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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 19 recordsLinked to original sources
PubMed1992

Augmentation of retinoic acid-induced granulocytic differentiation in HL-60 leukemia cells by serine/threonine protein phosphatase inhibitors.

To evaluate the involvement of protein phosphatases (PP) in differentiation of human myelogenous leukemia HL-60 cells, we made use of potent inhibitors of PP1 and PP2A, calyculin-A (CAL-A) and okadaic acid (OKA). CAL-A and OKA could augment all-trans retinoic acid (ATRA)-induced granulocytic differentiation, whereas the differentiation toward macrophage lineage by 12-o-tetradecanoylphorbol acetate (TPA) was unchanged in the presence of CAL-A. CAL-A augmented the phosphorylation of 18K, 23K and 30K proteins induced by ATRA. The PP1 and PP2A were identified and were present mainly in the cytosol of HL-60 cells. These results suggest that either PP1 or PP2A or both may be involved in regulating granulocytic differentiation of HL-60 cells.

Cell Adhesion↗
PubMed1992

Therapeutic effects of superoxide dismutase derivatives modified with mono- or polysaccharides on hepatic injury induced by ischemia/reperfusion.

Therapeutic effects of four types of recombinant superoxide dismutase (SOD) derivatives, conjugates with polysaccharides, carboxymethyl (SOD-CMD) and diethylaminoethyl (SOD-DEAED) dextrans and galactosylated (Gal-SOD) and mannosylated (Man-SOD) derivatives, on hepatic ischemia/reperfusion injury were studied in rats. Hepatic injury induced by transient occlusion and subsequent reflow of hepatic blood was evaluated by the analysis of biliary excretion of bromosulfophthalein (BSP) injected intravenously. At a dose of 10000 units/kg, native SOD and SOD-DEAE did not show any significant effect and SOD-CMD showed slight effect. On the other hand, Gal-SOD and Man-SOD, targeted to the liver parenchymal and nonparenchymal cells, respectively, by a receptor-mediated endocytosis, exhibited superior inhibitory effects. These results demonstrated that these glycosylated SOD derivatives were useful for the prevention of hepatic ischemia/reperfusion injury.

Animals↗
PubMed1992

Deletion mutagenesis of stem cell factor defines the C-terminal sequences essential for its biological activity.

We constructed a series of murine stem cell factor (mSCF) cDNAs which were sequentially truncated at the 3' termini. The resultant six mutant cDNA encode N-terminal 183, 179, 162, 149, 142 and 133 amino acid residues of the mature mSCF protein fused to the heterogeneous C-terminal peptides derived from the linker sequences. Each mutant cDNA was transiently expressed in COS cells, and the cultured supernatant was assayed for its ability to support the growth of a human factor-dependent cell line, TF-1 and to enhance colony formation by murine hematopoietic progenitor cells. The results showed that as few as N-terminal 142 but not 133 amino acid residues of mSCF remained biologically active in vitro, suggesting that the region of 9 amino acids from Asp134 to Ser142 containing a Cys138-mediated disulfide bond may contribute to the C-terminal end of the active subdomain of mSCF.

Amino Acid Sequence↗
PubMed1992

AE0047, a new dihydropyridine Ca2+ entry blocker, inhibits the responses to adrenergic nerve stimulation and substance P in dog mesenteric arteries.

AE0047, a new dihydropyridine-type Ca2+ entry blocker, significantly inhibited the contractions induced by transmural electrical stimulation and norepinephrine in dog mesenteric artery strips. The inhibition was greater in the case of the response to nerve stimulation. The 3H-overflow ratio evoked by electrical stimulation from strips previously soaked in [3H]norepinephrine was significantly reduced by AE0047 but not by nicardipine in a concentration sufficient to attenuate the response to norepinephrine. In aorta homogenate preparations, [3H]bunazosin binding was not replaced by AE0047 but by phentolamine. In strips treated with indomethacin, the endothelium-dependent relaxation caused by substance P and bradykinin was attenuated by treatment with AE0047 but not with nicardipine. The nitric oxide (NO)-induced relaxation was not influenced by AE0047. Cyclic GMP levels in the artery strips increased in response to substance P; the increase was markedly suppressed by AE0047 but not by nicardipine. In contrast to nicardipine, AE0047 appeared to inhibit the release of norepinephrine from adrenergic nerves and of NO from endothelial cells. The inhibition may be associated with the decreased transmembrane influx of Ca2+ in these tissues.

