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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 721 records · Page 40Linked to original sources

Identification of cortisone 5 beta-reductase as delta 4-3-ketosteroid 5 beta-reductase.

Cortisone 5 beta-reductase (4,5 beta-dihydrocortisone:NADP+ delta 4-oxidoreductase, EC 1.3.1.3) was purified from rat liver 100,000 X g supernate to a homogeneous state based on the catalytic activity. In the course of purification the activity was always accompanied by androstenedione 5 beta-reductase (3-oxo-5 beta-steroid:NADP+ delta 4-oxidoreductase, EC 1.3.1.23) and no fraction which revealed only cortisone 5 beta-reductase activity but lacked androstenedione 5 beta-reductase was observed. Partial denaturation of the purified enzyme with p-chloromercuribenzoate or wtih heat reduced both enzyme activities to a similar extent. When both substrates were added together at concentrations sufficient to saturate or nearly saturate the enzyme when added separately, the total rate of the reactions was much less than the sum of the rates of the reactions measured separately. Judging from these results it was concluded that cortisone 5 beta-reduction and that of androstenedione are catalyzed by the same catalytic site of a single protein.

Androstenedione↗

Characteristics of murine yolk sac erythroid progenitors and their population expansion in liquid culture.

Remarkable differences were found between late erythroid progenitors (CFU-e) in cultures of murine yolk sac cells and those of fetal liver cells with respect to frequency, erythropoietin responsiveness and colony size. Cultures of yolk sac on day 11 of gestation showed a CFU-e population of lower frequency, less sensitivity to erythropoietin and smaller colony size than those from cultures of day 14 fetal liver cells. As the proportion of CFU-e to BFU-e was much lower in yolk sac than that in fetal liver, 48-96 h liquid culture experiments were done with these cells to examine the capacity of their precursors to generate a certain amount of CFU-e subpopulations. The cultures of yolk sac cells produced large numbers of CFU-e which formed some large-sized colonies but those of fetal liver cells generated only a small amount of CFU-e.

Animals↗

Effects of ranitidine on plasma clearance of indocyanine green in patients with liver cirrhosis.

The effects of ranitidine on plasma clearance of ICG were investigated in 68 cirrhotic patients (9 were positive for HBsAg, 33 were alcoholics and 26 had cryptogenic cirrhosis). The ICG clearance test was performed before and after ranitidine administration. In 31 patients treated with ranitidine (150 mg perorally), the plasma ICG clearance were 233.6 +/- 20.4 ml/min (mean +/- S.E.) and 239.2 +/- 20.5 ml/min before and after ranitidine, respectively. In the 37 treated with intravenous ranitidine 50 mg, the corresponding values were 205.4 +/- 17.7 ml/min and 206.4 +/- 17.9 ml/min. There was no significant change in the plasma clearance of ICG or the elimination rate constant after ranitidine administration. Even in patients with decompensated liver cirrhosis, no significant change was demonstrated in the plasma ICG clearance after ranitidine. These results led to the conclusions that ranitidine does not reduce the hepatic blood flow and that it is a safe and useful drug for the treatment of gastrointestinal tract bleeding in patients with liver cirrhosis.

Adult↗

Changes in serum enzyme activity after transcatheter arterial embolization for hepatic neoplasm.

We assayed serum levels of certain enzymes and tumor markers in patients after transcatheter arterial embolization (TAE) to evaluate the effectiveness of this treatment. Twenty patients had hepatocellular carcinoma and two patients had metastases to the liver from colon cancer. Assays were first done immediately after TAE and were continued for the next 12 days. Glutamic oxaloacetic transaminase (GOT; EC 2.6.1.1, L-aspartate:2-oxoglutarate aminotransferase), glutamic pyruvic transaminase (GPT; EC 2.6.1.2, L-alanine:2-oxoglutarate aminotransferase), and lactate dehydrogenase (EC 1.1.1.27; (S)-lactate:NAD+ oxidoreductase) peaked 24 to 48 h after TAE and returned to the base lines in 7 to 10 days. Mitochondrial GOT (mGOT) and glutamate dehydrogenase (GLDH; EC 1.4.1.2, L-glutamate:NAD+ oxidoreductase) also peaked at the same time after TAE. alpha-Fetoprotein peaked 2 h after TAE and decreased to half of the baseline on day 7. Carcinoembryonic antigen peaked at 24 h and fell at 48 h only in the patients with colon cancer. The total amount of cytosolic GOT, GPT, mGOT, and GLDH released was correlated to the volume of the necrotic mass estimated by computed tomography scans. The correlation coefficients for mGOT and GLDH were r = 0.919 and r = 0.939 (both p less than 0.001), respectively. Assays of mGOT and GLDH may be useful to estimate the volume of the necrotic mass of a hepatoma or metastatic carcinoma in the liver.

