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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 829 records · Page 46Linked to original sources
PubMed1986

Effects of adenine arabinoside and corticosteroid on replication of duck hepatitis B virus DNA in the liver.

Adenine arabinoside (Ara-A) therapy and abrupt withdrawal of corticosteroids have both been used in the treatment of chronic infections due to hepatitis B virus (HBV). In order to better understand the effects and mechanism of action of these treatments, we treated ducks chronically infected with duck hepatitis B virus (DHBV) with different dosage regimens of the two therapies. We measured endogenous DNA polymerase activity and used sensitive molecular biological techniques to monitor serum and intrahepatic viral replicative forms during and after drug treatment. Ara-A had a transient, dose related inhibitory effect on DHBV replication. Viral plus strand synthesis was disproportionately affected. Following the cessation of Ara-A treatment markers of viral replication returned to their baseline values. We conclude that Ara-A exerts its effect through inhibition of viral DNA polymerase. Corticosteroid treatment results in an increase in DHBV replication, but steroid withdrawal results in a short-lived transient decrease in markers of viral replication to below pretreatment values. Our results suggest that steroid withdrawal decreases hepadna virus replication through a mechanisms of immune modulation. On the basis of these results and previous trials in HBV infected patients, we predict that neither agent will efficiently eliminate viral replication in chronic hepadna virus infection when used as the sole therapeutic modality. We suggest that the differences in the mechanisms of action of Ara-A treatment and corticosteroid withdrawal be exploited, and the use of combination therapy be explored.

Adrenal Cortex Hormones↗
PubMed1986

Portographic opacification of hepatic veins and (anomalous) anastomoses between the portal and hepatic veins in cirrhosis--indication of extensive intrahepatic shunts.

On the premise that extensive intrahepatic portal-venous anastomoses known to occur in cirrhosis would be demonstrated by contrast medium directly placed in the portal vein, percutaneous transhepatic portograms were analyzed in 82 patients with liver cirrhosis in relation to the estimated degree of shunting. The degree of intrahepatic shunt was measured during transhepatic portography using 99mTc-macroaggregated albumin. Hepatic veins began to opacify at 4 to 10 s after the start of injection of contrast medium during portography in 20 patients with cirrhosis who had intrahepatic shunt indices of 58.5 +/- 18.5%, but it was not visualized in 62 patients with cirrhosis whose shunt indices were 19.9 +/- 14.1%. Anomalous large anastomoses of 1 or 2 mm in size between the right portal vein and the right hepatic vein were clearly visualized during portography in 18 of 20 patients in whom the hepatic vein was opacified. Frequency and time of beginning opacification of the hepatic vein were closely correlated with the degree of intrahepatic shunt. Thus, opacification of the hepatic vein and abnormal anastomoses between the portal and hepatic vein systems in an early phase of portography indicates extensive intrahepatic shunts.

Hepatic Veins↗
PubMed1986

[Three cases of primary aldosteronism including one case with postoperative ventricular tachycardia].

Three patients with primary aldosteronism were treated surgically between February and September 1984. All patients had suffered from hypertension with U waves in ECG and laboratory examinations revealed hypokalemia, hyperaldosteronemia and suppressed plasma renin activity. The localization of the adrenal tumor was diagnosed accurately in all 3 patients by adrenal vein sampling and in 2 of the patients by PRP, CT scan, adrenal scanning with 131I-iodo cholesterol and adrenal venography. Adrenal tumors were surgically removed by unilateral adrenalectomy through the flank approach in all cases. Histological examinations of removed specimens showed adrenocortical adenoma. Removal of the adenoma caused a prompt reversal of the laboratory serum abnormalities and hypertension was normalized within 2 weeks postoperatively in all cases. Severe ventricular tachycardia (Torsades de Pointes) was observed suddenly in one of the patients after about 5 hours postoperatively. Therapy including conventional antiarrhythmic drugs, such as lidocaine or procainamide, and potassium administration failed to prevent the arrhythmia. Ventricular tachycardia was successfully treated and disappeared with the use of magnesium sulfate (MgSO4) intravenously. The serum potassium concentration was normal during the episode and the serum magnesium concentration, which was not detected before or just after the operation, was under the limit of normal range (1.4 mEq/l) after the use of magnesium sulfate. Hypomagnesemia which is retrospectively thought to be the result of primary aldosteronism may be responsible for the episode of postoperative ventricular tachycardia.

Adenoma↗
PubMed1985

Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients.

