regression analyses after adjustment for the time course and BMI revealed that serum levels of T3 were independently correlated with plasma leptin levels (r=0.928, P<0.0001). The plasma NEFA level was markedly elevated during the first 2 weeks and decreased thereafter. CONCLUSIONS: A rapid fall in leptin during the first week of LCD, coordinated by insulin, T3 and NEFA, should be beneficial for responding to decreased energy intake. Inversely, in view of the powerful effect of leptin on energy dissipation, the present findings suggest the potential usefulness of leptin in combination with caloric restriction for the treatment of obesity. SPONSORSHIP: The Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health, Labour and Welfare of Japan.

Adolescent↗
PubMed2002

A reduction in the number of peripheral CD28+CD8+T cells in the acute phase of influenza.

Influenza patients show a high incidence of T lymphocytopenia in the acute phase of the illness. Since CD8+ T cells play an important role in influenza virus infection, we investigated which subset of CD8+ T cells was involved in this lymphocytopenia. CD8+ T cells from eight patients with influenza A were studied for lymphocyte count, surface marker, and intracellular IFN-gamma production in the acute (days 1-3) and recovery phases (days 9-12). Total and T lymphocyte counts in the acute phase were approximately three times less than in the recovery phase; however, the CD4/8 ratio was the same in both phases. The cell count reduction in the acute phase was attributed predominantly to the CD28+ CD8+ subset, compared with the CD28- CD8+ subset. The memory/activation marker CD45RO on the CD8+ T cells was assessed. The CD28+ CD45RO- subset, a naive phenotype, was reduced significantly in number in the acute phase compared with the recovery phase. The CD28+ CD45RO+ subset, a memory phenotype, was also reduced in the acute phase, but the reduction was not statistically significant. Intracellular IFN-gamma in the CD8+ subset after mitogenic stimulation was measured by flow cytometry; the percentage of CD28+ IFN-gamma-/CD8+ subset in the acute phase was significantly less than in the recovery phase. These results indicated that the predominant reduction of peripheral CD8+ T cells in the acute phase of influenza was from naive-type lymphocytes, suggesting that these quantitative and qualitative changes of CD8+ T cells in influenza are important for understanding the immunological pathogenesis.

Acute Disease↗
PubMed2002

Bone induction in subcutaneous tissue in rats by a newly developed DNA-coated atelocollagen and bone morphogenetic protein.

A unique biomaterial, a mixture of DNA and collagen (DNA/collagen), was developed and its efficacy as a carrier matrix for bone morphogenetic protein (BMP) was evaluated histologically. The material was prepared as a composite of DNA from salmon milt and pepsin-digested type I collagen (atelocollagen) from bovine dermis. Phase-contrast and fluorescence microscopy showed atelocollagen fibres with DNA coating. The dose-response and time-course of bone induction by BMP in DNA/collagen (5 x 10 x 1 mm) in the subcutaneous tissue was investigated in 20 male Wistar rats. The BMP/DNA/collagen induced new bone in a dose-dependent manner (0, 25, 50 or 100 micrograms of BMP). Histological examination in the time-course study showed that the BMP (100 micrograms)/DNA/collagen induced bone formation, while the DNA/collagen alone resulted in the accumulation of fibroblasts. These results indicate that the DNA/collagen is effective as a carrier matrix for BMP. It provides a cell anchorage for differentiation of osteoblasts and is absorbed as bone matures.

Absorbable Implants↗
PubMed2002

Notch3 gene polymorphism and ischaemic cerebrovascular disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a type of hereditary stroke and dementia. More than 90% of patients with CADASIL have mutations in the Notch3 gene. All mutations either create or destroy a cysteine residue in the epidermal growth factor-like repeats. In addition, five polymorphisms, which lead to amino acid substitutions, have been identified within the Notch3 coding sequence. However, whether these polymorphisms affect Notch signalling or are involved in cerebrovascular diseases is unknown. In the present study, we investigated a possible association between a T6746C polymorphism in the Notch3 coding region and the occurrence of symptomatic ischaemic cerebrovascular disease (CVD) was investigated. Two hundred and thirty five patients with CVD, as confirmed by brain CT or MRI, and 315 age and sex matched control subjects were analyzed for genotype frequencies of the T6746C polymorphism in Notch3. The genotype distributions were: patients with CVD, C/C 14.0%, C/T 45.5%, and T/T 40.4%; controls, C/C, 14.3%; C/T, 47.9%; T/T, 37.8%. The Japanese population has a higher C allele frequency of the T6746C polymorphism than European populations. There was no significant difference between the T6746C polymorphism in patients with CVD and controls (chi(2)=0.414, p=0.813). This was confirmed by the results of multiple logistic regression analysis including established risk factors (chi(2) =4.65, p=0.311). In conclusion, the results indicate that T6746C polymorphism in the intracellular domain of the Notch3 gene is not associated with an increased risk for CVD.

