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Biomedical subjects

M Ishizuka

Publications and source records attributed to M Ishizuka.

At least 19 recordsLinked to original sources
PubMed1992

Enhancement of host resistance to opportunistic infections by ubenimex (bestatin).

Ubenimex is a low molecular biological response modifier (BRM) which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the effect of ubenimex on infection with Candida albicans was investigated in normal and immunosuppressed mice, and it showed a prophylactic effect. In normal mice, ubenimex prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with cyclophosphamide 4 days before infection, ubenimex at 5 mg/kg for 5 days significantly increased the number of survivors. Significant improvement in peritoneal leukocyte counts and in function of neutrophils including phagocytosis and release of activated oxygen was observed in ubenimex-treated mice. These results indicate that ubenimex is a potent BRM for prevention against opportunistic infections.

Animals↗
PubMed1992

Effect of 15-deoxyspergualin, a microbial angiogenesis inhibitor, on the biological activities of bovine vascular endothelial cells.

We found recently that 15-deoxyspergualin, an analog of spergualin, which is an antibiotic and includes a spermidine moiety in its structure, exhibits anti-angiogenic activity. We have now carried out in vitro experiments with bovine vascular endothelial cells to determine which events occurring during angiogenesis are affected by this microbial angiogenesis inhibitor. 15-Deoxyspergualin did not inhibit the production of urokinase-type plasminogen activator (u-PA) or type IV collagenase by vascular endothelial cells. The direct inhibition of u-PA activity by 15-deoxyspergualin was not observed either. The angiostatic antibiotic neither affected the migration of vascular endothelial cells nor inhibited the endothelial cell proliferation in a two-dimensional culture system. We also examined the effect of 15-deoxyspergualin on the proliferation of endothelial cells in a three-dimensional culture system involving collagen gel, in which cell growth resembles more closely the endothelial cell proliferation during in vivo angiogenesis than that in a two-dimensional culture system without collagen gel. The antibiotic inhibited cell proliferation in a dose-dependent manner, indicating that the three-dimensional culture system is useful for finding a new angiogenesis inhibitor with a different mode of action from those of angiogenesis inhibitors found by using a two-dimensional assay system; however, no cause-effect relationship has yet been established. Taken together, these results suggest the possible involvement of the inhibition of vascular endothelial cell growth by 15-deoxyspergualin in its angiogenesis-inhibitory effect. 15-Deoxyspergualin appears to be a promising candidate as an angiogenesis inhibitor for controlling aberrant angiogenic responses occurring in different states, including tumor development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Enhancement by ubenimex (bestatin) of host resistance to Candida albicans infection.

Ubenimex is a low molecular weight microbial metabolite which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the protective effect of ubenimex on Candida albicans infection was investigated in normal and immunosuppressed mice. In normal mice, treatment with ubenimex at 0.5, 5 and 25 mg/kg for 5 days prior to infection prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, ubenimex treatment at 5 mg/kg for 5 days significantly increased the number of survivors. Ubenimex-treated mice had a significant increase in number of peritoneal exudate cells with neutrophils as well as enhanced functions, including phagocytosis and active oxygen production. These results suggest the potential usefulness of ubenimex as a prophylactic agent for the management of patients with opportunistic fungal infections.

Animals↗
PubMed1992

Dethymicin, a novel immunosuppressant isolated from an Amycolatopsis. Fermentation, isolation, physico-chemical properties and biological activities.

In the course of screening for immunomodulators inhibiting the mixed lymphocyte culture reaction (MLCR), we found a novel immunosuppressant, dethymicin in mycelium of Amycolatopsis mediterranei MI710-51F6. From physico-chemical properties and biological activity it is different from immunosuppressants produced by microorganisms such as cyclosporins, FK506 and rapamycin. It inhibited immune responses in vitro and in vivo, and prolonged skin allograft in rats.

Actinomycetales↗
PubMed1991

The cytochrome C oxidase genes in blue-green algae and characteristics of the deduced protein sequence for subunit II of the thermophilic cyanobacterium Synechococcus vulcanus.

Blue-green algae (cyanobacteria) contain both primitive photosynthetic and respiratory systems in their membranes. The controversial genes coding for an alpha alpha 3-type cytochrome oxidase in cyanobacteria were examined. The DNA probe coding for the most conserved part of subunit I hybridized with DNA fragments from four cyanobacterial species. We have cloned the genes coding for subunits I and II from the genomic library of the thermophilic cyanobacterium Synechococcus vulcanus and determined the nucleotide sequence of the subunit II gene. The deduced protein sequence (327 amino acid residues) indicates that there are two hydrophobic segments near the N-terminus and a hydrophilic intermembrane domain containing ligands for CuA (the ESR-active Copper) similar to other subunit IIs. The S. vulcanus subunit II does not contain the cytochrome c moiety that is present in bacilli and thermophiles.

Amino Acid Sequence↗
PubMed1991

Leukemia cutis in acute myelomonocytic leukemia: infiltration to minor traumas and scars.

We describe a patient with acute myelomonocytic leukemia who demonstrated leukemic cell infiltration to scratched wounds and scars from trauma. A 65-year-old Japanese woman developed low grade fever, headache and exanthema. Hematology testing disclosed leukocytosis of 95,600/mm3 with 65% monocytes and 9% blast cells. Infiltrated erythema and nodules were disseminated over most of her body. Moreover, linear scratched wounds and traumatic scars were indurated. Skin biopsy showed dense atypical mononuclear cell infiltration with monocytic characteristics. We discuss the possible reasons for the infiltration of leukemia cells into the wounds and scars from trauma.

