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Biomedical subjects

K Inouye

Publications and source records attributed to K Inouye.

At least 127 records · Page 7Linked to original sources

Substance K: a novel mammalian tachykinin that differs from substance P in its pharmacological profile.

The primary structure of one of the bovine brain substance P precursors has shown the existence of a second mammalian tachykinin sequence, named substance K, that is remarkably homologous to that of the amphibian peptide kassinin. In this study, three substance K sequences were chemically synthesized and were submitted to parallel bioassays with kassinin, substance P and physalaemin. The results show that the three substance K peptides all possess biological activities characteristic of the tachykinin family and that their biological activities more closely resemble those of kassinin than those of substance P or physalaemin. This suggests that substance K may have a physiological role which is related to but different from that of substance P in mammalian organisms.

Animals↗

Receptor binding and biological activity of [SerB24]-insulin, an abnormal mutant insulin.

[SerB24]-insulin, the second structurally abnormal mutant insulin, and [SerB25]-insulin were semisynthesized and were studied for receptor binding and biological activity. Receptor binding and biological activity determined by its ability to increase 2-deoxy-glucose uptake in rat adipocytes were 0.7-3% of native insulin for [SerB24]-insulin and 3-8% for [SerB25]-insulin. Negative cooperative effect of these analogues was also markedly decreased. Immunoreactivity of [SerB24]-insulin was decreased whereas that of [SerB25]-insulin was normal. Markedly decreased receptor binding of [SerB24]-insulin appeared to be due to substitution of hydrophobic amino acid, Phe, with a polar amino acid, Ser, at B24.

Adipose Tissue↗

Chondrosarcoma of the nasal septum: a report of an uncommon lesion.

Chondrosarcoma of the nasal septum is an uncommon lesion. Review of the English literature reveals only 14 cases. This paper reports an additional case observed in a Japanese series of seven cases. The clinical features are reviewed, and a most effective treatment with minimum side effects is organized by an interdisciplinary group of specialists in surgery, radiotherapy and regional chemotherapy.

Adolescent↗

Early glottic carcinoma (T1N0). Results of irradiation with or without endoscopic microsurgery.

Seventy-nine patients with T1N0 glottic carcinoma were treated at the Department of Radiology, University of Tokyo, between 1967 and 1977. The average total dose varied from 73 Gy in the first year to 32 Gy in the last year of the period. Endoscopic microsurgery was introduced in the middle of the period. The overall local recurrence rate was 15 per cent within 5 years. Observed and adjusted five-year survival rates were 79 and 91 per cent, respectively. Endoscopic microsurgery was not an important factor for local control rates and survival rates. Patients with T1N0 glottic carcinoma were successfully treated with a total dose equivalent to a time-dose-fractionation of 80 to 100.

Adult↗

Three mutant insulins in man.

We have previously identified a structurally abnormal insulin in the serum and pancreas of a middle-aged man with diabetes mellitus which arose from a leucine for phenylalanine substitution at position 24 or 25 of the insulin B chain; further analysis of the patient's leukocyte DNA showed that one of the patient's insulin alleles had undergone mutation resulting in loss of an MboII restriction site normally present in the human insulin gene. Two additional and unrelated patients with the same clinical syndrome have now been identified (ref. 4 and unpublished results). All of these patients showed hyperglycaemia typical of diabetes and with marked hyperinsulinaemia typical of insulin resistance, but all three show normal tolerance to exogenously administered insulin. As the opportunity of examining pancreatic tissue from patients suspected of secreting insulin variants is rare, we have developed a method combining HPLC and radioimmunoassay to identify insulin variants isolated from human sera. By this method we have shown that all three patients noted above secrete structurally variant and chemically distinct insulins. In correction of our original assignment, one is identified as [LeuB25]insulin.

Amino Acid Sequence↗

Origin of slow conformer conversion of triostin A and interaction ability with nucleic acid bases.

The n.m.r. pattern of triostin A in weakly polar solvents was explained by the presence of two symmetrical conformers. Its S-benzyl derivative still shows the n.m.r. pattern of two conformers, while des-N-tetramethyltriostin A, which lacks the N-methyl groups, gives one conformer. Therefore the slow interconversion of two conformers arises from the cis-trans isomerization of the N-methyl peptide bonds, but not from the reversal of the chirality around the S-S bond. Only one of the two conformers of triostin A interacts with adenosine and guanosine derivatives. Des-N-tetramethyltriostin A can also interact with the purine nucleosides, but more preferentially with the adenosine derivative.

Adenosine↗

Characterization of [LeuB-24]- and [LeuB-25]-insulin analogues. Receptor binding and biological activity.

