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Biomedical subjects

K Okuda

Publications and source records attributed to K Okuda.

At least 703 records · Page 39Linked to original sources

The role of autoreactive T-cell hybridomas from autoimmune model mice.

Autoreactive IL-2-producing T-cell hybridomas were established from New Zealand Black and White (B/W) F1 and MRL/1 mice. In B/WF1 mice the frequency of IL-2-producing hybridomas increased with age. It is necessary for the cells to recognize autologous MHC molecules in order to release IL-2. Inoculation of hybridoma cells into several mouse strains via the footpad produced significant swelling responses in an H-2-restricted manner. Finally, several autoimmune abnormalities were induced in naive H-2-compatible mice by i.v. inoculation of certain hybridoma cells. These results demonstrate that self-MHC molecule recognition by T cells plays an important role in the development of autoimmunity.

Aging↗

Effect of 15-deoxyspergualin on experimental organ transplantation.

DSPG had a definite but relatively feeble immunosuppressive effect in rats undergoing heterotopic heart transplantation and in dogs after renal transplantation. The drug was toxic in both species, although less so in rats. In dogs, synergistic interactions with cyclosporine and steroids were not evident.

Animals↗

Amelioration of normothermic canine liver ischemia with prostacyclin.

A model of hepatic ischemia was developed in dogs using a pump-driven splanchnic-to-jugular vein bypass during crossclamping of the portal triad. An LD50 was established with three hours of ischemia. PGI2 given for one hour before the ischemic insult ameliorated the ischemic injury and increased survival.

Animals↗

Autoimmune interstitial nephritis induced in inbred mice. Analysis of mouse tubular basement membrane antigen and genetic control of immune response to it.

Purified murine tubular basement membrane (TBM) antigen (molecular weight, 32,000) induced interstitial lesions in Brown Norway (BN) rats. TBM antigen prepared from mice of 3 inbred strains--BALB/c, C3H/He, and C57BL/6--and outbred ddY mice possessed both antigenicity and nephritogenecity. Using these TBM antigens, the roles of humoral and cellular immunity in the development of interstitial nephritis (IN) and the genetic control of the induction of IN in inbred mice were investigated. BALB/c mice were highly susceptible to IN and showed a high antibody response and a high lymphocyte proliferative response to syngeneic and allogeneic TBM antigen, whereas C57BL/6 mice did not. C3H/He mice, in which minimal interstitial lesions developed, showed a high antibody response but a low proliferative response of T cells to TBM antigen. TBM antigen sensitized T cells induced interstitial lesions, but anti-TBM antisera did not do so. Thus, the development of IN seemed to be related closely to cellular immunity. Further studies with their hybrids, backcrosses, congenic mice, and recombinant mice suggested that the induction of IN and the immune response to TBM antigen are controlled by 1 or a few dominant genes, whose loci are within, or closely linked to, the H-2 complex.

Animals↗

Changing incidence of hepatocellular carcinoma in Japan.

A trend in the incidence of hepatocellular carcinoma (HCC) in Japan was studied from the data of the Osaka Cancer Registry (population, 8,512,351 in 1981) for the period of 1963-1983, the Vital Statistics of Japan, Ministry of Health and Welfare, and the Japan Autopsy Registry which contained 594,132 individually filed cases in the 26-year period from 1958 to 1983. Both cancer registry data and autopsy records showed a more than 2-fold increase in HCC incidence, particularly in the last 10 years or so, among males and a less pronounced increase in females. The same trend was borne out by the cancer registries of Nagasaki City and Miyagi Prefecture and the Vital Statistics. When studied with the autopsy data, it was found that the numbers of autopsies for cirrhosis without HCC and autopsies for HCC (with and without cirrhosis) were about the same in 1958-1961 and that currently (1980-1983) the latter is about 2 times the former. As one of the possible causes of increase in HCC incidence other than prolonged survival of patients with cirrhosis, chronic non-A, non-B hepatitis is discussed.

Age Factors↗

Purification and characterization of cholesterol 7 alpha-hydroxylase from rat liver microsomes.

Cholesterol 7 alpha-hydroxylase (cholesterol, NADPH: oxygen oxidoreductase, 7 alpha-hydroxylating, EC 1.14.13.17) was purified from liver microsomes of cholestryramine-fed male rats by using high-performance ion-exchange chromatography. The purified enzyme showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Mr = 52,000), and its dithionite-reduced CO complex exhibited an absorption maximum at 450 nm. The specific content of the enzyme was 9 nmol of cytochrome P-450/mg of protein. Upon reconstitution with NADPH-cytochrome P-450 reductase, the enzyme showed a high activity of cholesterol 7 alpha-hydroxylation with the turnover number of 50 min-1 at 37 degrees C. The reaction was inhibited neither by aminoglutethimide nor by metyrapone, but inhibited markedly by iodoacetamide and disulfiram. The reaction was also inhibited significantly by CO. The enzyme catalyzed hydroxylation of cholesterol with strict regio- and stereoselectivity and was inert toward other sterols which are intermediates in the conversion of cholesterol to bile acids, i.e. 7 alpha-hydroxy-4-cholesten-3-one (12 alpha-hydroxylation), 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol (25-hydroxylation), and taurodeoxycholate (7 alpha-hydroxylation). Unlike other cytochromes P-450 isolated from rat liver microsomes, the enzyme showed no activity toward testosterone and xenobiotics such as 7-ethoxycoumarin and benzo[a] pyrene. The NH2-terminal amino acid sequence of the enzyme was Met-Phe-Glu-Val(Ile)-Ser-Leu-, which was distinct from those of any other cytochromes P-450 of rat liver microsomes hitherto reported. These results indicate that the enzyme is a novel species of cytochrome P-450 so far not isolated from liver microsomes.

Amino Acid Sequence↗

Liver-specific F antigen in the serum of patients with liver diseases and the detection of early stage hepatocellular carcinoma.

Liver-specific F antigen was detected in serum using human-specific guinea pig antiserum, in 75 out of 121 patients with various liver diseases. The antigen was detectable in most of the patients (86.7%) with hepatocellular carcinoma, and the levels of F antigen were often high in these patients. There was no correlation between the levels of F antigen and alpha-fetoprotein. Temporal changes of serum F antigen level were also studied in patients with hepatocellular carcinoma. In 8 out of 13 patients with hepatocellular carcinoma, serum F antigen level remained continuously high, and in these patients, it had been significantly high for several months to one year before hepatocellular carcinoma became clinically detectable. Extracts of hepatocellular carcinomas obtained by necropsy was examined for the presence of F antigen, and it was found that most of hepatocellular carcinomas contained the human-specific determinant of F antigen, but lacked the species non-specific determinant of the antigen. The use of human-specific anti-F antiserum may facilitate early detection of hepatocellular carcinoma in some patients.

Adult↗