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Y Sakai

Publications and source records attributed to Y Sakai.

At least 19 recordsLinked to original sources
PubMed1992

Inactivation of glibenclamide-sensitive K+ channels in Xenopus oocytes by various calmodulin antagonists.

In follicle-enclosed Xenopus oocytes, extracellular application of cromakalim (a K+ channel opener) or intracellular injection of cAMP induces the smooth outward K+ current which is inactivated by glibenclamide. We found that cromakalim- or cAMP-induced K+ currents in the oocytes were rapidly, reversibly and dose-dependently blocked by various drugs having a calmodulin antagonizing activity in common, namely, by a selective calmodulin antagonist (W-7), antipsychotics (trifluoperazine, chlorpromazine, haloperidol), an antidepressant (amitriptyline), a beta-adrenoceptor blocker (propranolol), a local anesthetic (lidocaine) and a calcium antagonist (prenylamine). W-7, trifluoperazine, chlorpromazine and prenylamine were relatively potent blockers. For example, IC50 values to block cromakalim (100 microM)-induced K+ currents were 12 microM for trifluoperazine and 16 microM for W-7, which were close to their IC50 values to inhibit Ca2+/calmodulin-dependent phosphodiesterase (an index of the potency of calmodulin antagonists). IC50 values to inhibit cAMP (20 pmol/oocyte)-induced K+ currents were 126 microM for prenylamine and 129 microM for chlorpromazine. The IC50 values of all drugs tested to block cromakalim or cAMP responses were significantly correlated with their calmodulin-antagonizing potencies. Isoproterenol-induced K+ currents in the oocytes were also dose-dependently inhibited by glibenclamide, W-7 and trifluoperazine. These results suggest the possibility that the activity of glibenclamide-sensitive K+ channels in follicle-enclosed oocytes are regulated by calmodulin or a calmodulin-dependent process.

Animals↗
PubMed1992

Hemofiltration as treatment for patients with refractory heart failure.

Hemofiltration was performed in 15 patients with refractory congestive heart failure. All of these patients had oliguria, although intensive treatment with diuretics, digitalis, vasodilators, and catecholamines was prescribed. Hemofiltration was performed under hemodynamic monitoring in 14 patients. The water removal by hemofiltration decreased pulmonary arterial pressure, pulmonary capillary wedge pressure and right atrial pressure. Despite these hemodynamic improvements, nine patients (60%) died within one month after the start of hemofiltration; the causes were fatal arrhythmia in three, renal failure in two, sepsis in one and irreversible cardiogenic shock in three. Oliguria for over 15 h or a serum creatinine concentration of more than 4.0 mg/dl at the start of hemofiltration related to poor prognosis. In view of these results, hemofiltration for refractory heart failure should be started earlier and performed carefully in order to avoid arrhythmia, cardiogenic shock, and other complications.

Adult↗
PubMed1992

Left ventricular diastolic dysfunction in coronary artery disease: effects of coronary revascularization.

Left ventricular diastolic dysfunction was studied globally and regionally in patients with coronary artery disease, and the effects of coronary revascularization were evaluated. A total of 25 patients with angina pectoris who had a stenotic lesion (greater than or equal to 90%) in only left anterior descending branch underwent coronary revascularization [percutaneous transluminal coronary angioplasty (PTCA) in 13 patients and coronary artery bypass graft (CABG) in 12]. Nine patients with normal coronary artery were studied as controls. Left ventricular volume and radial axes were measured on serial frames of one cardiac cycle by cine left ventriculography. The radial axes were drawn from the left ventricular gravity to left ventricular wall at every 20 degrees. Left ventricular filling fraction and distension rate of radial axes were calculated at the times of 25%, 50%, 75%, and 100% of diastolic period, 100% being end-diastole. Although there were no significant changes of the systolic function by revascularization, the filling fraction increased from 11.2 +/- 2.6 to 14.5 +/- 3.5% (p less than 0.001) at 25% time of diastole, from 29.9 +/- 4.9 to 32.5 +/- 5.0% (p less than 0.05) at 50% time in the PTCA group, and from 11.8 +/- 3.7 to 13.4 +/- 3.8% (p less than 0.01) at 25% time in the CABG group. The distension rate of radial axis to the anterior wall also increased significantly at 25% and 50% time of diastole after revascularization, and the change was marked in the PTCA group. However, these increases did not apply to the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1992

Mapping of the mouse bilirubin UDP-glucuronosyltransferase gene (Gnt-1) to chromosome 1 by restriction fragment length variations.

