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Biomedical subjects

Y Okano

Publications and source records attributed to Y Okano.

At least 217 records · Page 12Linked to original sources
PubMed1990

Autoantibody to Th ribonucleoprotein (nucleolar 7-2 RNA protein particle) in patients with systemic sclerosis.

We studied sera of 371 consecutive new patients with systemic sclerosis (SSc; scleroderma) who were first evaluated during 1984-1988. All sera were tested for antinuclear antibodies by immunofluorescence staining using HEp-2 cells as substrate. We excluded 219 sera showing dark nucleoli and screened for antibodies to Th in the remaining 152 sera by immunoprecipitation of a 32P-labeled HeLa cell extract. Fifteen (4.0%) of 371 sera were anti-Th+. Anti-Th antibodies were present in 14 (8.4%) of 167 SSc patients with limited cutaneous involvement, in 1 of 167 with diffuse cutaneous involvement, and in 0 of 37 with SSc overlap syndrome. Among 244 controls with other connective tissue diseases, anti-Th was detected in only 3 patients, all having primary Raynaud's phenomenon of less than 2 years duration. In the subgroup with SSc with limited cutaneous involvement, the 14 anti-Th+ patients had a significantly greater frequency of puffy fingers, small bowel involvement, and hypothyroidism, and a significantly lower frequency of arthralgia and/or arthritis. Their cumulative survival rate from the time of onset of symptoms was lower than that for anti-Th- patients (78% versus 91% at 10 years), primarily due to 3 deaths from pulmonary arterial hypertension (2 from primary pulmonary hypertension and 1 from pulmonary hypertension secondary to pulmonary interstitial fibrosis). Serum anti-Th antibodies are present almost exclusively in patients with SSc with limited cutaneous involvement or in those with primary Raynaud's phenomenon whose disease may evolve to SSc with limited cutaneous involvement, and these antibodies may identify those patients who are at greater risk for reduced survival.

Autoantibodies↗
PubMed1990

Bradykinin induces inositol 1,4,5-trisphosphate-dependent hyperpolarization in K+ M-current-deficient hybrid NL308 cells: comparison with NG108-15 neuroblastoma x glioma hybrid cells.

External application of bradykinin (BK) to mouse neuroblastoma X mouse fibroblast hybrid NL308 cells and mouse neuroblastoma X rat glioma hybrid NG108-15 cells produced a transient outward (hyperpolarizing) current. In NG108-15 cells, BK also induced an inward (depolarizing) current associated with a decrease in input membrane conductance, which results from the inhibition of a voltage-sensitive potassium current, the M-current. However, in NL308 cells, either no depolarization was elicited by BK or, even if the BK-induced depolarization was evoked, it was associated with an increased conductance. To explain the above difference, the intracellular second messenger system of NL308 cells was examined in detail. BK induced the rapid accumulation (three- to fivefold higher than the control level) of inositol 1,4,5-trisphosphate (InsP3) in NL308 cells. The cytosolic Ca2+ concentration was also elevated to 540 nM from 180 nM at a basal level. This seems to be enough to activate a voltage-independent and Ca2(+)-sensitive K+ current, resulting in the hyperpolarization. Intracellular injection of InsP3 replicated the hyperpolarization. NL308 cells possess protein kinase C (C-kinase), with specific activities of C-kinase in cytosolic and membrane fractions being 233 and 24 pmol/min/mg protein, respectively. The activity associated with particulates became higher after phorbol dibutyrate (PDBu) treatment. But NL308 cells did not show the characteristic inward relaxation by step hyperpolarizations and the outward rectification in the current-voltage relationship, indicating that the M current is deficient in NL308 cells. Therefore, application of PDBu failed to mimic the inward current. The results suggest the role of InsP3 and C-kinase in controlling two K+ currents.

Animals↗
PubMed1990

Molecular genetics of PKU in eastern Europe: a nonsense mutation associated with haplotype 4 of the phenylalanine hydroxylase gene.