Carcinoma, Hepatocellular↗

Portal hemodynamics in idiopathic portal hypertension (Banti's syndrome). Comparison with chronic persistent hepatitis and normal subjects.

A comparative study of portal hemodynamics was made in 17 patients with idiopathic portal hypertension, 5 patients with chronic persistent hepatitis having no portal hypertension, and 21 healthy adults who served as the control for certain measurements. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, organ volume by computed tomography, and intrahepatic shunt index by 99mTc-macroaggregated albumin instilled in the portal vein. The patients with idiopathic portal hypertension were divided into two groups: group A (n = 8) and group B (n = 9), consisting of those who respectively had portal venous flow per liver volume above and below the mean + 2 SD of healthy adults. In group A, portal vein pressure was moderately elevated, portal venous flow was significantly increased compared with the control, and portal vascular resistance was not much altered. In group B, portal vein pressure was markedly elevated above that of control, portal venous flow was comparable, and portal vascular resistance was significantly elevated. Splenic venous flow measured in the splenic vein between the left and short gastric veins was markedly increased in groups A and B, the increase being greater in the former. It was concluded that in some patients with idiopathic portal hypertension, increased portal venous flow, partly a result of increased splenic venous flow secondary to splenomegaly of an undetermined process, is the main contributor initially to the elevation of portal vein pressure; in others, possibly later, increased portal vascular resistance plays an important role.

Adult↗

Prospective controlled trial of elective endoscopic sclerotherapy in comparison with percutaneous transhepatic obliteration of esophageal varices in patients with nonalcoholic cirrhosis.

The results of a prospective randomized controlled trial of elective endoscopic intravariceal sclerotherapy carried out over a 36-mo period in comparison with elective percutaneous transhepatic obliteration of varices (PTO) are presented. Sixty-six patients with nonalcoholic cirrhosis were randomized after they had stabilized, usually between 7 and 14 days after variceal bleeding had stopped following medical treatment (balloon tamponade and vasopressin infusion). Thirty-three patients were assigned to the sclerotherapy group and the other 33 patients were assigned to the PTO group. The mean follow-up period was similar in both groups. There was no significant difference in demographic, clinical, and laboratory data between the two groups. Six patients (18%) in the sclerotherapy group and 21 (64%) in the PTO group had at least one episode of gastrointestinal bleeding during the follow-up period (p less than 0.005). Three patients in the sclerotherapy group and 1 patient in the PTO group bled from lesions other than varices; therefore the incidence of variceal bleeding was 9% in the former and 61% in the latter (p less than 0.005). The cumulative variceal bleeding rate was significantly lower in the sclerotherapy group than the PTO group (p less than 0.05). Five patients in the sclerotherapy group died during the follow-up period but none died of recurrent variceal bleeding. Nineteen patients in the PTO group died and 10 of them died of bleeding from varices. The cumulative survival rate was significantly better in the sclerotherapy group (p less than 0.05). These results indicate that elective endoscopic intravariceal sclerotherapy is superior to elective PTO in the prevention of recurrent variceal hemorrhage and mortality in nonalcoholic cirrhosis.

Clinical Trials as Topic↗

Quantitative aspects of portal-systemic and arteriovenous shunts within the liver in cirrhosis.

To estimate vascular changes in chronic liver disease, we quantitated intrahepatic arteriovenous and portal-systemic shunts in 12 patients with cirrhosis and arteriovenous shunts alone in 4 patients with cirrhosis. An index was obtained for intrahepatic arteriovenous shunts by instilling technetium 99m-macroaggregated albumin into the proper hepatic artery and portal-systemic shunts, by the same procedure done in the portal trunk, near the porta hepatis on different days. Counts were taken over the liver and both lungs in the anterior as well as the posterior view for calculation of the shunt index: cpm in lungs divided by cpm in liver and lungs X 100%. In the 12 patients with cirrhosis in whom both shunts were measured, intrahepatic arteriovenous shunting was significantly lower compared with intrahepatic portal-systemic shunting (1.4% +/- 1.1% vs. 36.0% +/- 29.0%, p less than 0.001). Thus, it seems that in patients with cirrhosis, the development of intrahepatic arteriovenous shunts is not as great as that of portal-systemic shunts, which were found in this study to be considerable and variable in degree.

