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Biomedical subjects

S Inoue

Publications and source records attributed to S Inoue.

At least 1,081 records · Page 60Linked to original sources
PubMed1990

Effect of phosphate depletion on vasopressin secretion and kidney tissue vasopressin concentration in rats.

The effects of chronic phosphate depletion on vasopressin (ADH) secretion and kidney tissue ADH concentration were examined in rats fed on a diet containing 0.26% phosphorus (LP) or 0.99% phosphorus (NP). The concentration of plasma phosphorus (P) fell significantly in the LP rats after a 4-week period on the experimental diet. There was no significant difference between the LP and NP rats as regards their plasma ADH concentrations and kidney tissue ADH concentrations in normal hydration after a 4-week period on the experimental diets. Following hypertonic saline tests, the plasma ADH concentrations increased significantly in the LP and NP rats, but there was no significant difference between the groups. The kidney medulla and papilla ADH concentrations increased significantly with plasma ADH elevations in both groups. Again, no difference could be found in the cortico-medullary ADH concentration gradients between the two groups. These results indicate that chronic hypophosphatemia in phosphate depleted rats may not be related to ADH secretion and the distribution or tissue concentration of ADH in the kidney. Further, our data suggest that a low plasma P does not influence the ability of ADH to bind to kidney receptor in rats.

Animals↗
PubMed1990

[Investigation of adsorption, metabolism and excretion of cefuroxime axetil in volunteers of gastrectomized patients].

Adsorption, metabolism and excretion (ADME) of cefuroxime axetil (CXM-AX) 500 mg given orally at 30 minutes after meals to male volunteers who had undergone gastrectomy was compared with that of healthy volunteers. 1. The transition of the drug's serum concentrations was observed as follows: Tmax was somewhat shorter and T 1/2 longer in the gastrectomized volunteer group than in the healthy volunteer group. 2. Total urinary recovery rates of cefuroxime (CXM) were not significantly different between the 2 groups, averaging 53.6% for the gastrectomized volunteer group and averaging 54.5% for the healthy volunteer group. 3. Total urinary recovery rates of CXM-delta 2 were not significantly different between the 2 groups either, averaging 1.7% for the gastrectomized volunteer group and 1.3% for the healthy volunteer group. 4. The above results suggest that ADME of CXM-AX in the gastrectomized volunteers is not fundamentally different from that of the healthy volunteers. The absorption, however, may be reduced when peristalsis of the intestinal tract is accelerated as a result of gastrectomy.

Administration, Oral↗
PubMed1990

Schedule-dependent interaction of cytarabine plus doxorubicin or cytarabine plus mitoxantrone in acute myelocytic leukemia cells in culture.

Schedule-dependent interaction of 1-beta-D-arabinofuranosylcytosine (ara-C, cytarabine) plus doxorubicin or ara-C plus mitoxantrone was studied in vitro using HL-60 human acute myelocytic leukemia cell line. The cells were exposed for 1 hr to each drug simultaneously, or sequentially (up to a 28-hr interval), and cell kill effects were determined by clonogenic assay. The results were compared with controls in which cells were exposed to the individual drug only and seeded after appropriate intervals. Simultaneous exposure to two drugs produced lethal effects, but no more than those produced by doxorubicin or mitoxantrone alone. Ara-C followed by doxorubicin produced time-dependent increases in cell kill that was parallel to the doxorubicin alone control, indicative of no true potentiation. In contrast, ara-C followed by mitoxantrone produced striking increases in cell kill effects. Thus, ara-C followed by mitoxantrone resulted in more than 10-fold increases in cell kill at the intervals of greater than or equal to 8 hr between exposures, and the strong cell kill effects were maintained. Our data indicate that: (a) simultaneous exposure to ara-C and doxorubicin or mitoxantrone is less than additive; (b) ara-C followed by doxorubicin is probably only additive; and (c) ara-C followed by mitoxantrone is more than additive, and cell kill effects are sustained.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Stabilization of disulfide linkage in drug-polymer-immunoglobulin conjugate by microenvironmental control.