Phenylketonuria (PKU) is a genetic disorder secondary to a deficiency of hepatic phenylalanine hydroxylase (PAH). Several mutations in the PAH gene have recently been reported, and linkage disequilibrium was observed between RFLP haplotypes and specific mutations. A new molecular lesion has been identified in exon 7 of the PAH gene in a Hungarian PKU patient by direct sequencing of PCR-amplified DNA. The C-to-T transition causes the substitution of Arg243 to a termination codon, and the mutant allele is associated with haplotype 4 of the PAH gene. The mutation is present in two of nine mutant haplotype 4 alleles among Eastern Europeans and is not present among Western Europeans and Asians. The rarity of this mutant allele and its restricted geographic distribution suggest that the mutational event occurred recently on a normal haplotype 4 background in Eastern Europe.

Alleles↗
PubMed1990

Effects of metal ions on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex.

The effects of Cu2+, Fe2+ and Zn2+ on 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex were examined. Cu2+ and Zn2+ (0.05-0.5 mM) inhibited the activity of this enzyme in a dose-dependent manner. The concentration required for 50% inhibition was approximately 0.1 mM for Cu2+ and 0.15 mM for Zn2+. The inhibition by both metals was uncompetitive and non-competitive with regard to NAD+ and prostaglandin E2, respectively, indicating that the mechanisms of the inhibition on the enzyme of both metals may be the same. Fe2+ had no effect on the activity of this enzyme. These results suggest that Cu2+ and Zn2+ have the potential to modulate the catabolism of prostaglandins by the kidney cortex.

Animals↗
PubMed1990

Mitogenic signaling pathways of growth factors can be distinguished by the involvement of pertussis toxin-sensitive guanosine triphosphate-binding protein and of protein kinase C.

We have examined the possible involvements of pertussis toxin (PT)-sensitive guanosine triphosphate (GTP)-binding protein (Gp) and protein kinase C (PKC) in the mitogenic signaling pathways of various growth factors by the use of PT-pretreated and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA)-pretreated mouse fibroblasts. Effects of PT pretreatment (inactivation of PT-sensitive Gp) and TPA pretreatment (depletion of PKC) on mitogen-induced DNA synthesis varied significantly and systematically in response to growth factors: mitogenic responses of cells to thrombin, bombesin, and bradykinin were almost completely abolished both in PT- and TPA-pretreated cells; responses to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vanadate were reduced to approximately 50% both in PT- and TPA-pretreated cells compared with native cells; response to basic fibroblast growth factor (bFGF) was not affected in PT-pretreated cells but was inhibited to some extent in TPA-pretreated cells. Thus, growth factors examined have been classified into three groups with regard to the involvements of PT-sensitive Gp and PKC in their signal transduction pathways. Binding of each growth factor to its receptor was not affected significantly by pretreatment of cells with PT or TPA. Inhibitory effects of PT and TPA pretreatment on each mitogen-induced DNA synthesis were not additive, suggesting that the functions of PT-sensitive Gp and PKC lie on an identical signal transduction pathway. Although all three groups of mitogens activated PKC, signaling of each growth factor depends to a varying extent on the function of PKC. Our results indicate that a single peptide growth factor such as EGF, PDGF, or bFGF acts through multiple signaling pathways to induce cell proliferation.

Animals↗
PubMed1990

Serum zinc concentration in acute myocardial infaction.

The serum zinc concentration was examined in 61 patients with acute myocardial infarction who were admitted within twenty-four hours after the onset. Forty-two of 61 patients were admitted within twelve hours. The zinc level fell sharply as early as within three hours after the onset. The minimum values were attained two or three days after infarction and then rose to normal values within five to ten days. There was a mild degree of change and early recovery in 9 patients who underwent major abdominal surgery. The pathologic factors that could influence these two conditions are discussed. In those patients whose serum zinc concentrations were remarkably lowered, clinically estimated severity was far graver, and prognosis seemed to be much worse. It should be asked whether zinc supplementation would be of therapeutic benefit to patients with acute infarction.

