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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 1,009 records · Page 56Linked to original sources
PubMed1979

Gene copy number effects in the mer operon of plasmid NR1.

The level of resistance to Hg2+ determined by the inducible mer operon of plasmid NR1 was essentially the same for three gene copy number variants in Escherichia coli, less in Proteus mirabilis, and intermediate in P. mirabilis "transitioned" to a high r-determinant gene copy number. Cell-free volatilization rates of radioactive mercury indicated increasing levels of intracellular mercuric reductase enzyme from low- to high-gene copy number forms in P. mirabilis and from low- to high-copy number forms in E. coli, but the additional enzyme in E. coli was effectively cryptic.

Enterobacteriaceae↗
PubMed1979

Hypersensitivity to Hg2+ and hyperbinding activity associated with cloned fragments of the mercurial resistance operon of plasmid NR1.

The region of plasmid NR1 concerned with resistance to Hg2+ and organomercurials consists of sequences found on restriction endonuclease fragments EcoRI-H and EcoRI-I. When both fragments were cloned together into a derivative of plasmid ColE1, the hybrid plasmid conferred properties indistinguishable from those of the parental plasmid, NR1: resistance to Hg2+ and to the organomercurials merbromin and fluoresceinmercuric acetate and the inducible synthesis of the enzyme mercuric reductase. When fragment EcoRI-I was cloned into plasmid ColE1, cells containing the plasmid was as sensitive to Hg2+ and organomercurials as plasmidless strains. When fragment EcoRI-H was cloned into ColE1, cells with the hybrid plasmid were hypersensitive to Hg2+ and organomercurials. This hypersensitivity was inducible by prior exposure to low, subtoxic Hg2+ or merbromin levels. It was associated with an inducible hyperbinding activity attributed to a gene governing Hg2+ uptake and found on fragment EcoRI-H (which contains the proximal portion of a mercuric resistance [mer] operon).

Cloning, Molecular↗
PubMed1979

Cloning and physical mapping of the dnaA region of the Escherichia coli chromosome.

The dnaA gene of Escherichia coli K-12, supposedly present in the deoxyribonucleic acid (DNA) of specialized transducing phase lambda i21 dnaA-2, was cloned onto plasmid pBR322. The new plasmid was named pMCR501. Physical analyses of DNAs of lambda i21 dnaA-2 and pMCR501 revealed the following. The lambda i21 dnaA-2 DNA retained the delta sr I lambda 1-2 and ninR5 deletions and imm21 substitution which were originally present in the parental phage. The size reduction was compensated for by the insertion-substitution segment (tna-dnaA region) in lambda i21 dnaA-2 DNA. The fractional size of this segment was approximately 7 megadaltons (Md), or 10 kilobases, which was found to be the sum of the tna insertion subsegment of ca. 3.5 Md and the dnaA substitution subsegment of ca. 3.5 Md. Phage P1-mediated transductional mapping between the dnaA46 and tna mutations gave a cotransduction frequency of 84%, corresponding to approximately 5 kilobases. Thus, it is strongly suggested that the dnaA gene resides in the lambda i21 dnaA-2 DNA. Cleavage mapping with the restriction endonuclease of pMCR501 DNA confirmed that it was constructed by excising a BamHI fragment of 4.29 Md, containing the 3.5-Md dnaA substitution segment, from the lambda i21 dnaA-2 DNA, inserting it into the sole BamHI cleavage site on pBR322.

Bacteriophage lambda↗
PubMed1979

Conditionally lethal amber mutations in the dnaA region of the Escherichia coli chromosome that affect chromosome replication.

Three amber mutations, dna-801, dna-803, and dna-806, were isolated by localized mutagenesis of the dnaA-oriC region of the chromosome from an Escherichia coli strain carrying temperature-sensitive amber suppressors. When the mutations were not suppressed at 42 degrees C, the cells did not grow and DNA synthesis was arrested. They were very closely linked to each other and to the dnaA46 mutation. The mutant phenotype of each strain was converted to the wild type by infecting the mutants with specialized transducing phase lambda i21 dnaA-2 but not with lambda i21 tna. Derivatives of lambda i21 dnaA-2, each of which carried the amber mutation dna-801 dna-803, or dna-806, converted the dnaA mutant phenotype to Dna+ but did not convert rhe amber mutants to the wild-type phenotype. E. coli uvrB cells were irradiated with ultraviolet light and infected with each of these phage strains. An analysis of proteins synthesized in the cells revealed that two proteins with molecular weights of 50,000 and 43,000 were specified by lambda i21 dnaA-2 but not by lambda i21 tna. When the ultraviolet-irradiated cells did not carry an amber suppressor, the derivative phage with the amber mutation invariably failed to produce the 43,000-dalton protein, but when the host cell carried supF (tyrT), the protein was produced. The 50,000-dalton protein was unaffected.

Bacterial Proteins↗
PubMed1979

Anti-androgen TSAA-291. VII. On the mechanism of anti-androgenic action of 16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one (TSAA-291).

