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Biomedical subjects

M Iwami

Publications and source records attributed to M Iwami.

At least 55 records · Page 3Linked to original sources

The oncogenicity of avian adenoviruses. IV. Confirmatory evidence for recombination between viral and cellular DNA sequences and repetition of the recombinant in cells of a tumor line.

On the basis of hybridization analyses with viral DNA fragments as probes, we previously concluded that, in DNAs of many fowl adenovirus type 1-induced rodent tumors, units consisting of viral DNA segments flanked on both sides by cellular DNA segments are repeated more than 100 times per diploid genome of cell. Molecular cloning of virus-cellular junction fragments and analyses of their sequence arrangement in the present study confirmed that the previous conclusion was basically correct.

Adenoviridae↗

Structure and organization of four clustered genes that encode bombyxin, an insulin-related brain secretory peptide of the silkmoth Bombyx mori.

Four genes encoding bombyxin have been located in a 14-kilobase Bombyx genomic DNA segment. All of these genes encode preprobombyxin, the precursor molecule for bombyxin, with the domain organization of signal peptide/B chain/C peptide/A chain. Bombyxins are classified as family A or B according to their sequence homology. Two genes, each belonging to a different family, are closely apposed to form a pair with opposite orientation, presumably forming a regulatory unit for transcription. Genomic Southern blot hybridization suggested that there are many such gene pairs in the Bombyx genome. Differences between bombyxin genes and vertebrate insulin-family genes indicate that different mechanisms operate in the evolution of invertebrate and vertebrate insulin-family genes.

Amino Acid Sequence↗

FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. I. Taxonomy, fermentation, isolation, and physico-chemical and biological characteristics.

FK409, a novel vasodilator with anti-platelet aggregation activity, has been isolated from the acid-treated fermentation broth of Streptomyces griseosporeus No. 16917, which was cultured on a medium containing NaNO3 for 4 days. FK409 was purified from the culture-filtrate by extraction with ethyl acetate after adjusting the pH to 3.0 with HC1, followed by silica gel chromatography. The molecular formula of this compound was determined to be C8H13N3O4. In vitro, FK409 showed a potent relaxation activity on noradrenaline induced contraction of rat aorta. In addition to the vasodilating activity, this compound also showed potent anti-aggregation activities towards rabbit platelets. In vivo, intravenously administered FK409 resulted in marked blood pressure lowering in rats.

Animals↗

New antitumor antibiotic, FR-900462. I. Taxonomy of the producing strain.

A new species of the genus Streptomyces, the proposed name of which is Streptomyces tokashikiensis sp. nov., is described. Soil isolate, strain No. 7124, produces a new antitumor antibiotic FR-900462. The organism is characterized by the presence of spores on the substrate hyphae. Strain No. 7124 is closely related to Streptomyces spiralis in morphological and cultural characteristics, but there are differences in spore surface, growth-permissible temperature, and carbohydrate utilization pattern. Therefore, it was decided to designate strain No. 7124 as a new species within the genus Streptomyces.

Antibiotics, Antineoplastic↗

Phorbol esters can persistently replace interleukin-2 (IL-2) for the growth of a human IL-2-dependent T-cell line.

A selected clone from an IL-2-dependent human T-cell line was persistently propagated in the presence of phorbol esters with the ability to activate protein kinase C (PKC), such as 12-O-tetradecanoylphorbol-13-acetate (TPA) or phorbol-12,13-dibutylate (PDBu). Thus, a TPA(PDBu)-dependent T-cell line, designated TPA-Mat, was established from IL-2-dependent T cells. The TPA-dependency of TPA-Mat was not lost during cultivation for more than a year in the presence of TPA, and TPA-Mat cells still showed IL-2-dependent growth. However, the TPA (PDBu)-dependent growth of TPA-Mat did not seem to be mediated by an autocrine mechanism of IL-2 or by any other growth factor production, because these factors were not detected in TPA-Mat cell supernatants. Therefore, the phorbol esters substituted for IL-2 and may be directly involved in transduction of growth signals in TPA-Mat cells. Although activity of PKC was down-regulated, messenger ribonucleic acid (mRNA) of the PKC beta-gene was detected in TPA-Mat cells cultured with PDBu. Furthermore, the growth of TPA-Mat cells was stimulated not only by phorbol esters but also by nonphorbol ester tumor promoters with the ability to activate PKC. These observations suggest that the sustained activation of PKC by the phorbol esters could induce continuous growth of the IL-2-dependent TPA-Mat cells.