Aged↗
PubMed1990

Interaction of liposomes with cultured cells: possible involvement of lipid peroxidation in cell growth inhibition.

Systematic analyses of the interaction between liposomes and cells were examined. Liposomes were found to affect the growth of mouse NIH 3T3 cells depending upon their size, net charge, and cholesterol content. Among the charged compounds, stearylamine was the most inhibitory and showed complete inhibition of cell growth at 100 microM. The cholesterol-rich and small unilamellar vesicles were more suppressive compared to the cholesterol-poor and multilamellar ones, respectively. The binding assay of liposomes to the cells showed a positive correlation between liposome binding and the extent of growth inhibition. Suppression of liposome uptake by inhibitors of the cytoskeletal system and energy metabolism were suggestive of an endocytotic mechanism for the cellular uptake of liposomes. The growth inhibitory effect seemed secondary to the intracellular uptake of liposomes, and peroxidation of incorporated lipids would lead to cellular damage. Therefore, it is highly recommended that potential growth inhibitory effects associated with the particular composition and other properties of liposomes should be carefully assessed in any human studies, especially for long-term use.

Animals↗
PubMed1990

Missense mutations associated with RFLP haplotypes 1 and 4 of the human phenylalanine hydroxylase gene.

We report missense mutations associated with haplotype 1 and haplotype 4 alleles of the human phenylalanine hydroxylase (PAH) gene. Individual exon-containing regions were amplified by polymerase chain reaction from genomic DNA of a PKU patient who was a haplotype 1/4 compound heterozygote. The amplified DNA fragments were subcloned into M13 for sequence analysis. Missense mutations were observed in exons 5 and 7, resulting in the substitution of Arg by Gln at residues 158 and 261 of the enzyme, respectively. Expression analysis in heterozygous mammalian cells after site-directed mutagenesis demonstrated that the Arg158-to-Gln158 mutation is a PKU mutation, whereas the Arg261-to-Gln261 mutation is apparently silent in the assay system. Hybridization analysis using allele-specific oligonucleotide probes demonstrated that the Arg158-to-Gln158 mutation is present in two of six mutant haplotype 4 alleles among the Swiss and constitutes about 40% of all mutant haplotype 4 alleles in the European population. The mutation is not present in normal alleles or in any mutant alleles of other haplotypes. The results provide conclusive evidence that there is linkage disequilibrium between mutation and haplotype in the PAH gene and that multiple mutations have occurred in the PAH gene of a prevalent haplotype among Caucasians.

Base Sequence↗
PubMed1990

Recurrent mutation in the human phenylalanine hydroxylase gene.

We report the identification of a missense mutation of Glu280 to Lys280 in the phenylalanine hydroxylase (PAH) gene of a phenylketonuria (PKU) patient in Denmark. The mutation is associated with haplotype 1 of the PAH gene in this population. This mutation has previously been found in North Africa, where it is in linkage disequilibrium with haplotype 38. While it is conceivable that this mutation could have been transferred from one haplotype background to another by a double crossover or gene conversion event, the fact that the mutation is exclusively associated with the two different haplotypes in the two distinct populations supports the hypothesis that these two PKU alleles are the result of recurrent mutations in the human PAH gene. Furthermore, since the site of mutation involves a CpG dinucleotide, they may represent hot spots for mutation in the human PAH locus.

Alleles↗
PubMed1990

The effect of selenium ions on the catabolism of prostaglandin E2 in rabbit kidney cortex.

