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T Suga

Publications and source records attributed to T Suga.

At least 181 records · Page 10Linked to original sources
PubMed1990

Participation of the peroxisomal beta-oxidation system in the chain-shortening of PCA16, a metabolite of the cytosine arabinoside prodrug, YNKO1, in rat liver.

When PCA16, a metabolite of the cytosine arabinoside prodrug YNKO1, was incubated with isolated rat hepatocytes, time-dependent H2O2 generation was found. When the hepatocytes obtained from clofibrate-treated rat liver were used as an enzyme source, PCA16-dependent production of H2O2 was increased by around 6-fold. The activity of peroxisomal beta-oxidation for PCA16 assayed by H2O2 generation was 3-fold higher than that for palmitic acid, whereas the activity of mitochondrial beta-oxidation for PCA16 assayed by ketone body production was much less than that for palmitic acid. A subcellular distribution study revealed that the distribution of the activities of beta-oxidation and fatty acyl-CoA oxidase for PCA16-CoA coincided with those of cyanide-insensitive palmitoyl-CoA-dependent beta-oxidation and catalase, a marker enzyme of peroxisomes. The profile of the cofactor requirement for beta-oxidation of PCA16-CoA in isolated peroxisomes was similar to that for palmitoyl-CoA oxidation, and the reaction was not inhibited by KCN. The formation of CoA derivative prior to beta-oxidation reaction was essential. HPLC analysis of metabolites after incubation of PCA16-CoA with isolated peroxisomes demonstrated the production of four metabolites, two of which were identified as PCA14 and PCA12 by fast atomic bombardment-mass spectrometry. These results indicate that peroxisomal beta-oxidation participates in the shortening of the alkyl-side chain of PCA16 and plays an important role in the formation of antileukemic cytosine arabinoside from YNKO1.

Animals↗
PubMed1990

[Study on neoadjuvant chemotherapy of Borrmann 4 type carcinoma of stomach and its clinical significance].

Considering a high potential of biological malignancies of Borrmann 4 type carcinoma (abbr., Borr. 4) of the stomach, preoperative induction (neoadjuvant) chemotherapy was applied to patients with Borr. 4 as an initial therapy. Anticancer drugs used in this study were FAM-OK432, sequential MTX-5Fu or UFT-M through aortic infusion or induced hypertension chemotherapy (IHC) in order to obtain selective enhancement of drug delivery into tumor tissue. These trials were carried out on 24 patients who had Borr. 4 type carcinoma. The response to neoadjuvant chemotherapy showed CR in 1 case, PR in 3 cases and MR in 4 cases. The objective improvement except the primary gastric lesion showed shrinking of distant metastatic lymph nodes along paraaorta or Virchow of 50% (5/10), disappearance of pleural or peritoneal fluids 85. 7% (6/7) and marked decrease of tumor marker such as CEA, CA19-9 or CA125 100% (12/12). In one of 5 cases showing morphological improvement of primary gastric lesion, no viable cancer cells were seen in the stomach associated with multiple foci of granulofibromatous lesion of regional nodes. In 17 cases of 24 total gastrectomy was done with extended lymphadenectomy (R2-R3). While there was no difference in the median survival time (MST) among curable resection group, MST of non-curable resection group with neoadjuvant chemotherapy showed a fairly good prognosis for 14 months as compared to that of 4 months without chemotherapy. As for disease-free survival, patients whose tumor showed a high response to neoadjuvant chemotherapy had a good prognosis in non-curable resection group (p less than 0.01). In conclusion our results demonstrated that patients whose tumor were effectively destroyed by neoadjuvant chemotherapy against Borr. 4 carcinoma of stomach had an improved prognosis.

Adult↗
PubMed1990

Changes in the activities of dihydroxyacetone phosphate and glycerol-3-phosphate acyltransferases in rat liver under various conditions.