Human [LeuB-24]- and [LeuB-25]-insulins were semi-synthesized from porcine insulin by an enzyme-assisted coupling method. The receptor-binding ability of [LeuB-24]- and [LeuB-25]-insulins was 30--48% and 2--5% respectively of that of human insulin. There was no significant difference in degradation between human insulin and these analogues on incubation with isolated adipocytes. The decreased affinity of these analogues was due to an increased dissociation rate rather than a change in the association rate of their binding to human cultured lymphocytes. The negative co-operative effect of [LeuB-24]- and [LeuB-25]-insulin was decreased to 50 and 1% respectively of that of human insulin at a concentration of 100 ng/ml. The ability of [LeuB-24]- and [LeuB-25]-insulin to stimulate 2-deoxyglucose uptake in isolated rat adipocytes was 35 and 4% respectively of that of human insulin. These analogues did not have an antagonistic effect on the biological activity of human insulin. The immunoreactivity of [LeuB-25]insulin was similar to that of porcine or human insulin, whereas [LeuB-24]insulin demonstrated decreased binding to anti-(porcine insulin) antibodies. These findings suggest that B-chain phenylalanine-25 residue is more crucial for receptor binding and negative co-operativity, whereas the B-chain phenylalanine-24 residue may play a more important role in binding to anti-insulin antibody.

Adipose Tissue↗

Semisynthesis and biological properties of the [B24-leucine]-, [B25-leucine[- and [B24-leucine, B25-leucine]-analogues of human insulin.

Trypsin-catalyzed coupling of porcine desoctapeptide-insulin with synthetic octapeptides produced the [LeuB24]- (I), [LeuB25]- (II) and [LeuB24, LeuB25]- (III)analogues of human insulin. I, II and III displayed respectively 20--30%, 1--2% and 0.5% of the receptor binding activity of the normal hormone. Biological activities of these analogues seemed to be proportional to their binding potencies when assayed in vitro, while in an in vivo assay analogue I was fully active and II exhibited 10--20% of normal activity. III was less active than II in all assays tested.

Adipose Tissue↗

Distribution study of a synthetic ACTH analogue in rat tissue.

Tissue distribution of (Aib1, Lys17, 18, 19)-corticotrophin-(1-19)-nonadecapeptide amide (690024-S), iv injected to hypophysectomized rats, were surveyed by bioassay. Among the tissues examined. the largest amount of 690024-S was found in the liver during 3 h of search for the injection, while a higher concentration of the peptide per tissue weight was found in kidney. Though a small amount of 690024-S was detected in spleen, heart and lung at an early stage, it was not detectable in other tissues such as brain, stomach, small intestine, thigh muscle, fat or foetus. The peptide was found to be excreted into bile for the duration of about 2 h. It was also found that the elimination of 690024-S in blood followed biphasic first order kinetics.

Adrenocorticotropic Hormone↗

Motive force of the migrating pseudoplasmodium of the cellular slime mould Dictyostelium discoideum.

Motive forces of migrating pseudoplasmodia (slugs) of Dictyostelium discoideum were determined by application of a double-chamber method. The motive force of a whole slug was proportional to its volume, the value per unit volume being 5.85 x 10(-6) dyne/cm3 (58.5 N cm-3). The motive force was independent of temperature (13.5--26 degrees C) and decreased during prolonged migration. Motive force per unit volume of an anterior isolate of a slug was much larger than that of a posterior isolate, their weighted mean being approximately equal to that of a whole slug. These results agree well with the predictions previously made using a model based on analyses of migrating velocities of slugs. The motive force per unit volume of either isolate was soon regulated to reach the normal value of an intact slug after several hours of isolation, concurrently with conversion of cell types between prestalk and prespore cells. The possibility that motive force of each cell is determined by its cell type is discussed in relation to cell sorting.

Dictyostelium↗

Separation of some polypeptide hormones by high-performance liquid chromatography.

Twenty-one analogues of ACTH, three analogues of LH-RH and four insulins have been successfully separated on a commercial reversed-phase material with tartrate buffer--acetonitrile systems containing sodium 1-butanesulphonate and sodium sulphate as the mobile phase. The effect of the constituent amino acid residues on the order of elution has been studied in detail by using a variety of closely related peptides; the order of elution of a series of peptides, which differ by only one amino acid residue, can in most instances be explained in terms of the difference in the hydrophobicities of the amino acid residues concerned, but in some instances, such as in diastereoisomers or positional isomers, the order of elution must be interpreted in terms of the hydrophobicity of the whole peptide molecule. This chromatographic method has been proved to be very useful for the rapid examination of the purity of these peptide hormones and for the separation of closely related peptides with molecular weights up to ca. 6000.

Adrenocorticotropic Hormone↗