Adrenergic alpha-Agonists↗
PubMed1992

High-performance liquid chromatographic determination of pamaquine, primaquine and carboxy primaquine in calf plasma using electrochemical detection.

A high-performance liquid chromatographic method with electrochemical detection is described for quantification of pamaquine, primaquine and carboxy primaquine in calf plasma. After the proteins had been precipitated with acetonitrile, the drugs were separated on a 5-microns C18-modified polymer gel column with an isocratic mobile phase. The detection limit was 0.01 microgram/ml in plasma for all three compounds. The applicability of the method in pharmacokinetic studies was demonstrated by determining the plasma concentrations of the three substances in calves administered a single dose of pamaquine or primaquine.

Aminoquinolines↗
PubMed1992

Partial purification of phosphoramidon-sensitive endothelin converting enzyme in porcine aortic endothelial cells: high affinity for Ricinus communis agglutinin.

A membrane-bound endothelin converting enzyme (ECE) of porcine aortic endothelial cells (ECs) was solubilized with Lubrol PX with high efficiency and stability. The solubilized ECE was bound to Ricinus communis agglutinin (RCA) but not to peanut agglutinin (PNA) or wheat germ agglutinin (WGA), suggesting that the ECE has a galactosylated structure possessing a high affinity for RCA. The sequential chromatography on RCA-agarose, PNA-agarose and a TSKgel DEAE-5PW column attained 2,100-fold purification for the ECE over the membrane fractions. The purified ECE was sensitively inhibited by phosphoramidon but not by thiorphan. The present RCA and PNA affinity column procedures may be a powerful approach to isolation of ECE of EC origin.

Animals↗
PubMed1992

Purification and properties of a decapping enzyme from rat liver cytosol.

A decapping enzyme has been purified about 2400-fold from rat liver cytosol. The decapping enzyme was shown to be fairly homogeneous by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme had an apparent molecular weight of 110,000 and consisted of two equal subunits. The enzyme hydrolyzed m7Guo5'PPP5'Ado to m7GMP and ADP. Analysis of the products produced from radioactively capped oligonucleotides and intact mRNA having 3H-cap suggests that the enzyme can hydrolyze capped mono- to pentanucleotides (m7Guo5'PPP5'N (where N = 1-5 nucleotides)) but not intact mRNA. The existence of methyl group at the N7 position of guanosine moiety of cap structure was necessary for the action of the decapping enzyme. This was confirmed by the comparison of the rates of hydrolysis of m7Guo5'PPP5'Ado by the enzyme in the presence of various nucleotides. The activity of enzyme was slightly stimulated by Na+, K+, NH4+, Ca2+ and polyamines. Mg2+ and Mn2+ were without effect on the enzyme activity.

Animals↗
PubMed1992

Inhibitory and stimulatory actions of danazol in rat ovarian and uterine tissues.

We examined whether danazol has a direct action on ovarian steroid secretion and/or uterine prostaglandin (PG) F2 alpha catabolic activity in immature rats in which the first ovulation was induced and in adult ovariectomized rats. The preovulatory surge of estradiol and progesterone was markedly suppressed together with that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by danazol administration under conditions that blocked the first ovulation. Uterine weight and PGF2 alpha catabolic activity enhanced by endogenous estrogen were greatly decreased by danazol treatment at a dose that did not block the first ovulation in immature rats. When danazol (30 mg) was given s.c. once daily for 2 days to ovariectomized rats, the uterine weight and PGF2 alpha catabolic activity per uterus were clearly increased, and the compensatory increase in FSH levels as a result of castration was not influenced, although the compensatory increase in LH levels was inhibited. These results demonstrate that danazol has a direct action on the ovary and uterus, and give further support to the view put forward in our previous paper that these actions of danazol may contribute to its therapeutic effects.