Restriction endonuclease fragment length variations (RFLVs) were detected by using a rat cDNA probe for the bilirubin UDP-glucuronosyltransferase (UDPGT) gene between two mouse strains, 129/Sv and MOL-MIT. RFLVs of the gene were found by EcoRI and PvuII digestions. From linkage analyses of the three-point cross test using Elo and En-1 as marker genes, the bilirubin UDPGT gene was mapped at position 37 on chromosome 1. Bilirubin and phenol UDPGTs have been suggested to be expressed by a single gene by alternative splicing in human and rat. The mouse bilirubin UDPGT gene was named Gnt-1.

Animals↗
PubMed1992

A molecular genetic linkage map of mouse chromosome 10, including the Myb, S100b, Pah, Sl, and Ifg genes.

Restriction endonuclease fragment length variations (RFLV) on mouse chromosome 10 were detected in four genes, namely, the Myb protooncogene (Myb) and the genes for S100 beta protein (S100b), phenylalanine hydroxylase (Pah), and interferon-gamma (Ifg). RFLV were found in restriction patterns generated with BamHI for Myb, in those generated with BglII for S100b, in those generated with EcoRV for Pah, and in those generated with TaqI for Ifg. A multipoint backcross was carried out by the mating (129/Sv-Sl/+ x MOL-MIT)F1 x 129/SvJ(-)+/+. The Sl mutation has phenotypic effects which include deficiencies in pigment cells, germ cells, and blood cells. The following order of genes was derived from the results of the multipoint backcross, with distances between genes in parentheses: centromere--Myb--(34.9 cM)--S100b--(8.5 cM)--Pah--(8.5 cM)--Sl--(12.3 cM)--Ifg--telomere. Most laboratory strains and two strains of Mus musculus domesticus of wild origin carry the Myba, S100a, Paha, and Ifga alleles. In contrast, a strain of M. m. musculus, two strains of M. m. yamashinai, and two strains of M. m. molossinus carry the Mybb, S100b, Pahb, and Ifgb alleles. Other strains of wild origin carry various combinations of these alleles.

Alleles↗
PubMed1992

Alanine aminotransferase and HCV-RNA responses following interferon therapy of HCV-RNA positive chronic hepatitis.

Interferon (IFN) has been shown to be effective for chronic hepatitis C. This study investigated changes of alanine aminotransferase (ALT) and HCV-RNA in chronic hepatitis C patients treated with alpha-IFN. IFN was given to 73 patients with HCV-RNA positive chronic hepatitis C. The pattern of changes in ALT activity after IFN administration was classified into five types. Type 1 was characterized by normalization of ALT (< or = 25 K.U) during IFN administration and sustained normalization after the IFN therapy. Type 2 involved a rebound of ALT after termination of IFN therapy and subsequent normalization. Type 3 had no ALT normalization during IFN administration, with normalization after the completion of the therapy. Type 4 involved transient normalization of ALT level during IFN therapy, with a subsequent reversion to abnormal levels after the termination of IFN therapy. Type 5 showed sustained abnormally high levels of ALT activity both during and after treatment. Twenty four patients (32.9%) had sustained normalization ALT (< or = 25 K.U) after the termination of IFN treatment. The HCV-RNA negative rate at 6 months after IFN therapy in patients with sustained normalization of ALT was 87.5% (21/24).

Adult↗
PubMed1992

Possible involvement of protein kinase C and calcium in GSH efflux from Hep G2 cells.

We investigated the effects of protein kinase C modulations and calcium mobilization on GSH efflux in Hep G2 cells. GSH efflux from Hep G2 cells was increased by a phorbol ester. Staurosporine, an inhibitor of protein kinase C, diminished phorbol ester-stimulated GSH efflux from the cells. GSH efflux was negatively correlated with extracellular calcium concentrations. Verapamil enhanced GSH efflux, whereas ATP decreased GSH efflux. The latter effect was diminished in the absence of extracellular calcium. Protein kinase C and calcium mobilization may be crucial factors in GSH efflux from human hepatocytes.

