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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 901 records · Page 50Linked to original sources
PubMed1989

Gastrointestinal dialysis of disopyramide in healthy subjects.

The effect of oral activated charcoal on the clearance of disopyramide was investigated in six healthy subjects. Oral administration of multiple doses of activated charcoal at 4, 6, 8 and 12 h after ingestion of the drug reduced the serum levels of both disopyramide and its main metabolite, mono-N-dealkyldisopyramide (MND). The mean serum level of disopyramide at 24 h after oral administration of the drug was significantly decreased from 0.22 in the control to 0.091 micrograms/ml by multiple doses of activated charcoal. The serum half-life and AUC0-infinity were decreased to 67% and 81%, respectively, and the apparent total body clearance was increased to 122% as compared with the control treatment. The apparent volume of distribution was not significantly different between both treatments. The cumulative amounts of urinary excretion of both disopyramide and MND with activated charcoal treatment were decreased as compared with those in the control treatment. Mean residence time (MRT) of disopyramide obtained from the serum data decreased from 7.8 (control) to 6.9 h (charcoal treatment) and the values were approximately consistent with those obtained from the urinary data. These results indicate that oral administration of activated charcoal would enhance the clearance of disopyramide in acute drug poisoning even after the drug has been absorbed into the systemic circulation from the g.i. tract.

Adult↗
PubMed1989

[Salvage radiotherapy of recurrent breast cancer].

During 1972-1986, 217 cases of breast cancer patients following radical mastectomy received postoperative radiotherapy and chemotherapy at Chiba Prefectural Cancer Center Hospital. All patients had operable tumor (T1-3), and radiation was directed to the chest wall and regional nodes. A total of 57 patients have relapsed. Fourteen patients experienced isolated local-regional recurrence (11 chest wall, 2 supraclavicular and 1 axilla), and other cases developed distant metastases. Of these, forty patients (70%) died with different metastatic areas within three years, although salvage radiotherapy was effective in controlling the local or metastatic tumor. Of ten patients who survived three years or longer were, six were bone metastaes and four were chest wall recurrence.

Adult↗
PubMed1989

[Basic studies on optimal intra-arterial infusion rate of cisplatin].

The relationship between platinum concentration in tissues, free CDDP concentration in plasma and infusion rate was investigated in order to determine the optimal intra-arterial infusion rate of CDDP for chemotherapy of cervical carcinoma. Platinum concentrations in uterus were in the same level in the intravenous infusion groups independent of the infusion rate. In the intra-arterial infusion groups, platinum concentrations in the uterus increased as the infusion rate decreased from 24 to 0.8 mg/hr, although Cmax and AUC were decreased. Platinum concentrations in the ovary supplied by another artery were not influenced by the intra-arterial infusion rate. It is suggested that uptake of CDDP in the targeted tissues can be increased by control of intra-arterial infusion rate.

Animals↗
PubMed1989

Antigen-dependent and -independent proliferative T-cell populations in the peritoneal exudate cells of immunized mice.

In vitro proliferative responses of T lymphocytes in the peritoneal exudate cells of C3H/HeN(Iak) mice immunized with horse red blood cells (HRBC) were examined by determining the uptake of tritiated thymidine [( 3H]TdR) into the cells. Although the cells showed a basal proliferative response in the absence of antigen, addition of specific antigen increased the response sharply. Both the basal response and that stimulated by antigen disappeared if the cells had been previously treated with complement and anti-Iak antibody (AIak), anti-MAC-1 antibody (AMAC-1) or anti-Thy-1 antibody, but not anti-Ig antibody. Adding macrophages prepared from the peritoneal exudate cells of normal mice to AMAC-1-treated T-cell (i.e. Iak+ plus Iak- T-cell) cultures restored both of the responses, while adding them to AIak-treated T cells (i.e. Iak- T cells) only restored the antigen-specific response. These findings indicate that the basal proliferation is due to or dependent on the proliferation of Iak+ T cells, while the antigen-specific response is mainly due to Iak- T cells. Furthermore, interleukin (IL)-2 production was also examined. Immune T cells produced some IL-2 in the absence of antigen. The production by AMAC-1- or AIak-treated cells was impaired, but adding macrophages to the AMAC-1-treated cell cultures restored production. This result also suggests that the mode of IL-2 production by the Iak+ and Iak- cells is different. Proliferative responses of AMAC-1- or AIak-treated T cells to IL-2 were also examined. The AIak-treated cells dose-dependently responded to IL-2, while the response of Iak+ cells, which could be estimated by subtracting the response of AIak-treated cells from that of AMAC-1-treated cells, did not depend on the doses. These results indicate that in the immune peritoneal exudate the Iak+ T cells are functionally different from Iak- T cells.