Activities of enzymes relating to the acyl dihydroxyacetone phosphate (acyl DHAP) pathway were determined in rat liver under conditions known to elevate the peroxisomal beta-oxidation activity. In fasted and streptozotocin-induced diabetic rats, DHAP acyltransferase activity showed a small but significant increase, though the activities of glycerol-3-phosphate (GP) acyltransferase and alkyl DHAP synthase were not changed. After 2 weeks, feeding of 20% partially hydrogenated marine oil, the activity of DHAP acyltransferase also increased to 140% of the control. The feeding of 0.25% clofibrate and 2% di(2-ethylhexyl)phthalate (DEHP) increased the activities of both DHAP and GP acyltransferases by 2- to 3-fold, whereas alkyl DHAP synthase activity decreased under the same conditions. A fractionation study showed that the increases in the activities of DHAP acyltransferase and acyl/alkyl DHAP reductase in the liver of rats treated with DEHP occurred mainly in peroxisomes and microsomes, respectively. The phospholipid contents per mg protein of the isolated hepatic peroxisomes from rats were as follows (percent of the control): fasting, 62%; diabetic, 69%; high fat-diet, 89%; clofibrate-treated, 126%; DEHP-treated, 119%. These results suggest that glycerophospholipid metabolism might also be controlled by peroxisomal enzymes under physiological and pathological conditions.

Acyltransferases↗
PubMed1990

Different regulation of hepatic peroxisomal beta-oxidation activity in rats treated with clofibrate and partially hydrogenated marine oil.

Total RNAs from the livers of rats treated with clofibrate and partially hydrogenated marine oil (PHMO) were translated in a reticulocyte-lysate cell-free protein-synthesizing system. In clofibrate-treated rats, mRNA activity for acyl-CoA oxidase (AO), the rate-limiting enzyme of the peroxisomal beta-oxidation system, was increased markedly compared with the control, whereas the increase was less than 2-fold in PHMO-treated rats. When rats were treated with both clofibrate and PHMO in vivo, an additional increase in the hepatic AO activity was observed compared with either treatment alone, suggesting that increases in the activities of peroxisomal beta-oxidation in the rats treated with clofibrate and PHMO are based on two distinct mechanisms.

Acyl-CoA Oxidase↗
PubMed1990

Characteristics of the suppressive effect of nicardipine on peroxisome induction in rat liver.

In vivo administration of nicardipine, a known calcium antagonist, suppressed the clofibrate-evoked induction of activities of peroxisomal enzymes, such as catalase, the peroxisomal fatty acyl-CoA oxidizing system, carnitine acetyltransferase and mitochondrial carnitine palmitoyltransferase in rat liver. On a time-course study, the suppression of induction in the activities of the peroxisomal fatty acyl-CoA oxidizing system and carnitine acetyltransferase was found at 5 days after the treatment, whereas the induction by clofibrate was already observed at 1 day after the treatment, suggesting that in the process of peroxisome induction by clofibrate there might be two steps, i.e., a triggering step and an enhancing step, and nicardipine might act as suppressor for the later step. The precursor-incorporation studies with [3H]leucine showed that the rate of the synthesis of the peroxisomal bifunctional enzyme was increased by 4.2-fold after clofibrate-treatment, whereas nicardipine suppressed this enhancement to only 2.2-fold of the control. The rate of degradation of this enzyme was not affected by any treatment. These results show that nicardipine affects the regulation mechanism of the biosynthesis of this enzyme. Nicardipine showed hardly any suppressive-effect on the hepatic peroxisomal enzyme induction observed in high-fat diet fed rat. Furthermore, the suppression of clofibrate-evoked induction of peroxisomal enzymes was observed also in mice. These interesting findings suggest that there is a difference in the mechanism of peroxisome proliferation and/or the induction of peroxisomal enzymes between clofibrate and physiological conditions, such as high-fat diet feeding. The suppression of drug-induced peroxisome proliferation by calcium antagonists may help in dissecting the causal relationship between the multiple effects mediated by peroxisomal proliferators.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1990

Long-term effects of peroxisome proliferators on the balance between hydrogen peroxide-generating and scavenging capacities in the liver of Fischer-344 rats.

