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Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 109 records · Page 6Linked to original sources
PubMed2000

Singlet oxygen-dependent hydroxyl radical formation during uroporphyrin-mediated photosensitization in the presence of NADPH.

The conversion of singlet oxygen ((1)O2) to hydroxyl radical (*OH) during photosensitization of uroporphyrin (UP) in the presence of NADPH was examined by a spin-trapping technique with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Significant electron spin resonance (ESR) signals of DMPO-OH adduct were observed during irradiation of the UP-NADPH system with visible light. Scavengers of *OH reduced the signal intensity to 3-30% of control, indicating that more than 70% of DMPO-OH results from freely diffusing *OH. The ESR signal was almost completely lost when quenchers of (1)O2 were added, and was enhanced when the amount of deutrated solvent was increased. The appearance of (1)O2, as determined by the oxidation of 2,2,6,6-tetramethyl-4-piperidone (TEMPD), was delayed with an increase in the concentration of NADPH, whereas the production of *OH was upregulated. These observations indicate that conversion of (1)O2 to *OH occurs quickly in the presence of NADPH. Hydrogen peroxide (H2O2) was produced (1)O2-dependently during irradiation of UP in the presence of NADPH. However, neither catalase nor desferrioxamine decreased the DMPO-OH signal, and addition of H2O2 did not increase the signal. SOD increased the signal only slightly. These results suggest that the production of *OH from (1)O2 involves neither superoxide anion radical nor H2O2.

Animals↗
PubMed2000

Production of a single-chain variable fragment antibody recognizing type III mutant epidermal growth factor receptor.

The type III deletion mutant of the epidermal growth factor receptor (EGFR) is a potential target in diagnostic and therapeutic approaches for those glioblastomas characterized by its expression. We previously raised a mouse monoclonal antibody, 3C10 (IgG2b) specifically recognizing this mutant EGFR. In this study, a single-chain variable fragment (scFv) antibody was produced. Partial determination of its N-terminal amino acid sequence and preparation of adequate primers for variable heavy chain (V(H)) and variable light chain (V(L)) genes were performed to allow cloning by means of reverse transcriptase-polymerase chain reaction. The genes cloned were assembled with a linker, (Gly4Ser)3, and ligated into a bacterial expression vector to express the scFv as cytoplasmic inclusion bodies. After appropriate refolding, the antibody activity of the V(H)-V(L) scFv was examined in an enzyme-linked immunosorbent assay. 3C10 scFv showed a selective reactivity with the mutant peptide, similarly to the parental 3C10 antibody. A mouse transfectant expressing the type III mutant EGFR and a glioblastoma with type III deletion-mutant EGFR were positively stained by immunofluorescence. By Biacore analysis, the affinity (K(A)) of the parental 3C10 for the mutant peptide was 9.7 x 10(7) M(-1), while that of 3C10 scFv was 2.45 - 2.48 x 10(7) M(-1), being approximately 4-fold weaker. The results together suggested that the scFv antibody retained the appropriate structure to recognize a conformational epitope of the mutant receptor, similarly to the parental antibody.

3T3 Cells↗
PubMed2000

Cationic liposome conjugation to recombinant adenoviral vector reduces viral antigenicity.

Adenoviral (Ad) vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by immune responses that reduce transgene expression and decrease the efficacy of repeated vector administration. In this study, we demonstrated that conjugation of Ad vector with our novel cationic liposomes could reduce viral antigenicity in vivo. Mice subcutaneously injected with liposome-conjugated Ad vector showed a 6.5-fold reduction of anti-Ad antibodies with neutralizing activity, compared to those with unconjugated Ad vector. Interestingly, we also found that the conjugated vector is less susceptible to inactivation by neutralizing antibodies in vitro and in vivo. Our results suggest that liposome conjugation reduces viral antigenicity, shields vectors from neutralizing antibody, and may allow repeated Ad vector administration.

Adenoviridae↗
PubMed2000

Antibody to heat shock protein can be used for early serological monitoring of Helicobacter pylori eradication treatment.