Aged↗
PubMed1990

A fourth subunit is present in cytochrome c oxidase from the thermophilic bacterium PS3.

A new putative subunit was found in cytochrome c oxidase (aa3-type) of the thermophilic bacterium PS3. The N-terminal amino acid sequence of this approximately 12 kDa protein coincides with the deduced sequence of an open reading frame found downstream from the gene encoding subunit I of the PS3 cytochrome oxidase [(1988) J. Biochem. 103, 606-610]. This small hydrophobic protein, composed of 109 amino acid residues after the initial methionine residue has been processed, shows homology with the subunit IV (cyoD product) of cytochrome bo-type quinol oxidase of Escherichia coli.

Amino Acid Sequence↗
PubMed1990

Pathomorphological changes in rat brain choroid plexus due to administration of the amine-curing agent, bis(4-amino-3-methylcyclohexyl)methane.

Repeated oral administration of an amine-curing agent for epoxy resin, bis(4-amino-3-methylcyclohexyl)methane, gave rise to severe damage in the choroid plexus of rat brain. The damaged epithelium presented varying degrees of swelling and hydropic vacuolation on light microscopy, and varying numbers of vacuoles and inclusion bodies, frequently with lamellar structure, on transmission electron microscopy. Scanning electron microscopy of the choroid plexus disclosed some irregularity in the size of epithelial cells and occasional loss of microvilli. These changes in the choroid plexus were closely correlated with the dosage of the agent administered and the period of administration. In spite of the severe changes in the choroid plexus, no neurological abnormalities were observed in the animals during the experimental period.

Animals↗
PubMed1990

Nucleotide sequence of the gene coding for four subunits of cytochrome c oxidase from the thermophilic bacterium PS3.

The gene coding for four subunits of cytochrome aa3-type oxidase was isolated from a genomic DNA library of the thermophilic bacterium PS3 and sequenced. The N-terminus of each subunit was also sequenced to verify the initiation site of the reading frame. The deduced amino acid sequences contained 615 amino acid residues for subunit I (CO1/caaB product), 333 residues for subunit II (CO2/caaA product), 207 residues for subunit III (CO3/caaC product), and 109 residues for subunit IV (CO4/caaD product) after processing. Re-examination of the sequencing of caa revealed a longer open reading frame for CO1, which contains 14 transmembrane segments instead of 12 [Sone et al. (1988) J. Biochem. 103, 606-610], although the main portions of the sequences constituting cytochrome a (FeA), cytochrome a3 (FeB), and CuB are correct. PS3 CO2 has an additional sequence for cytochrome c after the CuA binding protein portion with 2 transmembrane segments, which is homologous to the mitochondrial counterpart. PS3 CO3 has DCCD-binding glutamyl residues but contains only 5 transmembrane segments, unlike the mitochondrial counterpart, which has 7 segments. The subunits of PS3 cytochrome oxidase (aa3-type) show clear similarity in amino acid sequences with those of cytochrome bo-type oxidase from Escherichia coli as well, in spite of the difference of hemes. PS3 CO3 and CO4 are much more similar to E. coli CO3 and CO4 than to mitochondrial CO3 and CO4, respectively.

Amino Acid Sequence↗
PubMed1989

Biological activities of IC201 ((3S,8E)-1,3-dihydroxy-8-decen-5-one), a low molecular weight immunomodulator produced by Streptomyces.

IC201 was found in cultured broth of Streptomyces cirratus as an antitumor antibiotic which was effective in retarding growth of the established solid tumor of Ehrlich carcinoma by treatment starting 8 days after tumor inoculation. It retarded growth of the established solid tumor of IMC carcinoma but had no cytotoxicity at 100 micrograms/ml. IC201 treatment kept NK cell activity of tumor-bearing mice at normal level and stimulated cytostatic activity of peritoneal macrophages. It stimulated phagocytosis of yeast and phorbol myristate acetate-elicited superoxide production by peritoneal macrophages. The addition of IC201 to P388D1 cell cultures enhanced release of interleukin 1 (IL-1) into cultured supernatant but it affected lipopolysaccharide-induced IL-1 production. Although the addition to macrophage-depleted cultures did not show any stimulatory effect, mixed lymphocyte culture reaction was augmented in cultures using spleen cells as stimulator cells taken from mice given IC201. Results indicate that IC201 primarily activates macrophages and the activation may cause modulation of immune responses.

Adjuvants, Immunologic↗
PubMed1988

Sequence and over-expression of subunits of adenosine triphosphate synthase in thermophilic bacterium PS3.

The primary structures of all the subunits of thermophilic ATP synthase were determined, and its alpha, beta and gamma subunits could be over-expressed in Escherichia coli, because these subunits were stable and reconstitutable. DNA of 7500 base pairs in length was found to contain a cluster of nine genes for subunits of ATP synthase. The order of their reading frames (size in base pairs) was: I(381): a(630): c(216): b(489): delta(537): alpha(1507): gamma(858): beta(1419): epsilon(396), I being a gene for a small hydrophobic, basic protein expressed in vitro. All the termini of TF0F1 subunits were confirmed by peptide sequencing. Large quantities of the overexpressed thermophilic alpha, beta and gamma subunits were prepared from the extract of E. coli, by a few purification steps.

Amino Acid Sequence↗