In order to clarify whether peroxisomal hydrogen peroxide (H2O2) plays an important role in peroxisome proliferator-induced hepatocarcinogenesis, we examined the change in metabolism of peroxisomal H2O2 in vivo and in vitro using male Fischer-344 rats fed clofibrate, bezafibrate and di(2-ethylhexyl)phthalate (DEHP) for up to 78 weeks. Hepatic peroxisomal fatty acyl-CoA oxidase activity increased 12-20-fold after 2 or 4 weeks treatment; later this level gradually decreased toward controls, and at 78 weeks activity was 3-10-times of control. Although hepatic H2O2 levels were increased slightly by clofibrate, bezafibrate and DEHP, the changes did not correlate with the changes in peroxisomal fatty acyl-CoA oxidase activity. In isolated hepatocytes, the rate of leakage of peroxisomal H2O2 from peroxisomes into the cytosol and the hepatocellular H2O2 content was measured. The rate of leakage of peroxisomal H2O2 into cytosol increased 2.5-4-fold when peroxisomal beta-oxidation activity was induced by peroxisome proliferators, and the increases in this rate corresponded with changes in the peroxisomal beta-oxidation activity. In contrast, the hepatocellular H2O2 contents were not affected by induced peroxisomal beta-oxidation. These data show that H2O2 leaking from peroxisome into cytosol would be quickly decomposed, and thus peroxisomal H2O2 does not appear to play an important role in hepatocarcinogenesis by such an oxidative stress mechanism after the long-term treatment with peroxisome proliferators.

Acyl-CoA Oxidase↗
PubMed1990

Long-term effects of hypolipidemic peroxisome proliferator administration on hepatic hydrogen peroxide metabolism in rats.

The effects of prolonged dietary administration of peroxisome proliferators, such as clofibrate, bezafibrate and di(2-ethylhexyl)phthalate (DEHP), on hepatic hydrogen peroxide (H2O2) level and on hepatic activities of the enzymes relating to H2O2 metabolism were examined. Male rats were treated for 79 weeks with the above three peroxisome proliferators. The activities of the peroxisomal beta-oxidation and catalase were increased 8- to 20-fold and 2- to 3-fold, respectively, after 2 or 4 weeks of treatment with these peroxisome proliferators. However at 79 weeks the peroxisomal beta-oxidation activity was 3-8 times that of control. The level of catalase activity was kept at approximately 2-fold even after prolonged treatment of peroxisome proliferators. Although the activities of glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) were decreased 50-60% at 4-12 weeks by the treatment with peroxisome proliferators, from 20 to 79 weeks those activities approached control levels in the case of clofibrate and bezafibrate but not DEHP-fed rats; GSH-Px and GST activities were kept at approximately 40% those of control. However hepatic capacities of H2O2-degrading enzymes, catalase and GSH-Px, apparently exceeded the H2O2-generating levels obtained on the basis of peroxisomal beta-oxidation activities in the livers of control and treated rats throughout the experimental period. The hepatic H2O2 levels increased only slightly but this increase did not correspond to changes in peroxisomal beta-oxidation. Our results suggest that a large part of H2O2 produced by peroxisomal beta-oxidation could be rapidly scavenged by catalase and GSH-Px in the liver of rats treated with peroxisome proliferators.

Animals↗
PubMed1990

Uptake of clarithromycin by rat lung cells.

To evaluate the affinity of clarithromycin (6-O-methylerythromycin A) for lung tissue, the in-vivo and in-vitro uptake of [14C]clarithromycin and [14C]erythromycin by rat lung cells was compared, and the characteristics of the uptake mechanism were investigated. After the administration into the external jugular vein of rats, clarithromycin was found in much higher concentrations in the lung tissue than erythromycin. In isolated lung cells, clarithromycin was also found in greater concentrations than erythromycin. The amount of clarithromycin was ten times that of erythromycin after 5 min incubation. This uptake profile was quite different from that observed in isolated liver cells. Uptake by lung cells for both antibiotics was shown to be an active process, as revealed by the need for cell viability, a suitable environmental temperature and ATP. Clarithromycin uptake proved to be dependent in part upon mitochondrial oxidative respiration. Kinetic analysis indicated that clarithromycin transport was saturable, with a relatively high binding affinity and velocity of uptake. Clarithromycin transport was significantly inhibited by 6-O-methylerythromycin analogues, but was not influenced by other analogues, including erythromycin. Competitive inhibition of clarithromycin uptake was demonstrated by 6,11,12.4"-tetra-O-methylerythromycin, one of the mutual inhibitors. These findings may suggest that clarithromycin utilizes a carrier-mediated transport system in the lung cells, which is common to 6-O-methylerythromycins. This difference of uptake mechanism between both antibiotics may account in part for the greater clarithromycin uptake by the lung cells.