Infection with Helicobacter pylori induces humoral immune responses against various antigens of the bacterium. Heat shock proteins (hsps) are immunodominant antigens in various diseases including H. pylori infection. In the present study, we measured the anti-hsp antibody titers in 42 patients with H. pylori-infected peptic ulcers during a bacterial eradication study. The patients were treated with a proton pump inhibitor and antimicrobial agents to eradicate the organism. Their sera were obtained at pretreatment and at 1 month and 6 months after the eradication therapy. The titers of immunoglobulin G antibodies to the H. pylori hsp, whole-cell lysate, and urease (30-kDa subunit) antigens in serum were measured by a capture enzyme-linked immunosorbent assay. The levels of H. pylori hsp60 antibodies in sera collected 1 month after treatment had declined significantly, even when changes in the titers of antibodies to whole-cell and urease antigens were not apparent. These results suggest that measurement of antibodies to H. pylori hsp60 in serum is useful for the early monitoring of the effectiveness of eradication therapy.

Adult↗
PubMed2000

Clinicopathological features of gastric mucosa associated lymphoid tissue (MALT) lymphomas: high grade transformation and comparison with diffuse large B cell lymphomas without MALT lymphoma features.

AIMS: To investigate the clinicopathological differences among gastric low grade MALT lymphomas (low MALT), large B cell lymphomas with low grade components (secondary high grade MALT lymphomas, high MALT), and diffuse large B cell lymphomas without low grade features (primary high grade MALT lymphomas, DLL). METHODS: Clinicopathological and morphological characters of 126 gastric lymphoma cases were studied: 82 cases of low MALT lymphoma including 40 that were surgically resected, 17 cases of high MALT lymphoma including 13 surgically resected, and 27 cases of DLL including 12 surgically resected. RESULTS: Age ranges were as follows: low MALT lymphoma, 34 to 85 years (mean 59.9); high MALT lymphoma, 53 to 88 years (mean 68.5); DLL, 29 to 83 years (mean 62.3). The average age for low and high MALT lymphomas was significantly different (p < 0.05), but there were no differences in other comparisons. There was a female predominance of low MALT lymphoma patients (female to male ratio, 47/35), while for high MALT patients the ratio was almost even (8/9), and for DLL patients there was a male predominance (11/16). Examination of surgically resected material showed that MALT lymphomas had a wider distribution in the gastric wall than DLL. CONCLUSIONS: The findings suggest that at least some of the high grade gastric lymphomas, especially in patients younger than the fifth decade, do not originate from high grade transformation of low MALT lymphomas. It seems to take about one decade at least for high grade transformation of low MALT lymphomas.

Adult↗
PubMed2000

Sprint performance is related to muscle fascicle length in male 100-m sprinters.

The purpose of this study was to investigate the relationship between muscle fascicle length and sprint running performance in 37 male 100-m sprinters. The sample was divided into two performance groups by the personal-best 100-m time: 10.00-10.90 s (S10; n = 22) and 11.00-11.70 s (S11; n = 15). Muscle thickness and fascicle pennation angle of the vastus lateralis and gastrocnemius medialis and lateralis muscles were measured by B-mode ultrasonography, and fascicle length was estimated. Standing height, body weight, and leg length were similar between groups. Muscle thickness was similar between groups for vastus lateralis and gastrocnemius medialis, but S10 had a significantly greater gastrocnemius lateralis muscle thickness. S10 also had a greater muscle thickness in the upper portion of the thigh, which, given similar limb lengths, demonstrates an altered "muscle shape." Pennation angle was always less in S10 than in S11. In all muscles, S10 had significantly greater fascicle length than did S11, which significantly correlated with 100-m best performance (r values from -0.40 to -0.57). It is concluded that longer fascicle length is associated with greater sprinting performance.

Adult↗
PubMed2000

The role of neuropeptide Y in the progesterone-induced luteinizing hormone-releasing hormone surge in vivo in ovariectomized female rhesus monkeys.