Animals↗
PubMed1989

[The influence of endotracheal tube size on the airway flow resistance and work in infants analyzed using a simulation technique].

The respiratory flow velocity of 74 infants under halothane-nitrous oxide-oxygen anesthesia was measured, and the statistical relationship between the age in months and the flow velocity was obtained with least square method. The flow resistance of endotracheal tubes (size of 2.5, 3.0, 3.5, 4.0, 4.5 and 5.0 mmI.D.) with the flow velocity below 45 ml.sec-1 was also measured in in vitro experiments. The standard respiratory flow velocity of 6, 12, 24, 36, 48 and 60 month old infants was estimated by the recurrent formula. The mean flow resistance and respiratory work with each size of endotracheal tube were calculated by simulation technique using these data. These data coincided well with the data obtained by calculation based on in vitro experiments.

Aging↗
PubMed1989

[The effects of biotin on the metabolism of ammonia and amino acids in urease-induced hyperammonemic rats].

The effects of oral and intraperitoneal administration of biotin in urease-induced hyperammonemic rats, as well as the influence of biotin deficiency, have been studied. Biotin deficiency was produced by feeding standard diet MF (Oriental Yeast Co.) supplemented with dry egg-white (egg-white group). Egg-white + biotin group had free access to 0.0014% of biotin solution at all time. Following an intraperitoneal injection of urease, 25 U/kg (B.W.), plasma ammonia levels in egg-white + biotin group were lower than in egg-white group, especially there was significance (p less than 0.05) at 8 hours after the urease injection. Similarly, plasma ammonia levels in biotin-injected rats, in which 1 mg of biotin had been injected intraperitoneally prior to the experiment, were significantly low compared with saline-injected controls at 4 and 6 hours after urease administration. Results of plasma amino acid analysis, 9 hours after the urease injection indicated that Fischer's molar ratio (Leu + Ileu + Val/Tyr + Phe) was significantly higher in the biotin-injected rats than the saline-injected control. It suggests that biotin might decrease blood ammonia by facilitating the detoxification mechanism as follow: L-glutamate + NH3----L-glutamine.

Amino Acids↗
PubMed1989

Antigenic variations of retrovirus in Japanese cancer patients.

Previously we demonstrated the prevalence of human T lymphotropic virus type I (HTVL-I) infection among cancer patients in Japan. This study was carried out to examine antigenic properties of retroviruses prevalent among Japanese cancer patients. Sera of 126 Japanese patients with cancer of different organs and with no history of blood transfusion, 94 in adult T cell leukemia (ATL)-endemic area and 32 in ATL-nonendemic area, were surveyed for antibodies to HTLV-I and HTLV-II by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunogold electron microscopy. Among patients who were seropositive to HTLV-I, 39 of 56 (69.6%) in ATL-endemic area and 9 of 9 (100%) in ATL-nonendemic area were seropositive also to HTLV-II. Of 48 sera positive to both HTLV-I and HTLV-II, 34 (70.8%) showed stronger reactivities to HTLV-I than to HTLV-II. Among patients who were seronegative to HTLV-I, 3 of 38 (7.9%) in ATL-endemic area and 5 of 23 (21.7%) in ATL-nonendemic area were seropositive to HTLV-II. Antibodies appearing and disappearing in sera of patients examined during the clinical course reacted with peptide species of HTLV-I and/or HTLV-II not always consistent with peptide species cross-reactive between HTLV-I and HTLV-II. These results indicate the antigenic diversity of retroviruses prevalent among Japanese cancer patients.