Administration, Oral↗
PubMed1992

Combined effects of ozone and cigarette smoke on airway responsiveness and vascular permeability in guinea pigs.

The effects of combined exposure to ozone and cigarette smoke on airway responsiveness and tracheal vascular permeability, compared with those of single exposure were examined in guinea pigs. Airway responsiveness was assessed by measuring the specific airway resistance (sRaw) as a function of increasing concentration of inhaled methacholine aerosol immediately, 5 hr, and 24 hr after exposure. In a parallel study, tracheal vascular permeability was quantified by measuring the tracheal extravasation of intravenously administered Evans blue dye. Neither exposure to 1 ppm ozone for 30 min nor 5 puffs of cigarette smoke increased airway responsiveness or vascular permeability at any time after exposure. Combined exposure to 1 ppm ozone for 30 min and 5 puffs of cigarette smoke caused airway hyper-responsiveness and increased vascular permeability immediately after exposure. Exposure to 1 ppm ozone for 90 min increased both airway responsiveness and vascular permeability immediately after exposure. Exposure to 10 puffs of cigarette smoke increased airway responsiveness but not vascular permeability immediately after exposure. Combined exposure to 1 ppm ozone for 90 min and 10 puffs of cigarette smoke increased both airway responsiveness and vascular permeability immediately after exposure. The combined exposure to ozone and cigarette smoke thus increased both airway responsiveness and tracheal vascular permeability to a greater extent than did exposure to a single agent, suggesting that a combination of air pollutants has a more deleterious effect both on airway responsiveness and on tracheal vascular permeability than does either agent alone in guinea pigs.

Airway Resistance↗
PubMed1992

DNA integration into recipient yeast chromosomes by trans-kingdom conjugation between Escherichia coli and Saccharomyces cerevisiae.

IncQ-derived conjugative shuttle vectors, which carried the yeast gene URA3 and/or the yeast autonomously replicating sequence (ARS1), were constructed. Both the ars-plus plasmid pAY205 and the ars-less plasmid pAY201 were successfully transmitted from E. coli to S. cerevisiae by the action of mob and tra. In this trans-kingdom conjugation, plasmid pAY205 could replicate and be retained in transconjugants. Plasmid pAY201 caused the formation of "micro-colonies" of abortive transconjugants due to its transient expression and rapid disappearance. Nevertheless, one per about 10(3) colonies caused by transmitted pAY201 plasmids were uncurable by integration into the homologous region of a yeast chromosome. Analyses by restriction enzyme mapping and Southern hybridization indicate that this integration is primarily caused by a double crossover during conjugation and not by a single reciprocal recombination.

Blotting, Southern↗
PubMed1992

Giant basal prolactinoma extending into the nasal cavity.

An unusual case of a giant prolactinoma extending to the nasopharynx and nasal cavity is presented. A 35-year-old man admitted for nasal obstruction and visual disturbances was found to have bilateral anosmia, right homonymous hemianopsia, and a right hemiparesis. The serum prolactin level was 13,300 ng/mL. Radiological examination revealed a large mass invading the skull base and extending into the suprasellar region and the left frontal lobe superiorly and into the nasopharynx inferiorly. Subtotal removal was done through a bilateral orbitofrontal craniotomy, which was followed by radiotherapy and bromocriptine administration. Immunohistochemical analysis confirmed a prolactinoma. The rarity of such a tumor, its location and extension, and the usefulness of magnetic resonance imaging and immunohistochemistry are stressed. Pertinent literature is reviewed.

Adult↗
PubMed1992

Endovascular coil embolization of a recurrent giant internal carotid artery aneurysm via the posterior communicating artery after cervical carotid ligation: case report.