Cell Line↗

Physiological analysis of bicozamycin high-producing Streptomyces griseoflavus used at industrial level.

Streptomyces griseoflavus, a bicozamycin-producing wild type strain and its high-producing one derived from it by multiple (greater than 15) mutagenic treatments, were analyzed physiologically and biochemically. The high-producing strain was characterized by: (1) An increased pool size of amino acids including leucine and isoleucine, precursors for bicozamycin synthesis, (2) an earlier and greater accumulation of intracellular ppGpp, (3) a more accentuated decrease in GTP pool size, (4) a higher specific activity of ornithine transcarbamylase which produces citrulline, (5) an increased ability to form aerial mycelium, and (6) an increased resistance to its own antibiotic. We propose that (1), (2) and (4) may be responsible for the high yields of bicozamycin and, possibly, of some other antibiotics produced by Streptomyces sp.

Amino Acids↗

FR-900520 and FR-900523, novel immunosuppressants isolated from a Streptomyces. I. Taxonomy of the producing strain.

A new subspecies of the genus Streptomyces, the proposed name of which is Streptomyces hygroscopicus subsp. yakushimaensis subsp. nov., is described. Soil isolate, strain No. 7238, produces the novel immunosuppressants, FR-900520 and FR-900523. The organism is characterized by its gray aerial mycelium color, hygroscopic spore mass and spiral spore chains with warty or spiny spore surfaces. It is nonchromogenic. Strain No. 7238 shows characteristics most closely related to Streptomyces antimycoticus and S. hygroscopicus, although there are differences in physiological characteristics and carbohydrate utilization. In terms of morphological characteristics, strain No. 7238 is different from S. antimycoticus, but resembles S. hygroscopicus. The differences are not sufficient to establish a new species. It would be most suitable to designate strain No. 7238 as a new subspecies within the species of S. hygroscopicus.

Immunosuppressive Agents↗

Occurrence of unmodified adenine and uracil at the first position of anticodon in threonine tRNAs in Mycoplasma capricolum.

Codon usage pattern in the threonine four-codon (ACN) box in Mycoplasma capricolum is strongly biased towards adenine and uracil for the third base of codons. Codons ending in uracil or adenine, especially ACU, predominate over ACC and ACG. This bacterium contains two isoacceptor threonine tRNAs having anticodon sequences AGU and UGU, both with unmodified first nucleotides. It would thus appear that ACN codons are translated in an unusual way; tRNA(Thr)(AGU) would translate the most abundantly used codon ACU exclusively, because adenine at the first anticodon position can, according to the wobble rule, pair only with uracil of the third codon position. The tRNA(Thr)(UGU) would mainly be responsible for translation of three other codons, ACA, ACG, and ACC. Anticodon UGU would also be used for reading codon ACU as a redundancy of tRNA(Thr)-(AGU), as deduced from the mitochondrial code where unmodified uracil at the first anticodon position can pair with adenine, cytosine, guanine, and uracil by four-way wobble. The tRNA(Thr)(AGU) has much higher sequence homology to tRNA(Thr)(UGU) from M. capricolum (88%), Bacillus subtilis (77%) and Escherichia coli (86%) than to tRNA(Thr)(GGU) from B. subtilis (66%) and E. coli (63%), suggesting that tRNA(Thr)-(AGU) has been derived from tRNA(Thr)(UGU), but not from tRNA(Thr)(GGU).

Adenine↗

A new antitumor antibiotic, FR-900482. I. Taxonomic studies on the producing strain: a new species of the genus Streptomyces.

