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Biomedical subjects

H Oda

Publications and source records attributed to H Oda.

At least 289 records · Page 16Linked to original sources
PubMed1994

Genomic structure and chromosome location of the human mutT homologue gene MTH1 encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion.

8-Oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is produced by active oxygen species in the nucleotide pool of the cell and can be incorporated into cellular DNA. Human cells contain enzyme activity that hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing occurrence of mutations, caused by misincorporation. When the cDNA for human 8-oxo-dGTPase was expressed in Escherichia coli mutT- mutant cells devoid of self 8-oxo-dGTPase activity, the elevated level of spontaneous A:T to C:G mutation frequency reverted to normal. We isolated the genomic sequence encoding the enzyme and named the gene MTH1 (for mutT human homologue). This gene is composed of at least 4 exons, spans approximately 9 kb, and is located on human chromosome 7p22.

Amino Acid Sequence↗
PubMed1994

Effect of biliary drainage on serum 7 alpha-hydroxycholesterol level in patients with obstructive jaundice.

Percutaneous transhepatic biliary drainage was performed in 15 patients with obstructive jaundice and the serum 7 alpha-hydroxycholesterol level was monitored for 2 weeks by capillary gas-liquid chromatography-mass spectrometry. Before biliary drainage, the serum 7 alpha-hydroxycholesterol level was 130 +/- 52 pmole/ml, which was significantly lower than the normal value (238 +/- 100 pmole/ml). After biliary drainage, the serum 7 alpha-hydroxycholesterol level was decreased to 117 +/- 48 pmole/ml on the first day. There were two groups of patients as classified by the behavior of the serum 7 alpha-hydroxycholesterol level after the third day. In one group of patients (responders), the serum level increased significantly up to 525 +/- 83 pmole/ml at the end of the 2 weeks. In another group (nonresponders), the serum level did not increase and remained 145 +/- 86 pmole/ml. The serum bilirubin level tended to improve faster in the responders (decline index = -0.234 +/- 0.152) than in the nonresponders (decline index = -0.057 +/- 0.067; P < 0.05) and a statistically significant correlation was found between the decline index and the total 7 alpha-hydroxycholesterol level on Days 7 or 14. As the serum 7 alpha-hydroxycholesterol level is considered to reflect hepatic bile acid synthesis, which is one of the important functions of the liver, we conclude that the increased serum 7 alpha-hydroxycholesterol level after biliary drainage in the responders indicates recovered liver function and that the low serum level in the nonresponders suggests more severe hepatocellular damage in patients with obstructive jaundice.

Aged↗
PubMed1994

Cloning and expression in Escherichia coli of the gene encoding the Proteus vulgaris chondroitin ABC lyase.

The structural gene encoding chondroitin ABC lyase from Proteus vulgaris was cloned and sequenced. This gene consists of a single open reading frame of 3,063 bp, including a sequence (72 bp) for a possible secretory protein leader peptide, preceded by a Shine-Dalgarno ribosomal binding site. Promoter-like and rho-independent terminator sequences were detected upstream and downstream of the open reading frame, respectively. The G+C content of the coding region was 38.6%. The transcription startpoint was located 41-bp upstream of the initiation codon (ATG). Chondroitin ABC lyase is composed of 997 amino acids, and has a relative molecular mass of 112,635. When the 5.2-kb fragment containing the 1.2-kb upstream from the gene was inserted into pSTV29, and cloned in Escherichia coli, chondroitin ABC lyase was induced in the medium containing chondroitin-6-sulfate as the carbon source. On the other hand, when a 4.2-kb fragment containing only 0.2 kb upstream was inserted into pSTV29(pCHS delta 6), and pCHS delta 6 was introduced into E. coli, the enzyme was constitutively produced, even in medium containing glucose as the carbon source. By immunoblot analysis, the polypeptide synthesized by E. coli cells carrying pCHS delta 6 appeared to be the same as that of the purified chondroitin ABC lyase from P. vulgaris.

Amino Acid Sequence↗
PubMed1994

Effects of pravastatin and ursodeoxycholic acid on cholesterol and bile acid metabolism in patients with cholesterol gallstones.

