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Y Kido

Publications and source records attributed to Y Kido.

At least 37 records · Page 2Linked to original sources
PubMed2000

Carbon-source-dependent transcriptional control involved in the initiation of cellular differentiation in Streptomyces griseus.

Carbon source is one of the environmental factors that affects cellular differentiation of Streptomyces. We have identified the craA gene as a putative negative regulator involved in the carbon-source-dependent initiation of cellular differentiation in Streptomyces griseus. Carbon-source-dependent transcriptional repression of craA, which is caused by binding of a putative repressor protein to its promoter region, is proposed to result in the initiation of aerial mycelium formation. The presence of a craA homologue in the chromosome of Streptomyces coelicolor A3(2) implicates the existence of a similar regulatory mechanism in this organism. The repression of craA-promoter activity in glucose media could be alleviated not only by replacing glucose with maltose but also by supplying copper, which suggests that the stimulatory effect of copper on cellular differentiation in Streptomyces is excerted via abolishment of glucose-repression of craA.

Amino Acid Sequence↗
PubMed2000

Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2.

Type 2 diabetes is characterized by abnormalities of insulin action in muscle, adipose tissue, and liver and by altered beta-cell function. To analyze the role of the insulin signaling pathway in these processes, we have generated mice with combined heterozygous null mutations in insulin receptor (ir), insulin receptor substrate (irs-1), and/or irs-2. Diabetes developed in 40% of ir/irs-1/irs-2(+/-), 20% of ir/irs-1(+/-), 17% of ir/irs-2(+/-), and 5% of ir(+/-) mice. Although combined heterozygosity for ir/irs-1(+/-) and ir/irs-2(+/-) results in a similar number of diabetic mice, there are significant differences in the underlying metabolic abnormalities. ir/irs-1(+/-) mice develop severe insulin resistance in skeletal muscle and liver, with compensatory beta-cell hyperplasia. In contrast, ir/irs-2(+/-) mice develop severe insulin resistance in liver, mild insulin resistance in skeletal muscle, and modest beta-cell hyperplasia. Triple heterozygotes develop severe insulin resistance in skeletal muscle and liver and marked beta-cell hyperplasia. These data indicate tissue-specific differences in the roles of IRSs to mediate insulin action, with irs-1 playing a prominent role in skeletal muscle and irs-2 in liver. They also provide a practical demonstration of the polygenic and genetically heterogeneous interactions underlying the inheritance of type 2 diabetes.

Adipose Tissue↗
PubMed2000

Genetic modifiers of the insulin resistance phenotype in mice.

Insulin resistance can result from genetic interactions among susceptibility alleles. To identify genetic loci predisposing to insulin resistance, we used crosses between different strains of mice with a targeted null allele of the insulin receptor gene. On the genetic background of B6 mice, the insulin receptor gene mutation causes mild hyperinsulinemia. In contrast, on the genetic background of 129/Sv mice, the same mutation causes severe hyperinsulinemia, suggesting that the 129/Sv strain harbors alleles that interact with the insulin receptor mutation and predispose to insulin resistance. As a first step to identify these alleles, we generated an F2 intercross between insulin receptor heterozygous mutant mice on B6 and 129/Sv backgrounds (B6IR x 129IR) and performed a genome-wide scan with polymorphic markers at a 20-cM resolution. We report the identification of loci on chromosomes 2 (logarithm of odds [LOD] 5.58) and 10 (LOD 5.58) that show significant evidence for linkage to plasma insulin levels as a quantitative trait. These findings indicate that targeted mutations in knockout mice can be used to unravel the complex genetic interactions underlying insulin resistance.

Alleles↗
PubMed2000

Blood-brain barrier transport of H1-antagonist ebastine and its metabolite carebastine.

The transport mechanism of the non-sedative H1-antagonist ebastine and its first-pass carboxylic acid metabolite carebastine at the blood-brain barrier (BBB) was studied. In rats, the brain uptake index (BUI) value of [14 C]carebastine was significantly lower than that of [14 C]ebastine. The BUI value of [14 C]carebastine was greatly increased by the addition of non-labeled carebastine. The steady-state uptake of [14 C]carebastine by P-glycoprotein-overexpressing K562/ADM cells was significantly lower than that by their parental drug-sensitive cell line K562. The decreased steady-state uptake of [14 C]carebastine by K562/ADM cells was reversed by verapamil. Steady-state uptake of [14 C]carebastine by primary cultured bovine brain capillary endothelial cells (bovine BCECs) was increased in the presence of metabolic inhibitors and verapamil. Non-labeled carebastine increased the steady-state uptake of a P-glycoprotein substrate, [3 H]vincristine, by bovine BCECs. The initial uptake of [3 H]mepyramine by bovine BCECs and RBEC1 (an immortalized cell line from rat brain capillary endothelial cells) was strongly inhibited by ebastine, while zwitterionic carebastine was slightly inhibitory. The values of brain-to-plasma unbound concentration ratio (Kp,f) in mdr1a(-/-) mice were increased 5.3-fold and 4.2-fold for [14 C ebastine and for [14 C]carebastine, respectively, compared with those in mdr1a(+/+) mice. Non-radiolabeled carebastine increased the Kp,f values of [14 C]carebastine in both types of mice. In conclusion, carebastine was shown to be a substrate for P-glycoprotein-mediated efflux from the brain at the BBB. A second efflux system may also be involved. The relatively low affinity of the uptake transport system for carebastine also limits the brain distribution of ebastine/carebastine.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

[A case of collapsing variant of FSGS].

