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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 1,387 records · Page 77Linked to original sources
PubMed1987

Urinary metabolites of N-nitrosodibutylamine in the rat: identification of N-acetyl-S-butyl-L-cysteine derivatives.

N-Acetyl-S-(butyl, 3-oxobutyl and 3-hydroxybutyl)-L-cysteines have been isolated and identified (as their methyl esters) from the urine of rats given N-nitrosodibutylamine (NDBA), N-nitrodibutylamine (NTDBA) and their corresponding alpha-acetoxy derivatives, N-nitroso-N-butyl(1-acetoxybutyl)amine and N-nitro-N-butyl(1-acetoxybutyl)amine, respectively. Greater amounts of these L-cysteine derivatives were detected in urine after administration of NDBA than of NTDBA. This suggests that the markedly different biological activities of NDBA and NTDBA might be due, in part, to a difference in their alkylating abilities in vivo.

Acetylcysteine↗
PubMed1987

Chemical and mutagenic properties of alpha-phosphonooxynitrosamines.

The chemical and mutagenic properties of the products of solvolysis of alpha-acetoxynitrosamines in phosphate buffer were investigated. alpha-Acetoxynitrosamines decomposed in two ways: O-acyl fission yielded alpha-hydroxynitrosamines, which decomposed into aldehydes and alcohols, while O-alkyl fission gave a resonance hybrid of alpha-N-nitrosocarbonium and -iminium ions, which was trapped with phosphate and afforded alpha-phosphonooxynitrosamine. Formation of alpha-phosphonooxynitrosamines was dependent on the structure of alpha-acetoxynitrosamines; those with a secondary alpha-phosphonooxy group, including cyclic nitrosamines, were easily formed, while among those with a primary phosphonooxymethyl group, only those with an alkyl group containing a branched alpha-carbon as isopropyl, sec-butyl and tert-butyl were isolated. They were good substrates of alkaline phosphatase and showed a nuclear magnetic resonance spectrum due to the presence of a phosphorus atom. They were decomposed by acid catalysis, and the rate was dependent on the structure. They were directly mutagenic in bacterial tester strains, except for a compound with a tert-butyl group. The activity was similar or stronger in Salmonella typhimurium TA1535 and much weaker in Escherichia coli WP2 and WP2 hcr- than those of alpha-acetoxynitrosamines. Stability in neutral aqueous solution and the strong mutagenicity of alpha-phosphonooxynitrosamines suggested their possible involvement in metabolic activation as a precursor of alpha-hydroxynitrosamines, and also in the organotropic carcinogenicity of N-nitrosodialkylamines as a transport form.

Chemical Phenomena↗
PubMed1987

[Experimental study on the control of cisplatin-induced emesis in dogs].

In order to search for methods of controlling cisplatin-induced emesis, a series of experiments were performed with dogs. Cisplatin was administered i.v. to dogs at three-day intervals, and the number of emetic episodes and latency period to the first episode following injection were examined. The dose of cisplatin was 0.3mg/kg at the first injection, and thereafter square root 2-fold higher doses than the preceding ones were injected up to a maximum of 2.4 mg/kg. Emesis was observed from 0.42 g/kg. The number of emetic episodes increased with escalation of the dose up to 0.85 mg/kg, but decreased at higher doses. On the other hand, the latency period shortened with increase of the dose up to the highest one. From these results, the latency period is concluded to be a reliable parameter for evaluating the emetic activity of cisplatin and the efficacy of anti-emetics. The anti-emetic effect of vagotomy, ethyl amino-benzoate or metoclopramide was then examined. When 1 mg/kg of cisplatin was administered i.v., mean values of latency period and the number of episodes in dogs of a control group were 200 minutes and 20 times, respectively. In vagotomized dogs, no emesis was observed. When ethyl amino-benzoate was administered p.o. at doses of 12, 24 and 48 mg/kg 30 minutes before and 90 minutes after cisplatin injection, the number of episodes decreased to between 8 and 4.3 times, but the latency period was not prolonged. When s.c. injections of 1 mg/kg metoclopramide were combined with cisplatin in a similar manner to ethyl amino-benzoate, the latency period was prolonged up to 343 minutes, and the number of episodes decreased to 2.7 times. These results suggest that the peripheral autonomic nervous system is involved in the mechanism of emesis induction by cisplatin. Finally, the anti-emetic effect of metoclopramide was examined using the following administration schedules of cisplatin: a single i.v. injection of 3.75 mg/kg and daily i.v. injections of 1.25 mg/kg for three days. Metoclopramide showed a superior anti-emetic effect in the latter schedule, when the dose of 2 mg/kg was given i.v. 30 minutes before and 90 and 210 minutes after the cisplatin injection.

Analysis of Variance↗
PubMed1986

Molecular cloning of a cDNA and assignment of the C-terminal of sarcotoxin IA, a potent antibacterial protein of Sarcophaga peregrina.

A previous paper described the complete amino acid sequences of sarcotoxins IA, IB and IC, which are a group of potent antibacterial proteins with almost identical primary structures produced by Sarcophaga peregrina (fleshfly) larvae [Okada & Natori (1985) J. Biol. Chem. 260, 7174-7177]. The present paper describes the cDNA cloning and complete nucleotide sequencing of a cDNA clone for sarcotoxin IA. The C-terminal amino acid residue of sarcotoxin IA deduced from the nucleotide sequence was glycine, whereas it was found to be arginine by amino acid sequencing of purified sarcotoxin IA. Analysis of the elution profiles on h.p.l.c. of the synthetic derivatives of sarcotoxin IA showed that the C-terminal amino acid residue of authentic sarcotoxin IA is amidated arginine, which is probably produced by enzymic cleavage of terminal glycine.