A total of 850 patients with hepatocellular carcinoma seen during the last 8 years were analyzed retrospectively for survival in relation to treatment and disease stage. A new staging scheme based on tumor size, ascites, jaundice and serum albumin was used. Clearly, the prognosis depended on disease stage. The median survival of 229 patients who received no specific treatment was 1.6 months, 0.7 month for Stage III patients, 2.0 months for Stage II, and 8.3 months for Stage I. The median survival of Stage I patients who had hepatic resection (n = 115) was 25.6 months and Stage II patients with resection (n = 42) was 12.2 months. In patients who had a small cancer (less than or equal to 25% of liver area in size) the median survival was 29.0 months. Survival of the surgically treated patients, which represented a highly selected group, was better than that of medically treated patients of a comparable stage. Median survival of Stage I medically treated patients (n = 124) was 9.4 months, for Stage II (n = 290) 3.5 months, and for Stage III (n = 50) 1.6 months. Medical treatment prolonged survival in Stage II and III patients, but not in Stage I. Transcatheter arterial embolization gave a better survival compared with chemotherapy, whether intra-arterial bolus administration of mitomycin C, systemic mitomycin C, or oral/rectal tegafur, in Stage II. Among various chemotherapeutic modalities, intra-arterial bolus injection was superior to systemic chemotherapy in survival in Stage II. In Stage III, chemotherapy improved survival as compared with no specific treatment. The major causes of death were hepatic failure and gastrointestinal bleeding, probably due to the coexistent advanced cirrhosis. These results in survival are much improved over the past reports, and the differences are probably a result of earlier diagnosis and frequent hepatic resections.

Adolescent↗
PubMed1985

Synthesis of poly(ethylene glycol)-bound NADP by selective modification at the 6-amino group of NADP.

The N-1 position of the adenine ring of NADP was selectively alkylated by the reaction of 2',3'-cyclic NADP with 3-propiolactone to yield 2',3'-cyclic 1-(2-carboxyethyl)-NADP (I). Derivative I was converted to a mixture of the isomers of N6-(2-carboxyethyl)-NADP with their phosphate groups at the 2' or 3' position (IIa and IIb) by chemical reduction, alkaline rearrangement and chemical reoxidation. Carbodiimide coupling of the mixture of IIa and IIb to alpha, omega-diaminopoly(ethylene glycol) gave the 2', 3'-cyclic derivative of poly(ethylene glycol)-bound NADP (III), which was enzymically hydrolyzed to yield poly(ethylene glycol)-bound NADP (PEG-NADP). PEG-NADP has good cofactor activity (16-100% of that of NADP) for NADP-specific and NAD(P)-specific dehydrogenases except isocitrate and glucose dehydrogenases. For NAD-specific enzymes, PEG-NADP has higher cofactor activity than NADP: for horse liver alcohol dehydrogenase, the cofactor activity of PEG-NADP is 40 times that of NADP and 14% of that of NAD. Kinetic studies show that for most of enzymes tested, Km values for PEG-NADP are larger than those for NADP and V values for PEG-NADP are similar to those for NADP. PEG-NADP proved to be applicable in a continuous enzyme reactor, in which reactions of glutamate dehydrogenase and glucose-6-phosphate dehydrogenase were coupled by the recycling of PEG-NADP.

Alkylation↗
PubMed1985

In vitro antigenic reactivity of synthetic lipid A analogues as determined by monoclonal and conventional antibodies.

Cross-reactivities of synthetic lipid A analogues with monoclonal and conventional antibodies against Salmonella lipid A were studied. It was shown that the in vitro antigenicity of a synthetic compound 506, beta-(1----6) D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3'-hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3-hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, was practically indistinguishable from that of the natural E. coli lipid A preparation, and that both phosphates in positions 1 and 4' as well as ester- and amide-linked fatty acyl residues, particularly 3-acyloxyacyl group, of the glucosamine disaccharide are involved in the cross-reactivity of lipid A as important antigenic determinants.

Animals↗
PubMed1985

Preparation and characterization of NADP derivatives alkylated at 2'-phosphate and 6-amino groups.

Reaction of NADP with 3-propiolactone at pH 6 gave new NADP derivatives carboxyethylated at the 2'-phosphate or 6-amino group, or both: 2'-O-(2-carboxyethyl)phosphono-NAD (I), N6-(2-carboxyethyl)-NADP (II), and 2'-O-(2-carboxyethyl)phosphono-N6-(2-carboxyethyl)-NAD (III). Their structures were assigned on the basis of ultraviolet, 1H-NMR and 31P-NMR spectra, and also treatment with nucleotide pyrophosphatase or alkaline phosphatase. Carbodiimide-promoted reaction of derivative I with 1,2-diaminoethane gave 2'-O-[N-(2-aminoethyl)carbamoylethyl]phosphono-NAD (IV); derivative III gave 2'-O-[N-(2-aminoethyl)carbamoylethyl]phosphono-N6-[N-(2-aminoethyl ) carbamoylethyl]-NAD (IV). The same reaction of derivative II, on the other hand, gave a mixture of N6-[N-(2-aminoethyl)carbamoylethyl]-NADP (Va) and its 3'-phosphate isomer (Vb). The mixture was converted to Va via the 2',3'-cyclic derivative (Vc). Their structures were assigned on the basis of ultraviolet and 1H-NMR spectra, and also treatment with alkaline phosphatase or 3'-nucleotidase. All the NADP derivatives obtained in this work could be reduced with yeast glucose-6-phosphate dehydrogenase.

