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Biomedical subjects

M Ohno

Publications and source records attributed to M Ohno.

At least 19 recordsLinked to original sources

Conversion factor for CT dosimetry to assess patient dose using a 256-slice CT scanner.

Recent rapid progress in CT technology has yielded equipment with large numbers of detector rows and standard computed tomography dose index (CTDI) is therefore no longer an adequate integration range. An integration range of 300 mm is necessary to accurately measure dose under a nominal beam width of 128 mm due to scattered radiation. However, such a long phantom is inconvenient to use routinely in cone-beam CT patient dose checking. To assess patient dose accurately with standard dosimetry methods, we determined a conversion factor (CF) which was calculated from the weighted dose profile integral (DPI(w)) for the 300 mm integration range with a 300 mm long CTDI phantom using a 300 mm long ionization chamber divided by that for the 100 mm integration range with a standard CTDI phantom (140 mm long) with a 100 mm long chamber. CF values increase with increasing nominal beam width and effective energy in the range from 1.5 to 2.0. CF values can also be adapted for use with other CT systems as their dose profiles are thought to be analogous to those for the 300 mm phantom and are useful in any hospital situation to assess accurate patient doses using standard dosimetry methods.

Humans↗

MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

We previously reported that 8-oxoguanine (8-oxoG) accumulates in the cytoplasm of dopamine neurons in the substantia nigra of patients with Parkinson's disease and the expression of MTH1 carrying an oxidized purine nucleoside triphosphatase activity increases in these neurons, thus suggesting that oxidative damage in nucleic acids is involved in dopamine neuron loss. In the present study, we found that levels of 8-oxoG in cellular DNA and RNA increased in the mouse nigrostriatal system during the tyrosine hydroxylase (TH)-positive dopamine neuron loss induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MTH1-null mice exhibited a greater accumulation of 8-oxoG in mitochondrial DNA accompanied by a more significant decrease in TH and dopamine transporter immunoreactivities in the striatum after MPTP administration, than in wild-type mice. We thus demonstrated that MTH1 protects the dopamine neurons from oxidative damage in the nucleic acids, especially in the mitochondrial DNA of striatal nerve terminals of dopamine neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Bioassay monitoring of waste PCB samples during chemical destruction treatments.

Capacitor oil samples (PCBs > 90%wt) were treated in a bench scale experiment to investigate the destruction of PCBs during chemical destruction processes (a catalytic hydrodechlorination treatment with palladium carbon and additional treatment with potassium tert-butyloxide). Using those results, this study confirmed the decrease of PCBs and other undesirable dioxin-like compounds such as PCDD/Fs in treated samples during the treatment. Dioxin-responsive chemical-activated luciferase expression (DR CALUX) AhR reporter gene bioassay was used to evaluate dioxin-like activity in the samples. During the treatment, the efficiency for PCB capacitor oil was around 99.99% or more in WHO-TEQ and CALUX-TEQ, whereas the sum of PCBs was reduced at a resulting efficiency of >99.9999%. In this study, a new cleanup procedure for separating PCBs from the mineral oil matrix was also developed for DR CALUX. The procedure consists of dimethylsulphoxide partitioning followed by silica gel-44% sulphuric acid reflux treatment and activated carbon chromatography. With the cleanup, CALUX-TEQ values were in good agreement with WHO-TEQ values and were as much as 3.3 times higher than WHO-TEQs for untreated/treated PCB-containing insulating oil samples. The DR CALUX results of mineral oil samples containing various PCB concentrations of 0.5-50 mg/kg (corresponding WHO-TEQs: 0.012-1.2 microg-TEQ/g) also correlated well with WHO-TEQs (CALUX-TEQ/WHO-TEQ ratio = 1.0-3.0), which was consistent with the theoretical quantification limit of the CALUX. These results supported the validity of the proposed clean-up method.

Animals↗

[Quality of life of long-term survivors of surgically treated lung cancer].

Quality of life (QOL) of long-term survivors (more than 3 years after surgery) of primary non-small cell lung cancer was studied. QOL was analyzed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, 30-Item version 3.0 (QLQ-C30) and Hospital Anxiety and Depression Scale (HADS). Sixty of 91 patients (66%) participated in this study 87 +/- 5 (38-172) months postoperatively. In QLQ-C30, calculated scores of physical (84.0 +/- 2.4), role (81.3 +/- 3.6), cognitive (79.7 +/- 2.6), emotional (86.8 +/- 1.9), and social (91.0 +/- 1.9) functioning, and global QOL (72.6 +/- 2.9) were obtained. Calculated HADS A (anxiety) was 3.3 +/- 0.3 and HADS D (depression) was 4.0 +/- 0.4. Postoperative follow-up duration was correlated with financial impact only. QOL of long-term survivors was influenced by gender histology, marital status, employment status, and academic carrier.

