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Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 649 records · Page 36Linked to original sources
PubMed1982

Physiological role of aldehyde dehydrogenase isozymes.

Our studies confirm that impaired acetaldehyde metabolism via a deficiency in aldehyde dehydrogenase isozyme composition plays an important role in the sensitivity to alcohol and the pathophysiology of alcoholism. Individuals with decreased activity of ALDH having less affinity to acetaldehyde in their liver, may be at a higher risk of acetaldehyde-related organ damage. In the case of Oriental subjects, the lack of ALDH I activity may also result in alcohol aversion. A protection of these individuals against alcoholism is suggested.

Alcohol Drinking↗
PubMed1981

The three-dimensional structure of the lysozyme produced by Streptomyces erythraeus.

Streptomyces erythraeus lysozyme is different in its amino acid composition, primary structure, and specificity from all other mammalian lysozymes. The structure of the crystalline enzyme has been determined by x-ray diffraction analysis to a resolution of 2.9 A using multiple isomorphous replacement. The primary structure of the enzyme is only partially known and therefore the electron density map has been fitted with all the atoms of the main polypeptide chain and some atoms of the side chain. The enzyme consists of three different domains, and about 18% of the structure has helical conformation. A comparison of the tertiary structure of the bacterial lysozyme with either the mammalian or phage lysozyme does not show any obvious similarities.

Amino Acids↗
PubMed1981

Mechanisms of enhancement of Epstein-Barr virus-induced transformation of peripheral blood lymphocytes by a tumor promoter, TPA, with special reference to lowering of cytotoxicity of T cells.

The mechanism of the previously observed enhancement of Epstein-Barr virus (EBV)-induced cell transformation of human lymphocytes by 12-0-tetradecanoyl-phorbol-13-acetate (TPA) was studied. A concentration of TPA (0.5 ng/ml) was used. In cultures of human cord blood lymphocytes infected with EBV in the presence of TPA, a larger number of EBV-associated nuclear antigen (EBNA)-positive and/or DNA synthesizing cells was observed than in the absence of TPA. In the virus-infected lymphocyte cultures of EBV-seropositive adult donors, in vitro regression of transformation, which is known to be caused by T lymphocytes, was suppressed by TPA, EBV-specific and -non-specific cytotoxicity of T cells generated in mixed cultures of peripheral blood lymphocytes (PBL) of seropositive adults and autologous lymphoblastoid cell line (LCL) cells was markedly lowered by the presence of TPA in the cultures, However, TPA had little effect on proliferation of T cells in stimulated cultures, and addition of TPA to the reaction mixture for the cytotoxicity test did not lower the cytotoxicity. These results suggest that TPA has an inhibitory effect on T cells which suppress EBV-transformation. THe effect on T cells, together with the direct promoting effect on proliferation of EBV-transformed cells, may explain the outcome of enhancement of EBV-induced LCL establishment from PBL of seropositive donors by TPA previously observed.

Adult↗
PubMed1981

Enhancement of outgrowth of EB virus-transformed cells from normal human peripheral blood by a tumor promoter, TPA.

Effect of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the establishment of lymphoblastoid cell lines (LCL) following spontaneous tranformation of B cells by Epstein-Barr virus (EBV) from peripheral lymphocytes of healthy EBV-seropositive adults was examined. In the lymphocyte culture with TPA (0.5 ng/ml), the frequency of establishment of LCL increased and the time required for appearance of transformation decreased. A larger number of EBV-positive cells in the peripheral blood were detected in the assay by co-cultures with cord blood lymphocytes in the presence of TPA than in the absence of it. The enhancement of LCL establishment by TPA was largely abolished in the culture with EBV neutralizing antibody-containing human umbilical cord serum. This suggests that the enhancement by TPA may be caused mostly by transformation of coresident B lymphocytes infected with active virus induced from the EBV genome-positive cells by TPA.

Adult↗
PubMed1981

A search for the Indianapolis-variant of human alcohol dehydrogenase in liver autposy samples from North Germany and Japan.

Human liver alcohol dehydrogenase (ADH) variants were screened in random autopsy specimens from 53 North German and 34 Japanese individuals. Based on pH-activity profile and electrophoretic pattern, only ADH2 and ADH3 variants were detected. In relatively fresh specimens, an "anodic band" or "pi-ADH" band was also observed. The recently reported new molecular forms collectively called "ADH Indianapolis" (Bosron et al. 1980) could not be demonstrated and therefore may be confined hitherto only to the American black population.

Alcohol Oxidoreductases↗
PubMed1981

Three phases in transformation of human lymphocytes by Epstein-Barr virus, as revealed by colony formation in soft agar.

Human cord lymphocytes were examined for colony formation in soft agar medium at various times after infection with Epstein-Barr virus (EBV). The transformation process could be divided into the following three sequential phases: (1) A pre-early phase, lasting about 10 hr post infection (pi), during which the number of transformed colonies was virus dose dependent. (2) An early phase, between about 10 and 60 hr pi, during which cloning efficiency was markedly lower than that of the pre-early phase. (3) A later phase, starting at about 60 hr pi, during which cloning efficiency was restored and the number of colony formers increased in an exponential fashion. EBV-associated nuclear antigen-positive cells first appeared at the beginning (12 hr pi) of the early phase and increased continuously thereafter. Increased DNA synthesis began at about 48 hr pi. These results suggest that the cloning efficiency of the infected cells changes during the transformation process, possibly reflecting altered cell sensitivity to agar.

Antigens, Viral↗
PubMed1981

Racial differences in biological sensitivity to ethanol: the role of alcohol dehydrogenase and aldehyde dehydrogenase isozymes.

Electrophoretic and kinetic studies of autopsy liver specimens from individuals of different racial groups revealed a polymorphism in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). About 85% of the Japanese livers had an atypical ADH and 52% of the livers an unusual ALDH. Only 13% of German liver specimens had the atypical ADH and none showed the unusual form of ALDH which lacks in the isozyme with low Km for acetaldehyde. Using hair roots as the source of ADH and ALDH, individuals showing sensitivity to ethanol were examined. Data on the distribution of phenotypes in random European and Japanese population as well as family studies suggest a direct relationship between the lack of low Km isozyme of ALDH and alcohol-induced biological sensitivity. Our findings suggest that the alcohol sensitivity quite common in individuals of Mongoloid origin might be due to delayed oxidation of acetaldehyde by an unusual type of ALDH.

Alcohol Oxidoreductases↗
PubMed1981

Negative inotropic effects and the hydrophobicity of beta-adrenergic blocking agents.

The negative inotropic actions of 12 beta-adrenergic blocking agents, all of which are aryloxyisopropylaminopropanols were studied in isolated left atria from reserpinized guinea-pig hearts. At concentrations between 10 and 1000 microM, all these drugs, with the exception of atenolol, reduced the contractile force by more than 40%. The following order of potency, as measured as ED40, was thus derived:propranolol, alprenolol, D-25, Ko 707, pindolol, oxprenolol, Kö 592, befunolol, metoprolol, Kö 1313, acebutolol and atenolol. On the other hand, the order of the octanol/water partition coefficient (P) was as follows: propranolol, alprenolol, D-25, Kö 707, Kö 592, oxprenolol, befunolol, acebutolol, metoprolol, pindolol, Kö 1313 and atenolol. A significant correlation was found between log l/ED40 and log P. The results indicate that hydrophobicity is a major determinant for the negative inotropic effects of these beta-adrenergic agents.

Adrenergic beta-Antagonists↗