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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 901 records · Page 50Linked to original sources

Infection with delta agent in Japan.

It is estimated that approximately 70 to 80% of the world's HBsAg carriers live in Southeast Asia, but studies of delta infection in this area are still limited. We studied 323 HBsAg seropositive patients in Japan, and 4 (1.2%) of them were found to be positive for anti-delta antibody, with none positive for delta antigen. These four patients did not belong to the known high-risk groups for delta infection. One HBeAg positive female gave birth to a baby girl, and perinatal transmission of hepatitis B virus and delta was successfully blocked by a combination of hepatitis B immunoglobulin and vaccine. This study in the Tokyo-Chiba area showed delta infection, though low in frequency, among ordinary Japanese citizens. It has been reported that delta antigen is highly infectious to HBsAg carriers and that its infection will cause severe liver damage. Once introduced, it could become epidemic among non-drug users in a country where hepatitis B virus infection is endemic. At this moment, the only way of preventing such a disaster appears to be to reduce the number of chronic carriers by interruption of vertical transmission.

Adolescent↗

[Development of 1,2-dimethylhydrazine-induced colonic neoplasia in rats and changes in cellular proteins of colonic mucosa].

Development of 1,2-dimethylhydrazine (DMH) induced colonic neoplasia were studied using male Wistar rats given 120 mg DMH per kg s.c. weekly for 5 weeks. During the course of colon carcinogenesis, changes in cellular proteins of colonic mucosa were analysed by two-dimensional gel electrophoresis. Rats were sacrificed just before and at 10, 15 and 20 weeks after the initial DMH treatment together with controls. Incidence and number of colorectal tumors gradually increased. At the 20th week, colon carcinoma was found in every rat. Most tumors (92%) were found in the major flexure and the distal colon and rectum, while only 1% and 7% were found in the cecum and proximal colon, respectively. Histologically, most (92%) were classified as well differentiated or moderately differentiated adenocarcinoma. Eighty-five percent of the tumors were semipedunculated or sessile without depression, and the remainder were sessile with depression. All of the latter were carcinomas with invasion to the submucosa or further. Two-dimensional gel electrophoresis revealed 180 spots in cellular proteins before and after the initial treatment. Three new spots appeared and four spots greatly increased during the course of carcinogenesis, while one spot disappeared. The above results suggest that the appearing and increasing spots may be associated with cancer and that the disappearing spot may be associated with the normal colon.

1,2-Dimethylhydrazine↗

Gross anatomic features of hepatocellular carcinoma from three disparate geographic areas. Proposal of new classification.

A comparison of the gross pattern of hepatocellular carcinoma (HCC) was made using autopsy material from Japan (378 cases), the United States (90 cases), and South Africa (61 cases). The tumor could be placed in three major gross patterns only if subcategories of each were created. The common major patterns were expanding, spreading, and multifocal. There was a relationship of gross pattern to the presence or absence of prior liver disease, and there were differences in frequency of occurrence of the various gross types in the material from the above-mentioned countries.

Aged↗

Differentiation of cultured epidermal keratinocytes related to sterol metabolism and its retardation by chemical carcinogens.

The amount of 5 beta-cholest-7-en-3 beta-ol of mouse dorsal skin was increased after parturition until 10 days of age, reaching a maximum 5 beta-cholest-7-en-3 beta-ol/5-cholesten-3 beta-ol ratio of 0.43. [2-14C]Acetate was incorporated almost exclusively into 5-cholesten-3 beta-ol in the basal cell culture of epidermal keratinocytes. However, when the concentration of calcium was changed from 0.07 to 1.9 mM to induce terminal differentiation of keratinocytes, a definite amount of radioactive acetate was incorporated into 5 beta-cholest-7-en-3 beta-ol. The extent of the incorporation was increased at least until 72 h after changing medium, and the ratio of radioactive 5 beta-cholest-7-en-3 beta-ol/radioactive 5-cholesten-3 beta-ol was constantly increased in this period, indicating that the accumulation of 5 beta-cholest-7-en-3 beta-ol in the cell is concomitant with the differentiation of the cell. Pretreatment with chemical carcinogens such as 7,12-dimethylbenz[a]anthracene and 20-methylcholanthrene inhibited the incorporation of radioactive acetate into 5 beta-cholest-7-en-3 beta-ol in the high calcium medium at least for the initial 24 h. After that, the incorporation was gradually restored to the normal level. Pretreatment with a tumor promoter, such as 12-O-tetradecanoyl-phorbol 13-acetate, however, did not inhibit the incorporation. Thus, sterol metabolism is suggested to be a useful indicator for differentiation of epidermal keratinocytes.