We report a case of collapsing variant of FSGS. An 82-year-old man without HIV-1 infection or a history of intravenous drug abuse was admitted to our hospital with the chief complaints of acute onset of generalized edema and loss of appetite. Laboratory findings were consistent with nephrotic syndrome. He developed acute renal insufficiency. Initially, we suspected minimal change nephrotic syndrome and started steroid pulse therapy but the nephrotic syndrome was refractory and a renal biopsy was performed. The pathologic findings were judged to be consistent with a collapsing variant of focal segmental glomerulosclerosis (FSGS). This form was described by Weiss et al. in 1986 as a clinically and pathologically distinct variant of FSGS. Valeri et al. further reported that the incidence of this idiopathic collapsing type of FSGS which is devoid of evidence of HIV-1 infection or intravenous drug abuse has progressively increased over the past two decades. They reported that cyclosporin is effective for the treatment of this type of FSGS with a remission rate of about 30%. The present case also had a nearly complete remission after 2 month-cyclosporin treatment. In Japan, no adult case of this type of FSGS has been reported according to our review of the literature.

Aged↗
PubMed2000

[Evaluation of CT appearance of Mycobacterium avium complex infection--comparison with bronchiectasia].

We compared computed tomographic pictures (CT) of primary pulmonary mycobacterium avium complex (MAC) infection with bronchiectasia (BE). These patients were examined during the period from 1988 to 1996. There were 51 patients of pulmonary MAC infection group (13 males and 38 females) with a mean age of 67.5 years and 27 patients of BE group (8 males and 19 females) with a mean age of 53.9 years. The results were as follows: 1. In both groups, bronchiectasis was most commonly found in the middle lobe and in the lingula. In pulmonary MAC infection group, 38 patients (74.5%) had bronchiectasis in the middle lobe, and 40 patients (78.4%) had them in the lingula. In BE group, 18 patients (66.7%) had them in the middle lobe and in the lingula respectively. In the lower lobe, bronchiectasis of BE group was observed more frequently. And in pulmonary MAC infection group, 15 patients (29.4%) had bronchiectasis in the central zone, 42 patients (82.4%) had them in the intermediate zone, and all 51 patients had them in the peripheral zone. On the other hand, in BE group, 18 patients (66.7%), 27 patients (100%) and 21 patients (77.8%) had them in the central zone, in the intermediate zone and in the peripheral zone respectively. Bronchiectasis of pulmonary MAC infection was observed in peripheral zone more frequently than that of BE group. 2. By the type of bronchiectasis, saccular bronchiectasis was observed more frequently in BE group than in pulmonary MAC infection group. 3. Nodules were seen in pulmonary MAC infection group significantly more than in BE group. They were seen in 96% of lobes with bronchiectasis, and 50% of lobes without bronchiectasis in pulmonary MAC infection group. It was thought that the bronchiectasis with nodules predominantly in the peripheral zone was a characteristic CT finding of primary pulmonary MAC infection. As this finding was different from that of BE, it is suggested that primary pulmonary MAC infection caused this type of bronchiectasis.

Aged↗
PubMed2000

Limited distribution of new quinolone antibacterial agents into brain caused by multiple efflux transporters at the blood-brain barrier.

Transport of new quinolone antibacterial agents (quinolones) at the blood-brain barrier (BBB) was studied in vitro by using immortalized rat brain capillary endothelial cells RBEC1, and in vivo by using the brain perfusion method in rats and multidrug-resistant mdr1a/1b gene-deficient mice. The permeability coefficient of grepafloxacin measured by brain perfusion was increased by an excess of unlabeled grepafloxacin, suggesting a participation of a saturable BBB efflux system. Uptake coefficients of [(14)C]grepafloxacin, [(14)C]sparfloxacin, and [(14)C]levofloxacin by RBEC1 cells at the steady state were increased in the presence of the unlabeled quinolones. The steady-state uptake of [(14)C]grepafloxacin was increased in the presence of various quinolones. Brain distributions of [(14)C]grepafloxacin and [(14)C]sparfloxacin evaluated in terms of the brain-to-plasma free concentration ratio in mdr1a/1b gene-deficient mice were significantly higher than those in wild-type mice, demonstrating an involvement of P-glycoprotein as the efflux transporter. Anionic compounds, including 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and genistein, increased the steady-state uptake of [(14)C]grepafloxacin by RBEC1 cells. Because [(14)C]grepafloxacin was transported by multidrug resistance-associated protein (MRP), in MRP1-overexpressing cells and because RBEC1 and primary cultured brain capillary endothelial cells expressed MRP1, this protein may be an additional efflux transporter for quinolones. Furthermore, the permeability coefficient of [(14)C]grepafloxacin across the BBB was increased by DIDS or in the absence of bicarbonate ions in the brain perfusion method. DIDS or bicarbonate ion did not affect MRP1 function. Accordingly, the brain distribution of quinolones is restricted by the action of multiple efflux transporters, including P-glycoprotein, MRP1, and an unknown anion exchange transporter.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1999

