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T Hiroshima

Publications and source records attributed to T Hiroshima.

14 recordsLinked to original sources
PubMed1999

[Relationship between biological activity and heparin-affinity sites of recombinant human basic fibroblast growth factor CS23 mutein].

A recombinant human basic fibroblast growth factor CS23 mutein (rhbFGF-CS23) obtained from Escherichia coli cells has proliferation-stimulating activity for a fetal bovine heart endothelial cell line, ATCC CRL 1395 (biological activity), and strong affinity for heparin (heparin-affinity) similarly to the natural human basic fibroblast growth factor. Plural species having different kinds of heparin-affinity were formed by acetylation of rhbFGF-CS23 with acetic anhydride. To clarify the relationship between the sites with heparin-affinity and the biologically active sites, we have investigated the acetylation sites by peptide mapping and the biological activity of the acetylated species. Consequently, the sites with heparin-affinity in rhbFGF-CS23 are found to be Lys26, Lys119, Lys125, Lys129, and Lys135 in the primary structure, and these sites with heparin-affinity except Lys26 are also clarified to be very important to retain the biological activity of the factor.

Acetylation↗
PubMed1996

[Heparin affinity high-performance liquid chromatography as an alternative to bioassay of CS23 mutein of recombinant human basic fibroblast growth factor].

We investigated whether a chemical assay by high-performance liquid chromatography (HPLC) as an alternative to the complicated and time-consuming bioassay for CS23 mutein of recombinant human basic fibroblast growth factor (rhbFGF-CS23) using the fetal bovine heart endothelial cell line ATCC CRL 1395. Physically, chemically or enzymatically denatured rhbFGF-CS23 was subjected to heparin affinity (HA)-HPLC and the bioassay. Good agreement was observed between the results obtained by these two methods. Moreover, HA-HPLC gave much more reproducible results (RSD = 1.9%, n = 6) than the bioassay (RSD = 7.4%, n = 18). HA-HPLC is therefore a simple, accurate and reproducible alternative to the bioassay for quality control and stability studies for rhbFGF-CS23 preparations. HA-HPLC is also considered to be applicable to assays for FGFs which have heparin affinity and biological activity similar to those of the CS23 mutein.

Animals↗
PubMed1995

The role of renal dopamine in the reduction of high blood pressure by beta 1-selective beta-blocker with intrinsic sympathomimetic activity in spontaneously hypertensive rats.

The present experiments were undertaken to clarify the difference of renal dopamine production from beta 1-selective beta-blocker with and without intrinsic sympathomimetic activity (ISA). Either beta-blocker with ISA, celiprolol (100 or 300 mg/kg/day; CEL-100 or CEL-300) or beta-blocker without ISA, atenolol (50 mg/kg/day; ATE-50) was administered to the SHR from 19 to 26 weeks. Degrees of lowering blood pressure in CEL-300 SHR and in ATE-50 SHR were similar, but decrease in heart rate was significantly less in CEL-300 SHR than in ATE-50 SHR. Urine output, which was significantly less in control SHR than in control WKY, was significantly greater in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. Urinary excretions of noradrenaline (u-NA) and dopamine (u-DA) were significantly higher in control SHR than in control WKY and a comparable u-DA/u-NA ratio was found in these two groups. U-DA and the ratio of u-DA/u-NA were significantly elevated in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. There was a significant positive correlation between u-DA/u-NA ratio and urine output and a significant negative correlation between the ratio of u-DA/u-NA and change of blood pressure in control SHR, CEL-100 SHR and CEL-300 SHR. These results suggest that an enhancement of renal dopamine production by ISA (beta 2 stimulation) of beta 1-selective beta-blocker may contribute, at least in part, to the antihypertensive effect of this drug.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1992

Deamidation at asparagine-88 in recombinant human interleukin 2.

Reversed-phase high-performance liquid chromatography (RP-HPLC) and protein-chemical analysis revealed that only Asn88 in recombinant human interleukin 2 (rIL-2) is liable to be deamidated during a long period of storage in aqueous solutions (pH 5.0) at 25 degrees C, even though there are eight asparagine and six glutamine residues. The deamidation occurred more easily at 40 degrees C than at 25 degrees C but did not occur at all at temperatures below 5 degrees C. The biological activity of Asn88-deamidated rIL-2 was found to be almost the same as that of intact rIL-2, whereas its isoelectric point (pI 7.6) is different from that of intact rIL-2 (pI 7.9).

Amides↗
PubMed1989

Oxidation of methionine residues of recombinant human interleukin 2 in aqueous solutions.

When recombinant human interleukin 2 (rIL-2) was stored for a long period in aqueous solutions, its methionine residues were spontaneously oxidized to the corresponding methionine sulfoxides. To clarify the oxidation process, rIL-2 was treated with hydrogen peroxide, and three oxidation products were separated by reversed-phase high-performance liquid chromatography. By means of amino acid analyses after cyanogen bromide cleavage of these products, we found that Met104, Met23, and Met39 were consecutively oxidized in this order; Met46 was not oxidized easily. The substances generated by extended storage of rIL-2 in aqueous solutions were identified by comparison of their peptide maps with those of the chemically oxidized products. The protein-chemical properties of these products, except for the modifications of the methionine residues, were similar to those of intact rIL-2; their biological activities were almost the same.

Humans↗
PubMed1977

Termination of early pregnancy by ONO-802 (16,16-dimethyl-trans-delta2-PGE1 methyl ester).

ONO-802 was infused into the uterine cavity for the termination of early pregnancy in 45 healthy volunteers. Forty two (93%) of the 45 cases had complete abortions and two had incomplete abortions. Nine (20%) of the 45 volunteers complained of nausea, 7 (16%) vomited and 5 (11%) complained of abdominal pain. Neither diarrhea nor weakness was observed. These results suggest that ONO-802 is more acceptable for the termination of early pregnancy than is PGF2alpha.

Abortion, Induced↗
PubMedDate not supplied

Synthesis of 3-ethoxy-4,4-diisopropyl-1,2-dioxetanes bearing a benzo(b)furan-2-yl or a benzo(b)thiophen-2-yl group: CIEEL-active dioxetanes emitting red light.

Low-temperature singlet oxygenation of 1-ethoxy-2, 2-diisopropylethylenes substituted with a benzo(b)furanyl or a benzo(b)thiophenyl group bearing a t-butyldimethylsiloxy at the 5-, 6- or 7-position of the aromatic ring afforded the corresponding 1, 2-dioxetanes in moderate to high yields. On treatment with tetrabutylammonium fluoride in DMSO, dioxetanes with a trigger (siloxy group) at the 5- or 7-position of the aromatic ring decomposed to emit red light (lambda(max) = 615-628 nm), irrespective of the aromatic ring being benzofuran or benzothiophene. For both series of benzofuran-analogues and benzothiophene-analogues, an 'odd/even' relationship between the position of an oxyanion on the aromatic ring relative to the attachment point to the dioxetane and the chemiluminescent properties, lambda(max), Phi(CL), and t(1/2), is observed, as in the case for dioxetanes bearing a phenolic or naphtholic substituent.

Ethers, Cyclic↗