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Biomedical subjects

M Kuwano

Publications and source records attributed to M Kuwano.

342 records · Page 19Linked to original sources
PubMed1971

Growth inhibition and appearance of the membranous structure in Escherichia coli infected with bacteriophage fd.

Thirty-six mutants of fd, a virus that infects but does not kill Escherichia coli, were isolated; 35 mutants were categorized into six complementation groups. Abortive infection with mutants in genes 1, 3, 4, 5, and 6, but not in gene 2, produced a cessation of host cell growth, generally linked to low burst size and to the formation of aberrant intracytoplasmic membranous structures. The membranous structure was studied during infection with various phage and hosts. Appearance of the membranous structure was linked specifically to incomplete phage maturation at the cell membrane, rather than solely to the inhibition of host cell growth or to infection with mutant phage, since (i) in one host, cell growth was inhibited, but no membranous structure developed; and (ii) when antibody against virus was added to cells infected with wild-type phage, phage extrusion was inhibited, cell growth stopped, and the membranous structure once again developed.

Agar↗
PubMed1970

Ribonuclease V of Escherichia coli: susceptibility of heated ribosomal RNA and stability of R17 phage RNA.

Native ribosomal RNA anid inttact pliage R17 RNA are insensitive to attack by ribonuclease V, an exonucleolytic activity associated with ribosome movement on the substrate RNA. However, ribosomal RNA becomes a substrate when it is heated under conditions that make it a template for protein synthesis, and R17 RNA is attacked if it is either heated or fragmnented. Accessibility of the 5' terminus of an RNA molecule is probably inzcreased by heating or fragmnentation and may determine its susceptibility to ribonuclease V.

Coliphages↗
PubMed1970

Binding of adenosine 3':5'-cyclic phosphate to G factor of Escherichia coli, and its effects on GTPase, RNase V, and protein synthesis.

Unique among adenine nucleotides tested by filter binding assays, 3':5'-cyclic AMP binds to the G translocation factor. Binding is dependent on the presence of GTP, and is inhibited by GDP, by the analog 5'-beta,gamma-methylene GTP, and by the antibiotic fusidic acid. The cAMP seems to be released during the ribosome-dependent translocation of charged tRNA catalyzed by G factor. Bound cAMP inhibits GTPase and ribosome-associated degradation of messenger RNA, but does not inhibit protein synthesis. cAMP might thereby regulate the ratio of productive to degradative transits of ribosomes on messenger RNA, and this may account for some part of its profound effect on levels of specific bacterial messenger RNA species.

Adenine Nucleotides↗
PubMed1969

Ribonuclease V of escherichia coli. I. Dependence on ribosomes and translocation.

A new RNase activity, tentatively named RNase V, was found in cell-free extracts of E. coli. This activity requires ribosomes, G and T factors, tRNA, K(+) or NH(4) (+), Mg(2+), GTP, and a sulfhydryl compound to degrade poly U, poly A, T4 phage mRNA, or E. coli mRNA. RNase V is specific for mRNA; it does not attack ribosomal RNA. It is inhibited by antibiotics that decrease breakdown of mRNA in vivo, such as chloramphenicol and streptomycin, and by such agents as 5'-beta, gamma-methylene-guanosine triphosphate, and fusidic acid, which inhibit ribosome-dependent GTPase and translocation of ribosomes along mRNA. The evidence suggests that RNase V is either an integral part of the ribosome or is tightly associated with it, and that it selectively degrades mRNA in intact cells.

Anti-Bacterial Agents↗
PubMed1969

Mutations to spectinomycin resistance which alleviate the restriction of an amber suppressor by streptomycin resistance.

Unlike mutations to streptomycin resistance, which restrict the function of an SU II amber suppressor, mutations to spectinomycin resistance have no restrictive effect. Furthermore, mutations to spectinomycin resistance counteract the restrictive action of streptomycin-resistant mutations when combined in a single strain. The mutations to drug resistance, singly or in combination, do not themselves lead to any detectable suppressor activity. The effects on SU II are interpreted in terms of interactions between ribosomal elements.

Coliphages↗
PubMed1969

Phenotypic suppression by streptomycin of amber mutants in the ribonucleic Acid bacteriophage coat protein cistron.