To investigate the effects of pravastatin and ursodeoxycholic acid (UDCA) on cholesterol and bile acid metabolism in humans, 41 patients with cholesterol gallstone disease were allocated to four groups and treated with pravastatin (20 mg/day), UDCA (600 mg/day), both pravastatin and UDCA, or neither drug (control) for 1-2 weeks prior to elective cholecystectomy. Cholesterol 7 alpha-hydroxylase activity and serum levels of total 7 alpha-hydroxycholesterol were significantly increased by pravastatin and unaffected by UDCA. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was markedly increased by pravastatin and decreased by UDCA. UDCA significantly decreased biliary cholesterol concentration and the cholesterol saturation index and prolonged the nucleation time; however, pravastatin alone had little effect on biliary lithogenicity. Serum total and low-density lipoprotein (LDL)-cholesterol levels were reduced most by the combined administration of pravastatin and UDCA. In conclusion, at a dose of 20 mg/day, pravastatin increased bile acid synthesis but did not decrease biliary lithogenicity. UDCA had no significant effect on bile acid synthesis, but markedly decreased biliary lithogenicity.

Adult↗
PubMed1994

Identification of asynergic but viable myocardium in patients with chronic coronary artery disease by gated blood pool scintigraphy during isosorbide dinitrate and low-dose dobutamine infusion: comparison with thallium-201 scintigraphy with reinjection.

To evaluate the ability of low-dose dobutamine and isosorbite dinitrate (ISDN) gated blood pool scintigraphy (GBPS) and thallium SPECT with reinjection to identify viability in asynergic myocardium, both procedures were performed in 38 consecutive patients with chronic coronary artery disease and left ventricular dysfunction. Twenty-two of the 38 patients with successful revascularization were analyzed. GBPS was performed at the baseline and during continuous infusion of low dose dobutamine (5 micrograms/kg/min) and ISDN (2 micrograms/kg/min). Cine mode GBPS wall motion was scored from normal (0) to dyskinesis (4) semiquantitatively. Forty-seven of 110 segments with severe asynergy at the baseline were analyzed. Viability determined by GBPS was defined as wall motion score improvement by more than 1 grade. Thallium viability was defined as the segment with redistribution or fill in with severe initial perfusion defect. GBPS was 76.7% sensitive and 70.6% specific for predicting post vascularization wall motion improvement (p < 0.005). Of 47 segments with severe asynergy, concordance of judgement was obtained in 40 segments (85.1%), and reversibility was correctly diagnosed in 34 of 40 patients (85.0%), but thallium with reinjection correctly identified tissue viability in 6 of 7 segments with discordance between 2 studies. These data suggest that most cases of reversible asynergy (hibernating myocardium) respond to ISDN and dobutamine, suggesting the possibility of predicting improvement by revascularization, although some underestimation of tissue viability remained to be resolved. Thallium with reinjection is superior to low-dose dobutamine + ISDN GBPS for the assessment of myocardial viability.

Adult↗
PubMed1994

Serum 7 alpha-hydroxycholesterol reflects hepatic bile acid synthesis in patients with obstructive jaundice after external biliary drainage.

To examine the hypothesis that serum levels of 7 alpha-hydroxycholesterol reflect bile acid synthesis in the liver, we analyzed serum 7 alpha-hydroxycholesterol and bile acid output in 13 patients with obstructive jaundice after relief of biliary obstruction. Before biliary drainage, the serum level of 7 alpha-hydroxycholesterol was 92 +/- 12 pmol/ml (mean +/- S.E.M.) and was significantly lower than the control value (226 +/- 26 pmol/ml, p < 0.01). After biliary drainage, serum 7 alpha-hydroxycholesterol level and biliary bile acid outputs began to rise in some patients, indicating reversible liver dysfunction. In other patients, serum 7 alpha-hydroxycholesterol levels and bile acid outputs did not increase, suggesting severe or irreversible liver dysfunction. On and after the third day of biliary decompression, serum 7 alpha-hydroxycholesterol levels correlated well with bile acid excretion (p < 0.01, r = 0.93). Other liver function parameters, such as serum bilirubin, serum bile acids, albumin, and bile flow, also revealed significant correlation with serum 7 alpha-hydroxycholesterol levels. We conclude that the serum 7 alpha-hydroxycholesterol level clearly reflects bile acid synthesis in the liver and that it may serve as a useful parameter for the assessment of hepatic functional recovery in patients with obstructive jaundice after biliary drainage.

Aged↗
PubMed1994

DNA adduct formation and assessment of aberrant crypt foci in vivo in the rat colon mucosa after treatment with N-methyl-N-nitrosourea.