The case of a 29-year-old man with a giant fusiform aneurysm of the left internal carotid artery (ICA) is presented. The aneurysm, treated by cervical ICA ligation and extracranial-intracranial bypass, recurred 4 years later owing to recruitment of the posterior communicating artery (PCoA). Because of the previous bypass surgery a direct surgical approach was excluded. After an initial failure with balloon embolization, the aneurysm was embolized successfully with occlusive platinum microcoils through the microcatheter navigated into the aneurysm via the enlarged PCoA. Endovascular coil embolization may be useful in the treatment of cerebral aneurysms not amenable to direct surgery or balloon embolization.

Adult↗
PubMed1992

Analysis of the eicosapentaenoic acid (EPA) metabolite delta 17-6-keto-PGF1 alpha in human plasma by GC/SIM using [18O] delta 17-6-keto-PGF1 alpha.

A method of the microdetermination of delta 17-6-keto-PGF1 alpha, a hydrolyzed metabolite of PGI3, is described. An authentic delta 17-6-keto-PGF1 alpha (120 mg) was prepared from eicosapentaenoic acid (EPA) incubated with homogenate of bovine aortic intima. [18O]delta 17-6-Keto-PGF1 alpha was synthesized by repeating base-catalyzed hydrolysis of methyl ester derivatives in [18O]water, to obtain an internal standard in gas chromatography/selected ion monitoring (GC/SIM) of delta 17-6-keto-PGF1 alpha. Good linear response over the range of 10 pg-10ng was demonstrated. Chromatographic conditions using a MP-65HT column presented nearly baseline separation of delta 17-6-keto-PGF1 alpha and 6-keto-PGF1 alpha. We were able to detect delta 17-6-keto-PGF1 alpha in the range from 6 to 26 pg/ml of the human plasma. The present method can be applied to the determination of delta 17-6-keto-PGF1 alpha in the human urine and plasma.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Separation and concentration of delta 17-6-keto-PGF1 alpha using monoclonal antibody to omega 3-olefin structure of trienoic prostanoids.

A monoclonal antibody against cis-3-hexen-1-ol was prepared and used to separate and/or concentrate delta 17-6-keto-prostaglandin F1 alpha (PGF1 alpha) in the human sera. cis-3-Hexen-1-ol was conjugated with the human serum albumin (HSA) according to the N-succinimidylester method and hyperimmunized to BALB/c mouse. The monoclonal antibodies were obtained from hybridoma clones established by a fusion between SP2/0-Ag14-k13 mouse myeloma cells and splenocytes of a mouse. A monoclonal antibody, named 4G9-12B, recognized the epitope characteristic for omega 3-olefin structure. The 4G9-12B antibody became more specific for delta 17-6-keto-PGF1 alpha than 6-keto-PGF1 alpha by applying inhibition ELISA using amino-residue coating plates. Using the prepared immunoaffinity columns of this antibody, delta 17-6-keto-PGF1 alpha was clearly detected in 6 pg/ml of the human blood sera by GC/MS analysis. These results suggest that the monoclonal antibody to the partial structure of trienoic prostanoid, omega 3-olefin unit, and that its immunoaffinity columns are useful in separating and concentrating delta 17-6-keto-PGF1 alpha in the human blood or urine.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

A role for protein kinase C in the growth of human erythroid progenitor cells.