Progesterone induces a LHRH surge in estrogen-primed ovariectomized rhesus monkeys, with a concomitant increase in the pulse frequency of neuropeptide Y (NPY) release. However, the role for NPY in the positive feedback action of progesterone on LHRH release in primates is unknown. The present study examines the effect of an antisense oligodeoxynucleotide for NPY messenger RNA (AS NPY) on the progesterone-induced LHRH surge in vivo using push-pull perfusion. The AS NPY was directly infused into the stalk-median eminence (S-ME), whereas perfusates were collected for assessment of LHRH release. For a control, a scrambled oligodeoxynucleotide was infused. The results indicate that 1) the scrambled oligodeoxynucleotide did not interfere with the progesterone-induced LHRH surge, 2) whereas AS NPY blocked the progesterone-induced increase in LHRH release, and 3) no LHRH surges were induced by oil as a control for progesterone, but the AS NPY also reduced LHRH release in oil controls. These data suggest that 1) AS NPY infusion into the S-ME results in reduction in LHRH release; and 2) NPY release in the S-ME is important for the positive feedback effects of progesterone on LHRH release in estrogen-primed ovariectomized monkeys.

Animals↗
PubMed2000

Optically active antifungal azoles. XI. An alternative synthetic route for 1.

New routes for the synthesis of the optically active antifungal triazoles 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-1-tetrazolyl)phenyl]-2-imidazolidinone (1b) and the 3-14-(1H-1,2,3-triazol-1-yl)phenyl]-2-imidazolidinone analog (1a) that possess an imidazolidine nucleus were established. The key synthetic intermediates, (2R,3R)-3-(2,2-diethoxvethyl)amino-2-(2,4-difluorophenyl)-1-(1H1,2,4-triazol-1-yl)-2-butanol (8) and (2R,3R)-2-(2,4-difiuorophenyl)-3-(2-h ydroxyethyl)amino-1-(1H-1,2,4-triazol-1-yl)-2-butanol (14), were prepared by the ring-opening reaction of the oxirane (2) with the corresponding 2-substituted ethylamines. The acetal (8) was converted to the imidazolidinones (1a, b) by condensation with the carbamates (10a, b) followed by treatment with hydrochloric acid and subsequent catalytic hydrogenation. The candidate selected for the clinical trials, 1b (TAK-456), was alternatively prepared from the hydroxyethylamino intermediate (14) via two reaction steps: condensation with the carbamate (10b) to the urea (15) and subsequent cyclization to the imidazolidinones. This newly developed synthetic route could be applied to a large scale preparation of 1b.

Antifungal Agents↗
PubMed2000

Contribution of cyanide-insensitive respiratory pathway, catalyzed by the alternative oxidase, to citric acid production in Aspergillus niger.

In Aspergillus niger, a cyanide (CN)- and antimycin A-insensitive and salicylhydroxamic acid (SHAM)-sensitive respiratory pathway exists besides the cytochrome pathway and is catalyzed by the alternative oxidase (AOX). In this study, A. niger WU-2223L, a citric acid-producing strain, was cultivated in a medium containing 120 g/l of glucose, which is the concentration usually needed for citric acid production, and the effects of 2% (v/v) methanol, an inducer of citric acid, 2 microM antimycin A, and 1 mM SHAM on AOX activities and citric acid production were investigated. The AOX activity, measured as duroquinol oxidase, was localized in the purified mitochondria regardless of the presence of any additives. When WU-2223L was cultivated with antimycin A or methanol, both citric acid production and citric acid productivity, shown as the ratio of production per mycelial dry weight, increased with the increase of both the activity of AOX and the rate of CN-insensitive and SHAM-sensitive respiration. On the other hand, when WU-2223L was cultivated with SHAM, an inhibitor of AOX, the CN-insensitive and SHAM-sensitive respiration was not detected and the citric acid production and the productivity drastically decreased, although mycelial growth was not affected. These results clearly indicated that the CN-insensitive and SHAM-sensitive respiration catalyzed by AOX, localized in the mitochondria, contributed to citric acid production by A. niger.

Aspergillus niger↗
PubMed2000

Wing-shaped end-to-end anastomosis for the treatment of high jejunal atresia.