Aged↗
PubMed2001

The reaction of fullerene C(60) with 4,6-dimethyl-1,2,3-triazine: formation of an open-cage fullerene derivative.

A thermal reaction of fullerene C(60) with 4,6-dimethyl-1,2,3-triazine (4) in o-dichlorobenzene gave azacyclohexadiene-fused fullerene derivative 5, by the reaction with intermediate azete 11, and then, after flash chromatography over SiO(2), open-cage fullerene derivative 6 having an eight-membered ring orifice on the C(60) cage. Compound 6 is assumed to be formed via addition of diradical intermediate 13 to C(60). Compound 6 underwent a further photochemical reaction with singlet oxygen with the cleavage of one of the double bonds at the rim of the orifice to afford triketone derivative 8 having a 12-membered ring orifice.

Carbon↗
PubMed2001

Structural features of a wheat plastome as revealed by complete sequencing of chloroplast DNA.

Structural features of the wheat plastome were clarified by comparison of the complete sequence of wheat chloroplast DNA with those of rice and maize chloroplast genomes. The wheat plastome consists of a 134,545-bp circular molecule with 20,703-bp inverted repeats and the same gene content as the rice and maize plastomes. However, some structural divergence was found even in the coding regions of genes. These alterations are due to illegitimate recombination between two short direct repeats and/or replication slippage. Overall comparison of chloroplast DNAs among the three cereals indicated the presence of some hot-spot regions for length mutations. Whereas the region with clustered tRNA genes and that downstream of rbcL showed divergence in a species-specific manner, the deletion patterns of ORFs in the inverted-repeat regions and the borders between the inverted repeats and the small single-copy region support the notion that wheat and rice are related more closely to each other than to maize.

DNA, Chloroplast↗
PubMed2001

Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection.

Mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels play a key role in ischemic preconditioning of the heart. However, the mechanism of cardioprotection remains controversial. We measured rhod-2 fluorescence in adult rabbit ventricular cardiomyocytes as an index of mitochondrial matrix Ca(2+) concentration ([Ca(2+)](m)), using time-lapse confocal microscopy. To simulate ischemia and reperfusion (I/R), cells were exposed to metabolic inhibition (50 minutes) followed by washout with control solution. Rhod-2 fluorescence gradually increased during simulated ischemia and rose even further with reperfusion. The mitoK(ATP) channel opener diazoxide attenuated the accumulation of [Ca(2+)](m) during simulated I/R (EC(50)=18 micromol/L). These effects of diazoxide were blocked by the mitoK(ATP) channel antagonist 5-hydroxydecanoate (5HD). In contrast, inhibitors of the mitochondrial permeability transition (MPT), cyclosporin A and bongkrekic acid, did not alter [Ca(2+)](m) accumulation during ischemia, but markedly suppressed the surge in rhod-2 fluorescence during reperfusion. Measurements of mitochondrial membrane potential, DeltaPsi(m), in permeabilized myocytes revealed that diazoxide depolarized DeltaPsi(m) (by 12% at 10 micromol/L, P<0.01) in a 5HD-inhibitable manner. Our data support the hypothesis that attenuation of mitochondrial Ca(2+) overload, as a consequence of partial mitochondrial membrane depolarization by mitoK(ATP) channels, underlies cardioprotection. Furthermore, mitoK(ATP) channels and the MPT differentially affect mitochondrial calcium homeostasis: mitoK(ATP) channels suppress calcium accumulation during I/R, while the MPT comes into play only upon reperfusion.

Bongkrekic Acid↗
PubMed2001

Protective effect of phytic acid on oxidative DNA damage with reference to cancer chemoprevention.

