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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 1,099 records · Page 61Linked to original sources
PubMed1984

Importance of Fe2+-ADP and the relative unimportance of OH in the mechanism of mitomycin C-induced lipid peroxidation.

The mechanism of mitomycin C-induced lipid peroxidation has been studied at pH 7.5, using systems containing phospholipid membranes (liposomes) and an Fe3+-ADP complex with purified NADPH-cytochrome P-450 reductase. Both O2- and H2O2 are generated during the aerobic enzyme-catalyzed reaction in the presence of mitomycin C. Hydroxyl radical is formed in the reaction by the reduction of H2O2. This is catalyzed by the Fe2+-ADP complex in a phosphate buffer or to a lesser extent when in a Tris-HCl buffer. The reduction of Fe3+-ADP to Fe2+-ADP is mainly achieved by O2-. The resulting Fe2+-ADP in the presence of O2 forms a perferryl ion complex which is a powerful stimulator of lipid peroxidation. However, the formation of such an iron-oxygen complex is strongly inhibited by phosphate ions, which do not interfere with the generation of OH radicals. These findings suggest that, since lipid peroxidation occurs in a Tris-HCl buffer (but not in a phosphate buffer), the OH radical is unlikely to be involved in the observed lipid peroxidation process.

Adenosine Diphosphate↗
PubMed1984

Intraoperative radiotherapy for advanced carcinoma of the pancreas.

A detailed retrospective analysis of the efficacy of intraoperative radiotherapy (IOR) in advanced carcinoma of the pancreas is presented. During a 10-year period from 1973 through 1982, 70 patients with advanced carcinoma of the pancreas were treated by multimodal methods, separate or combined therapy of surgery, IOR, and chemotherapy in two different institutions. Among these, 33 patients underwent IOR, mostly combined with additive surgery. A single dose of 20.1 to 40.0 Gy with 8 to 25 meV electrons was delivered through radiation cones ranging from 6 to 10 cm in diameter. Excellent relief was noticed in 50% of the patients who had complained of pain. Among Stage IV patients, a significant difference of survival rate was observed between IOR and control groups (P less than 0.05); the mean survival time of the IOR group was 4.6 +/- 2.6 (SD) and that of the control group 2.5 +/- 1.4 (SD) months. Intraoperative radiotherapy proved to be effective in prolonging the survival of patients with advanced stage of the lesion.

Adult↗
PubMed1984

Renal trehalase: two subsites at the substrate-binding site.

Phlorizin, phloretin, Tris and beta-methylglucoside are competitive inhibitors, with respect to the substrate trehalose, of purified renal trehalase. Mercuric chloride is a noncompetitive inhibitor. The active site of trehalase was examined further by multi-inhibition kinetic studies involving combinations of inhibitors. Phlorizin vs. phloretin and phlorizin vs. Tris were mutually non-competitive. In contrast, phloretin vs. Tris was mutually competitive. These findings suggest that the binding site of phlorizin to the enzyme differed from that of phloretin or Tris, and that phloretin and Tris might bind at a common site. These findings suggest a model in which trehalase has two binding sites at the substrate-binding site, a phlorizin (glucosyl) and a phloretin (phenyl) binding site, analogous to the model proposed previously for the glucose carrier. In addition, mercuric chloride vs. beta-methylglucoside was mutually competitive, although mercuric chloride and beta-methylglucoside, respectively, were noncompetitive and competitive inhibitors with respect to the substrate. Thus, it is suggested that the substrate binding and the SH-inhibitor binding sites are located very close to each other.

Animals↗
PubMed1984

Identification of benzo[a]pyrene quinone in soybean leaves.

Soybean seeds (Glycine max) were grown in soil containing 10 ppm of benzo[a]pyrene (BaP). After 76 days growth, three kinds of quinones, namely BaP-1,6-, 3,6- and 6,12-quinones, were isolated and identified. However, the formative mechanism of the quinones in leaves has yet to be determined.

Benzo(a)pyrene↗
PubMed1984

[The applicability of pions to cancer radiotherapy. III. Measurement of x-ray and gamma-rays by NaI detector for the determination of the peak-region in pi- meson exposure].

