Biomedical subjects

T Onodera

Publications and source records attributed to T Onodera.

At least 19 recordsLinked to original sources

PubMed1992

Antitumor effect of methionine-depleting total parenteral nutrition with doxorubicin administration on Yoshida sarcoma-bearing rats.

Methionine-depleting total parenteral nutrition (methionine-depleting TPN), which infuses an amino acid solution devoid of L-methionine and L-cysteine as the sole protein source, showed enhancement of the effect of several anti-cancer agents. In this study, the combined effect of the methionine-depleting TPN with the administration of doxorubicin was examined in Yoshida sarcoma (YS)-bearing rats with regard to effects on the primary tumor growth, the extension of metastasis, and the host animal's life span. In the first experiment, immediately after receiving methionine-depleting TPN for 8 days, the animals were killed. Pathologic findings evaluated tumor growth in the implanted site and extension of the metastasis. In the second experiment, the survival period was determined after animals received methionine-depleting TPN for 10 days, with subsequent oral feeding until they died naturally. Proliferation of YS was markedly suppressed. In particular, hematogenous metastasis, which is a characteristic of YS, was suppressed, and a longer survival period (42.7 +/- 15.6 days, mean +/- SD) was attained in rats in the group treated with the methionine-depleting TPN combined with the administration of doxorubicin.

Animals↗

PubMed1992

A specific RFLP type associated with the occurrence of sheep scrapie in Japan.

We have investigated restriction fragment length polymorphism (RFLP) on the PrP gene and the frequencies of RFLP patterns in 35 healthy Suffolk sheep randomly collected. According to the combinations of PrP encoding DNA fragments generated by restriction enzymes Eco RI and Hind III, the RFLP patterns were classified into six types and designated as types I to VI. The frequencies of these types were as follows: I, 8.6%; II, 11.4%; III, 17.6%; IV, 11.4%; V, 28.6%; and VI, 22.9%. In 10 sheep diagnosed as having natural scrapie, RFLP types, I, III, IV, and V were determined. To examine the correlation between the RFLP type and the occurrence of scrapie, the frequencies of RFLP types in sheep infected with natural scrapie were compared with those in healthy sheep. It was found that the frequency of type I in the sheep with natural scrapie was 70%, about eight times higher than that in randomly collected healthy sheep. In the 13 experimentally infected sheep that had been used for other purposes, however, no relationship between the RFLP type and onset of scrapie was found.

Animals↗

PubMed1992

Induction of protective immunity and neutralizing antibodies to pseudorabies virus by immunization of anti-idiotypic antibodies.

Xenogenic anti-idiotypic antibodies (anti-Id) were prepared in rabbits against three murine neutralizing monoclonal antibodies (MAbs) directed to pseudorabies virus glycoproteins. These anti-Id were highly specific to idiotopes on the corresponding MAb molecules. Because the binding of MAb to the corresponding anti-Id was inhibited by the addition of viral envelope protein, these anti-Id seemed to contain a subpopulation of antibodies against the antigen-combining site (paratope) or the region related to the paratope of the MAb molecules. One of the anti-Id to a MAb directed against glycoprotein gp50 induced neutralizing antibodies to PrV. Mice immunized with the anti-Id were protected from lethal infection of PrV.

Animals↗

PubMed1992

Macrophage function in the acute phase of lactic dehydrogenase virus-infection of mice: suppression of superoxide anion production in normal mouse peritoneal macrophages by interferon-alpha in vitro.

The effect of interferon (IFN)-alpha on the release of superoxide anions (O2-) by normal mouse macrophages (PEM) was examined. Sera from LDV-infected mice at 1 day, but not at 7 days post-infection, suppressed the O2- release by PEM. When PEM were exposed in vitro for 24 h to IFN-alpha, their capacity to release O2- was significantly suppressed. Progressive suppression of O2- release with increasing IFN-alpha concentration was observed. These results suggest that IFN-alpha in the circulation may be one of several suppressive factors on macrophage function in the early phase of infection and IFN-alpha may play a modulatory role in inflammation and immunity.

Animals↗

PubMed1992

Increased superoxide anion release by peritoneal macrophages in mice with a chronic infection of lactic dehydrogenase virus.