Adult↗

Correlation of hepatitis B virus DNA and antigens in the liver. A study in chronic liver disease.

Hepatitis B virus deoxyribonucleic acid (DNA) and antigens (HBsAg and HBcAg) were studied in liver biopsy specimens from 105 HBsAg-positive patients with chronic liver diseases. Free or integrated viral DNA, or both, was detected in 83 of 105 (79%) patients, whereas HBsAg and HBcAg were demonstrated immunohistologically in 96 (91%) and 39 (37%), respectively. Of 60 patients with detectable free viral DNA, 38 (63%) were positive for HBcAg, whereas only 1 of 45 (2%) with either integrated viral DNA alone (n = 23) or no detectable viral DNA (n = 22) was positive for HBcAg (p less than 0.001). Furthermore, the amount of HBcAg was positively correlated with the amount of free viral DNA in the liver tissue. In contrast, HBsAg was well expressed not only in the liver with free viral DNA, but also in the liver with integrated DNA. These data suggest that the synthesis of HBcAg is primarily directed by free viral DNA, whereas that of HBsAg may be directed by free as well as integrated viral DNAs.

Adult↗

Comparison of N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase activities for evaluation of microangiopathy in diabetes mellitus.

The activities of urinary N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) were measured in 207 diabetic patients and 57 healthy controls, and the relationship of these enzymes to different stages of diabetic microangiopathy was studied. Diabetics with clinical proteinuria had higher urinary NAG and AAP (17.7 +/- 1.9 and 42.8 +/- 4.9 U/g creatinine, mean +/- SE, respectively) than healthy controls (1.8 +/- 0.1 and 10.0 +/- 0.4) or diabetics without proteinuria. Among diabetics without proteinuria, NAG excretion in those with retinopathy was slightly higher than in those without (6.4 +/- 0.5 v 5.4 +/- 0.4), and AAP in those with retinopathy was significantly higher than in those without (23.0 +/- 1.5 v 17.4 +/- 0.8, P less than 0.01). Urinary albumin measured by radioimmunoassay and lysozyme in diabetics with retinopathy but without proteinuria was higher than those without retinopathy (P less than 0.001 and P less than 0.01). The increase in albumin was the greatest in diabetics with long duration of the disease (greater than or equal to 8 years); however, NAG and AAP increased more significantly in those with high hemoglobin A1c than in patients with long duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

Leukemic blasts detected by the Technicon H-1 blood cell counter.

The authors studied the usefulness of the flagging system of the Technicon H-1 Cell Counter using samples from 45 patients with acute leukemia, 24 with acute lymphoblastic leukemia (ALL), and 21 with acute nonlymphoblastic leukemia (ANLL). Results by the automated method were compared with those by the eye-count method. Four out of 24 specimens were falsely negative; no false positive results were found. For ANLL specimens, there were no false positives or negatives. When 1% or more of the cells were blasts by the eye-count method, the automated system almost always flagged the sample. The results suggested that the flagging system programmed in the H-1 is useful for the diagnosis and follow-up of leukemia.

Blastomeres↗

Induction of suppressor T cells by intravenous administration of monoclonal anti-I-A antibody.

Intravenously administered monoclonal anti-I-A antibodies successfully induced suppressor T (Ts) cells specific for alloantigen-specific delayed-type hypersensitivity (DTH) responses in mice. These Ts cells exerted their effects in the effector phase and had no H-2 restrictions. Phenotypic analysis revealed L3T4 antigens on their cell surface but failed to reveal Lyt-2 antigen. Ts cell activity was abrogated by a 30-min incubation with the anti-I-A antibodies used for Ts cell induction. Incubation in the anti-I-A-antibody-coated plate also abrogated the Ts cell activity. Since anti-I-A antibody is idiotypic for the I-A antigen, it is suggested that these Ts cells might express antiidiotypic receptors for I-A antigens. These findings are considered to be consistent with previous observations of hapten-specific systems, in which antiidiotypic Ts cells are inducible by idiotypic antibodies.

Animals↗

Purification and characterization of a thiol-protease from Bacteroides gingivalis strain 381.