A method of externally observing the stop-region of pi- meson for monitoring during exposure to a patient is discussed. Negative pi mesic X-rarys, gamma-rays and neutrons are emitted from the region where pi- mesons stop and produce stars. These radiations can be detected outside the exposed patient. Water phantom as normal tissue equivalent material was exposed by pi- mesons at various depths. The resulting gamma-ray yields were determined by counting the gamma-rays in coincidence with incident pi- mesons using a sodium iodide (NaI) detector. This type of gamma-ray measuring system is useful to make sure that the peak position of the depth-dose distribution in the patient is exactly situated at the desired one during exposure. It is suggested that the scintillation camera with a multiholecollimator is a powerful and convenient tool for the two dimensional peak positioning.

Gamma Rays↗
PubMed1984

Inhibition by the protein ceruloplasmin of lipid peroxidation stimulated by an Fe3+-ADP-adriamycin complex.

Self-reduction of an Fe3+-ADP-adriamycin complex under anaerobic conditions and reduction of ferricytochrome c by the complex under aerobic conditions were strongly inhibited by ceruloplasmin, but not by superoxide dismutase or albumin at the same protein concentration. Ceruloplasmin, a protein with ferroxidase activity, is able to catalyse oxidation of Fe2+ to the ferric state. The inhibitory activity of ceruloplasmin towards reactions stimulated by the complex suggests that Fe2+ is formed during the self-reduction process. As expected, the Fe3+-ADP-adriamycin complex stimulated lipid peroxidation in which the Fe2+ moiety was implicated. This stimulation was again effectively prevented by ceruloplasmin but not by superoxide dismutase.

Adenosine Diphosphate↗
PubMed1984

Muscle D-glyceraldehyde-3-phosphate dehydrogenase from Caiman sp. II New data for enzyme characterization.

Muscle GPDH from Caiman sp. was activated by dithioerythritol and 2-mercaptoethanol. Maximal activation was obtained with the reducing agent at 10mM final concentration. The binding of NAD to the apoenzyme occurs at four sites per tetramer, but ligand affinity seems to be heterogeneous. Incubation of the holo or the apoenzyme with NADH at 37 degrees C caused inactivation of the enzyme, with partial loss of SH-titrable groups. Incubation of the holo or the apoenzyme with G3P at 37 degrees C caused partial inactivation of the enzyme. The apoenzyme was demonstrated to be more stable than the respective holoenzyme, in the assay conditions used.

Alligators and Crocodiles↗
PubMed1984

Mephenytoin and sparteine pharmacogenetics in Canadian Caucasians.

The frequency of genetically deficient hydroxylation of mephenytoin (M-defect) was studied in 83 healthy Caucasians living in Toronto. The M-defect was compared with the widely studied genetic polymorphism of sparteine/debrisoquine oxidations (S-defect). After ingestion of mephenytoin and sparteine, urine samples (0 to 24 hr) were analyzed for p(4')-hydroxymephenytoin and urine samples over 0 to 12 hr were analyzed for sparteine and 2-and 5-dehydrosparteine by gas chromatographic methods. Nirvanol, the N-demethylation product of mephenytoin, was determined by a newly developed gas chromatographic/mass spectrometric method. Frequency distributions of both p-hydroxymephenytoin and dehydrosparteine excreted in urine were discontinuous (bimodal), while nirvanol and sparteine data were normally distributed. Two poor metabolizers of mephenytoin excreted 2% to 3% of the dose as p-hydroxymephenytoin and excreted normal amounts of nirvanol, but they were extensive metabolizers of sparteine. Six poor metabolizers of sparteine were found to be extensive metabolizers of mephenytoin (34% to 42% excreted in urine as p-hydroxyme-phenytoin). Thus the M-defect occurs among Canadian Caucasians with a frequency of 2% (0.0% to 7.5% with a confidence limit of 99%) and is independent of the S-defect.

Administration, Oral↗
PubMed1984

Effect of muramyl dipeptide analog on Salmonella enteritidis infection in beige mice with Chediak-Higashi syndrome.

