Biomedical subjects
Publications and source records attributed to T Hatakeyama.
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The saccharide binding ability of the low affinity (LA-) binding site of ricin D was abrogated by N-bromosuccinimide (NBS)-oxidation, while in the presence of lactose the number of tryptophan residues eventually oxidized decreased by 1 mol/mol and the saccharide binding ability was retained (Hatakeyama et al., (1986) J. Biochem. 99, 1049-1056). Based on these findings, the tryptophan residue located at the LA-binding site of ricin D was identified. Two derivatives of ricin D which were modified with NBS in the presence and absence of lactose were separated into their constituent polypeptide chains (A- and B-chains), respectively. The modified tryptophan residue or residues was/were found to be contained in the B-chain, but not in the A-chain. From lysylendopeptidase and chymotryptic digests, peptides containing oxidized tryptophan residues were isolated by gel filtration on Bio-Gel P-30 and HPLC. Analysis of the peptides containing oxidized tryptophan revealed that three tryptophan residues at positions 37, 93, and 160 on the B-chain were oxidized in the inactive derivative of ricin D, in which the saccharide binding ability of the LA-binding site was abrogated by NBS-oxidation. On the other hand, the modified residues were determined to be tryptophans at positions 93 and 160 in the active derivative of ricin D which was modified in the presence of lactose, indicating that upon binding with lactose, the tryptophan residue at position 37 of the B-chain was protected from NBS-oxidation. From these results, it is suggested that tryptophan at position 37 on the B-chain is the essential residue for saccharide binding at the LA-binding site of ricin D.
The nature of the saccharide-binding site of ricin D, which is a galactose- and N-acetylgalactosamine-specific lectin, was studied by chemical modification and spectroscopy. With excitation at 290 nm, ricin D displayed a fluorescence spectrum with a maximum at 335 nm. Upon binding of the specific saccharides, the spectrum shifted to shorter wavelength by 3 nm. However, binding of galactosamine and N-acetylgalactosamine failed to induce such a change in the fluorescence spectrum. The interaction of ricin D with its specific saccharides was analyzed in terms of the variation of the intensity at 320 nm as a function of saccharide concentration. The results indicate that the change in the fluorescence spectrum induced by saccharide binding is attributable to the binding of saccharide to the low-affinity (LA-) binding site of ricin D. The cytoagglutinating activity of ricin D decreased to 2% upon modification of two tryptophan residues/mol with N-bromosuccinimide at pH 4.0, but in the presence of galactose or lactose one tryptophan residue/mol remained unmodified, and a fairly high cytoagglutinating activity was retained. Galactosamine and N-acetylgalactosamine did not show such a protective effect. Spectroscopic analyses indicate that the decrease in the cytoagglutinating activity of ricin D upon tryptophan modification is principally due to the loss of the saccharide binding activity of the LA-binding site. The results suggest that one tryptophan residue is essential for saccharide binding at the LA-binding site, which can bind galactose and lactose but lacks the ability to bind N-acetylgalactosamine and galactosamine.
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We propose a mathematical model of the human hypothalamus-anterior pituitary-thyroid system regulating basal metabolism, and practice computer simulation concerning primary thyropathy such as Graves' disease, hypothyroidism, T4-toxicosis and T3-toxicosis by use of this model. In order to throw light on properties of the system, indicial responses of the hormones, T4, T3, rT3, and TSH, and the function of the thyroid gland are computed. Medical treatments for Graves' disease and for hypothyroidism are simulated with a view to enhancing clinical significance. Performance of the simulation leads to an interesting result that when the convertion rate of blood T4 to blood T3 increases, explicit T3-toxicosis occurs, although the function of the thyroid gland is normal.
The interaction of ricin D with specific saccharides was investigated by ultraviolet difference spectroscopy. Upon binding to saccharides, ricin D displayed ultraviolet difference spectra with maxima at 280 nm and 288 nm. Such difference spectra suggest that the environment of a tyrosine residue(s) located at or near the saccharide-binding site is changed by the binding of saccharide. In addition to the two positive peaks, a small trough was observed around 300 nm in the complexes with galactose-containing saccharides but not in the complex with N-acetylgalactosamine or galactosamine, suggesting the participation of tryptophan in the binding with galactose-containing saccharides. The magnitude of the difference maxima increased with increasing concentration of saccharides until the binding site was saturated. From the variation of the maximum at 288 nm as a function of saccharide concentration, the association constants were obtained for the binding of saccharides to ricin D at various temperatures and pH's. The saccharide binding of ricin D decreased with increasing temperature and with decreasing pH below pH 6.0. It was suggested that difference maximum at 288 nm observed in the ricin D-saccharide interaction reflects the binding of saccharides to the high-affinity saccharide-binding site of ricin D.
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Milk samples from eight cynomolgus monkeys whose lactation period ranged 44-119 days were investigated for their gross chemical composition such as total solids, crude protein, lipids, lactose and ash. Nitrogen distribution, compositions of fatty acids, amino acids and triglycerides as well as major minerals were also determined. These analytical data were compared with those reported for man, simian and cow, and cynomolgus monkey milk was found to have close similarities to human milk.
New-born cynomolgus monkeys were sucessfully reared by artificial nursing that was started just afterbirth with a 12% solution of a commercially prepared powdered-milk (Yukijirushi, P 7a) containing 13.3g of protein per 100g. Marked growth-retardation was observed in baby cynomolgus monkeys fed on a 12% solution of the modified P 7a milk containing only 6.6g of protein per 100g to which lactose was supplemented to give a baby monkey the same caloric value as that of the original P 7a milk. These artificially reared cynomolgus monkeys manifested various kinds of abnormal behavior such as self-clasping, autism-like self mouthing, huddling, stereotype rocking, head-knocking, autoerotism, fear, aggression, etc.. Generally, development of these abnormal behaviors was more noticeable in the monkeys nursed with a milk bottle fixed to the side of a cage without human contact than in the monkeys nursed by a care-taker with bodily touching. These qualitative observational results indicate that the new-born cynomolgus monkey can be used as a model of the human baby for research into the relationship between malnutrition and abnormal physical and mental growth.
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