The optimum pH of serum alkaline phosphatase (alk. P., EC 188.8.131.52) was investigated in adult male rats, mice and rabbits after fasting or after the induction of cholestasis by a single oral dose of 200 mg/kg alpha-naphthylisothiocyanate (ANIT). The nature of serum alk.P. was also studied with the inhibitory effects of three L-amino acids (L-phenylalanine, L-homoarginine and L-cystine) and by electrophoresis. In the rat, fasting as well as ANIT-treatment shifted the optimum pH of alk.P. from 9.4 to 10.0 due to a decrease in intestinal isoenzymes or due to newly appeared liver isoenzymes, while no shifting occurred in mouse and rabbit.
The effects of various inducers on the activities of drug-metabolizing enzymes including aflatoxin B1 activation were studied in Syrian golden hamsters. Activity for aflatoxin B1 was determined by aflatoxin B1-DNA adducts formation. The treatments of hamsters with 3-methylcholanthrene, α-naphthoflavone and benzo(a)pyrene elevated markedly the activity for aflatoxin B1 by 2460, 1380 and 450%, respectively. Phenobarbital induced slightly and isosafrole and ethanol did not induce the activity for aflatoxin B1. Pregnenolone-16α-carbonitrile decreased aflatoxin B1 activation to 51% of that of the non-treated animals. These results were in good accordance with the induction rate of a form of cytochrome P-450(P-450AFB) which has potent activity to aflatoxin B1. Characteristics in the induction of mixed function oxidases of hamsters by these inducers, especially in respect to benzo(a)pyrene metabolizing enzyme, seemed to differ from those of rats. These results suggest that the activity for aflatoxin B1 in hamster is inducible by 3-methylcholanthrene-type inducers and that hamster is a suitable animals model to study the mechanism of aflatoxin B1-hepatocarcinogenesis.
Conceptual methods of setting national ambient air quality standards in Japan are discussed in comparison with case of occupational exposure limits in industrial health. The air quality standards are set by the national government, based on recommendations of the Central Council on Countermeasures for Environmental pollution, in conformity with the Fundamental Act on Countermeasures for Environmental Pollution. In setting the standard values, thresholds and the existence of specific groups in the people with high susceptibility to a certain pollutant are taken into account. The standards are set following minimum effect reports in three branches of health effect studies on air pollution: animal experiments, human exposure, and epidemilogy. Safe levels take into account the absence of effects, suspicion of irreversible effects, dwellings of the elderly/infant/sick, epidemiologic growth of nonspecific diseases such as asthma, and so on. Under these conditions, air quality standards become far severer than in the case of industrial health limits.
Micromanipulation of embryos provide a new and valuable biological tool for animal agriculture and medical fields. Current techniques for embryo manipulation are in practice but some of techniques is still way off for application. The present status in new biotechnology appling to animal science and medicine is reviewed and its future is also discussed.
Recent advances in biotechnologies have made it possible to manipulate mammalian embryos. This technology in combination with the recombinant DNA technology provides embryos with new and purpose oriented genetic information. Subsequent embryo transfer to the pseudopregnant females also makes these manipulated embryos develop to term as transgenic animals. Transgenes integrated in the transgenic animals are usually transmitted to their off-spring according to the Mendel's Law. Therefore, once we obtained a particular transgenic animal, we could rear them as a strain non-existent in nature. In this report, methods of producing transgenic mouse and a few examples which were applied to the analyses of biological functions are mentioned .
Expression of cytochrome P-450s, drug metabolizing enzymes, from their coding sequences in heterologous cells were developed and the enzymatically active P-450s were synthesized. cDNAs of various chimera or mutant P-450s were constructed and expressed. Thus, regions or residues important for the function of cytochrome P-450 were analyzed.
Several strains of human fibroblast were identified as good producers of human interferon-beta (HuIFN-β), amoung DIP-2 cell was one of the best. We have developed an improved microcarrier culture system for both the mass culture of such cells and the large scale HuIFN-β production. A routine pilot plant, and successively a large plant, have been accomplished for preparation, purification and preclinical or clinical trials of HuIFN-β. The purified and lyophilized HuIFN-β was assayed for its safety for clinical use under the regulation of the National Institute of Health of Japan. Using this HuIFN- preparation, the clinical trials on various viral diseases and malignant tumors were started from the middle of 1979. More recently, the Ministry of Health and Welfare approved this HuIFN-β as a new drug against melanoma, glioblastoma and chronic active B type hepatitis.