A new species in the genus Streptomyces, for which the name Streptomyces sandaensis sp. nov. is proposed, is described. Soil isolate strain No. 6897 (FERM-P 7654), produces a new antitumor substance FR-900482. The strain has a gray to red spore mass color, Rectus Flexibilis to Retinaculum-Apertum spore chain morphology, smooth spores, and is nonchromogenic. Strain No. 6897 is closely related to Streptomyces aburaviensis and Streptomyces nitrosporeus. But, there are many differences in cultural characteristics and in the utilization of carbohydrates.

Antibiotics, Antineoplastic↗

FR-900452, a specific antagonist of platelet activating factor (PAF) produced by Streptomyces phaeofaciens. I. Taxonomy, fermentation, isolation, and physico-chemical and biological characteristics.

A PAF antagonist, designated as FR-900452, was isolated from fermentation products of Streptomyces phaeofaciens and the molecular formula was determined as C22H25N3O3S. The compound inhibited PAF-induced rabbit platelet aggregation with an IC50 of 3.7 X 10(-7)M, but was much less active against collagen-, arachidonic acid- or ADP-induced aggregation (IC50; 6.4 X 10(-5), greater than 10(-4) or greater than 10(-4)M, respectively).

Adenosine Diphosphate↗

A new antitumor antibiotic, chromoxymycin. I. Taxonomic studies on the producing strain: a new subspecies of the genus Streptomyces.

A new subspecies of the genus Streptomyces, for which the name S. libani subsp. rubropurpureus subsp. nov. is proposed, is described. Soil isolate, strain No. 6362, produces a new antitumor substance chromoxymycin. The strain has a gray or red spore mass color, spiral spore chains with smooth spores, is nonchromogenic, and utilizes most carbon sources. Strain No. 6362 is most closely related to S. libani, although there are differences in colorization of reverse colony and spore chain morphology between each other. Those differences are not enough to establish a new species. It is suitable to consider that strain No. 6362 is identified as a new subspecies in the species of S. libani.

Antibiotics, Antineoplastic↗

UGA is read as tryptophan in Mycoplasma capricolum.

UGA is a nonsense or termination (opal) codon throughout prokaryotes and eukaryotes. However, mitochondria use not only UGG but also UGA as a tryptophan codon. Here, we show that UGA also codes for tryptophan in Mycoplasma capricolum, a wall-less bacterium having a genome only 20-25% the size of the Escherichia coli genome. This conclusion is based on the following evidence. First, the nucleotide sequence of the S3 and L16 ribosomal protein genes from M. capricolum includes UGA codons in the reading frames; they appear at positions corresponding to tryptophan in E. coli S3 and L16. Second, a tRNATrp gene and its product tRNA found in M. capricolum have the anticodon sequence 5' U-C-A 3', which can form a complementary base-pairing interaction with UGA.

Biological Evolution↗

Studies on WB-3559 A, B, C and D, new potent fibrinolytic agents. I. Discovery, identification, isolation and characterization.

WB-3559 A, B, C and D were produced by a bacterium which was classified as a member of the genus Flavobacterium. These compounds were purified by solvent extraction followed by chromatography on silica gel and then isolated by HPLC. The chemical structures were determined on the basis of chemical and spectroscopic evidence as in the succeeding papers. WB-3559 A, B, C and D stimulated rabbit plasma euglobulin clot lysis time. A chemically synthesized compound (WB-3559 D-syn) stimulated mouse plasma euglobulin clot lysis time when injected intravenously.

Animals↗

New antitumor antibiotics, FR-900405 and FR-900406. I. Taxonomy of the producing strain.

An actinomycete which was isolated from a soil sample produces new antitumor substances. The morphological and cultural characteristics of the strain resemble those of the genera Streptomyces Waksman and Henrici 1943 and Actinomadura Lechevalier and Lechevalier 1970. Cell wall composition analysis showed that strain No. 6049 contained meso-2,6-diaminopimelic acid in its cell wall, and madurose in whole-cell sugars. No sporangia, zoospores or fragmentations of vegetative mycelium are observed. From these results, strain No. 6049 is designated as Actinomadura pulveracea sp. nov.

Actinomycetales↗