Adenosine Triphosphate↗
PubMed1992

Modulating effect of tanshinones on mutagenic activity of Trp-P-1 and benzo[a]pyrene in Salmonella typhimurium.

The modulating effects of the Chinese medicinal plant 'Tan-shen', the radix of Salvia miltiorrhiza Bunge, on the mutagenic activities of Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole) and B(a)P (benzo[a]pyrene) were investigated using Salmonella typhimurium TA98. Ether- and hot water-extracted 'Tan-shen' enhanced both mutagens at low concentrations, but suppressed them at high concentrations. Extracts by ether treatment were more effective than those extracted by hot water. Dihydrotanshinone I, cryptotanshinone, tanshinone I, and tanshinone IIA were isolated from the ether extract by high performance liquid chromatography (HPLC) and were recognized to be the mutagenic modulators. 4 tanshinones enhanced the mutagenicity of Trp-P-1 by 8-24-fold at 20 micrograms/plate and the enhancement was reduced at the higher concentration. Dihydrotanshinone I suppressed Trp-P-1 activity completely at 100 micrograms/plate.

Abietanes↗
PubMed1992

Increase in estrogen receptor levels in MNU-induced thyroid tumors in LE rats.

Estrogen receptor (ER) levels were evaluated in thyroid tumors induced by N-methyl-N-nitrosourea (MNU) and low iodine diet (LID) or propylthiouracil (PTU) in intact and estrogen (E2) loaded Long-Evans (LE) rats. MNU at 40 mg/kg body wt was injected in 50 day-old LE rats of both sexes. The animals were killed 17-22 weeks later and the thyroid tissues were subjected to ER assay. In LID-treated groups, cytosolic ER (cER) levels were 6.7 +/- 5.8 (fmol/mg protein, mean +/- SE) in females and 0.7 +/- 1.4 in males, E2 increased the ER levels. In E2-loaded LID groups, cER levels were 12.9 +/- 3.7 in females and 1.7 +/- 1.7 in males. PTU treatment produced almost comparable ER levels as LID treatment. PTU treatment as well as LID treatment increased the serum TSH levels with E2 treatment producing additional elevation. In evaluating ER levels by histological type of thyroid tumors, the level in cER plus nER showed the lowest value of 6 +/- 6.4 (fmol/mg DNA, mean +/- SE) in hyperplasia, followed by 129 +/- 52.3 in adenoma and 289 +/- 51.7 in carcinoma. The rates of BrdU incorporation in thyroid follicles indicated higher proliferation activity in the area of adenoma and carcinoma rather than in the hyperplastic area. These data suggested that E2 treatment increases the ER levels in MNU and LID/PTU-induced thyroid tumors. The level of ER was correlated to the histological type of thyroid tumors.

Adenoma↗
PubMed1992

Skinfold thickness and cardiovascular risk factors in American and Japanese telephone company executives.

Data from a cross-sectional study of cardiovascular disease risk factors in 962 US and 827 Japanese male telephone company executives were used to determine the associations of skinfold thickness measurements (abdominal, subscapular, triceps, ulnar) with blood pressure, blood glucose, serum cholesterol, and serum triglycerides. These associations were assessed within each group of executives and were compared between the groups. Most skinfolds showed association with risk factors in univariate regression. After adjusting for age and body mass index, the abdominal skinfold continued to be significantly associated with blood pressure and triglycerides in both groups, while the subscapular skinfold showed associations only with triglycerides. After adjustment, the peripheral skinfolds showed no association with risk factors in the US men, however, in the Japanese men the ulnar skinfold continued to be associated with blood pressure. These findings suggest that abdominal and ulnar skinfold measurement may be useful in adjusting for the effect of obesity on coronary heart disease risk in epidemiological studies.

Administrative Personnel↗
PubMed1992

An ubiquitous modulating function of rabbit tracheal epithelium: degradation of tachykinins.