A protease from the culture supernatant of Bacteroides gingivalis 381, which hydrolyzes the chromogenic substrate Na-benzoyl-DL-arginine-p-nitroanilide (BAPNA), was partially purified by ammonium sulfate precipitation, gel filtration, and anion exchange chromatography. The molecular weight of this protease was determined by SDS-PAGE to be ca. 49,000. The optimum pH was around 7.6. The protease was stable at neutral pH and up to 40 degrees C. The isoelectric point was 4.9. The enzyme activity was enhanced by dithiothreitol, L-cysteine, and 2-mercaptoethanol and inhibited by p-chloromercuribenzoic acid, N-ethylmaleimide, and iodoacetic acid.

Bacterial Proteins↗

Taxonomic study of spirochetes isolated from human periodontal lesions.

Nineteen strains of spirochetes obtained from subgingival plaque of 19 patients with advanced periodontitis were studied morphologically, biochemically, and genetically and compared with type strains of Treponema denticola and Treponema socranskii. The results showed that 16 strains which biochemically resembled T. denticola could be divided into two groups based on G + C content and DNA homology. Two isolates appeared to belong to the T. socranskii species. One intermediate size isolate did not fit any known Treponema species.

Adult↗

Effects of habitual alcohol intake and cigarette smoking on the development of hepatocellular carcinoma.

To study the effects of habitual alcohol intake and cigarette smoking on the latency period for the development of hepatocellular carcinoma (HCC), 455 patients with HCC were analyzed with respect to age at diagnosis. They were divided into hepatitis B virus (HBV) positive and negative patients based on HbsAg and high titer anti-HBc in serum. HBV-positive and negative HCC patients were further subdivided into four subgroups based on the history of drinking more than one small bottle of Japanese "sake" or its equivalent per day for more than 10 yr and the history of smoking more than one cigarette per day for more than 10 yr. Among HBV-positive HCC patients, the average age of those with a drinking and a smoking habit (50 +/- 10 yr) was younger compared with that of patients with a drinking habit but without a smoking habit (56 +/- 14 yr, not significant, NS), of those who were smokers and nondrinkers (55 +/- 10 yr, NS) and of those who did not drink nor smoke (59 +/- 8 yr, p less than 0.005). Among HBV-negative HCC patients, patients with drinking and smoking habits (57 +/- 9 yr) were younger compared with those with a drinking habit without smoking (59 +/- 9 yr, NS), those who were smokers and nondrinkers (62 +/- 9 yr, p less than 0.005), and those who were nondrinkers and nonsmokers (63 +/- 12 yr, p less than 0.005). These data suggest that habitual alcohol intake may promote the development of HCC if the patients smoke cigarette regardless of the status of HBV seromakers.

Adult↗

Hemagglutinating activity of lipopolysaccharides from subgingival plaque bacteria.

Lipopolysaccharide (LPS) preparations from the Bacteroides species B. endodontalis, B. intermedius, B. denticola, and B. melaninogenicus and from Fusobacterium nucleatum, Haemophilus actinomycetemcomitans, Capnocytophaga gingivalis, and Eikenella corrodens directly agglutinated erythrocytes of some kinds of animals. LPSs from the Bacteroides species B. gingivalis, B. asaccharolyticus, B. corporis, and B. loescheii and from Capnocytophaga ochracea did not possess any hemagglutinating activity. Pretreatment of LPSs with lipase and phospholipase C completely eliminated the hemagglutinating activity. The hemagglutinating activity was also affected by human serum, saliva, colistin, and polymyxin B but was not affected by sugars, amino acids, EDTA, or proteolytic enzymes. The role of this hemagglutinating activity in colonization by these microorganisms of the periodontal region is discussed.

Dental Plaque↗

Obesity-related nonalcoholic fatty liver: CT features and follow-up studies after low-calorie diet.

The features on computed tomographic (CT) scans of nonalcoholic fatty liver were investigated in 24 patients with nonalcoholic fatty liver related to overweight. CT examinations were performed before and after 3 months of a low-calorie diet. The reversibility of fatty infiltration during diet therapy could be monitored by changes in appearance on repeated CT scans. Hepatic steatosis improved, as assessed from increases in attenuation values on CT scans after 3 months of the diet, and the improvement was accompanied by a decrease in the elevated serum glutamic-pyruvic transaminase activity. Hepatic fatty infiltration in these patients was not always uniform, and attenuation values in the right lobe of the liver were significantly lower than those in the left lobe. After the 3-month diet therapy, the mean liver volume was significantly reduced, while the spleen volume was unchanged. Two sequential CT examinations, performed before and after diet therapy, may be useful for evaluating obese patients with elevated serum transaminase activity.

Adult↗