Adult↗

[Ball thrombus in the right atrium: report of a case].

A 63-year-old man visited our hospital because of intermittent claudication due to an embolic episode in the left femoral artery. He had a long history of arterial fibrillation but had received no anticoagulant therapy. Echocardiography showed a large floating ball-shaped shadow in the right atrium, without any sign of tricuspid stenosis. Pulmonary perfusion scintigram was normal. At the operation, the thrombus which attached to the superior atrial septum with a thin string was removed. The thrombus was 54 x 40 x 25 mm in size and 23.8 g in weight, whose cut surface was in layers. There was neither atrial septal defect nor foramen ovale to suggest possibility of paradoxical embolism. The postoperative course was uneventful and he was discharged on the 9th postoperative day. Although the mechanism of the thrombus formations is unknown, it is considered to be important to continue anticoagulant therapy to avoid reccurence of intracardiac thrombus.

Cardiac Surgical Procedures↗

Selective induction of DeltaFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of DeltaFosB and galectin-1 in neuroprotection and neurogenesis.

Transient forebrain ischemia causes selective induction of DeltaFosB, an AP-1 (activator protein-1) subunit, in cells within the ventricle wall or those in the dentate gyrus in the rat brain prior to neurogenesis, followed by induction of nestin, a marker for neuronal precursor cells, or galectin-1, a beta-galactoside sugar-binding lectin. The adenovirus-mediated expression of FosB or DeltaFosB induced expression of nestin, glial fibrillary acidic protein and galectin-1 in rat embryonic cortical cells. DeltaFosB-expressing cells exhibited a significantly higher survival and proliferation after the withdrawal of B27 supplement than the control or FosB-expressing cells. The decline in the DeltaFosB expression in the survivors enhanced the MAP2 expression. The expression of DeltaFosB in cells within the ventricle wall of the rat brain also resulted in an elevated expression of nestin. We therefore conclude that DeltaFosB can promote the proliferation of quiescent neuronal precursor cells, thus enhancing neurogenesis after transient forebrain ischemia.

Adenoviridae↗

[Changing pattern of the respiratory function associated with resected lung lobe].

Respiratory function before and 2 months after lung lobectomy was analyzed associated with resected lobe. Post- or preoperative ratios of FEV1.0 or VC were compared among (1) predicted value by the number of subsegments using bronchofiberscopy, (2) predicted value by the lobar volume ratio using computed tomography (CT), and (3) actually measured value. Using subsegments method, post- or preoperative predicted VC ratios were 85 +/- 1% after right upper lobectomy (RU), 69 +/- 1% after right lower lobetomy (RL), 74 +/- 1% after left upper lobectomy (LU), and 75 +/- 1% after left lower lobectomy (LL). Using CT method, post- or preoperative predicted VC ratios were 80 +/- 2% after RU, 76 +/- 4% after RL, 74 +/- 2% after LU, and 79 +/- 3% after LL. Actually measured post- or preoperative FEV1.0 ratios were 82 +/- 3% after RU, 89 +/- 8% after RL, 73 +/- 3% after LU, and 86 +/- 5% after LL, and the VC ratios were 88 +/- 5% after RU, 79 +/- 3% after RL, 77 +/- 4% after LU, and 94 +/- 3% after LL. In the FEV1.0 analysis using both subsegments method and CT method, the predicted value was correlated with upper lobectomy but was overestimated in case of lower lobectomy. This phenomenon might be caused by the postoperative bronchial branching deformity after upper lobectomy. In the VC analysis using subsegments method, the predicted value was correlated with upper lobectomy but was overestimated in case of lower lobectomy. Meanwhile, in the VC analysis using CT method, the predicted value was correlated with RL or LU but was overestimated in case of RU or LL. This may due to the fact that RL and LU had large lobar volumes. In conclusion, postoperative predicted and actually measured values were different associated with resected lobe. In the FEV1.0 and VC analysis using subsegments method, the predicted value was strongly correlated with upper lobectomy but was overestimated (10%) in case of lower lobectomy.

Adult↗

CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers.

CYP3A5 expression is regulated by single-nucleotide polymorphisms (SNPs). The CYP3A5 genotype might contribute to a marked interindividual variation in CYP3A-mediated metabolism of drugs. Nifedipine is a typical substrate of CYP3A4 and CYP3A5 in vitro. The aim of this study was to elucidate the influence of the CYP3A5 genotype on nifedipine disposition in healthy subjects. A single capsule containing 10 mg of nifedipine was administered to 16 healthy male Japanese subjects (eight subjects: CYP3A5(*)1/(*)3; eight subjects: CYP3A5(*)3/(*)3). Blood samples were collected to analyze the pharmacokinetics of serum nifedipine and nitropyridine metabolite (M-I). The area under the plasma concentration-time curve (AUC), the peak plasma concentration (C(max)) and the terminal half-life (t(1/2)) of nifedipine, and the ratio of the nifedipine AUC to M-I AUC showed large intragroup variations, but no significant differences between the two genotypes. Based on the present findings, the functional relevance of CYP3A5 polymorphism should be re-evaluated in clinical trials.