After mutagenesis with nitrosoguanidine or ultraviolet light, 298 streptomycin high-resistant and 98 streptomycin high-dependent mutants were isolated from HfrC Su(-). They were tested for their ability to phenotypically suppress five different amber ribonucleic acid (RNA) bacteriophage mutants in the presence of streptomycin. The phage mutants are all in the coat protein, which is 129 amino acids long; the uracil-adenine-guanine codons were at the following positions: sus3 and amB2, 6; amB11, 50; amB21, 54; sus11, 70. Only sus3 and amB2 could be phenotypically suppressed by streptomycin; this was clearly demonstrated in nine mutant strains, seven str-HR and two str-HD. The suppression was always dependent upon added streptomycin and was dose-dependent in all cases. None of the mutants showed measurable suppression in absence of the drug. Among revertants to streptomycin independence from streptomycin-dependent strains that could show phenotypic suppression, most of those that were still resistant to streptomycin (10 mug or more) retained the capacity to show phenotypic suppression; whereas among those revertants sensitive to 10 mug of streptomycin or less, none retained the capacity. Eight different amber polar mutants (strong and weak) in gene 34 of phage T4 were also tested for pleiotypic suppression by streptomycin in all the streptomycin-resistant and -dependent strains isolated. No suppression was found in any of the 396 strains tested.

Journal Article↗
PubMedDate not supplied

Reversal of P-glycoprotein associated multidrug resistance by new isoprenoid derivatives.

To find a drug to overcome P-glycoprotein associated multidrug resistance, we synthesized 43 new isoprenoid derivatives. Ten compounds were effective in an in vitro assay with the human MDR-type resistant carcinoma KB/VJ-300 and MRP-type KB/VP-4 cell lines. One of the most effective compounds, N-5228 [trans-N,N'-bis(3,4-dimethoxybenzyl)-N-solanesyl-1,2-diaminocyclohexane, mol. wt 1100.481, was tested in P388/VCR-bearing mice. It showed a antitumor effect on MDR-type resistant tumor cells. Moreover, N-5228 potentiated the accumulation of [3H]vincristine in drug-resistant cells and blocked [3H]azidopine photoaffinity labeling of P-glycoprotein molecules in MDR-type resistant cell membranes. We think that N-5228 is promising as a lead compound in the screening of resistance reversing drugs for multidrug resistant cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Transcriptional upregulation of the human MRP2 gene expression by serine/threonine protein kinase inhibitors.

Transcriptional regulation by cellular signalling pathways of multidrug resistance proteins that pump anticancer drugs out of cells is one of key issues in the development of the multidrug resistance phenotype. In our study, we have used the reporter gene approach as well as determination of mRNA levels in two cancer cell lines of human origin, MCF-7 and A549, to study the regulation of multidrug resistance proteins 2 and 3 (MRP2 AND MRP3) by serine/threonine protein kinases. Since a prototypic PKC inducer, PMA, caused a marked upregulation of transcription from both human MRP2 and MRP3 promoters, a role for PKC isoforms in positive control of expression of these proteins could be postulated. Interestingly, broad-spectrum serine-threonine protein kinase inhibitors which also inhibit PKC, staurosporine and H-7, stimulated expression from the MRP2 promoter instead of inhibiting it. This effect was not seen for MRP3. MRP2 induction by staurosporine and H-7 was shown to have phenotypic consequences in whole cells, rendering them more resistant to etoposide and increasing their ability to export calcein through the plasma membrane. These results point to the involvement of serine/threonine protein kinases in negative regulation of the human MRP2 gene and to the necessity of testing novel anti-cancer drugs acting as protein kinase inhibitors with regard to their potential ability to induce multidrug resistance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMedDate not supplied

Altered drug sensitivities to anticancer agents in radiation-sensitive DNA repair deficient yeast mutants.

We studied whether cellular sensitivity to anticancer agents was correlated with a repair deficiency in three yeast epistasis groups of radiation sensitive mutants. All these mutants were hypersensitive to cisplatin and mitomycin C. By contrast, both rad51 and rad52 mutants deficient in double-strand breaks repair were hypersensitive to adriamycin and bleomycin, but the rad1 and rad10 mutants deficient in nucleotide excision repair were not. These results were confirmed by examining the cellular sensitivity of either revertants or strains carrying wild RAD+ protein expression plasmids to various drugs. Cellular damage by the above anticancer agents is discussed in relation to the DNA repair mechanisms.

Antineoplastic Agents↗