Antigenic Variation↗
PubMed1988

Mechanism of O2- generation in reduction and oxidation cycle of ubiquinones in a model of mitochondrial electron transport systems.

O2- generation in mitochondrial electron transport systems, especially the NADPH-coenzyme Q10 oxidoreductase system, was examined using a model system, NADPH-coenzyme Q1-NADPH-dependent cytochrome P-450 reductase. One electron reduction of coenzyme Q1 produces coenzyme Q1-. and O2- during enzyme-catalyzed reduction and O2+ coenzyme Q1-. are in equilibrium with O2- + coenzyme Q1 in the presence of enough O2. The coenzyme Q1-. produced can be completely eliminated by superoxide dismutase, identical to bound coenzyme Q10 radical produced in a succinate/fumarate couple-KCN-submitochondrial system in the presence of O2. Superoxide dismutase promotes electron transfer from reduced enzyme to coenzyme Q1 by the rapid dismutation of O2- generated, thereby preventing the reduction of coenzyme Q1 by O2-. The enzymatic reduction of coenzyme Q1 to coenzyme Q1H2 via coenzyme Q1-. is smoothly achieved under anaerobic conditions. The rate of coenzyme Q1H2 autoxidation is extremely slow, i.e., second-order constant for [O2][coenzyme Q1H2] = 1.5 M-1.s-1 at 258 microM O2, pH 7.5 and 25 degrees C.

Anaerobiosis↗
PubMed1988

Highly sensitive and reliable chemiluminescence method for the assay of superoxide dismutase in human erythrocytes.

Superoxide dismutase in human erythrocytes was assayed by the inhibition of highly diluted erythrocyte lysates on 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazol[1,2-alpha]pyra zin-3-one- dependent luminescence induced by the hypoxanthine-xanthine oxidase system. Our chemiluminescence procedure gave 95-times higher sensitivity than the cytochrome c method. The concentration of superoxide dismutase in erythrocytes of Down's syndrome patients was approx. 1.8-times higher than that of normal humans.

Cytochrome c Group↗
PubMed1988

Selective accumulation of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine (FdUrd-C8) and sustained release of its active metabolites in VX-2 rabbit hepatoma following intraarterial administration of FdUrd-C8 solution in Lipiodol.

Selective accumulation/retention of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine (FdUrd-C8) and sustained release of its active metabolites, 5-fluoro-2'-deoxyuridine (FdUrd) and 5-fluoro-2'-deoxyuridylate (FdUMP), in the rabbit hepatoma (VX-2) were achieved following intrahepatic arterial administration of FdUrd-C8 solution in Lipiodol. Though no significant difference in the FdUrd-C8 levels among the tumor and nontumorous liver was observed immediately after administration, slower elimination of FdUrd-C8 from the tumor (t 1/2 = 15.8 h) than that from nontumorous sites (t 1/2 = 3.8-4.2 h) resulted in selective retention of FdUrd-C8 (17- to 157-fold) in the tumor. Selectively higher levels of FdUrd and FdUMP in the tumor were also achieved (5- to 35-fold) and kept for 72 h after administration. The selective accumulation was also demonstrated in radioactivity distribution after administration of [6-3H]-FdUrd-C8. The ratio of radioactivity in the tumor divided by that in the blood (T/B ratio) was in a range of 870 to 5400 during a 15- to 1440-min period after administration. A trace of radioactivity was found in the stomach, duodenum, kidneys, and bone marrow. Roles of activation and deactivation enzymes on the selective distribution of FdUrd-C8 were also investigated. Esterase activity, which is responsible for the regeneration of FdUrd from FdUrd-C8, was relatively low in the tumor before administration and gradually increased after administration. Phosphorylase activity, which is related to phosphorolytic cleavage of FdUrd, in the tumor was about 3/5 as much as that in the nontumorous liver. These enzyme activities seem to play limited roles in the selective accumulation/retention and regeneration of the drug.

Animals↗
PubMed1988

A new and suitable reconstructed system for NADPH-dependent microsomal lipid peroxidation.