N-Nitroso-compound DNA adduct formation in vivo and occurrence of aberrant crypt foci (ACF) were studied in the rat colon mucosa after a single, local treatment with a carcinogen, N-methyl-N-nitrosourea (MNU), using a simple surgical approach. A segment of F344 rat colon was ligated to make a pouch and injected with MNU solution. For the study of DNA adduct formation, the solution contained 50 microCi of [3H]MNU. The results demonstrated that similar ranges of carcinogen dose, i.e. 0.15 x 10(-2) - 1.5 x 10(-2) M MNU, could induce both DNA adduct formation and appearance of ACF in the rat colon with both parameters showing a nearly linear dose dependence. HPLC analysis revealed the DNA adducts to include both 7-methylguanine (7-mGua) and O6-methylguanine (O6-mGua) with the 7-mGua/O6-mGua ratio being 8.2-11.3:1 in the system used. Assessment of ACF development from 4 to 16 weeks after MNU treatment at a dose of 7.5 x 10(-2) M showed the numbers to increase up to the 8th week, followed by a decrease at weeks 12 and 16, when 40% of the ACF counted at the peak time point were still present. The percentage of large ACF (> or = 4 crypts/ACF) significantly increased with time. These results indicate a clear relation between DNA adducts and preneoplastic lesions, i.e. ACF. In conclusion, DNA adduct formation and ACF can be efficiently and simply detected in vivo by using the method described in the present paper.

Animals↗
PubMed1994

Detection and cloning of human papillomavirus DNA associated with recurrent respiratory papillomatosis in Thailand.

Recurrent respiratory papillomatosis (RRP) is highly prevalent in Thailand. In this study, we examined the presence of human papillomavirus (HPV) DNA in 25 RRP patients in Thailand by means of dot blot analysis and/or polymerase chain reaction. Eighty-four percent (21/25) of cases and 4% (1/25) of cases were positive for HPV-11 DNA and HPV-6 DNA, respectively. Three cases (3/25) were negative for all of the examined HPV types. No cases were positive for HPV-16 or 18. Furthermore, we isolated the recombinant HPV-11 DNA clone from a genomic library constructed with the DNA of RRP tissue. The restriction map of the cloned HPV DNA was identical with the map of known HPV-11 DNA. These results suggest at least that no specific HPV type or subtype is likely to be associated with RRP in Thailand.

Base Sequence↗
PubMed1994

O6-methylguanine-DNA methyltransferase activity in the human lung persists with advancing age.

O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in the repair of DNA lesions induced by alkylating carcinogens in a wide range of animals. To determine the relationship between DNA repair activity and tumor susceptibility with advancing age the activity of MGMT was measured in normal lung tissue extracts from 66 patients with primary or metastatic lung cancer obtained at surgery. The age of the patients whose lung MGMT activity was measured ranged from 40 to 79 years (males) and from 40 to 80 years (females), and the values varied over 10-fold in both sexes (33 males and 33 females). Our results indicate that the MGMT enzyme protein is expressed at appreciable levels throughout life, and on age-associated rapid decline is not a feature in the human lung. Thus, any age-associated increase in lung cancer incidence cannot be ascribed to any change in MGMT activity. In order to assess other possible factors which might exert a modulating influence we examined the MGMT activity in relation to sex, tumor type and smoking. However, in none of these cases was any significant correlation evident.

Adenocarcinoma↗
PubMed1994

Alcohol and coronary spasm.