The function of macrophages in mice chronically infected by lactic dehydrogenase virus (LDV) was studied. Superoxide anion (O2-) release was examined by using peritoneal macrophages. O2- release increased markedly from 3 weeks to 12 months, but not at 1 week post infection. O2- release was 1.2 to 1.5 times greater than in uninfected mice. Increased O2- release from macrophages in LDV-infected mice may explain, at least in part, suppressive effects on tumour growth seen in the chronic phase of infection.

Animals↗

PubMed1992

Detection of the binding of IgG2a and IgG2b on the surface of macrophages from mice chronically infected with lactic dehydrogenase virus.

This study showed that sera from mice chronically infected with lactic dehydrogenase virus (LDV) contained virus-antibody complexes (IC). IgG2a and IgG2b, but not IgG1, IgG3, IgM or IgA, were demonstrated on the surface of macrophages from chronically infected mice. These results suggest that IC in the circulation may bind to Fc receptors for IgG2a and IgG2b on the surface of macrophages and lead to the modulation of macrophage function seen in chronically LDV-infected mice.

Animals↗

PubMed1992

Impairment of macrophage function in Mongolian gerbils.

Chemiluminescence studies on superoxide generation by phagosomes using opsonized zymosan showed the highest fluorescence in murine splenic macrophages among four different kinds of splenic or peritoneal macrophages from mice or gerbils. Murine splenic macrophages phagocytized two to three times more latex particles than gerbil splenic macrophages, but peritoneal macrophages did not show a significant difference in phagocytic activity between mice and gerbils. Phagocytosis by macrophages was determined by a technique based on measurement of the release of hydrogen peroxide and myeloperoxidase from phagosomes using microspheres conjugated with 3-(p-hydroxyphenyl) propionic acid (HPPA-MS). HPPA is a substrate of lysosomal myeloperoxidase. The fluorescence of HPPA-HPPA-MS produced by phagocytized HPPA-MS was measured with an immunoreaction analysis system (IMRAS), and the enzyme activities of the four different kinds of peritoneal or splenic macrophages from mice and gerbils were compared. All four kinds of macrophages produced HPPA-HPPA-MS in their phagosomes during phagocytosis and murine splenic macrophages showed the highest level of enzyme activity.

Animals↗

PubMed1992

Production of hydroxyl radicals and their disassociation from myocardial cell injury during calcium paradox.

The production of hydroxyl radicals during calcium paradox injury was investigated by measuring the production of 2,5-dihydroxybenzoic acid (2,5-DHBA) from salicylate. Four groups of rats were analyzed. In the first group, isolated hearts were perfused with calcium-free medium for 10 minutes followed by perfusion with medium containing Ca++ for 10 minutes. In the other groups, 0.25 microM N,N'-diphenyl-1,3-phenylenediamine (DPPD), 80 microM cytochrome c, or 450 U/ml catalase was added. Coronary effluent was analyzed for the presence of 2,5-DHBA, and tissue sections were examined using light microscopy. In the first group, 2,5-DHBA production began during the calcium-free period, peaked tenfold 60-90 sec. into the Ca repletion period, and declined thereafter. The increase in 2,5-DHBA was accompanied by severe cell damage. Cytochrome c reduced 2,5-DHBA production, and catalase almost completely inhibited 2,5-DHBA production, while DPPD had no effect on 2,5-DHBA production. None of the three additives provided any complete morphological protection. The data provide evidence for the production of hydroxyl radicals during calcium-paradox injury, that their production is dependent upon the presence of hydrogen peroxide, and that cell damage in the calcium paradox is not primarily mediated by the extracellular hydroxyl radicals.

Animals↗

PubMed1992

Quantification of hydroxyl radical and its lack of relevance to myocardial injury during early reperfusion after graded ischemia in rat hearts.