Animals↗
PubMed1990

Rheumatoid factors and glomerulonephritis.

It is presently unknown whether rheumatoid factors have a pathogenic role in the development of various types of glomerulonephritis with immune deposits. Three isotypes of rheumatoid factors (RFs), which are autoantibodies to IgG, were measured using the solid-phase fluorescence immunoassay in sera from patients with diffuse proliferative lupus nephritis (DPLN), membranous lupus nephritis (MLN), IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN). RF activity of immunoglobulins deposited in the glomeruli from these patients was also studied by examining the binding of the FITC-conjugated human IgG and Fc portion of IgG to the glomeruli of renal biopsy specimens. IgG, IgA and IgM RFs were significantly increased in sera from patients with DPLN, and the increase was significantly lower in patients with MLN, IgAN and MN. Human IgG bound to immunoglobulin on the glomeruli only in DPLN, but not in MLN, IgAN or MN. The Fc portion of IgG was demonstrated to be involved in this reaction. It was suggested that RFs and IgG may play a major role in immune deposits on the glomeruli in DPLN and may be involved in the development of DPLN; however, this is not likely in MLN, IgAN or MN.

Antigen-Antibody Complex↗
PubMed1990

Autobacteriographic studies of clarithromycin and erythromycin in mice.

The antimicrobial activity of clarithromycin was compared with that of erythromycin in experimentally infected mice by whole-body autobacteriography. In mice with systemic staphylococcal infections, the number of vital microbes in the body was relatively low in the early period after oral administration of erythromycin, but increased thereafter to the levels found in nonmedicated control mice. On the other hand, with clarithromycin treatment, a significantly smaller number of microbes was evident throughout the body. The microbes were scarcely seen in the parenchyma of any organs during the examination period. This potent antimicrobial activity of clarithromycin compared with that of erythromycin was further demonstrated in mice with respiratory infections. On the other hand, to examine the distribution properties of both antibiotics in the whole body, an autoradiographic study was carried out with [N-methyl-14C]clarithromycin and [N-methyl-14C]erythromycin. Both labeled antibiotics were distributed widely throughout the body after oral administration in both uninfected control mice and mice with systemic infections. However, the radioactivity was more marked and persistent for [14C]clarithromycin than it was for [14C]erythromycin, particularly in the lungs. The observations described above indicate the superior in vivo antimicrobial activity of clarithromycin compared with that of erythromycin and suggest that the superiority of clarithromycin is largely attributed to its favorable distribution properties. The advantages of whole-body autobacteriography, coupled with whole-body autoradiography, are discussed.

Administration, Oral↗
PubMed1990

[Long-term arterial infusion chemotherapy to the cancer patients].

Arterial infusion chemotherapy is an effective method for unresectable and recurrent cancer patients. But this method had some problems, in terms of efficacy, side effect and safety. Thus, we studied these problems in 33 patients. We inserted the tube into the proper hepatic artery in 25 cases and into the aorta in 8 cases, and used anticancer drugs, such as MMC, ADM and CDDP. In this study, no serial or severe side effects were noted. On the other hand, the obstruction of catheter and artery was found in a few cases. We encountered 2 cases of CR and 11 cases of PR. The effectiveness of this method is approximately 46.4%. These results suggested that long term arterial infusion chemotherapy for outpatients was a safe and effective method from the view point of quality of life in cancer patients.

Adult↗
PubMed1990

[Study of intraarteric infusion chemotherapy with drug delivery system].