Differential signaling of insulin and IGF-1 receptors to glycogen synthesis in murine hepatocytes.

We have used SV40-transformed hepatocytes from insulin receptor-deficient mice (-/-) and normal mice (WT) to investigate the different abilities of insulin and IGF-1 receptors to stimulate glycogen synthesis. We report that insulin receptors are more potent than IGF-1 receptors in stimulating glycogen synthesis. Both receptors stimulate glycogen synthesis in a PI 3-kinase-dependent manner, but only the effect of insulin receptors is partially rapamycin-dependent. Insulin and IGF-1 receptors activate Akt to a similar extent, whereas GSK-3 inactivation in response to IGF-1 is considerably lower in both -/- and WT cells, compared to the effect of insulin in WT cells. The findings indicate that (i) the potency of insulin and IGF-1 receptors in stimulating glycogen synthesis correlates with their ability to inactivate GSK-3, (ii) the extent of GSK-3 inactivation does not correlate with the extent of Akt activation mediated by insulin or IGF-1 receptors, indicating that the effect of insulin on GSK-3 requires additional kinases, and (iii) the pathways required for insulin stimulation of glycogen synthesis in mouse hepatocytes are PI 3-kinase-dependent and rapamycin-sensitive.

Androstadienes↗
PubMed1999

Production of monoclonal antibody and development of enzyme-linked immunosorbent assay for kanamycin in biological matrices.

Monoclonal antibodies (MAbs) against kanamycin were prepared by using a kanamycin-bovine gamma-globulin conjugate for the immunization of mice. Splenocytes from BALB/c immunized mice were fused with P3X63Ag8U.1 myeloma cells. This resulted in two hybridoma cell lines. Fifty per cent inhibition concentrations (IC50) for the MAbs were 2 and 5 ng ml-1. One MAb (IC50 = 2 ng ml-1) was named #22 and was used to develop quantitative assays for kanamycin by means of an enzyme-linked immunosorbent assay (ELISA). The detection limit was 0.2 ng ml-1 and the standard deviations were 0.2-4.4% for intra-assay and 0.6-4.7% for inter-assay, respectively. The detection limits using peroxidase were 4 ppb in cattle milk, cattle plasma, cattle urine, swine plasma, swine urine and chicken plasma. Using the MAb #22 produced, a rapid test kit based on an immunochromatographic method was developed. The detection limits using the kit were 50 ppb in cattle milk, cattle plasma, cattle urine and chicken plasma.

Animals↗
PubMed1999

Prognostic factors and relative risk for survival in N1-3 oral squamous cell carcinoma: a multivariate analysis using Cox's hazard model.

The records of 136 patients with N1-3 oral squamous cell carcinoma treated by surgery were investigated retrospectively, with the aim of finding out which factors were predictive of survival on multivariate analysis. Four independent factors significantly influenced survival in the following order: pN stage; T stage; histological grade; and N stage. The most significant was pN stage, the five-year survival for patients with pN0 being 91% and for patients with pN1-3 41%. A further study was carried out on the 80 patients with pN1-3 to find out their prognostic factors for survival and the independent factors identified by multivariate analysis were T stage and presence or absence of extracapsular spread to metastatic lymph nodes.

Adult↗
PubMed1999

Vitamin A prevents the decline in immunoglobulin A and Th2 cytokine levels in small intestinal mucosa of protein-malnourished mice.