Amino Acid Sequence↗
PubMed1986

[Phosphotyrosine]protein phosphatase in rat brain. A major [phosphotyrosine]protein phosphatase is a 23 kDa protein distinct from acid phosphatase.

A [phosphotyrosine]protein phosphatase (PTPPase) was purified almost to homogeneity from rat brain, with [32P]p130gag-fps, an oncogene product of Fujinami sarcoma virus, as substrate. The characteristics of the purified preparation of PTPPase were as follows: the enzyme was a monomer with a molecular mass of 23 kDa; its optimum pH was 5.0-5.5; its activity was not dependent on bivalent cations; its activity was strongly inhibited by sodium vanadate, but was not inhibited by ZnCl2, L(+)-tartrate or NaF; it catalysed the dephosphorylation of [32P]p130gag-fps, [[32P]Tyr]casein, p-nitrophenyl phosphate and L-phosphotyrosine, but did not hydrolyse [[32P]Ser]tubulin, L-phosphoserine, DL-phosphothreonine, 5'-AMP, 2'-AMP or beta-glycerophosphate significantly. During the purification, most of the PTPPase activity was recovered in distinct fractions from those of conventional low-molecular-mass acid phosphatase (APase), which was reported to be a major PTPPase [Chernoff & Li (1985) Arch. Biochem. Biophys. 240, 135-145], from DE-52 DEAE-cellulose column chromatography, and those two enzymes could be completely separated by Sephadex G-75 column chromatography. APase also showed PTPPase activity with [32P]p130gag-fps, but the specific activity was lower than that of PTPPase with molecular mass of 23 kDa, and it was not sensitive to sodium vanadate. These findings suggested that PTPPase (23 kDa) was the major and specific PTPPase in the cell.

Acid Phosphatase↗
PubMed1986

Interleukin 1 alpha mRNA in virus-transformed T and B cells.

IL-1 alpha cDNA clone was isolated from a T cell line infected by the human T lymphotropic retrovirus type-I (HTLV-I/ATLV). We found significant amounts of mRNA hybridizing to IL-1 alpha cDNA not only in HTLV-I-transformed T cells but also in Epstein-Barr Virus-transformed B cells. A part of IL-2 receptor inducing activity in Adult T cell leukemia (ATL) cell line seems to be due to IL-1 alpha.

B-Lymphocytes↗
PubMed1986

Tissue structure of rat brain after microwave irradiation using maximum magnetic field component.

A novel microwave instrument has recently been designed by New Japan Radio Co. Ltd., to provide more homogeneous distribution of the rapidly deposited heat in the rodent brain. Being the first commercial unit which concentrates the maximum magnetic field component of irradiation, rather than the usual electric field, it provides complete enzymatic inactivation in a typical rat brain when a power of 9 kW (90% of maximum) is applied for 0.80 s at the standard operating frequency of 2450 MHz. Tissue structural integrity was investigated in animals sacrificed by this approach or by the usual decapitation to see if any tissue disruption or pressure-induced spreading, a major problem with other microwave devices, might also be of concern for this new unit. Histological examination of tissue samples employed both light and electron microscopy. Using Luxol Fast Blue in the light microscopy, the microwave irradiated tissues exhibited a decreased affinity for the staining agent, an appearance of slight vacuoles, and the disappearance of fine fibrils in the parenchyma. However, the interfacial areas between distinct brain regions remained well preserved. Electron microscopic observation indicated that microwave irradiated tissue caused protein denaturation accompanied by the aggregation of nuclear chromatin, the disappearance of Nissl bodies, ribosomes and neurofilaments, and noticeably irregular myelin sheaths. However, the essential structure of nerve cell membranes and synaptic membranes were maintained, and synaptic vesicles were clearly defined. These results indicated that the rapid heating of brain tissue with maximal magnetic field concentration of the irradiation does not result in significant tissue disruption, pressure-induced spreading or cell breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Immunologic and molecular characterizations of T cell-derived T cell activating factor.

Culture supernatants from several subclones of a human T hybrid line (24A) stimulated with PMA showed co-stimulatory activity in the proliferation of Con A-stimulated murine thymocytes, but did not show any IL 2 activity. Some subclones did not show co-stimulatory activity even when stimulated with PMA, excluding the possibility of a carry-over effect. The factor found in the culture supernatants increased IL 2 production in normal T cells stimulated with a suboptimal concentration of PHA. The factor also induced IL 2 production in a T hybrid clone, T-394.1, when the latter was stimulated with a suboptimal concentration of mitogens, indicating a direct effect by this T cell-derived factor on mitogen-stimulated T cells inducing IL 2 production. This factor also induced the generation of other lymphokines such as BCDF and IFN-gamma. Northern blot analysis showed that the factor induced an increase in mRNA for IL 2 as well as IL 2 receptor. These results indicated that T cells could secrete a factor with IL 1-like activity. However, Northern blot analysis showed that mRNA from a T hybrid clone does not cross-react with cDNA for IL 1 (beta) derived from human monocytes.

Animals↗
PubMed1986

Ultrastructure of concentric laminations in primary human brain tumors.

Ultrastructural concentric laminations have previously been thought to be specific to oligodendroglioma. However, these structures were also recognized in fibrillary astrocytomas, a mixed glioma and a glioblastoma. These laminations continued or closely related to attenuated processes or cytoplasm of astrocytic tumor cells. In addition, some lamellae contained glial filaments. It is considered that the concentric laminations are derived from attenuated astrocytic processes and have no relationship with myelin.

Adolescent↗