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Biomedical subjects

T Hiroshima

Publications and source records attributed to T Hiroshima.

6 recordsLinked to original sources

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

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

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