Alkylating Agents↗
PubMed1985

Coenzymic activity of NADP derivatives alkylated at 2'-phosphate and 6-amino groups.

Coenzymic activities of the following NADP derivatives were investigated: 2'-O-(2-carboxyethyl)phosphono-NAD (I), N6-(2-carboxyethyl)-NADP (II), 2'-O-(2-carboxyethyl)phosphono-N6-(2-carboxyethyl)-NAD (III), 2'-O-[N-(2-aminoethyl)carbamoylethyl]phosphono-NAD (IV), N6-[N-(2-aminoethyl)carbamoylethyl]-NADP (Va), 2',3'-cyclic NADP, and 3'-NADP. Derivatives I and IV show the effects of modification at the 2'-phosphate group, and derivatives II and Va show those at the 6-amino group of NADP. As for enzymes, alcohol, isocitrate, 6-phosphogluconate, glucose, glucose-6-phosphate, and glutamate dehydrogenases were used. These enzymes were grouped on the basis of the ratio of the activities for NAD and NADP into NADP-specific enzymes (ratio less than 0.01), NAD(P)-specific enzymes (0.01 less than ratio less than 100), and NAD-specific enzymes (ratio greater than 100). For NADP-specific enzymes, modifications at the 2'-phosphate group of NADP caused great loss of cofactor activity. The relative cofactor activities (NADP = 100%) of derivatives I and IV for these enzymes were 0.5-20 and 0.01-0.5%, respectively. On the other hand, NAD(P)-specific enzymes showed several types of responses to the NADP derivatives. The relative cofactor activities of I and IV for Leuconostoc mesenteroides and Bacillus stearothermophilus glucose-6-phosphate dehydrogenases and beef liver glutamate dehydrogenase were 60-200%; whereas, for B. megaterium glucose dehydrogenase and L. mesenteroides alcohol dehydrogenase, the values were 0.8-8%. For NAD-specific enzymes, these values were 20-50%. The relative cofactor activities of 2',3'-cyclic NADP and 3'-NADP were very low (less than 0.2%) except for beef liver glutamate dehydrogenase, B. stearothermophilus glucose-6-phosphate dehydrogenase, and horse liver alcohol dehydrogenase. Kinetic studies showed that the losses of the cofactor activity of NADP by these modifications were mainly due to the increase of the Km value. The mechanisms of coenzyme specificity of dehydrogenases are discussed. Unlike the 2'-phosphate group, the 6-amino group is common to NAD and NADP, and the effects of modification at the 6-amino group were independent of the coenzyme specificity of enzymes used for the assay. Derivatives II and Va had high relative cofactor activities (65-130%) for most of the enzymes except for isocitrate and glucose dehydrogenases (less than 1%) and L. mesenteroides alcohol dehydrogenase (20-60%). The cofactor activity of derivative III was generally lower than those of I and II.

Alkylation↗
PubMed1985

Discordance of hepatitis B e antigen/antibody and hepatitis B virus deoxyribonucleic acid in serum. Analysis of 1063 specimens.

Hepatitis B virus DNA was determined in 1063 serum samples from 252 patients with hepatitis B surface antigen by the spot hybridization technique. The results were correlated with hepatitis B e antigen and antibody. Hepatitis B virus DNA was detected in 87% of hepatitis B e antigen-positive patients, in 18% of hepatitis B e antibody-positive patients, and in 18% of those negative for both. Discordance of antigen/antibody and hepatitis B virus DNA, i.e., the presence of the DNA in antibody-positive sera or the absence of the DNA in antigen-positive sera, was observed in 209 of 997 (21%) samples. Of 121 patients with histologic diagnosis, this discordance was observed in none of 20 patients with nonspecific changes, in 13% of 39 with chronic persistent hepatitis, in 21% of 38 with chronic active hepatitis, and in 38% of 24 with cirrhosis. Thus, hepatitis B e antigen/antibody testing alone failed to predict the presence or absence of circulating hepatitis B virion in a significant proportion of patients with advanced chronic liver disease.

Adult↗
PubMed1985

Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B. A controlled study.

The efficacy of adenine arabinoside (Ara-A) alone or in combination with prednisolone utilizing its withdrawal effect was studied in 43 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis. Ten patients were treated with 10 mg/kg body wt of Ara-A alone for 4-8 wk. In 9 cases, prednisolone (40 mg/day) was given at a constant dosage for 4 wk before Ara-A treatment. Fourteen patients received oral prednisolone alone for 4 wk, and 10 patients served as untreated controls. Six of 9 patients (67%) undergoing the combination therapy became seronegative for hepatitis B e antigen, whereas only 4 of 24 patients (17%) treated either with Ara-A alone or prednisolone alone lost the antigen. Two of the 10 untreated patients became seronegative for hepatitis B e antigen during the same follow-up period of 9 mo. This prospective controlled study suggests that the combination of immunomodulation by steroid withdrawal and subsequent Ara-A is more effective in the treatment of patients with chronic liver disease and active hepatitis B virus replication than treatment with Ara-A alone.

Adult↗