The effect of selenium ions on the catabolism of prostaglandin E2 by 15-hydroxy prostaglandin dehydrogenase and prostaglandin delta 13 reductase in rabbit kidney cortex was examined. Selenium ions had no effect on the 15-hydroxy prostaglandin dehydrogenase activity. On the other hand, selenium ions inhibited the prostaglandin delta 13 reductase activity at concentrations ranging from 0.05 to 0.5 mM. The effect was concentration-dependent. The inhibition by selenium ions was non-competitive with regard to NADH and 15-keto PGE2, respectively. These results suggest that selenium ions have the potential to increase 15-keto PG levels in the kidney by inhibiting the prostaglandin delta 13 reductase activity and that such action of selenium ions may participate in renal damage of selenium poisoning.

Animals↗
PubMed1990

[Progression of idiopathic mitral valve prolapse estimated by echocardiography].

To evaluate the progression of idiopathic mitral valve prolapse (MVP), a long time follow-up study (mean 7.1 years) was performed using echocardiography in 27 cases (11 males, 16 females, mean age: 50.4 years). Morphological changes, the degree of prolapse of the mitral valve, left atrial dimension (LAD) and left ventricular end-diastolic dimension (LVDd) were estimated at the first and last examinations. The degree of prolapse was assessed by measuring the distance of the dislocation between the anterior and posterior leaflets at the area of coaptation (degree I:5 mm or less, degree II: 6 to 10 mm, degree III: 11 mm or greater). The results were as follows: 1. The degree of prolapse did not progress in all 27 cases. 2. LAD increased with an advance of age. A remarkable increase of LAD was recorded in cases older than 45 years with atrial fibrillation or prolapse of degree II and III or with ruptured chordae tendineae. 3. The mitral ring was enlarged over 5 mm in six of 15 cases with prolapse of degree II and III. 4. Mitral regurgitation evaluated by Doppler echocardiography in patients with posterior leaflet prolapse was more severe than that in patients with anterior leaflet prolapse in the last examination. 5. LVDd increased gradually. In the present study, LAD was increased in most cases of MVP and it seemed to depend on complications (atrial fibrillation and ruptured chordae tendineae) or severity of regurgitation rather than the degree of prolapse.

Adult↗
PubMed1989

Effects of vasoactive intestinal contractor (VIC) and endothelin on intracellular calcium level in neuroblastoma NG108-15 cells.

Effects on [Ca2+]i levels of endothelin-l (ET) and vasoactive intestinal contractor peptide (VIC), which is a novel member of the endothelin family, were examined in fura 2-loaded neuroblastoma NG108-15 cells. VIC was found to be a very effective stimulus for intracellular Ca2+ mobilization and to be more potent than ET. Intracellular calcium response to sequential addition of two stimulants exhibited the homologous desensitization of either ET or VIC, but no heterologous desensitization between ET and VIC. This indicates evidence suggesting that these two peptides act through distinct receptors.

Calcium↗
PubMed1989

Morphologic characteristics of pancreatic carcinoma with diabetes mellitus.

For 81 cases of resectable pancreatic carcinoma, the site of cancer origin, cancer histologic features, and hyperplasia in the noninvolved duct were studied in relation to diabetes. They were classified into the following three groups: (1) fasting blood sugar (FBS) of less than 120 mg/dl (Group A, 26 cases); (2) FBS of more than 120 mg/dl with less than 2-year history of diabetes (Group B, 38 cases); and (3) FBS of more than 120 mg/dl with more than a 2-year history of diabetes (Group C, 17 cases). Although neither tumor size nor tumor location differed between the three groups, both the highest resectability (47%) and the lowest rate (71%) of extrapancreatic invasion were seen in Group C. A pancreatic ductogram showed that the pattern of the main pancreatic duct was intact in 0% in Group C versus 35% in Group A (P less than 0.05). Histologically, papillary/well-differentiated adenocarcinoma was present in 35% of Group A patients versus 61% of Group B and 71% of Group C patients (P less than 0.05). Papillary hyperplasia was present in the ducts of 27% of the patients in Group A; this was significantly lower than the other two groups. Atypical duct hyperplasia was present in 47% of Group C patients; this was significantly higher than in the other two groups. It appears that cells in the main pancreatic duct are vulnerable to hyperplastic and well-differentiated cancerous changes in patients with a history of diabetes of more than 2 years duration.