In order to evaluate the O-2 participation in NADPH-dependent microsomal lipid peroxidation, we used reconstructed system which contained detergent-solubilized NADPH-dependent cytochrome P-450 reductase, cytochrome P-450, phospholipid liposomes, NADPH and Fe3+-ADP. Lipid peroxidation, monitored by the formation of thiobarbituric acid-reactive substance, was increased with increasing concentration of detergent-solubilized NADPH cytochrome P-450 reductase, cytochrome P-450 or Fe3+-ADP. Cytochrome P-450-dependent lipid peroxidation was parallel to O-2 generation monitored by chemiluminescence probe with 2-methyl-6-(p-methoxyphenol)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one. Lipid peroxidation was significantly inhibited by superoxide dismutase, but not by catalase or sodium benzoate. The reconstructed system herein described is considered to be very close to NADPH-dependent microsomal lipid peroxidation system.

Animals↗
PubMed1988

Properties of a coenzyme, pyrroloquinoline quinone: generation of an active oxygen species during a reduction-oxidation cycle in the presence of NAD(P)H and O2.

The oxidation of NAD(P)H by pyrroloquinoline quinone (PQQ) was non-enzymatically carried out at physiological pH in the presence of O2. The PQQ-NAD(P)H system requires about 1 mol of O2 for the oxidation of 1 mol of NAD(P)H. The oxidation of NAD(P)H occurred at a pseudo-first-order rate with respect to NAD(P)H and was of zero order with respect to PQQ concentration in in the presence of O2: k0[PQQ] [NAD(P)H] = k1 [NAD(P)H], where k0[PQQ] = k1, in which [PQQ] represents the initial concentration of PQQ. k0 values for NADH and NADPH were 3.4.10(2) M-1.min-1 and 2.0.10(2) M-1.min-1, respectively, at 25 degrees C and at 258 microM O2 (initial concentration). The system produced O-2, probably by the interaction of PQQ.H and/or NAD(P).with O2, during the oxidation of NAD(P)H. PQQH2 and PQQ.H were easily oxidized to PQQ in the presence of O2, yielding H2O2.

Coenzymes↗
PubMed1988

Endotoxin-induced interferon-gamma production in culture cells derived from BCG-infected C3H/HeJ mice.

The cultured cells prepared from the spleens and peritoneal exudate cells of the C3H/HeJ strain of mice produce very little or no interferon (IFN) by stimulation of bacterial lipopolysaccharide (LPS). However, the cells taken from LPS-non-responder C3H/HeJ mice which had been infected with Mycobacterium bovis bacillus Calmette-Guérin (BCG) prior to the experiment were capable of producing IFN in culture in the presence of LPS. The peritoneal exudate cells of BCG-primed C3H/HeJ mice were separated into adherent cell and nonadherent cell populations by their adhesiveness to plastic culture dishes. IFN production required the presence of both these cell populations in the same culture, and the IFN activities produced were mainly IFN-gamma. The cultures with nonadherent cells and fixed adherent cells still produced IFN, but the cell cultures reconstituted with the BCG-primed cell population and unprimed cell population produce little if any IFN-gamma. Moreover, when both of the populations were cultured in Marbrook culture vessels separated by a membrane filter, the cultures produced very little or no IFN-gamma. These results indicate that there is a mechanism of IFN-gamma induction by LPS which requires the direct contact between adherent cells and nonadherent cells without the participation of any soluble factor(s) from the adherent cells. The producer cells were mainly in the nonadherent cell population. Previous treatment of nonadherent cells with anti-Thy-1.2 antibody, anti-Lyt-1.1 antibody, anti-L3T4 antibody, or anti-asialo-GM1 antibody and complement diminished the ability of the cells for LPS-induced IFN production with the help of adherent cells. Therefore, it is concluded that both T cells (presumably L3T4+T cells) and asialo-GM1+ natural killer cells in the BCG-primed C3H/HeJ cell cultures produced IFN-gamma in the presence of LPS, and the production was supported by the function of macrophages.

Animals↗