The stability of disulfide linkage in the conjugate composed of the anti-cancer agent adriamycin, poly(ethylene glycol)-poly(aspartic acid) block copolymer, and immunoglobulin G was studied. The disulfide linkage between the block copolymer and immunoglobulin G was found to be resistant to reduction with dithiothreitol (DTT). This extraordinary resistance is considered to be brought about by steric hindrance of the poly(aspartic acid) chain binding adriamycin.

Aspartic Acid↗
PubMed1989

Amino acid sequences of cytotoxin-like basic proteins derived from cobra venoms.

Amino acid sequences of cytotoxin-like basic proteins (CLBPs), purified from the venoms of Formosan cobra (Naja naja atra) and Indian cobra (Naja naja), were reinvestigated. The determined sequences differed from those reported previously by Takechi et al. [(1985) Biochem. Int. 11, 795-802; (1987) Biochem. Int. 14, 145-152]. The sequence of CLBPs at residues 25-30 was found to be hydrophilic as compared with those of cytotoxins. The difference in the hydrophobicity of this region might be responsible for the difference in their cytotoxic activities.

Amino Acid Sequence↗
PubMed1989

Isolation and structures of glycoprotein-derived free sialooligosaccharides from the unfertilized eggs of Tribolodon hakonensis, a dace. Intracellular accumulation of a novel class of biantennary disialooligosaccharides.

Novel acidic oligosaccharides were isolated in abnormally large amounts (about 200 ng/egg) from the unfertilized eggs of Tribolodon hakonensis (a dace, "ugui" in Japanese). The free oligosaccharides were found to consist of a mixture of disialylated species most of which end with beta-mannosyl N-acetylglucosamine structure at their reducing termini, i.e. greater than Man beta 1-4GlcNAc. A minute portion of the sialooligosaccharides was found to have the reducing terminal structure, di-N-acetylchitobiose, i.e. greater than Man beta 1-4GlcNAc beta 1-4GlcNAc. From the structural analysis of these free sialooligosaccharides, the following structures are proposed: (sequence; see text) Occurrence of such a symmetrically or dissymmetrically branched form of the biantennary nonreducing periphery as revealed here is novel. Although it is unknown why and how such high amounts of free oligosaccharides are accumulated in unfertilized eggs, these were presumably protein-linked components and must be released at certain stages of oogenesis.

Animals↗
PubMed1989

Steroidogenesis in liposomal system containing adrenal microsomal cytochrome P-450 electron transfer components.

Purified adrenal microsomal P-450C21 and/or P-45017 alpha,lyase were incorporated with purified NADPH-cytochrome-P-450 reductase into liposome membranes composed of phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine at a molar ratio of 5:3:1. The rate dependences of reduction of liposomal P-450C21 in the fast phase as well as progesterone hydroxylation activities of P-450C21 and P-45017 alpha,lyase on the reductase concentration in the liposome membranes suggested that electrons were delivered through random collisions between the reductase and cytochrome P-450s in the liposome membranes. A rapid exchange of the steroid metabolic intermediate between vesicles was observed in a reaction system consisting of P-450C21-proteoliposomes and P-45017 alpha,lyase-proteoliposomes. Using the combined liposomal system, it was definitely proved that androstenedione was formed from progesterone mainly by a successive hydroxylation reaction without the intermediate 17 alpha-hydroxyprogesterone leaving from P-45017 alpha,lyase. It was also found that 21-hydroxylation of 17 alpha-hydroxyprogesterone into 11-deoxycortisol was inhibited by a physiological concentration of progesterone.

Adrenal Glands↗
PubMed1989

Isolation and characterization of deaminated neuraminic acid-rich glycoprotein (KDN-gp-OF) in the ovarian fluid of rainbow trout (Salmo gairdneri).