To elucidate the pathophysiological role of the hydroxyl radical (.OH) during the postischemic reperfusion of the heart, we measured the .OH product in the coronary effluent from isolated perfused rat heart during a 30-minute reperfusion period after various ischemic intervals of 5, 10, 15, 20, 30, and 60 minutes. Salicylic acid was used as the probe for .OH, and its derivative, 2,5-dihydroxybenzoic acid (2,5-DHBA), was quantified using high-performance liquid chromatography with ultraviolet detection. 2,5-DHBA was negligible in the effluent from nonischemic hearts, but a significant amount was detected from the hearts rendered ischemic for 10 minutes or longer. The peak of 2,5-DHBA was seen within 90 seconds after the onset of reperfusion in every group. The accumulated amount of 2,5-DHBA was maximal in the group with 15-minute ischemia (6.73 +/- 1.04 nmol/g wet heart wt after 30 minutes of reperfusion); it decreased as the ischemic time was prolonged and was 2.38 +/- 0.84 nmol/g wet wt after 30 minutes of reperfusion in the group with 60-minute ischemia. In the model of 15-minute ischemia/30-minute reperfusion, there was no correlation between the accumulated amount of 2,5-DHBA and functional recovery (+/- dP/dt, heart rate, and coronary flow), lactate dehydrogenase release, and morphological damage. Although treatment with 0.5 mM deferoxamine, an iron chelator, significantly decreased 2,5-DHBA (from 6.73 +/- 1.04 to 2.29 +/- 0.80 nmol/g wet wt after 30 minutes of reperfusion, p less than 0.01), it failed to reduce the postischemic myocardial injury in the group with 15-minute ischemia. The results suggest that .OH production is influenced by the preceding ischemic interval and that .OH does not exert an immediate direct effect on postischemic damage during early reperfusion in the isolated perfused rat heart, although a possibility remains that the small portion of .OH trapped by salicylic acid may not be intimately associated with myocardial injury.

Animals↗

PubMed1992

Hydroxyl radical production during early reperfusion after different periods of ischemia in rat hearts and its effect on myocardial function. .OH in postischemic heart.

To elucidate the significance of hydroxyl radical (.OH) in postischemic reperfusion injury, we measured the .OH production in the coronary effluent collected from isolated perfused rat hearts during reperfusion period of 15 minutes after various ischemic intervals ranging from 5 to 60 minutes. Salicylic acid was used as a probe for .OH formation, and its derivative, 2,5-dihydroxybenzoic acid (2,5-DHBA), was quantified using high performance liquid chromatography. A significant amount of 2,5-DHBA was detected from the hearts rendered ischemic for 10 minutes and longer. The peak of 2,5-DHBA was seen within 90 seconds after the onset of reperfusion in every group, and the accumulated amount of 2,5-DHBA was maximal in 15 minutes ischemia group (3.97 +/- 0.49 nmol/g/15 minutes reperfusion) in contrast to 1.22 +/- 0.30 nmol/g/15 minute in 60 minutes ischemia. This study demonstrated an ischemic time-dependent .OH production during reperfusion, and no direct effect of .OH was observed on the post-ischemic injury related to myocardial function.

Analysis of Variance↗

PubMed1992

Ultrastructural effects of hydrogen peroxide on the sarcolemma of rat heart.

Ultrastructural effects of hydrogen peroxide (H2O2) on the sarcolemma of the isolated rat heart were investigated with transmission electron microscopy combined with biochemical, enzyme histochemical, and freeze fracture techniques. Three hundred microM H2O2 were continuously administered to the Langendorff perfused isolated rat hearts. A significant amount of lipid peroxidation associated with depressed Na-K-ATPase activity was observed after 15 minutes of H2O2 perfusion (Group I), and consequently the cell membrane permeability was greatly increased. When 2.5 mM,N'-diphenyl-1,4-phenylenediamine (DPPD), a potent antioxidant, was added to the perfusate, the lipid peroxidation was totally inhibited (Group II). DPPD prevented an increase in the cell membrane permeability. However, Na-K-ATPase activity was not restored by DPPD. Decreased cytochemical staining of Na-K-ATPase was associated with an increase in cell membrane permeability. H2O2 appears to affect, not only lipids but also, intramembranous proteins embedded in the cell membrane. The combined effects of H2O2 on the membrane lipid and proteins result in the formation of membranous blebs.

Animals↗

PubMed1992

Effect of exogenous hydrogen peroxide on myocardial function and structure in isolated rat heart.