Alcohol is known to sometimes cause coronary spasm, the mechanism of which is still unknown. The authors monitored changes in plasma levels of prostanoids (thromboxane [TX B2], 6-keto prostaglandin F1 alpha [PGF1 alpha]), catecholamines (CA), serotonin (5-HT), cyclic nucleotides (cyclic adenosine monophosphate--cAMP, cyclic guanosine monophosphate--cGMP), and platelet aggregation after alcohol ingestion (Japanese rice wine 400 mL) in 8 patients with alcohol-induced variant angina and 8 healthy men as controls. Coronary spasm was confirmed to have been induced in 4 patients nine hours after alcohol challenge (VA[+]), when their plasma ethanol levels had already returned to a null level. Neither CA nor 5-HT levels showed any change after alcohol ingestion either in patients or controls, though controls showed high levels of CA during alcohol ingestion. TX B2 in VA(+) patients increased gradually after alcohol ingestion to reach up to a statistically significantly high level just before attack, as compared with those of controls and VA(-) patients, who, on the contrary, did not show such changes. The levels of 6-keto PGF1 alpha, however, which were significantly lower in patients than in controls before the test, exhibited a gradual increase in VA(+) patients in parallel with the increase in TX B2. No significant changes in cAMP levels between either controls or patients were present. On the contrary, cGMP levels had a gradual decrease in patients after alcohol ingestion. Especially six hours after alcohol ingestion, cGMP levels in VA(+) patients decreased so much as to make a statistically significant difference, as compared with the level in controls. Platelet aggregability in controls showed a decrease after alcohol ingestion, in spite of no change or even increase in patients. These data suggest that low levels of PGF1 alpha and the decrease of cGMP levels from alcohol ingestion play important roles in the mechanism of coronary spasm induced by alcohol ingestion.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Acute occlusion due to coronary dissection as a PTCA complication resolved by reentry achieved by pulling an inflated balloon in the true lumen.

We experienced 2 patients in whom conventional percutaneous methods were not useful for acute occlusions sequel to coronary angioplasty. Acute occlusions seemed to be caused by large dissections. Pulling an inflated balloon at the dissected lesions achieved reentry from the false lumen to the true lumen, thus resolving collapse of the true lumen and recanalizing the occluded coronary artery.

Angioplasty, Balloon, Coronary↗
PubMed1994

Induction of cytochrome P-450s and expression of liver-specific genes in rat primary hepatocytes cultured on different extracellular matrices.

Freshly isolated hepatocytes were cultured on an EHS-gel prepared from EHS-tumor, poly-N-p-vinylbenzyl-D-lactonamide (PVLA), and type I collagen (TIC). Hepatocytes on EHS-gel showed a spherical shape and much more strongly maintained the inducible expression of cytochrome P-450 genes which were lost on PVLA and TIC. Further, the expression of liver-specific genes were maintained on EHS gel at the highest level, and then higher on PVLA than TIC.

Animals↗
PubMed1994

Erythromycin inhibits neutrophil chemotaxis in bronchoalveoli of diffuse panbronchiolitis.

The efficacy of low dose long-term erythromycin (EM) therapy in the treatment of chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB), has been reported, but its therapeutic mechanism is still unclear. In 13 patients receiving oral EM therapy the accumulation of neutrophils in bronchoalveolar lavage (BAL) fluid was significantly reduced (p < 0.05), this reduction corresponds with an improvement in clinical symptoms. We sought to determine whether neutrophil chemotactic activity (NCA) in lavage fluid obtained from these 13 patients with DPB would respond to EM therapy. Pretreatment NCA in all patients was significantly elevated compared with levels in normal healthy nonsmoking volunteers (p < 0.001), and the level was greatly reduced after EM therapy (p < 0.001). In addition, this reduction correlated with increased percentages of neutrophils in the BAL fluid (r = 0.737, p < 0.01). Gel-filtration chromatography was also performed to characterize chemotactic factors. Pre-EM treatment BAL fluid revealed four NCA peaks (about molecular weight 15,000, 8,000, 1,500, and 300 daltons) in the elution profile, and chemotactic activity was reduced in all areas after EM therapy. These findings indicate that NCA in lavage fluid from patients with DPB consists of various components. Although it was not clear which component is predominantly affected, these results indicate that EM may inhibit the migration of neutrophils to inflammatory sites by reducing the intrapulmonary chemotactic gradient, thus, ultimately reducing pulmonary inflammation.

Adult↗
PubMed1994

An autopsy case of pyruvate kinase deficiency anemia associated with severe hemochromatosis.

We report an autopsy case of pyruvate kinase deficiency anemia with severe hemochromatosis. This anemia is rarely associated with hemochromatosis. In this case, the autopsy findings showed hemochromatosis of the heart, pancreas, liver, kidneys, thyroid gland, adrenal glands, testes and skin. Microscopic examination showed iron depositions in these organs, but not in the bone marrow. A family study showed negative data for iron overload and no known HLA type suggestive of idiopathic hemochromatosis. To explain this rare association, we suggest that this patient's iron overload was an acquired type, which might have mainly been caused by increased iron absorption due to the severe hemolytic anemia.

Adult↗