A novel highly acidic glycoprotein (deaminated neuraminic acid-rich glycoprotein; KDN-gp) was first discovered as an integral component of the vitelline envelope of rainbow trout eggs [Inoue, S., et al. (1988) Biochem. Biophys. Res. Commun. 153, 172-176]. Another member of this class of glycoprotein has now been found in the ovarian (or coelomic) fluid of ovulating rainbow trout. This ovarian fluid KDN-glycoprotein is designated as KDN-gp-OF and its amino acid and carbohydrate compositions were compared with those of the vitelline envelope KDN-gp (KDN-gp-VE). KDN-gp-OF was similar to KDN-gp-VE in the carbohydrate composition and molecular weight. However, a small but definite difference in amino acid composition and the molecular weight range was found between KDN-gp-OF and KDN-gp-VE. The results suggest that in KDN-gp-OF some peptide sequences presumably present at either the C- or N-terminus are deleted from KDN-gp-VE. Possible biological function of KDN-gp-OF is discussed.

Amino Acids↗
PubMed1989

Site-specific DNA damage induced by sulfite in the presence of cobalt(II) ion. Role of sulfate radical.

The reactivities of sulfite (SO23-) with DNA in the presence of metal ions were investigated by a DNA sequencing technique using 32P-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene. Sulfite caused DNA damage in the presence of Co2+, Cu2+ and Mn2+, although sulfite alone or metal ion alone did not. The order of inducing effect on sulfite-dependent DNA damage (Co2+ much greater than Cu2+ greater than Mn2+ Fe3+) was consistent with that of accelerating effect on the initial oxygen consumption rate of sulfite autoxidation. The DNA damage induced by sulfite plus Co2+ was inhibited by 3,5-dibromo-4-nitrobenzenesulfonate, primary and secondary alchols, whereas it was not inhibited by SOD, catalase and tert-butyl alcohol. Incubation of DNA with sulfite plus Co2+ followed by the piperidine treatment led to the predominant cleavage at the positions of guanine especially located 5' to guanine. Sulfite plus Cu2+ gave a DNA cleavage pattern different from that induced by sulfite plus Co2+. The photolysis of peroxydisulfate (S2O28-), which is known to produce SO-4 radicals, gave a DNA cleavage pattern similar to that induced by sulfite plus Co2+. ESR studies using spin-trapping reagent revealed the production of spin adduct possibly of SO-3 radical in a solution of sulfite plus Cu2+, whereas much less spin adduct was produced by sulfite plus Co2+. The results suggest that sulfite is rapidly autoxidized in the presence of Co2+ to produce SO4- radical causing site-specific DNA damage.

Alcohols↗
PubMed1989

Structural studies of fertilization-associated carbohydrate-rich glycoproteins (hyosophorin) isolated from the fertilized and unfertilized eggs of flounder, Paralichthys olivaceus. Presence of a novel penta-antennary N-linked glycan chain in the tandem repeating glycopeptide unit of hyosophorin.

New glycoproteins of 100-120 kDa were isolated from the unfertilized eggs of flounder, Paralichthys olivaceus. Compositionally indistinguishable glycopeptides of 6 kDa were also purified from the activated or fertilized eggs. These high and low molecular mass glycoproteins are characterized by high (about 85%) carbohydrate content. Although some heterogeneities exist in the amino acid sequences, the 6-kDa glycopeptides (decapeptides with single large N-linked glycan chains), isolated from the fertilized eggs are the repeating units of the high molecular mass glycoproteins. As judged from several distinctive features the 100-120-kDa glycoproteins are apparently major components of cortical alveoli of flounder eggs and are regarded as members of glycoproteins we have defined under the name of "hyosophorin" (Kitajima, K., Inoue, S., and Inoue, Y. (1989) Dev. Biol. 132, 544-553). Composition analysis, Smith degradation, hydrazinolysis-nitrous acid deamination, permethylation analysis, and 400-MHz 1H NMR spectroscopy provided evidence for the structure of a novel penta-antennary glycan chain attached to the repeating unit (decapeptide) of the protein core. The structure thus determined is: (Formula: see text). The presence of a unique class of carbohydrate-rich glycoproteins (H-hyosophorin) in the unfertilized eggs, their conversion to the repeating unit (L-hyosophorin) at fertilization, and the finding of a free glycan chain that was formed by scission between the GlcNAc and Asn residues of L-hyosophorin, in the fertilized eggs including embryos of 4-11-h postinsemination, support the view that these molecules may be important in fertilization and subsequent development.