A time- and dose-dependent effect of exogenous hydrogen peroxide was determined on myocardial function, structure, high energy phosphate and lipid peroxidation in the isolated perfused rat heart. Hydrogen peroxide induced a dose-dependent decrease in cardiac function whereas 200 microM hydrogen peroxide reduced +dP/dt to 50% of control value after 10 mins. The effect of 300 microM hydrogen peroxide was more severe after 15 mins; changes observed with this dose were reversible within 10 mins of perfusion, becoming irreversible after 15 mins. Lipid peroxidation and severe morphological damage were observed after 10 mins of perfusion with 300 microM hydrogen peroxide. When 16 mEq potassium ions were added in the perfusion buffer during hydrogen peroxide perfusion, the degree of tissue damage and loss of ATP were attenuated. However, lipid peroxidation was not inhibited by high potassium ions. When 0.25 microM N,N'-diphenyl-1,4-phenylenediamine, a potent antioxidant, was added to the perfusate, lipid peroxidation was totally inhibited and the degree of tissue damage was decreased. However, depletion of tissue ATP and functional deterioration were not influenced. These results suggest that hydrogen peroxide-mediated ATP loss was independent of lipid peroxidation.

Adenosine Triphosphate↗

PubMed1992

[A clinical trial of arterial infusion chemotherapy combined with calcium antagonist for liver metastases].

Calcium antagonists enhance the effect of some anticancer agents, but only limited administration is feasible because of their cardiovascular action. We noticed their inactivation in liver and investigated the possibility of combined intra-arterial chemotherapy. Both verapamil (0.5 mg/kg) and adriamycin were infused into hepatic artery in 8 patients with liver metastases. The serum concentration of verapamil in hepatic vein was 182 +/- 178 ng/ml at maximum. Blood pressures, heart rates and electrocardiograms were quite stable. Tumors became nearly necrotic after the therapy in three hepatectomized cases. A more appropriate dose, infusion method and prognosis should be studied in future.

Adult↗

PubMed1991

Detection of hydroxyl radicals in the post-ischemic reperfused heart using salicylate as a trapping agent.

The formation of hydroxyl radical in the post-ischemic reperfused heart was measured with high performance liquid chromatography and ultraviolet detection using salicylic acid. Hydroxyl radicals react with salicylic acid yielding 2,3- and 2,5-dihydroxybenzoic acid, which can be separated by the liquid chromatography. Isolated rat hearts were perfused with 1 mM salicylic acid and were subjected to 30 mins of global ischemia followed by aerobic or anaerobic reperfusion at 37 degrees C. The effluent from the hearts was collected at various intervals, extracted with ether, and injected into the high performance liquid chromatography unit. 2,5-dihydroxybenzoic acid was present only after aerobic reperfusion and was not detected before ischemia. The liquid chromatography peak of 2,3-dihydroxybenzoic acid was too small for quantitation. The concentration of 2,5-dihydroxybenzoic acid was the highest within 300 s of reperfusion. 2,5-dihydroxybenzoic acid was not detected in the ischemic hearts during anaerobic reperfusion. In ischemic hearts perfused with mannitol, the amount of 2,5-dihydroxybenzoic acid after reperfusion was reduced. These data suggest that hydroxyl radicals are produced in the post-ischemic reperfused heart and that the present method is useful and reliable for the measurement of hydroxyl radicals in the heart.

Animals↗

PubMed1991

Reperfusion injury in dog hearts with permanent occlusion of a coronary artery, probably due to reperfusion via collateral vessels.

