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Biomedical subjects

Y Kiso

Publications and source records attributed to Y Kiso.

At least 163 records · Page 9Linked to original sources

Atrial natriuretic peptide antagonists: biological evaluation and structural correlations.

A collection of analogues of atrial natriuretic peptide (ANP) were screened for their ability to inhibit ANP-induced cGMP stimulation. The antagonists revealed through this screen are structurally related; almost all are substituted at either aspartate-13 or phenylalanine-26. This tendency is consistent throughout several families of small ANP analogues, suggesting that these two amino acid residues are involved in the process of ANP/cGMP signal transduction. One compound, A74186, was studied in some detail. A74186 is a potent inhibitor of the activation of guanylate cyclase by ANP; it acts with a pA2 of 7.12 in rat vascular smooth muscle cells and shifts the ANP/cGMP dose-response curve by 3 orders of magnitude at a 10 microM concentration. It also inhibits cGMP release in vivo, and at an infusion rate of 10 micrograms/kg-min it completely abolishes ANP-induced natriuresis and diuresis. A74186 does not, however, antagonize the hypotensive or vasorelaxant effects of ANP; in fact it acts as an agonist in these assays. It thus appears that cGMP, although it may mediate the renal responses to ANP, is not responsible for the vascular and hemodynamic effects that result from the action of the hormone.

Animals↗

Substance P induces granulocyte infiltration through degranulation of mast cells.

Substance P, a potent vasodilatory neuropeptide, is released from peripheral nerve endings of sensory neurons by various stimuli. Although in vitro incubation of rat and human mast cells with substance P causes their degranulation, it is not known whether inflammatory changes induced by substance P are mediated by degranulation of mast cells. We investigated this point by using genetically mast cell-deficient WBB6F1-W/Wv and WCB6F1-Sl/Sld mice. The s.c. injection of substance P induced degranulation of mast cells in the skin of WBB6F1-+/+ mice, and then a marked eosinophil infiltration around the degranulated mast cells. However, WBB6F1-W/Wv and WCB6F1-Sl/Sld mice showed little or no eosinophil infiltration in the skin after the injection of substance P. When the mast cell deficiency of WBB6F1-W/Wv mice was rescued either systemically by bone marrow transplantation or locally by injection of cultured mast cells, injection of substance P induced the infiltration of eosinophils, suggesting that substance P-induced eosinophil infiltration was mediated through degranulation of mast cells.

Animals↗

Synthesis of palmitoyl derivatives of insulin and their biological activities.

In order to improve the lipophilicity of peptides, bovine insulin was chosen for the chemical modification using palmitic acid. The N-hydroxysuccinimide ester of palmitic acid was used for attachment to terminal amino groups, and p-methoxybenzoxycarbonyl azide was used for protection of the glycine-A1 amino terminus. We obtained two purified derivatives of insulin, B1-monopalmitoyl- and B1,B29-dipalmitoyl-insulin, which were confirmed to be more lipophilic than the parent insulin on high-performance liquid chromatography (HPLC). The hypoglycemic effects of both products were measured in rats after intravenous and intramuscular injections. The mono derivative was more active than the di derivative and produced a longer effect duration than the native insulin after intravenous injection. The derivatives were also shown to be less immunoreactive as judged by an enzyme immunoassay.

Amino Acids↗

Solution syntheses of two enkephalin-containing peptides, peptide E and dynorphin(1-24), using Nin-(2,4,6-triisopropylphenylsulfonyl)tryptophan.

Two enkephalin-containing peptides, peptide E and dynorphin(1-24), were synthesized by conventional solution methods employing a new Trp derivative, Nin-(2,4,6-triisopropylphenylsulfonyl)tryptophan [Trp(Tps)]. All protecting groups employed including the Tps group were removed by treatment with 1 M trifluoromethanesulfonic acid (TFMSA)-thioanisole in trifluoroacetic acid (TFA) at the final steps of these syntheses. Subsequent purifications by Sephadex G-25 chromatography, CM-Biogel A ion exchange chromatography, and reversed-phase high-performance liquid chromatography afforded highly purified samples. Both synthetic peptide E and dynorphin(1-24) exhibited high in vitro opioid activity. The usefulness of this new tryptophan derivative for practical peptide synthesis was established through these syntheses of complex Trp-containing peptides.

Amino Acid Sequence↗

Tetrafluoroboric acid, a useful deprotecting reagent in peptide synthesis.

We have found that tetrafluoroboric acid (HBF4) in trifluoroacetic acid (TFA) in the presence of thioanisole cleaves various protecting groups currently used in peptide synthesis. HBF4 in TFA cleaves an amino acid amide from 4-methylbenzhydrylamine resin more effectively than trifluoromethanesulfonic acid in TFA. Lamprey gonadotropin-releasing hormone (a 10-residue peptide amide) was synthesized using 1 M HBF4-thioanisole in TFA by both solution-phase and solid-phase methods.

Amino Acid Sequence↗

A case of refetoff syndrome: selective venous sampling for TSH is useful in differentiating thyroid hormone resistance from TSH secreting tumor.