9,10-Dimethyl-1,2-benzanthracene↗

Purification of cytochrome P-450 catalyzing 25-hydroxylation of vitamin D3 from rat liver microsomes.

Cytochrome P-450 catalyzing 25-hydroxylation of cholecalciferol (cytochrome P-450 cc25 ) was purified from rat liver microsomes based on its catalytic activity at each purification step. The specific cytochrome P-450 content of the final preparation was 15.1 nmol/mg of protein. Reconstituted activity of 25-hydroxylation of cholecalciferol with the purified enzyme was 2.3 nmol/min/mg of protein, which was 4,300 times as high as that in microsomes. The minimum molecular weight of the enzyme was 50,000 based on SDS-polyacrylamide gel electrophoretogram. Amino terminal sequence of the P-450 cc25 was H2N-Met-Asp-Pro-Val-Leu-Val-. Immunochemical study showed that the purified P-450 cc25 was homogeneous and the cytochrome was immunochemically different from either cytochrome P-450(PB-1) or cytochrome P-448(MC-1).

Amino Acid Sequence↗

Purification and characterization of delta 4-3-ketosteroid 5 beta-reductase.

delta 4-3-Ketosteroid 5 beta-reductase was purified about 230-fold from 100,000 X g supernatant of rat liver homogenate using 7 alpha-hydroxy-4-cholesten-3-one as substrate throughout. The purified enzyme was electrophoretically homogeneous, and its molecular weight determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was 37,000 and that determined by gel filtration chromatography on calibrated Sephadex G-100 column was 37,200. The absorption spectrum of the purified enzyme showed only a peak at 276 nm due to aromatic amino acids, precluding the presence of a prosthetic group such as flavine in the molecule. The enzyme is highly labile in a low buffer concentration, but is markedly stabilized in the presence of 20% glycerol in 10 mM phosphate buffer. Higher buffer concentration such as 300 mM potassium phosphate buffer was also effective to prevent deterioration in the absence of glycerol, but the effect was somewhat lower compared to glycerol. The purified enzyme showed the activity toward a variety of substrates including testosterone, cortisol, cortisone, progesterone, 4-androstene-3,17-dione, 7 alpha-hydroxy-4-cholesten-3-one, and 7 alpha,12 alpha-dihydroxy-4-cholesten-3-one. The optimal pH for the 5 beta-reduction of 7 alpha-hydroxy-4-cholesten-3-one was 7.4, and the cofactor required for the reaction was NADPH, while NADH revealed no effect. The enzyme activity was inhibited by p-chloromercuribenzoate, but its inhibition was prevented by the presence of a reduced form of glutathione.

Animals↗

[The response of ovarian function to HMG-HCG and bromocriptine therapies in hyperprolactinemic patients].

Plasma hormonal changes were analysed in patients with hyperprolactinemia who conceived following Bromocriptine therapy. Following the administration of HMG-HCG and Bromocriptine, serial plasma samples were collected from the cases. Plasma levels of FSH, LH, prolactin (PRL), estrone (E1), estradiol (E2), 17-hydroxyprogesterone (17-P), 20 alpha-dihydroprogesterone (20 alpha-P), progesterone (P) were determined simultaneously using specific radioimmunoassays. Pretreatment PRL levels, 180--420 ng/ml, were normalized by 7.5--12.5 mg/day of Bromocriptine treatment causing a rapid decrease in plasma PRL, reaching a plateau within several days. The first LH surge at midcycle after the start of the Bromocriptine treatment was established at 10--50 days. In the patients the first mid-cycle LH surge was observed, but the luteal phase was definitely short, as demonstrated by plasma progestins levels. The results from the present longitudinal studies on hyperprolactinemia revealed characteristic changes accompanied by the restoration of the hypothalamic-pituitary-ovarian function during the treatment period.

Adult↗

Polymorphism of human liver alcohol dehydrogenase: identification of ADH2 2-1 and ADH2 2-2 phenotypes in the Japanese by isoelectric focusing.