Adenocarcinoma↗
PubMed1989

Bradykinin-induced translocation of protein kinases C in neuroblastoma NCB-20 cell: dependence on 1,2-diacylglycerol content and free calcium.

Bradykinin (BK)-induced production of 1,2-diacylglycerol (1,2-DG) and translocation of protein kinases C (PKCs) were examined in neuroblastoma-derived hybrid NCB-20 cells. Mass analysis of 1,2-DG exhibited a biphasic increase by 1 microM BK stimulation: the first transient phase and the second broad sustained phase. Among three subspecies of PKC expressed in these cells, types II and III were observed to translocate from cytosol to membrane in response to BK as well as PBt2 by Western blotting analysis. Type II translocated more rapidly and distinctly than type III. However, after treatment with quin 2/AM, the second phase of 1,2-DG formation completely disappeared and PKCs translocation by BK or PBt2 was completely abolished. BK-induced IP3 (1,4,5) formation was temporally consistent with the first transient phase of 1,2-DG formation. These findings suggest that PKCs translocation by BK stimulation is caused by 1,2-DG produced not only via phosphoinositide metabolism, but via other phospholipid breakdown which is Ca2+-dependent.

Animals↗
PubMed1989

Anomalous increase of Ca2+ current by high concentration K+ stimulation in whole cell clamped GH3 cells.

We examined the effect of high concentration K+ (50 mM K+) stimulation to neurosecretory GH3 cells under voltage clamp control and unexpectedly found a considerable increase in the inward current evoked by depolarizing pulses. This augmented current was present in Na+-free solution containing Ca2+, tetraethylammonium+ and tetrodotoxin and showed similarity in its voltage dependence to the Ca+ channel current in the control (5 mM K+) solution. The augmented current was significantly reduced by Ca2+ channel blockers, Co2+ (5 mM) and nifedipine (2.5 microM), and was increased by the raise of external Ca2+ concentration. Correspondingly, Quin-2 experiments in GH3 cells showed that the rise in cytosolic free Ca2+ concentration in response to high K+ stimulation was suppressed by the same concentration of nifedipine. These data suggest that, in addition to its depolarizing effect, high K+ may modify voltage-sensitive Ca2+ channels such that they exhibit increased permeability although their voltage dependence of activation and pharmacological sensitivity remain largely unchanged.

Animals↗
PubMed1989

Inhibition by cyclic AMP of guanine nucleotide-induced activation of phosphoinositide-specific phospholipase C in human platelets.

Phosphoinositide-specific phospholipase C (PLC) activity of human platelet membranes was activated by the nonhydrolyzable guanine nucleotide GTP gamma S. This activation did not occur in either membranes prepared from dibutyryl cyclic AMP-pretreated platelets (A-membranes) or those prepared from untreated cells and subsequently incubated with cyclic AMP (cAMP) (B-membranes). This cAMP-mediated inhibition was abolished in the presence of inhibitors of cAMP-dependent protein kinase (A-kinase), suggesting that the inhibition was due to phosphorylation of (a) protein component(s). No significant differences were observed in the basal PLC activity and the extent of pertussis toxin-catalyzed ADP-ribosylation among control membranes and the two types of phosphorylated membranes (A- and B-membranes). GTP-binding activities of Gs, Gi and GTP-binding proteins of lower molecular masses were not altered by the phosphorylation of the membranes. These findings suggest that a GTP-binding protein is involved in the GTP gamma S-mediated activation of PLC and that cAMP (plus A-kinase) inhibits this activation by phosphorylating a membrane protein (probably a 240-kDa protein), rather than the GTP-binding protein or PLC itself. It is likely that this phosphorylation uncouples the GTP-binding protein from PLC.

Affinity Labels↗