Adult↗

TRA-418, a novel compound having both thromboxane A(2) receptor antagonistic and prostaglandin I(2) receptor agonistic activities: its antiplatelet effects in human and animal platelets.

TRA-418 is a novel compound that has been found in our screening for compounds having both thromboxane A2 (TP) receptor antagonistic and prostaglandin I2 (IP) receptor agonistic activities. In the binding assays, TRA-418 showed a 10-fold higher affinity to TP-receptors than IP-receptors. TRA-418 inhibited platelet aggregation induced by the TP-receptor agonist, U-46619 and by arachidonic acid at concentrations lower than those required for inhibition of ADP-induced aggregations. Furthermore, TRA-418 inhibited not only platelet aggregation induced by ADP alone, but also that induced by ADP in the presence of the TP-receptor antagonist, SQ-29548. When the IC50 values of TRA-418 for platelet aggregation were estimated in platelet preparations from monkeys, dogs, cats, and rats using ADP and arachidonic acid as the platelet stimulating agents, it was found that the values estimated in monkey platelets were quite similar to those estimated in human platelets. In ex vivo platelet aggregation in monkeys, TRA-418 exhibited significant inhibitory effects on arachidonic acid-induced aggregation in platelet preparations from monkeys treated at 3 micro g kg min-1 or higher doses, where neither a significant decrease in blood pressure nor a significant increase in heart rate was observed. These results are consistent with the fact that TRA-418 has a relatively potent TP-receptor antagonistic activity together with a relatively weak IP-receptor agonistic activity.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Effects of liposteroid on the hemophagocytic syndrome in systemic lupus erythematosus.

Hemophagocytic syndrome (HPS) is a life-threatening disorder characterized by pancytopenia and activation of macrophages. Recently, corticosteroid incorporated in lipid microspheres (liposteroid) has been reported to be taken up by macrophages and to suppress their functions. Here we present a case of systemic lupus erythematosus complicated by HPS that was successfully treated with liposteroid in addition to an oral corticosteroid and intravenous high-dose cyclophosphamide therapy. The serum levels of tumor necrosis factor-alpha and ferritin that have been reported to be associated with activity of macrophages remarkably reduced after liposteroid administration. This case suggests that liposteroid is useful for the treatment of HPS.

Administration, Oral↗

Development of a membrane dialysis bioreactor and its application to a large-scale culture of a symbiotic bacterium, Symbiobacterium thermophilum.

A simple membrane dialysis bioreactor was developed for a large-scale axenic culture of Symbiobacterium thermophilum, a symbiotic thermophile that requires co-cultivation with an associating thermophilic Bacillus strain S for normal growth. The bioreactor consisted of an outer- and an inner-coaxial cylindrical compartment bordered across a dialyzing membrane, which enabled a 1 l-scale dialysis culture with exchange of low molecular metabolites between the two compartments to be performed. Using the bioreactor, growth characteristics of S. thermophilum and Bacillus strain S were assessed under two medium conditions. The growth of S. thermophilum was measured by quantitative PCR because the bacterium formed no visible colonies and gave abnormally low turbidity. In medium containing 2% tryptone peptone, S. thermophilum proliferated up to 4x10(7) cells/ml, and strict dependence on the co-culture with Bacillus strain S was observed. On the other hand, medium containing 0.5% yeast extract not only facilitated the growth of S. thermophilum in the co-culture (6x10(7) cells/ml), but also allowed limited pure growth independent of Bacillus strain S (1x10(7) cells/ml), implying that some component of yeast extract can partially replace the growth requirement of S. thermophilum supplied by Bacillus strain S. Both the oxidative redox potential values and the cell morphology in the independently growing culture suggested the occurrence of marked unbalanced growth possibly caused by significant metabolic changes. The bioreactor is applicable to the analyses of culturing characteristics in symbiotic systems between free-living microorganisms.

Bioreactors↗

Dysregulation of the granulocyte-macrophage colony-stimulating factor receptor is one of the causes of defective expression of CD80 antigen in systemic lupus erythematosus.