We have studied the effect of intraarteric infusion chemotherapy with missile chemotherapy, induced hypertensive chemotherapy and/or two-route infusion chemotherapy in 14 liver tumors (7 cases with liver metastasis from gastric cancer, 3 cases with liver metastasis from colonic cancer, 4 cases with hepatoma). Results indicated that PR in 6 (46.1%) out the 13 evaluated cases. The toxicity was not evident except for slight bone marrow depression with 5 cases and a low grade fever with 2 cases. These results indicate that intraarterial infusion chemotherapy with drug delivery system can be considered one of the treatment therapies available for a nonresectable tumor.

Aged↗
PubMed1990

Influenza antibody titers after vaccination of chronic renal failure patients; before and during hemodialysis, or on continuous ambulatory peritoneal dialysis.

Anti-influenza antibody (Ab) titers were measured in order to elucidate whether there are any disturbances in Ab production in chronic renal failure (CRF) patients. A total of 55 CRF patients plus 15 normal individuals were vaccinated with influenza vaccine twice, 4 weeks apart of the 55 CRF patients, 15 were not on dialysis, 10 were undergoing hemodialysis (HD), and 30 were on continuous ambulatory peritoneal dialysis (CAPD). Of the 30 CAPD patients, 14 had peritonitis. Serum Ab titers were measured by complement fixation (CF) and hemagglutination inhibition (HI) tests, and IgG and IgM class specific antibodies by ELISA. All groups responded to immunization, but CAPD patients with peritonitis and CRF patients not yet on dialysis did not show a significant elevation in IgM class Ab titers. The number of CAPD patients with peritonitis who achieved positive titers was significantly lower in HI (p less than 0.01) and IgG class antibodies (p less than 0.05) compared with normal controls. Two patients with frequent peritonitis did not show any response to vaccination. It was concluded that patients with renal dysfunction have some abnormalities in Ab production against influenza vaccine, the effects of which were more pronounced in the CAPD patients with frequent peritonitis.

Adolescent↗
PubMed1990

[Peroral endoscopical diagnosis for the early stage of cancer in bilio-pancreatic system].

PCPS (peroral cholangio-pancreatoscopy), a modality of mother and baby scope systems, was very useful for the diagnoses of bile duct tumors. The endoscopical findings and pathological findings obtained on the biopsy specimen collected under the direct view were valuable. For the diagnosis of pancreatic diseases, PMPS (peroral micro-pancreatoscopy), in which ultrathin quartz fibers are used for the baby scope, was useful. By this method, we could observe the inside of the pancreatic duct through an untreated normal papilla. This is very helpful for endoscopical diagnosis of small pancreatic cancers. EUS (endoscopic ultrasonography) was also a useful method for the diagnosis of small pancreatic cancers. EUS could draw the three layers of the common bile duct and gall bladder walls, and could distinguish a cholesterol polyp from a non-cholesterolic one. Combined application of these methods will aid in the discovery of early stages of cancers in the bilio-pancreatic system.

Biliary Tract Neoplasms↗
PubMed1989

Participation of peroxisomes in lipid biosynthesis in the harderian gland of guinea pig.

Peroxisomal enzyme activities in the guinea-pig harderian gland, which has a unique lipid composition, were studied. Activities of catalase, acyl-CoA oxidase and the cyanide-insensitive acyl-CoA beta-oxidation system in this tissue were comparable with those in rat liver. The activities of dihydroxyacetone phosphate acyltransferase (DHAPAT, EC 2.3.1.42) and alkyl-DHAP synthase (EC 2.5.1.26) were appreciable, and the distributions of both activities were consistent with that of sedimentable catalase activity. Glycerol-3-phosphate acyltransferase (GPAT, EC 2.3.1.15), which is localized in both microsomes (microsomal fractions) and mitochondria in the rat liver, was a peroxisomal enzyme in the harderian gland, though the activity was only about one-tenth of the DHAPAT activity. These enzymes had different pH profiles and substrate specificity. The existence of high activities of enzymes of the acyl-DHAP pathway in peroxisomes suggests the physiological significance of peroxisomes in the biosynthesis of glycerol ether phospholipid and 1-alkyl-2,3-diacylglycerol in the guinea-pig harderian gland.

Acyltransferases↗