Six infants with jejunal atresia, one infant with ileal atresia, and one infant with colonic atresia were managed by a newly developed wing-shaped end-to-end anastomosis. The technique was accomplished by anastomosing the tip of the dilated proximal bowel to the diminutive distal bowel, which had been divided into two parts, including the mesentery. The completed anastomosis resembled extended wings, and this technique was therefore named wing-shaped anastomosis. This technique for anastomosis is effective in preventing functional obstruction because no axial deviation between the proximal and distal anastomotic bowels exists, and the mucosal absorptive surface is completely preserved.

Anastomosis, Surgical↗
PubMed2000

Transduction efficiency of adenoviral vectors into human glioma cells increased by association with cationic liposomes.

Replication-deficient adenoviral vectors are promising agents for human gene therapy of the greater transduction efficiency than other vectors. However, there are distinct disadvantages, including high immunogenicity, which limits the administration to human organs, particularly the brain. Injection of adenoviral vectors into the human brain causes inflammatory responses and induces cerebral edema. The combined effect of adenoviral vectors and cationic liposomes in vitro was investigated in an effort to reduce the immune reaction against the antigens of adenoviral vectors. No toxicity of adenoviral vector-associated liposomes was observed within optimal lipid concentration. The transduction efficiency of the adenoviral vectors containing the beta-galactosidase gene increased almost 10-fold when associated with the cationic liposomes. Furthermore, greater cytotoxicity was induced when the adenoviral vector containing herpes simplex virus-thymidine kinase gene was combined with cationic liposomes than with only the adenoviral vector. These results suggest that the combination of adenoviral vectors and cationic liposomes allows the doses of adenoviral vectors to be reduced while maintaining transduction efficiency.

Adenoviridae↗
PubMed2000

Percutaneous microcompression of the trigeminal ganglion for elderly patients with trigeminal neuralgia and patients with atypical trigeminal neuralgia.

Percutaneous microcompression of the trigeminal ganglion (PMTG) was performed in nine elderly patients (> 70 years) with trigeminal neuralgia and six patients with atypical neuralgia under short-acting anesthesia using propofol. Two patients had postherpetic neuralgia and two had postoperative neuralgia following removal of a posterior fossa neurinoma. Four patients had recurrent neuralgia following microvascular decompression (MVD). PMTG provided complete relief in 10 patients and the other five patients reported at least 50% improvement. No major complications occurred. PMTG is effective for typical trigeminal neuralgia in elderly patients, patients with atypical trigeminal neuralgia, and patients with recurrence after MVD.

Aged↗
PubMed2000

Midgut malrotation in adulthood.

A 29-year-old man was admitted to our hospital with a history of recurrent right upper quadrant abdominal pain and vomiting. These symptoms appeared intermittently for 7 years. Various examinations revealed a diagnosis of midgut malrotation. Laparotomy was performed and revealed reverse rotation of the duodenum with paraduodenal hernia and a normal rotating colon. This case suggests that recurrent abdominal complaints in an adult should arouse suspicion of midgut malrotation.

Abdominal Pain↗
PubMed2000

[Correlation between DNA topoisomerase II alpha expression and sensitivity to etoposide in human glioma cell lines].

The expression of topoisomerase II alpha (Topo II alpha) was investigated in six human glioma cell lines as a function of doubling time, cell cycle distribution, and sensitivity to an antineoplastic agent, etoposide (ETP). The Topo II alpha level was determined by immunohistochemical and flow cytometric studies using monoclonal antibody, 8D2, specific for Topo II alpha. In all cell lines, the Topo II alpha level correlated directly with sensitivity to ETP, but not with doubling time or percentage of cells in any phase of the cell cycle. These findings suggest that the cytocidal activity of ETP may be mediated by qualitative and quantitative changes in Topo II alpha in human glioma cells. We speculate that better knowledge of Topo II alpha expression in surgical specimens may lead to more individualized use of ETP in patients with malignant glioma.

Antigens, Neoplasm↗
PubMed2000

[Gangliocytoma].

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Adolescent↗