1. To examine the role of epithelium in the responsiveness of tracheal smooth muscle in rabbit, we measured the contractile responses to acetylcholine (ACh), KCl, 5-hydroxytryptamine (5-HT), histamine, substance P (SP), neurokinin A (NKA), and electrical field stimulation EFS) in intact and epithelium-denuded preparations. 2. Removal of epithelium did not alter the contractile response to any agonist examined, except SP. 3. Removal of epithelium enhances the contractile response to SP. In the presence of phosphoramidon, the contractile response to SP was not significantly different in either group. The results suggest that the effect of epithelium is largely due to degradation of SP by enzymes in the epithelium. 4. Arachidonic acid metabolites did not seem to be related to the responses induced by contractile agonists or EFS. 5. In the presence of SP, the contractile responses and [3H]-choline outflow evoked by EFS were dose-dependently enhanced. Contractile responses to EFS and [3H]-choline outflow evoked by EFS were enhanced by SP significantly more than by NKA. Both were abolished by atropine or tetrodotoxin. 6. These results suggest that rabbit tracheal epithelium may modulate SP-induced contractions, both direct and indirect, by inactivation of SP. This phenomenon is widespread in mammals. The rabbit may be a useful model to examine airway cholinergic functions.

Animals↗
PubMed1992

Directed mutagenesis in an asporogenous methylotrophic yeast: cloning, sequencing, and one-step gene disruption of the 3-isopropylmalate dehydrogenase gene (LEU2) of Candida boidinii to derive doubly auxotrophic marker strains.

A model system for one-step gene disruption for an asporogenous methylotrophic yeast, Candida boidinii, is described. In this system, the 3-isopropylmalate dehydrogenase gene (C. boidinii LEU2) was selected as the target gene for disruption to derive new host strains for transformation. First, the C. boidinii LEU2 gene was cloned, and its complete nucleotide sequence was determined. Next, the LEU2 disruption vectors, which had the C. boidinii URA3 gene as the selectable marker, were constructed. Of the Ura+ transformants obtained with these plasmids, more than half showed a Leu- phenotype. Finally, the double-marker strains of C. boidinii were derived. When vectors with repeated flanking sequences of the C. boidinii URA3 gene were used for gene disruption, Leu- Ura+ transformants changed spontaneously to a Leu- Ura- phenotype ca. 100 times more frequently than they did when plasmids without the repeated sequences were used. Southern analysis showed that these events included a one-step gene disruption and a subsequent popping out of the C. boidinii URA3 sequence from the transformant chromosome.

3-Isopropylmalate Dehydrogenase↗
PubMed1992

[Evaluation of enzyme-linked immunosorbent assay for serodiagnosis of Bordetella bronchiseptica infection in guinea pigs].

An enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of Bordetella bronchiseptica (B. bronchiseptica) infection in guinea pigs was evaluated. An isolate of B. bronchiseptica from lung lesion of a guinea pig was used as antigen after ultrasonication. In the experimental infection, specific pathogen-free guinea pigs inoculated with the bacterium intranasally were examined every 5 or 10 days. The organism was recovered from all animals between 5 and 30 days post-inoculation (p.i.). Only one animal was sero-positive by agglutination test 30 and 50 days p.i.; whereas, by ELISA, one animal was positive 5 days p.i., and all the animals showed strong reaction 20 to 50 (end of experiment) days p.i. Field samples obtained from 1983 to 1989 were tested by ELISA. The results corresponded to those of macroscopic observations and bacterial isolation. The ELISA proved to be useful method for detection of B. bronchiseptica infection in guinea pigs.

Animals↗
PubMed1992

[Two kindreds with familial Alzheimer's disease--analysis of the APP717 mutation and the mutated genes for the prion protein].