Liver homogenate-supernatants from most Japanese exhibit an "atypical" pH optimum for ethanol oxidation at pH 8.8 instead of 10.5, the "typical" pH-activity optimum. It has been proposed that atypical livers contain alcohol dehydrogenase isozymes with beta 2 subunits while typical livers contain isozymes with beta 1 subunits, both produced by the ADH2 gene. Because it is difficult to differentiate the atypical ADH2 2-2 phenotype from the ADH2 2-1 phenotype by starch gel electrophoresis, an agarose isoelectric focusing procedure was developed that clearly separated the atypical Japanese livers into two groups, A1 and A2. The beta beta isozymes in A1 and A2 livers were purified. Type A1 livers contained a single beta beta isozyme with an atypical pH-rate profile; it was designated beta 2 beta 2. Three beta beta isozymes were isolated from A2 livers, two of which corresponded to beta 1 beta 1 and beta 2 beta 2. A third, absent from the typical and the atypical A1 livers, had an intermediate mobility; it was designated beta 2 beta 1. Type A1 livers are, therefore, the homozygous ADH2 2-2 phenotype, and type A2 livers, the heterozygous ADH2 2-1 phenotype. The ADH2 2-2 phenotype was found in 53% of 194 Japanese livers, and the ADH2 2-1 phenotype, in 31%. Accordingly, the frequency of ADH2(2) was 0.68.

Adult↗

Bacteriological study of transhepatically aspirated bile. Relation to cholangiographic findings in 295 patients.

The purpose of this study was to elucidate the frequency of bacterial infection of intrahepatic bile in relation to biliary tract pathology. Bile was aspirated during percutaneous transhepatic cholangiography, with or without combined biliary tract drainage, and subjected to bacteriological investigations in 295 patients with various hepatobiliary diseases. Bile was infected in 89% of the 92 patients who had high fever and were on antibiotics at the time of study. Positive cultures were obtained in 39% of the patients who were not so ill as to require antibiotics. The overall incidence of biliary infection was 90% in bile duct stones, particularly high in patients with primary intrahepatic stones, regardless of the presence of stones in the common bile duct, and in patients who had dilation of the common bile duct, presumably due to obstructive involvement of the ampulla of Vater. E. coli and Klebsiella were the most frequent among the aerobic species isolated, and mixed infection involving these organisms was common. Anaerobes were much less frequent, always mixed with aerobes, but positive cultures would increase with more rigorous anaerobic conditions for culture. Duodenal fluid collected simultaneously did not always grow the same microorganisms, but showed a 86-87% coincidence with intrahepatic bile in terms of positive or negative cultures. It is recommended that bile be cultured at the time of percutaneous transhepatic cholangiography.

Ampulla of Vater↗

Chronic portal-systemic encephalopathy with normal portal vein pressure possibly due to noncirrhotic portal fibrosis.

This is the report of a 50-year-old man with a more than 20-year history of chronic progressive portal-systemic encephalopathy. Liver tests were normal except for increased serum ammonia and indocyanine green plasma retention. The liver pathology was compatible with idiopathic portal hypertension or noncirrhotic portal fibrosis, demonstrating localized surface nodularity and portal fibrosis. Percutaneous transhepatic catheterization of the portal vein revealed near top normal portal vein pressure and a large shunt connecting the left gastric or superior mesenteric vein and the left renal vein. Presumably, the patient had portal hypertension in the past and formation of a short, large-caliber shunt between the portal system and the renal vein effectively decompressed the portal circulation.

Catheterization↗

Morphological changes in the bacterium Bacteroides melaninogenicus subspecies melaninogenicus isolated from the human mouth and grown in culture without added blood components.

Striking polymorphism in the cellular morphology could be induced by removal of blood components from the liquid growth medium, but the cells of Bacteroides gingivalis and B. melaninogenicus subspecies intermedius did not exhibit polymorphism when grown under these conditions. The major changes observed with light microscopy were an increase in cell size and extreme polymorphism. Electron microscopy of the polymorphic forms of B. melaninogenicus subspecies melaninogenicus strains showed that such cells lacked both the outer cell membrane and peptidoglycan layer. Serum promoted the growth of these strains, suggesting that some blood component is either conducive to the synthesis of the cell wall or masks an unknown inhibitor for cell-wall synthesis contained in the medium.

Bacteroides↗

Reduction of portal vein pressure with the enlargement of portal-systemic shunts: observation made in one patient.

Whether portal vein pressure is reduced as spontaneous portal-systemic shunts are enlarged has long been disputed. We measured portal vein pressure directly by percutaneous transhepatic catheterization in one patient with cirrhosis at a 4-year interval, and demonstrated a significant reduction in portal vein pressure that had occurred along with enlargement of a collateral paraumbilical vein and splenorenal shunt during this period.

Catheterization↗