A 22-year old man with a goiter and clinical manifestations of mild thyrotoxicosis (finger tremor, palpitation, tachycardia) was diagnosed as a syndrome of inappropriate secretion of TSH. Serum concentrations of T4, free T4, T3 and TSH were 24.1 micrograms/100 ml, 4.07 ng/100 ml, 261 ng/100 ml and 1.72 microU/ml, respectively. Thyroidal 131I uptake at 24 hr was 80%. The BMR was within the normal range. He had a normal TSH response to TRH (500 micrograms) with a peak level of 23.8 microU/ml. The basal level of alpha-subunit of TSH was not elevated (0.35 ng/ml). Oral 1-T3 administration (75 and 150 micrograms daily) raised serum T3 concentration, reduced basal TSH and blunted TSH response to TRH. The diurnal variation of TSH was maintained. There was no evidence of abnormalities in the secretion of other pituitary hormones. These findings were compatible with thyroid hormone resistance. However, the presence of a microadenoma in the pituitary gland was suspected with CT scan. Bilateral and simultaneous venous sampling for TSH from inferior petrosal sinus showed no gradient in TSH concentration indicating that a TSH secreting pituitary tumor was unlikely. These data suggest that inappropriate TSH secretion in the present patient is resulted from resistance to thyroid hormone. In the present study selective venous sampling is useful to differentiate the thyroid hormone resistance from a TSH secreting tumor.

Adult↗

Prenatal and postnatal development of the small intestine in the insectivore Suncus murinus.

The development of the small intestine in the insectivore Suncus murinus was noted during the period from 21 days' gestation to 20 days after birth. At 21 days of gestation, the proximal small intestine exhibited the beginning of villus formation, whereas the distal small intestine preserved the stratified epithelium. Stratified epithelium in the distal small intestine changed into a single layer by 24 days' gestation. At 26 days' gestation, each epithelial cell was immature; but by 28 days mature-looking epithelial cells were found. The shape of the villi changed from cuboid to columnar during the same period. The connective-tissue cores of the villi began to develop at 7 days after birth in the proximal small intestine and at 15 days after birth in the distal small intestine. Crypts appeared at 15 days after birth. Endocytosis of epithelial cells took place at 28 days of gestation. In the proximal small intestine, supranuclear vesicle clusters were observed first at birth; they began to decrease both in number and size at 10 days' gestation and then disappeared completely by 20 days after birth. In the distal small intestine, large supranuclear vacuoles were observed first at 28 days of gestation. Although these vacuoles invariably were found up to 15 days after birth, they also disappeared completely by 20 days. Epithelial cells showed a structure similar to those of the adult after weaning.

Animals↗

Properties of thyrotropin (TSH) binding to plasma membranes prepared from rat fat tissues.

Rat fat membranes were prepared from male Sprague-Dawley rats. At 37 degrees C, TSH binding to rat fat membranes was rapid and unstable, although the binding reached a steady state after 2 hr and unchanged up to 24 hr at 4 degrees C. The binding to rat fat membranes was significantly inhibited by 50 mM NaCl and almost completely inhibited by 150 mM NaCl. TSH binding to rat fat membranes was not affected by 10 mM dithiothreitol (DTT) or 1 mM diamide although the binding to human thyroid membranes was inhibited by 10 mM DTT significantly. Conventional Scatchard analysis revealed a single class of binding site which had lower Ka value (2.6 X 10(8) M-1) than that of high affinity binding site of human thyroid membranes (9.3 X 10(8) M-1). Immunoglobulin G (IgG) from patients with Graves' disease inhibited the binding of TSH to rat fat membranes. A significant correlation was observed between the inhibiting activity of Graves' IgG measured with rat fat and human thyroid membranes (r = 0.82, p less than 0.01). In conclusion, TSH receptors on rat fat membranes were not identical to those on human thyroid membranes, but TSH receptor antibodies crossreacted with TSH receptors in rat fat tissue.

Adipose Tissue↗

Isotachophoretic determination of mobility and pKa by means of computer simulation. V. Evaluation of mo and pKa of twenty-eight dipeptides and assessment of separability.

Isotachophoretic qualitative indices, RE, for twenty-eight dipeptides were measured in the range pH 7.4-9.6. The absolute mobility, mo, and pKa values were evaluated by the use of the least-squares method, utilizing a simulation of the isotachophoretic steady state. The mo values were newly evaluated and the pKa values were in good agreement with literature values. By comparison of the evaluated mo and pKa values of the dipeptides with those of the constituent amino acids, simple relationships were found which may be used to estimate the mo and pKa values of other dipeptides. The separability of the dipeptides was also evaluated by considering the differences between their simulated effective mobilities. It is concluded that isotachophoresis is very convenient for the separation of dipeptides and their constituent amino acids.

Amino Acids↗

Antihepatotoxic actions of Cochlospermum tinctorium rhizomes.

The antihepatotoxic activity of the rhizomes of Cochlospermum tinctorium was investigated using carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes. Because the methanol and ethanol extracts of C. tinctorium rhizomes exhibited antihepatotoxic effects, the former was fractionated in order to elucidate the active constituents. Polyphenol compounds (gallic and ellagic acids) were detected in the active fractions and may account for much of the antihepatotoxic activity. Carotenoids could also be implicated in the activity of the total extracts.

Alanine Transaminase↗

Observation of fallout in Hiroshima caused by the reactor accident at Chernobyl.

Fallout from the reactor accident at Chernobyl has been surveyed at Hiroshima. gamma-rays from samples of aerosol, rain water and tap water were measured using low-background gamma-ray spectrometers and concentrations of activities were followed. Almost all of the nuclides detected in Europe were observed in Hiroshima. In addition to dominant volatile fission products of 131I, 132Te-132I and 103Ru, long-lived fission products 137Cs, 106Ru-106Rh, 125Sb and activities produced through the (n, gamma) process in the reactor such as 134Cs, 136Cs and 110mAg were observed in relatively high concentrations.

Accidents↗