Numerous Caucasian familial Alzheimer's disease (FAD) pedigrees have been described in the literature, while only 21 Japanese FAD families have been reported to date. Here we report the clinical findings and the result of molecular genetic analysis of 4 patients from two FAD kindreds, OS-2 and OS-3. The proband in OS-2 family has developed loss of recent memory and place disorientation age at 43. A brain CT showed severe diffuse cortical atrophy. Her younger brother had dementia at 42 years and her mother and other 3 siblings had also dementia symptoms suspected to be Alzheimer's disease. The proband in OS-3 family showed declining recent memory at 49 years and developed dysphagia, gait disturbance and emotional incontinent with cerebral atrophy at 52 years. His father and elder brother demonstrated dementia signs at 60 and 54 years old, respectively. Recently it was reported that affected members from 2 Caucasian kindreds with FAD had missense mutation in exon 17 of the gene for amyloid precursor protein (APP). Patients from three different Japanese kindreds with FAD also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile) at codon 717 by this mutation is responsible for FAD in at least some kindreds. We used genomic DNA from 4 affected members of 2 families to determine whether the disease in these families is associated with a APP717 mutation and the mutated codons, 102, 117, 129, 178 and 200, on the gene for protease-resistance prion protein (PrP) which cause transmissible dementia, Creutzfelt-Jacob disease (CJD) and Gerstmann-Strausler syndrome (GSS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of calmodulin inhibitors on amylase secretion from rat pancreatic acini.

To investigate the role of calmodulin in stimulus-secretion coupling in pancreatic acinar cells, we studied the effects of W-7, a calmodulin inhibitor, and KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (Ca2+/CaM kinase II), on amylase secretion from rat pancreatic acini. Calmodulin inhibitor (W-7, 100 microM) and Ca2+/CaM kinase II inhibitor (KN-62, 10 microM) reduced amylase secretion stimulated by cholecystokinin (CCK) or carbachol. W-7 and KN-62 also inhibited amylase secretion stimulated by both calcium ionophore (A23187) and phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA). To clarify the role of calmodulin in the interaction of intracellular mediators, pancreatic acini were permeabilized with streptolysin O. Following permeabilization, amylase secretion was stimulated by submicromolar free Ca2+, and this Ca(2+)-dependent amylase secretion was enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP gamma S), TPA or cyclic adenosine 3',5'-monophosphate (cAMP). W-7 and KN-62 had no effects on amylase secretion stimulated by Ca2+ alone, but inhibited the enhancement in Ca(2+)-dependent amylase secretion by GTP gamma S, TPA or cAMP. These data suggest that calmodulin plays an important role in Ca(2+)-dependent amylase secretion from pancreatic acinar cells and in the interaction between Ca2+ and other intracellular messengers.

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

[Left ventricular filling disturbances in cardiac amyloidosis: a study of atrial sound and diastolic inflow velocities].

Cardiac amyloidosis is characterized by left ventricular filling disturbances in a relatively early stage. To investigate such disturbances more precisely, we studied atrial sound and left ventricular inflow velocity patterns. Twelve cases diagnosed as cardiac amyloidosis according to the clinical criteria including rectal biopsies and serum amyloid proteins or at autopsy were reviewed and analyzed. Their mean age was 60.9 +/- 12.5 years. Twelve age-matched cases with hypertrophic cardiomyopathy (HCM) served as the controls. We measured the amplitude of atrial sound by low-frequency phonocardiograms and the ratio of the heights of the A wave of apexcardiograms (ACG) to the total amplitude of the ACG. The mitral inflow velocity patterns were recorded using pulsed Doppler echocardiography. The rapid filling wave (R), atrial filling wave (A) and the ratio of A to R (A/R) were measured. In the amyloidosis group, atrial sound moderately increased in 2 cases, it was faint in 9 and not manifest in the remaining one. The A wave in the amyloidosis group was significantly smaller than that in the HCM group (p < 0.001) (12.4 +/- 3.9 vs 22.4 +/- 5.6%). In the left ventricular inflow velocity patterns, the R in amyloidosis was smaller than that in HCM (41.7 +/- 16.0 vs 56.4 +/- 12.1 cm/sec) (p < 0.02). The A in amyloidosis was also smaller than that in HCM (40.5 +/- 13.4 vs 58.1 +/- 13.0 cm/sec) (p < 0.006). The A/R was 1.0 +/- 0.34 in amyloidosis and 1.1 +/- 0.32 in HCM (N.S.). Both A and R were significantly less in amyloidosis than those in HCM.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