To clarify whether or not reperfusion injury occurs in the permanent occlusion of a coronary artery, we analyzed quantitatively contraction band necrosis as an indicator of early recanalization, coagulation necrosis, infarct size and measured regional blood flow in dog hearts with collateral circulation. Fifty mongrel dogs were divided into four groups: 15 dogs with a 24-hour occlusion of the left anterior descending coronary artery just distal to the first diagonal branch (permanent occlusion group): 15 dogs a with 3-hour occlusion followed by 24-hour recanalization (recanalization group); 10 dogs with a 2-hour occlusion without recanalization (transient occlusion group); 10 dogs with a 4-hour occlusion without recanalization (transient occlusion group). The regional blood flow in the subepicardium and subendocardium determined by the generated hydrogen gas clearance method was greatly decreased 30 minutes after occlusion (14 + 8%/12 +/- 9%) and was relatively restored from 180 minutes (31 +/- 21%/21 +/- 14%) to 24 hours later (41 + 19%/26 + 16%) in spite of complete occlusion of the coronary artery. The percentage infarct area in the risk area was significantly greater in the permanent occlusion group (60 +/- 26%) than in the recanalization group (35 +/- 31%). Although most of the infarct was occupied by contraction band necrosis in the recanalization group (86 +/- 12%), contraction band necrosis was diffusely seen even in the permanent occlusion group (54 +/- 27%). In both the permanent and recanalization groups, contraction band necrosis was the main histological feature of small infarcts occupying less than 30% of the risk area, while coagulation necrosis was the main feature in very large infarcts occupying more than 80% of the risk area. In the occlusion groups without recanalization, the percentage area of contraction band necrosis in the risk area was 6 +/- 8% after the 2-hour occlusion, 23 +/- 17% after the 4-hour occlusion and 31 +/- 21% after permanent occlusion; the difference between the 4-hour and permanent occlusion groups was not significant. In the permanent occlusion group, the percentage infarct area in the risk area was inversely correlated with regional blood flow during occlusion, an indicator of collateral flow. It was concluded that reperfusion injury occurs even in hearts without recanalization. The pathogenesis may involve reperfusion in the risk area via collateral circulation. Protection against reperfusion injury is important to minimize the infarct size even in hearts with permanent occlusion, although the presence of collateral flow is an important factor in limiting infarct size.

Animals↗

PubMed1991

Hepatotoxicity of DR-3438, tienilic acid, indacrinone and furosemide studied in vitro.

A new diuretic antihypertensive, DR-3438, and marketed diuretic drugs were evaluated for their toxicity in vitro. Hepatocytes were isolated from male rats by the collagenase perfusion method and incubated in Dulbecco's modified Eagle medium containing various doses of DR-3438, tienilic acid, indacrinone or furosemide. Tienilic acid decreased cell viability and glutathione content in hepatocytes and increased lipid peroxidation in the cells. Indacrinone also decreased cell viability, but neither cell viability nor glutathione content was affected by furosemide or DR-3438.

Animals↗

PubMed1991

Decrease in neutrophil migration induced by endotoxin and suppression of interleukin-1 production by macrophages in lactic dehydrogenase virus-infected mice.

Neutrophil (PMN) migration into the peritoneal cavity after intraperitoneal injection of lipopolysaccharide (LPS), chemotactic activity of PMN, interleukin-1 (IL-1) production by macrophages (M phi) and its ability to attract PMN in mice chronically infected with lactic dehydrogenase virus (LDV) were compared with those in uninfected control mice. PMN migration into the peritoneal cavity decreased in infected mice when LPS was injected intraperitoneally. PMN chemotactic activity did not show any difference following infection. To assess the mechanism of this decreased PMN migration, IL-1 production, which is responsible for PMN attraction, was studied in LDV-infected mice. IL-1 production by M phi derived from infected mice decreased and its ability to attract PMN was weak. IL-1 production by M phi from control and infected mice increased after treatment by indomethacin and LPS. PMN migration into the peritoneal cavity increased after treatment with indomethacin and LPS in both control and infected mice. However, the rate of increase of IL-1 production and PMN migration was greater in infected mice. These results suggest that the excess activation of cyclo-oxygenase-derived products (prostaglandins) in infected mice might be responsible for the suppression of IL-1 production by M phi, resulting in decreased PMN migration induced by endotoxin.

Animals↗

PubMed1991

Inhibition of contact sensitivity by interferon in mice infected with lactic dehydrogenase virus.

The effect of acute lactic dehydrogenase virus (LDV) infection was studied with respect to contact sensitivity (CS) to 2,4-dinitrofluorobenzene (DNFB). CS reaction was severely inhibited in the acute phase but not in the chronic phase of infection. The role of interferon (IFN) was studied to understand further the inhibition of CS during LDV infection. IFN in the blood was detected only in the acute phase, but not in the chronic phase of infection. When anti-IFN (alpha/beta) was administered to infected mice, no inhibition of CS was seen. CS was inhibited in uninfected mice treated with IFN (alpha/beta). These results suggest that IFN production in the blood may be responsible, at least in part, for inhibition of CS observed in the acute phase of LDV infection.

Animals↗