Amino Acid Sequence↗
PubMed1989

Thyroid hormones inhibit platelet function and myosin light chain kinase.

We examined the extranuclear effects of thyroid hormones on human platelets. Pretreatment with DL-thyroxine or DL-triiodothyronine inhibited collagen-induced aggregation, in a dose-dependent manner, but other derivatives of thyroid hormone had no significant effects. In contrast to collagen, 12-O-tetradecanoylphorbol-13-acetate-induced aggregation was not affected by thyroid hormones at the same concentration range. Thyroxine also inhibited the release of [14C] serotonin from collagen-stimulated platelets, with a marked reduction in the phosphorylation of 20,000-dalton protein. Thyroxine and triiodothyronine had inhibitory effects on myosin light chain kinase purified from human platelets and inhibited more markedly the myosin light chain kinase than protein kinase C (Ca2+/phospholipid-dependent enzyme) and cAMP-dependent protein kinase. In addition, L-thyroxine behaved as a competitive inhibitor of myosin light chain kinase toward calmodulin, and the Ki value was calculated to be 2.6 microM. To determine whether or not thyroxine directly binds myosin light chain kinase, we prepared an affinity column, using L-thyroxine as the ligand. Myosin light chain kinase was selectively bound to the column while calmodulin passed through. We also designed a procedure for the purification of myosin light chain kinase from human platelets, using L-thyroxine-affinity chromatography. A markedly increased purification was thus achieved, and DEAE-cellulose and L-thyroxine-affinity chromatography were made feasible. These results suggest that thyroxine can serve as a pharmacological tool for elucidating the biological significance of myosin light chain kinase-mediated reactions and is a pertinent ligand which can be used to purify myosin light chain kinase from platelets as a substitute for calmodulin.

Blood Platelets↗
PubMed1989

ESR evidence for superoxide, hydroxyl radicals and singlet oxygen produced from hydrogen peroxide and nickel(II) complex of glycylglycyl-L-histidine.

ESR studies using spin traps, 5,5-dimethylpyrroline-N-oxide and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone, revealed that hydroxyl radical adducts are produced by the decomposition of hydrogen peroxide in the presence of nickel(II) oligopeptides. Order of catalytic activities of nickel(II) oligopeptides used in the production of hydroxyl radical adducts was tetraglycine greater than pentaglycine greater than triglycine greater than GlyGly, GlyHis. Ni(II) GlyGlyHis plus hydrogen peroxide produced superoxide in addition to hydroxyl radical adduct. Trapping experiments with 2,2,6,6-tetramethyl-4-piperidone suggested that singlet oxygen was generated by the reaction of hydrogen peroxide with Ni(II) GlyGlyHis, but not in the case of tetraglycine, pentaglycine, triglycine, GlyGly or GlyHis.

Catalysis↗
PubMed1989

The influence of ventricular extrasystoles and postextrasystoles on cardiovascular dynamics in anesthetized dogs.

The influence of ventricular extrasystoles and postextrasystoles on cardiovascular dynamics were assessed in terms of maximum rate of rise of left ventricular pressure (max dP/dt), ascending aortic flow, left ventricular stroke volume, and left ventricular end-diastolic transverse dimension in anesthetized dogs. A single ventricular extrasystole, two and three consecutive ventricular extrasystoles (couplet and triplet) were induced by applying mechanical stimulation to the surface of the right ventricule. In any of these ventricular extrasystoles, max dP/dt, stroke volume and end-diastolic transverse dimension were decreased, compared with those in preceding sinus beats, i.e., pre-extrasystoles. Over the several postextrasystoles, max dP/dt was increased and gradually returned to its control level. This increase in max dP/dt, i.e., postextrasystolic potentiation paralleled an increase in ascending aortic peak flow but did not always bring about an increase in stroke volume, even when a left ventricular contraction was initiated by a significantly greater end-diastolic transverse dimension. The postextrasystolic potentiation seems to be associated with the Frank-Starling mechanism and does not compensate for the decreased in stroke volume elicited by the ventricular extrasystoles. In conclusion, not only ventricular extrasystoles per se but also postextrasystoles exert the adverse influence on cardiovascular dynamics consecutively.