We searched for a possible role for protein kinase C in the growth of human erythroid progenitor cells, using pharmacologic approaches. Two protein kinase C inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and staurosporine, dose-dependently inhibited the growth of immature erythroid progenitor cells (BFU-E) induced by interleukin 3 (IL-3) plus erythropoietin (Ep) or granulocyte macrophage colony-stimulating factor (GM-CSF) plus Ep whereas a weaker analog of H-7, N-(2-guanidinoethyl)-5-isoquinoline sulfonamide (HA-1004), had no effect on the number of BFU-E. These three compounds had no effect on the growth of mature erythroid progenitor cells (CFU-E) stimulated by Ep. The culture of accessory cell-depleted bone marrow demonstrated that the effects of these compounds on colony formation do not appear to be mediated by accessory cells. The potential of these compounds to inhibit the GM-CSF-dependent growth of KG-1 cells correlated well with the extent of their inhibitor of protein kinase C activities from KG-1 cells. Thus, the protein kinase C system is apparently involved in the growth of BFU-E, supported by IL-3 or GM-CSF. The growth signal for CFU-E transduced by Ep may be achieved through other systems.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Inhibition of platelet aggregation by the cAMP-phosphodiesterase inhibitor, cilostamide, may not be associated with activation of cAMP-dependent protein kinase.

We examined the involvement of cAMP-dependent protein kinase (A kinase)2 in the inhibition by cilostamide, a specific inhibitor of the low Km cAMP-phosphodiesterase (PDE), on 9,11-epithio-11,12-methanothromboxane A2 (STA2)-induced platelet aggregation. For comparative purposes, the PGE1 analogue, 17S-20-dimethyl-trans-delta 2-PGE1 (OP-1206) was used. OP-1206 (IC50 = 18 +/- 0.55 nM) and cilostamide (IC50 = 40 +/- 4.5 nM) were both potent inhibitors of the platelet aggregation induced by STA2 (1 microM). OP-1206 and cilostamide dose-dependently inhibited elevations in intracellular free Ca2+ ([Ca2+]i) caused by STA2. OP-1206 caused an almost complete inhibition of Ca2+ mobilization, but cilostamide did not prevent the STA2-induced elevation in [Ca2+]i to the same extent as OP-1206, even at a high concentration (greater than 200 nM). Cilostamide did not increase the cAMP level at concentrations (5-100 nm) which affected STA2-induced aggregation. OP-1206 significantly increased cAMP contents in platelets, and the degree of aggregation inhibition by OP-1206 appears to be related to the size of increase in cAMP. OP-1206 increased phosphorylation of the 50,000 mol. wt vasodilator-stimulated phosphoprotein, at concentrations of 7.9-79 nM, which inhibited aggregation induced by STA2. Cilostamide treatment resulted in a marginal increase in the 50,000 mol. wt phosphorylation at concentrations (10-100 nM) which completely inhibited the STA2-induced aggregation. (8R*, 9S*, 11S*)-(-)-9-Hydroxy-9-n-hexyloxy-8-methyl-2,3,9,10- tetrahydro-8,11-epoxy-1H, 8H, 11H-2, 7b, 11a-triazadibenzo(a,g)-cycloocta(c,d,e)trinden-1-one (KT-5720), a specific inhibitor of A kinase, not only reversed the inhibition by OP-1206 of STA2-induced platelet aggregation, but also inhibited the OP-1206-induced protein phosphorylation. However, the inhibition by cilostamide of STA2-induced aggregation was not prevented by pretreatment with KT-5720. Inhibition of the STA2-induced aggregation by OP-1206 may be associated with cAMP-dependent protein phosphorylation, while cilostamide may have inhibitory effects on STA2-induced platelet activation through mechanisms other than the activation of A kinase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Evaluation of the Pharmacia CAP System, a new test for allergic diagnosis (cedar pollinosis).

For the diagnosis of allergic rhinitis we measured the specific IgE and the total serum IgE in the blood. Although we had measured them by the conventional Phadebas RAST and the Pharmacia IgE RIA before, we now adopted the new Pharmacia CAP System (CAP RAST FEIA and CAP IgE FEIA). To compare these methods, we measured the specific IgE to the cedar pollen and total serum IgE in the same blood of 224 hospital staff at the regular physical examination. As a result the new Pharmacia CAP System proved to be simpler, safer, faster, easier, more specific, and more sensitive than the Phadebas RAST and the Pharmacia IgE RIA. And also these methods correlated well with each other.

Adult↗