Phytic acid (myo-inositol hexaphosphate) is one of the most promising cancer chemopreventive agents. We investigated the mechanism by which phytic acid expresses preventive action to cancer. Phytic acid inhibited the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in cultured cells treated with an H2O2-generating system, although it did not scavenge H2O2. Site-specific DNA damage by H2O2 and Cu(II) at GG and GGG sequences was inhibited by phytic acid, but not by myo-inositol. Phytic acid alone did not cause DNA damage and thus, it should not act as a prooxidant. We conclude that phytic acid acts as an antioxidant to inhibit the generation of reactive oxygen species from H2O2 by chelating metals, resulting in chemoprevention of cancer.

Binding Sites↗
PubMed2001

c-Fos/activator protein-1 transactivates wee1 kinase at G(1)/S to inhibit premature mitosis in antigen-specific Th1 cells.

M-phase promoting factor is a complex of cdc2 and cyclin B that is regulated positively by cdc25 phosphatase and negatively by wee1 kinase. We isolated the wee1 gene promoter and found that it contains one AP-1 binding motif and is directly activated by the immediate early gene product c-Fos at cellular G(1)/S phase. In antigen-specific Th1 cells stimulated by antigen, transactivation of the c-fos and wee1 kinase genes occurred sequentially at G(1)/S, and the substrate of wee1 kinase, cdc2-Tyr15, was subsequently phosphorylated at late G(1)/S. Under prolonged expression of the c-fos gene, however, the amount of wee1 kinase was increased and its target cdc2 molecule was constitutively phosphorylated on its tyrosine residue, where Th1 cells went into aberrant mitosis. Thus, an immediate early gene product, c-Fos/AP-1, directly transactivates the wee1 kinase gene at G(1)/S. The transient increase in c-fos and wee1 kinase genes is likely to be responsible for preventing premature mitosis while the cells remain in the G(1)/S phase of the cell cycle.

Animals↗
PubMed2001

Mechanism of metal-mediated DNA damage induced by metabolites of carcinogenic 2-nitropropane.

2-Nitropropane (2-NP), a widely used industrial solvent, is carcinogenic to rats. To clarify the mechanism of carcinogenesis by 2-NP, we investigated DNA damage by 2-NP metabolites, N-isopropylhydroxylamine (IPHA) and hydroxylamine-O-sulfonic acid (HAS), using 32P-5'-end-labelled DNA fragments obtained from genes that are relevant to human cancer. In the presence of Fe(III) EDTA, both IPHA and HAS caused DNA damage at every nucleotide position without marked site preference. The damage was inhibited by free hydroxyl radical (-*OH) scavengers, catalase and deferoxamine mesilate, an iron chelating agent. These results suggest that the DNA damage was caused by -*OH generated via H(2)O(2) by both IPHA and HAS. In contrast, in the presence of Cu(II), IPHA frequently caused DNA damage at thymine. The Cu(II)-mediated DNA damage caused by IPHA was inhibited by catalase, methional and bathocuproine, a Cu(I)-specific chelator, suggesting the involvement of H(2)O(2) and Cu(I). These results suggest that the DNA damage induced by IPHA in the presence of Cu(II) was caused by a reactive oxygen species like the Cu(I)-hydroperoxo complex. On the other hand, HAS most frequently induced DNA damage at 5'-TG-3', 5'-GG-3' and 5'-GGG-3' sequences. Catalase and methional only partly inhibited the Cu(II)-mediated DNA damage caused by HAS, suggesting that the reactive oxygen species and another reactive species participate in this process. Formation of 8-oxodG by IPHA or HAS increased in the presence of metal ions. This study suggests that metal-mediated DNA damage caused by 2-NP metabolites plays an important role in the mutagenicity and the carcinogenicity of 2-NP.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Oxidative DNA damage by an N-hydroxy metabolite of the mutagenic compound formed from norharman and aniline.