Beige mutant (bg/bg) mice with Chediak-Higashi syndrome (CHS) were much more sensitive to virulent Salmonella enteritidis No. 11 strain than parental C57 BL/6 (+/+) or heterozygous (bg/+) mice, and they had weaker bactericidal activity against the organisms. Muramyl dipeptide (MDP) and N alpha-(N-acetyl-muramyl-L-alanyl-D-isoglutamyl)-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)], a synthetic derivative of MDP, failed to confer any protection against the infection, but the MDPs showed some ability to stimulate the bactericidal activity in the peritoneal cavities and spleens of these mice. The bactericidal effect of MDP-Lys(L18) was dose-dependent, and the greatest effect was seen when it had been injected 24 hr before the infection. Multiple injections of MDP were much more beneficial than a single injection. Previous injection of N2,O2'-dibutyryl guanosine 3' : 5'-cyclic monophosphate (DB-cGMP) improved the impaired bactericidal capacity in beige mice, but the simultaneous injection of N6,O2-dibutyryl adenosine 3' : 5'-cyclic monophosphate (DB-cAMP) with DB-cGMP abolished the effect of DB-cGMP. The augmentation of bactericidal capacity by MDP-Lys(L18) was not affected by the injection of either DB-cGMP or DB-cAMP, suggesting that the effect of the MDPs was not related directly to cyclic nucleotide regulation in beige mice.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Augmentation of protective and antibacterial activity induced by muramyl dipeptides in CBA/N defective mice with X-linked immunodeficiency for Salmonella enteritidis infection.

Stimulation of resistance induced by muramyl dipeptide (MDP) and its analog, N alpha-MDP-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)], was examined in experimental salmonellosis in CBA/N defective mice with X-linked immunodeficiency to virulent Salmonella enteritidis no. 11. An injection of either MDP or MDP-Lys(L18) did not induce any effective protection, but repeated injections of MDP-Lys(L18) (100 micrograms per mouse per day for 3 days consecutively) to the mice before bacterial challenge gave some protection. Multiple injections with MDPs once a day for several days consecutively strongly increased bactericidal capacity in the peritoneal cavities and spleens of the mice. Moreover, previous injection of the MDPs could elevate the phagocytic function of the reticuloendothelial system in the defective mice. These results indicate that nonspecific resistance of CBA/N defective mice to salmonella infection can be improved by previous administrations of MDPs.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

A radiometric assay for debrisoquine 4-hydroxylase in human liver microsomes.

A radiometric method to assay debrisoquine 4-hydroxylase activity in human liver microsomes was established. Following incubation with 14C-labelled debrisoquine, unreacted debrisoquine was extracted with chloroform; 4-hydroxydebrisoquine was derivatized with hexafluoroacetylacetone, extracted, and subjected to high performance thin-layer chromatography (HP-TLC) followed by liquid scintillation counting. The Km values for debrisoquine 4-hydroxylase were 70 and 120 microM and the Vmax values were 8 and 24 pmol per milligram microsomal protein per minute. By application of this assay, it was possible to show that 4-hydroxydebrisoquine formation was competitively inhibited by sparteine. Antipyrine up to a concentration of 4 mM had no effect.

Carbon Radioisotopes↗
PubMed1984

A human cytochrome P-450 characterized by inhibition studies as the sparteine-debrisoquine monooxygenase.

The present study compares the debrisoquine monooxygenase and the sparteine monooxygenase activities of human liver microsomes. In the presence of 14 competitive inhibitors, apparent inhibition constants (Ki) as determined by these two activities ranged over four orders of magnitude with a correlation coefficient 0.99. These in vitro results represent the strongest evidence to date that the debrisoquine monooxygenase and the sparteine monooxygenase are identical and involve a single isozyme of cytochrome P-450.

Cytochrome P-450 CYP2D6↗
PubMed1984

Detection of purine nucleoside phosphorylase in paraffin sections by the immunoperoxidase method.

A method is described for immunohistochemical demonstration of purine nucleoside phosphorylase (PNP: EC 2.4.2.1) in paraffin sections from routine surgical histology specimens. A peroxidase-antiperoxidase (PAP) method was employed, using specific rabbit antiserum against human PNP, which was purified from postmature human erythrocytes. In human lymph nodes, intensive staining for PNP was observed in the vast majority of small lymphocytes in paracortical areas, in many small lymphocytes in medullary cords, and in a few small-to medium-sized lymphocytes in germinal centers. Small lymphocytes in the primary follicles and those in the mantle zones of secondary follicles were negative for PNP staining. Tingible body macrophages, lymphatic sinus cells, and most of the large cells in germinal centers did not stain with anti-human PNP (hPNP) antibody. Endothelial cells of small vessels in the cortex and plasma cells did not show any constant pattern of PNP staining intensity. Histochemistry revealed that the distribution pattern of PNP activity was quite similar to that demonstrated on paraffin sections by the PAP method.

Electrophoresis, Polyacrylamide Gel↗