Activation of 2-acetylaminofluorene in the nuclei of rat liver.
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Biomedical subjects
Publications and source records attributed to E Hara.
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The interactions between Bifidobacterium bifidum N4 (B. bifidum) and Escherichia coli K-12 (E. coli) were investigated in their mixed cultures. Under conditions in which both bacteria grew well in their pure culture, B. bifidum inhibited the growth of E. coli even when the latter was inoculated at 10(4)-fold and preincubated for 41 hr. The inhibition in the mixed cultures appeared when the pH values were reduced below 4.6. When the lowering of pH was prevented by the addition of NaOH, no inhibition was observed. At the same initial pH of 6.5, lactic acid and acetic acid, metabolites of B. bifidum, had more inhibitory effect on the growth of E. coli than other aliphatic fatty acids. On the other hand, in the mixed cultures with E. coli, B. bifidum grew in the absence of its essential vitamins, riboflavin and pantetheine and, furthermore, aerobically.
Covalent binding of 2-acetaminofluorene[9-14C] with exogenous Torula yeast RNA and endogenous protein was investigated in liver microsome system in vitro. The binding to protein was 100 times higher than that to RNA. Requirement of NADPH, effectiveness of methylcholanthrene treatment, and inhibition by 7,8-benzoflavone suggest possible involvement of mixed-function oxidases in this binding. The binding was not due to contaminated cytosol in the microsome fraction. Addition of cytosol, sulfate ion, and ATP diminished the binding. Parallel experiments using N-hydroxy-2-acetaminofluorene[9-14C] denied major contribution of this metabolite to the binding of 2-acetaminofluorene in the microsome system. Ring-hydroxylated product was suggested as a possible metabolite for the binding.
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PURPOSE: To evaluate the clinical performance of a five-zone refractive multifocal intraocular lens (AMO, model MPC-25NB, Array). METHODS: We performed a retrospective clinical trial of 31 cataract patients (mean age 64.3 years). The parameters studied were intraoperative and postoperative complications, distance and near visual acuity, spectacle use, decreased number of corneal endothelial cells, contrast sensitivity, percentage of glare disability, near binocular vision, and depth of focus. RESULTS: Intraoperatively, iris damage occurred in two eyes (4.2%), vitreous loss in one eye (2.1%), and consecutive rupture of Zinn's zonule and vitreous in one eye (2.1%). Postoperatively, posterior capsule opacification was observed in two eyes (4.2%), temporary intraocular pressure increase in one eye (2.1%), and cystoid macular edema in one eye (2.1%). Uncorrected distance visual acuity of 20/40 or better was achieved by 34 of 37 eyes (91.9%) with less than 1.5 diopters of preoperative keratometric astigmatism; best corrected distance acuity of 20/20 or better was achieved by 41 of 45 eyes (91.1%). Near visual acuity with distance correction of 20/40 or better was achieved by 29 of 43 eyes (67.4%). These data were compared retrospectively with data from control patients who received monofocal lenses, and no significant differences in the decreased number of corneal endothelial cells were found. Mean contrast sensitivities were within normal range for all spatial frequencies. Percentage of glare disability and near binocular vision were within normal limits. CONCLUSIONS: Eyes implanted with the five-zone refractive multifocal lens showed better near visual acuity than control eyes and compared favorably in other aspects of visual function, indicating that these lenses are effective and safe.
Interleukin-12 (IL-12) is a heterodimeric cytokine. In order to transduce both cDNAs for p35 and p40 of IL-12 in the tumor cells, a polycistronic retroviral vector was constructed by inserting the internal ribosome entry site gene of encephalomyocarditis virus between two cDNAs. On the other hand, two cDNAs were sequentially transfected in the tumor cells. Both polycistronic gene transfectants and double transfectants produced biologically active mouse IL-12. IL-12-expressing tumor cells were all rejected in syngeneic mice, and induced cytotoxic T lymphocyte activity. The capacity to induce anti-tumor memory may depend on the amount of IL-12 produced by the transfectants, because the relatively higher IL-12 producer tumor cell line induced the anti-tumor memory in the rejected mice, but the lower producer did not.
Human promyelocytic leukemia (HL-60), human squamous carcinoma (HSC-2, HSC-4, NA) and rat pheochromocytoma (PC-12) cell lines consumed nonpolar (Leu, Ile, Val, Cys, Met, Phe), neutral polar (Gln, Ser, Thr, Tyr) and basic polar amino acids (Arg, Lys, His), whereas they produced nonpolar (Gly, Pro, Ala) and acidic polar amino acids (Glu). The consumption rate of Ser and Arg by HL-60 cells was significantly higher than that of other cell lines. During apoptosis of HL-60 cells induced by either sodium ascorbate, sodium 5,6-benzylidene-L-ascorbate (SBA) or dopamine, the consumption of nonpolar and polar amino acids (neutral or acidic) generally declined, except for Cys, Met and Arg, whereas the production of Gly and Glu was slightly increased. Since the intracellular concentration of cGMP was not significantly changed before and after ascorbate treatment, nitric oxide might not be involved in the ascorbate-induced apoptosis. The present data demonstrates that consumption rate of nonpolar and polar amino acid, whether neutral, acidic or basic, was reduced almost evenly during the apoptosis induction. This suggests that apoptosis-associated changes in the amino acid utilization might not be significantly affected by ATP depletion, which might be caused by mitochondrial dysfunction.
Possible changes in the intracellular concentrations of amino acids and polyamines were investigated during the apoptosis of human promyelocytic leukemic HL-60 cells. Treatment of HL-60 cells with sodium 5,6-benzylidene-L-ascorbate (SBA) or sodium ascorbate induced apoptotic cell death characterized by chromatin condensation, nuclear fragmentation, loss of microvilli, and production of numerous vacuoles and apoptotic bodies. The apoptosis was accompanied by a significant increase in the intracellular concentration of almost all neutral and basic amino acids (regardless of their polarity). On the other hand, the concentration of glutamic acid, the most abundant amino acid in the cells, was significantly reduced. These data suggest the reduced amino acid utilization and possible membrane impairment, especially in SBA-treated cells. Among three major polyamines, the intracellular concentration of putrescine rapidly declined, whereas that of spermidine and spermine was almost unchanged during apoptosis. Conversely, the concentration of putrescine, but not that of spermidine and spermine, was significantly increased during the chemically-induced carcinogenesis of mouse liver tissue. The present study demonstrates that the putrescine level is the most sensitive to the proliferation capability of the cells, among three polyamines, and provides an early marker for apoptosis and proliferation.