The mechanism of anti-androgenic action of a steroidal compound, TSAA-291, was summarized and discussed in reference to its drug-designing and structure-activity relationship. The target of the drug-design was to obtain a substance which is inactive in androgenic activity and is capable of antagonistically competing with androgen for the receptor. With this intention, the androgen molecule was rendered with a steric hindrance influencing upon the functional 17 beta-hydroxy group. Introduction of a bulky group at the steroidal position-13 or -16 led to anti-androgenic properties. Intense steric hindrance by introducing an enormously bulky group or complete elimination of the 17 beta-hydroxy group rather decreased the anti-androgenic activity. Of these anti-androgens thus synthesized, TSAA-291 proved to be the most active in the anti-androgen assay and also antagonistic against the uptake of [3H]testosterone by the rat ventral prostate.

Androgen Antagonists↗
PubMed1979

[Treatment with NK 631 (new bleomycin analog) of oral and maxillofacial cancer (author's transl)].

Eight cases of malignant tumors of the head and neck were treated with NK 631 on a dosage schedule of 10 mg at a time 3 times weekly, by intravenous one-shot injection or intravenous drip infusion, to observe its therapeutic effects and adverse reactions. The treatment was assessed markedly effective in 3, moderately effective in 1 and ineffective in 4 of them. The treatment was also assessed moderately or markedly effective in 3 and ineffective in 2 out of squamous cell carcinoma cases. Hematologic findings, serum electrolytes and enzymologic findings were normal, but the pulmonary function examinations revealed a tendency for PaO2 to decrease slightly. In 1 case where frequent cough was observed, the cough was mitigated on withdrawal of the treatment. The adverse reactions that evolved included fever, alopecia, eruptions, nausea and vomiting, and pigmentation of the nail. To summarize these findings, the authors were impressed with NK 631 and that the agent would exert an excellent antitumor effect, compared with bleomycin, and that its effect would evolve at the early stage of its treatment. Fixed drug eruption was observed as an adverse reaction of this drug in 1 case; however, the adverse reactions of this bleomycin analog appear similar to those of its parent compound, bleomycin.

Adenocarcinoma↗
PubMed1978

Mapping of the resistance genes of the R plasmid NR1.

The drug resistance genes on the r-determinants component of the composite R plasmid NR1 were mapped on the EcoRI restriction endonuclease fragments of the R plasmid by cloning the fragments using the plasmid RSF2124 as a vector. The sulfonamide (Su) and streptomycin/spectinomycin (Sm/Sp) resistance genes are located on EcoRI fragment G of NR1. The expression of resistance to mercuric ions (Mer) requires both EcoRI fragment H and I of NR1. The expression of chloramphenicol (Cm) and fusidic acid (Fus) resistance requires EcoRI fragments A and J of NR1. The kan fragment of the related R plasmid R6-5 can substitute for Eco RI fragment J of NR1 in the expression of Cm and Fus resistance. The structural genes for Cm and Fus resistance appear to be a part of an operon whose expression is controlled by the same promoter.

Chloramphenicol↗
PubMed1978

Coexistence of bilateral pheochromocytoma and pancreatic islet cell tumor: report of a case and review of the literature.

A 14-year-old Japanese male with a previously undescribed combination of bilateral pheochromocytoma and an islet cell tumor of the pancreas is presented. The combination of endocrine neoplasms in this patient overlaps multiple endocrine neoplasia (MEN) Type 1 and Type 2. A total of 14 reported cases of MEN overlapping Type 1 and Type 2 is reviewed. Of the 14, 7 patients with acromegaly developed a paraganglioma(s), 2 patients with Sipple syndrome had a pituitary adenoma, and in the other 5 patients, an intestinal carcinoid or a pancreatic islet-cell tumor occurred in association with either a thyroid medullary carcinoma or a paraganglioma(s). We believe that the occurrence of MEN overlapping Type 1 and Type 2 is more than a fortuitous association, and can be explained on the basis of the neuroectodermal origin.

Adenoma, Islet Cell↗
PubMed1978

Bacteriophage lambda carrying the Escherichia coli chromosomal region of the replication origin.

A transducing phage lambdaasn was isolated. The late gene region of its genome was found to have been substituted by an Escherichia coli chromosomal segment containing the genes bgIR, bgIC, glmS, uncA, and asn. Restriction endonuclease cleavage mapping and electron microscopic analysis of the lambdaasn DNA revealed that the size of the bacterial segment is approximately 1.75 X 10(7) daltons, corresponding to about 26.4 kilobases. The circular DNA of lambdaasn was digested with restriction endonuclease EcoRI, diluted, and sealed with DNA ligase. When the reaction mixture was used to transform a recipient E. coli strain, a small plasmid of about 1 X 10(7) daltons (named pMCR115) was obtained. Restriction endonuclease cleavage mapping of pMCR115 and other evidence suggested that it contained the replication origin (oriC) of the E. coli chromosome.

Chromosomes, Bacterial↗