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Biomedical subjects

I Tsuboi

Publications and source records attributed to I Tsuboi.

41 records · Page 3Linked to original sources

Evaluation of the effects of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA) on HIV-1 production in vitro.

Effects of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), an inhibitor of the common Adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4.), on HIV-1 production was evaluated in vitro. Reverse transcriptase (RT) activity in the supernatant was inhibited by nearly 50% in EHNA-treated HIV-1 infected H9 cells, when compared with untreated but infected H9 cells. There was also a significant decrease in cell viability, but this was reversed following the addition of deoxycytidine (dC) to these cultures. The combined treatment was also effective in suppressing HIV-1 release from HIV-1-infected U937 cells. This combined EHNA plus dC treatment had no effect on RT activity in the cell lysates, suggesting that the inhibition of HIV-1 production may be due to the disturbance of virus release from infected cells.

Adenine↗

Abnormal synthesis of cartilage-characteristic proteoglycan in azaserine-induced micromelial limbs.

Administration of azaserine (250 micrograms) to day-4 chick embryos in ovo was shown to induce micromelial limbs. In the present study, biosynthesis of cartilage-characteristic proteoglycan H (PG-H) as an index of limb chondrogenesis was examined in normal and micromelial hind limbs from day-7 chick embryos by biochemical and immunological methods. (1) Metabolic labelling of the micromelial limbs with [6-3H]-glucose and [35S]sulphate, followed by analysis of labelled proteoglycans by glycerol-density-gradient centrifugation under dissociative conditions, showed a marked reduction in PG-H synthesis. (2) PG-H synthesized by micromelial limbs differed from that synthesized by normal limbs in possessing a slower sedimenting velocity and much lower amounts of chondroitin sulphates. (3) The amount of PG-H core protein in micromelial limbs was significantly decreased to about 19% on a per limb basis and about 42% on a per DNA basis of that in normal limbs, as determined by e.l.i.s.a. (4) The transition from PG-M to PG-H during limb formation was retarded in micromelial limbs as judged by an indirect immunofluorescence technique using antibodies against PG-M and PG-H. (5) The deficiency of incorporation of labelled glucose into chondroitin sulphate chains of PG-H in micromelial limbs was partially restored by using [6-3H]-glucosamine as a precursor, suggesting that the synthesis of UDP-N-acetylhexosamine, required for chondroitin sulphate chain synthesis of PG-H in micromelial limbs, was decreased. These results suggest that the reduction in the synthesis of PG-H as well as the production of an abnormal form of PG-H during a critical period of limb morphogenesis may be important factors in explaining the micromelia induced by azaserine.

Abnormalities, Drug-Induced↗

[Effect of salazosulfapyridine and its metabolites on immunocompetent cells].

Long-term administration of SASP does offer clinical benefit and has a demonstrable disease modifying effect in rheumatoid arthritis, though its mode of action remains obscure. We have studied the in vitro effects of SASP and its metabolites, that is SP, ASA, AcSP and AcASA, on the blast-formation of lymphocytes, the cytotoxic activity of NK cell, the phagocytosis and H2O2 production of monocyte and the fMLP-induced chemotaxis and superoxide anions production of PMNs. We have obtained the following results: (1) the blast-formation of lymphocytes by PHA and Protein A was significantly inhibited by SASP, but not by the metabolites; (2) the cytotoxic activity of the NK cell was inhibited by SP and AcSP, but not by SASP, ASA and AcASA; (3) on monocyte, SP, AcSP and AcASA inhibited phagocytosis, and all of drugs had no effect on the production of H2O2; (4) on PMNs, SASP, SP and ASA significantly inhibited fMLP-induced chemotaxis, and SASP and all of its metabolites significantly inhibited a release of superoxide anions by stimulation of fMLP and PMA; (5) SASP and ASA scavenged superoxide radical at the concentration comparable to clinical doses. In vivo, the above effects may be exhibited in proportion to each blood concentrations of drugs. In particular, it appears that SASP, SP and AcSP play an important role in the therapeutic efficacy in rheumatoid arthritis.

Chemotaxis, Leukocyte↗

Human polymorphonuclear leukocyte activating factor isolated from Aleurites Fordii Hemsl. (Euphorbiaceae) seed.

A human polymorphonuclear leukocyte (PMN) activating factor (AFH-S) was isolated from a tropical plant seed, Aleurites Fordii Hemsl. (AFH) in PBS. It is found that the AFH-S stimulate human PMNs and induced superoxide generation and chemotaxis. Superoxide generation was affected by the extracellular calcium ion or pretreatment with H-7 (PK-C inhibitor), but not by mepacrine (PLA2 inhibitor) or pertussis toxin (islet-activating protein: IAP). Furthermore, a lag time exists dose-dependently. In addition the cytosolic calcium was not increased by the stimulation with AFH-S. Thus, the receptor for AFH-S was suggested to be independent from Ni-like protein, PI-response, or PLA2-activation, and stimulate PMNs through activation of PK-C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