Journal Article↗
PubMed1989

A new technique of identifying the epidural space "dripping infusion method".

We developed a new visual technique o identifying the epidural space, using the hydrostatic pressure produced by a suspended micro-drip intravenous apparatus. When the needle pierces the ligamentum flavum, the resistance to positive pressure disappears and the saline in the apparatus flows freely into the epidural space. Thus, the entry of the needle point into the epidural space is visually confirmed by the appearance of dripping flow in the drip bulb (dripping infusion sign). This procedure was clinically evaluated at the thoraco-cervical area in 114 patients; the thoracic area in 116; and the lumbar area in 272, respectively. In 491 (97.8%) of the patients, the epidural space was identified with facility. In the remaining 11 patients (2.2%), a false dripping infusion sign appeared at the more superficial site than expected. If the pressure waveform in the epidural space is analyzed, the correct positioning of the needle can be easily confirmed. We believe that this method is one of the most accurate visual methods of identifying the epidural space and useful for teaching the epidural blockade to students and residents.

Journal Article↗
PubMed1989

Free sialooligosaccharides found in the unfertilized eggs of a freshwater trout, Plecoglossus altivelis. A large storage pool of complex-type bi-, tri-, and tetraantennary sialooligosaccharides.

Unfertilized eggs of Plecoglossus altivelis (a kind of freshwater trout, "Ayu" in Japanese) were found to contain a relatively large pool of three sialooligosaccharides. These free oligosaccharides were accumulated in the cytoplasm up to concentrations of about 35 ng per egg, which correspond to about 107 micrograms/g. Their structures were determined by a combination of chemical (composition and methylation analysis and Smith degradation) and instrumental (fast atom bombardment-mass spectrometry, secondary ion mass spectrometry, and 400-MHz1H NMR) analyses. The structures established represent a typical type of bi-, tri-, and tetraantennary sialooligosaccharides all of which end with di-N-acetylchitobiose structure (-GlcNAc beta 1-4GlcNAc) and alpha -2,3-linked NeuAc at reducing and nonreducing termini, respectively. These data show that these free sialooligosaccharides, which were originally protein-linked components, must be released during oogenesis. Although a specific functional requirement for their release is not known, the occurrence of such free sialooligosaccharides in normal animal cells or tissues has not been previously reported.

Animals↗
PubMed1989

Human DNA damage induced by 1,2,4-benzenetriol, a benzene metabolite.

Reactivities of benzene metabolites (phenol, catechol, hydroquinone, 1,4-benzoquinone, 1,2,4-benzenetriol) and related polyphenols (resorcinol, pyrogallol, phloroglucinol) with DNA were investigated by a DNA sequencing technique using 32P 5'-end-labeled DNA fragments obtained from human c-Ha-ras-1 protooncogene, and the reaction mechanism was studied by UV-visible and electron-spin resonance spectroscopies. 1,2,4-Benzenetriol caused strong DNA damage even without alkali treatment. Alkali-labile sites induced by 1,2,4-benzenetriol were base residues of guanine and adjacent thymine. Catalase, superoxide dismutase and methional inhibited the DNA damage completely, but sodium formate did not inhibit it. 1,2,4-Benzenetriol-induced DNA damage was inhibited by the addition of a Cu(I)-specific chelating agent, bathocuproine, and was accelerated by the addition of Cu(II). The addition of Fe(III) did not create any significant effects on 1,2,4-benzenetriol-induced DNA damage. Electron-spin resonance studies using spin traps demonstrated that addition of Fe(III) increased hydroxyl radical production during the autoxidation of 1,2,4-benzenetriol, whereas the addition of Cu(II) did not. The results suggest that DNA damage was caused by an unidentified active species which was produced by the autoxidation of 1,2,4-benzenetriol in the presence of Cu(II), rather than by hydroxyl radicals. The possibility that 1,2,4-benzenetriol-induced DNA damage is one of the primary reactions in carcinogenesis induced by benzene is discussed.

Chelating Agents↗