CD80 and CD86, expressed on the antigen-presenting cells (APCs) provide costimulatory signals for T lymphocytes. Recently, defective expression of CD80 has been reported in systemic lupus erythematosus (SLE) although its mechanism is unclear. Here, expression of the B7 antigens induced by interferon-gamma, interleukin-4 or granulocyte-macrophage stimulating-factor (GM-CSF) along the differentiation process of APCs was investigated. In contrast to CD86, expression of CD80 on the CD14+ cells induced by GM-CSF was reduced in SLE. GM-CSF receptor (GM-CSFR) was down-regulated by GM-CSF or phorbol 12-myristate 13-acetate in both of the normal controls and SLE patients, while this change was more remarkable in the latter. In the presence of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, the PMA-induced down-regulation of GM-CSFR was reversed in the normal controls but not in SLE. These data suggest that dysregulation of the GM-CSFR might be associated with the defective expression of CD80, leading to dysfunction of the APCs in SLE.

Adult↗

Increased ash contents and estimation of dissolution from chemical changes due to in-vitro fluoride treatments.

The in-vitro fluoride treatment technique has been introduced to investigate the composite behavior of bone tissue. Bone tissue with different mechanical properties can be obtained by varying the concentration, pH and immersion time in fluoride ion solutions. The chemical and physical changes in intact pieces of bone treated in-vitro with different concentrations of fluoride ions are studied. The amount of bone mineral that does not contribute to the mechanical behavior of bone tissue is estimated from the dissolution occurring in the fluoride treated bones. Cortical bones from 18-month-old steers were treated in-vitro with 0.145, 0.5 and 2.0 M sodium fluoride (NaF) solutions for three days. The dissolved bone mineral precipitates as calcium fluoride-like (CaF2/P with some phosphate [P] ions) and fluorapatite(FAp)/fluorhydroxyapatite(FHAp)-like materials within the bone tissue. The dissolution estimated from the presence of the precipitated fluoride phases is 5.6, 11.7, and 13.1% of the initial bone mineral content for the 0.145 M, 0.5 M, and 2.0 M NaF treatments respectively. Estimates of dissolution based on the measurements of phosphate and carbonate ions are lower and higher respectively when compared to the fluoride ion measurements. The wet and dry densities decreased slightly due to dissolution and re-precipitation while the ash content (ratio of the ash weight to dry weight) increased a small amount with increasing concentration of fluoride ion treatments. The increased ash content was due to the excess loss of water in the fluoride treated bones as compare to controls (untreated bone samples) during the drying process. The increased removal of water during the drying process may explain the increased ash contents in some in-vivo treatments.

Animals↗

Lecithinized Cu, Zn-superoxide dismutase limits the infarct size following ischemia-reperfusion injury in rat hearts in vivo.

Covalent binding of 4 molecules of phosphatidylcholine palmitoyl to human recombinant superoxide dismutase (SOD) results in a compound (lecithinized SOD) that has a longer half-life and greater affinity to the cell membrane than unmodified SOD. We investigated whether lecithinized SOD played a protective role against myocardial ischemia-reperfusion injuries in rats. Rats underwent 45 min of myocardial ischemia by occluding the left coronary artery followed by 120 min of reperfusion. They were randomly assigned to receive either lecithinized SOD, polyethylene glycol conjugated SOD (PEG-SOD), unmodified SOD, free lecithin derivative, or PBS intravenously at 5 min prior to reperfusion. Myocardial infarct area assessed by TTC staining was smaller in lecithinized SOD group than PEG-SOD, unmodified SOD, free lecithin derivative or control group. Blood pressure and heart rate was similar in each group. ELISA demonstrated SOD level in the heart was significantly high in lecithinized SOD group, especially in the heart of ischemia at risk. Although serum SOD level of PEG-SOD was as high as lecithinized SOD, SOD level of the heart was low. These data suggested lecithinized SOD had a protective effect in myocardial ischemia-reperfusion injuries through its increased bioavailability.

Animals↗

Lecithinized copper, zinc-superoxide dismutase ameliorates ischemia-induced myocardial damage.

We have reported that lecithin-conjugated recombinant human Cu, Zn-superoxide dismutase (lecithinized SOD) has greater pharmacological potency than unmodified SOD through an increase in cell membrane affinity and half-life in plasma. Recently, ischemia or hypoxia alone has been suggested to result in increased superoxide anions, which lead to apoptosis in cardiomyocytes. We tested the effect of lecithinized SOD in reducing the infarct size following prolonged myocardial ischemia without reperfusion. Rats were subjected to a 24-h left coronary occlusion. Lecithinized SOD, unmodified SOD, free lecithin derivative or PBS was administered intravenously 30 min before coronary occlusion. SOD concentration of the heart, measured by ELISA, was higher in the lecithinized SOD-treated group than in the other groups 24 h after administration. The infarct area ratio of the heart, assessed by TTC staining, in the lecithinized SOD-treated group was significantly smaller than those of the other groups. Both TUNEL-positive cardiomyocytes and DNA laddering were attenuated in the ischemic area of the heart treated with lecithinized SOD. Single bolus administration of lecithinized SOD had a cardioprotective effect against ischemia without reperfusion in the rat model of acute myocardial infarction, possibly due to its sustained high tissue concentration.

Animals↗