Norharman (9H-pyrido[3,4-b]indole), which is a heterocyclic amine included in cigarette smoke or cooked foodstuffs, is not mutagenic itself. However, norharman reacts with non-mutagenic aniline to form mutagenic aminophenylnorharman (APNH), of which DNA adducts formation and hepatocarcinogenic potential are pointed out. We investigated whether N-OH-APNH, an N-hydroxy metabolite of APNH, can cause oxidative DNA damage or not, using 32P-labeled DNA fragments. N-OH-APNH caused Cu(II)-mediated DNA damage. When an endogenous reductant, beta-nicotinamide adenine dinucleotide (NADH) was added, the DNA damage was greatly enhanced. Catalase and a Cu(I)-specific chelator inhibited DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). Typical -*OH scavenger did not inhibit DNA damage. These results suggest that the main reactive species are probably copper-hydroperoxo complexes with DNA. We also measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation by N-OH-APNH in the presence of Cu(II), using an electrochemical detector coupled to a high-pressure liquid chromatograph. Addition of NADH greatly enhanced 8-oxodG formation. UV-VIS spectra and mass spectra suggested that N-OH-APNH was autoxidized to nitrosophenylnorharman (NO-PNH). We speculated that NO-PNH was reduced by NADH. Cu(II) facilitated the redox cycle. In the presence of NADH and Cu(II), very low concentrations of N-OH-APNH could induce DNA damage via redox reactions. We conclude that oxidative DNA damage, in addition to DNA adduct formation, may play an important role in the expression of genotoxicity of APNH.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamine neurons: an electrophysiological study.

In this study, we determined the activity of midbrain dopamine (DA) neurons in male albino rats following the intracerebroventricular (i.c.v.) administration of antisense oligodeoxynucleotide (aODN) against the mRNA for the NR1 subunit of the NMDA receptor. In addition, the effect of aODN on the specific binding of the NMDA receptor ligand [(3)H]MK-801 was also examined in various brain areas, including the midbrain. Antisense ODN against the NR1 mRNA, the corresponding sense ODN (sODN) or saline was continuously administered into the right ventricle of rats by osmotic minipumps for 7 days (20 nmol/day). Autoradiographic binding studies indicated that aODN significantly reduced the density of [(3)H]MK-801 binding by an average of 20-30% in several forebrain regions, including the anterior cingulate cortex, caudate putamen, and nucleus accumbens. However, [(3)H]MK-801 binding was not significantly altered in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNC). Subsequently, using the technique of extracellular single-unit recording, the number, as well as the firing pattern, of spontaneously active DA neurons was determined in the VTA and SNC. The administration of aODN did not significantly alter the number of spontaneously active VTA and SNC DA neurons compared to saline- of sODN-treated animals. Furthermore, the firing pattern of spontaneously active SNC DA neurons was not significantly altered. However, for spontaneously active VTA DA neurons, the administration of aODN significantly decreased the percent events in bursts, number of bursts, and percentage of DA neurons exhibiting a bursting pattern compared to saline- and sODN-treated animals, i.e., neurons show less bursting activity. The present results suggest that subchronic aODN treatment against the mRNA for the NR1 subunit of the NMDA receptors can reduce NMDA receptor number and can result in an altered activity of spontaneously active VTA DA neurons in anesthetized rats.

Action Potentials↗
PubMed2001

Hormonal regulation of the human ghrelin receptor gene transcription.

The aim of this study is to clarify the hormonal regulation of the human ghrelin receptor gene expression in GH(3) cells transfected with our previously cloned 5'-flanking region inserted into a luciferase reporter vector. Phorbor 12-tetradecanoate 13-acetate (TPA) with simultaneous addition of Bay K8644 mimicking ghrelin action caused a significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -669 but not to -608 base pairs (bp). Glucocorticoid caused a weak but significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -531 but not to -475 bp. Electrophoretic mobility shift assay resulted in binding of oligonucleotides between -669 and -640 bp, and between -520 and -491 bp to GH(3) cell nuclear proteins unlike AP(2) or glucocorticoid receptor. These results suggest that both TPA/Bay K8644 and glucocorticoid downregulate human ghrelin receptor gene expression through the transcriptional mechanism involving some nuclear factors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Dual action of eicosapentaenoic acid in hepatoma cells: up-regulation of metabolic action of insulin and inhibition of cell proliferation.

Exogenous administration of eicosapentaenoic acid (EPA) improves insulin sensitivity, but its precise mechanism remains unknown. Here we show that EPA stimulates the intracellular insulin signaling pathway in hepatoma cells. Exposure of these cells to EPA caused up-regulation of several insulin-induced activities including tyrosine phosphorylation of insulin receptor substrate-1, insulin receptor substrate-1-associated phosphatidylinositol 3-kinase, and its downstream target Akt kinase activity as well as down-regulation of gluconeogenesis. In contrast, EPA decreased mitogen-activated protein kinase activity and inhibited cell proliferation. These findings raise the possibility that EPA up-regulates metabolic action of insulin and inhibits cell growth in humans.

Adaptor Proteins, Signal Transducing↗