We examined whether vitamin A improved mucosal immune depression in mice with wasting protein deficiency. In male C3H/HeN mice fed a semi-purified 1% protein diet for 2 wk, plasma retinol and immunoglobulin A (IgA) concentrations in the small intestinal mucosa were 50 and 55%, respectively, of those in mice fed a semi-purified 20% protein diet, (P < 0.05). Daily supplementation of 0.3 mg of retinyl acetate to protein-deficient mice for 2 wk increased the plasma retinol level to the value in the protein-sufficient mice. However, 1 mg/d of retinyl acetate was required to prevent the decline of the IgA level caused by the protein deficiency. Mice fed the low-protein diet had lower concentrations of IL-4 and IL-5 in the small intestinal mucosa and fewer IL-4- and IL-5-containing cells in the lamina propria (P < 0. 05). Retinyl acetate (1 mg) significantly restored the IL-5 level and the number of IL-4- and IL-5-containing cells. After immunization with 20 microg of cholera toxin (CT), the intestinal mucosa of protein-deficient mice contained significantly less CT-specific IgA than control mice. Treatment with 1 mg of retinyl acetate prevented the decline of anti-CT IgA level in the protein-deficient mice, improving their survival rate after an exposure to 0.1 mg of CT. These results suggest that large oral supplements of vitamin A may preserve mucosal IgA level during protein malnutrition, possibly by stimulating Th2 cytokine production and thereby, inducing resistance against infection.

Animals↗
PubMed1999

Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1.

The participation of the monocarboxylic acid transporter MCT1 in the intestinal absorption of weak organic acids has been clarified by functional characterization, by use of stably transfected cells, and by immunohistochemical location of the transporter in intestinal tissues. Immunohistochemical analysis by use of the anti-MCT1 antibody showed that MCT1 is distributed throughout the upper and lower intestines, especially in the basolateral membrane and, to a lesser extent, in the brush-border membrane. When the transporter gene rat MCT1 was transfected into MDA-MB231 cells, transport of benzoic acid, a model weak organic acid that has been generally believed to be transported across the cell membranes by passive diffusion, and lactic acid in rat MCT1-transfected cells was significantly increased compared with transport in cells transfected with the expression vector pRc-CMV alone (mock cells). The observed transport was pH-dependent and activity increased between pH 7.5 and pH 5.5, whereas pH-dependence in mock cells was moderate. Rat MCT1-mediated benzoic acid uptake was saturable, with an apparent Km value of 3.05 mM. In addition, MCT1 increased the efflux of [14C]benzoic acid from the cells. Several weak organic acids were also transported by rat MCT1. These results show that pH-dependent intestinal absorption of weak organic acids, previously explained in terms of passive diffusion according to the pH-partition hypothesis, is at least partially accounted for by MCT1-mediated transport energized at acidic pH by utilization of the proton gradient as a driving force.

Amino Acid Sequence↗
PubMed1998

Cloning, functional expression, and chromosomal localization of the human and mouse gp180-carboxypeptidase D-like enzyme.

We previously reported that a host cell glycoprotein, gp180, binds duck hepatitis B virus particles, and is encoded by a member of the carboxypeptidase gene family (Kuroki, K., Eng, F., Ishikawa, T., Turck, C., Harada, F., Ganem, D., 1995. gp180, a host cell glycoprotein that binds duck hepatitis B virus particles, is encoded by a member of the carboxypeptidase gene family. J. Biol. Chem. 270, 15022-15028). After that report, carboxypeptidase D (CPD) was subsequently purified from bovine pituitary and characterized as a novel carboxypeptidase E (CPE)-like enzyme, with many characteristics in common with duck gp180 (Song, L., Fricker, L.D., 1995. Purification and characterization of carboxypeptidase D, a novel carboxypeptidase E-like enzyme, from bovine pituitary. J. Biol. Chem. 270, 25007-25013). CPD is now supposed to play an important role in a secretory pathway. To clarify the function of gp180 further, we have isolated and analyzed human and mouse homologues of duck gp180. cDNA clones derived from human HepG2 cells and mouse livers have been isolated on the basis of homology to the duck gp180. The suggested open reading frames of the human and mouse cDNA encode 1380 and 1377 amino acid proteins, respectively and have three carboxypeptidase homologous domains (A, B, and C). Domains A and B have completely conserved the residues known to have the enzymatic activity of carboxypeptidase, but domain C in each cDNA does not. Northern blotting revealed a ubiquitous tissue distribution of human gp180 mRNA with several transcript species. Expression of human gp180 cDNA in transfected 293T cells exhibited carboxypeptidase activity upon radiometric assay. The human and mouse homologues of duck gp180 have many characteristics in common with bovine CPD. Fluorescence in-situ hybridization reveals that the gene encoding human gp180 is located in region 17q11.2.

Amino Acid Sequence↗
PubMed1998

A compact vacuum-ultraviolet beamline for synchrotron radiation photoelectron spectroscopy combined with an ion-scattering spectrometer, SORIS.

Apparatus for high-resolution synchrotron radiation photoelectron spectroscopy combined with high-resolution medium-energy ion scattering, named 'SORIS', has been developed for simultaneous investigations of electronic states and atomic structures on surfaces. For this purpose, a compact vacuum-ultraviolet beamline of photon energy from 5 to 700 eV has been designed for the small storage ring 'Aurora' installed at Ritsumeikan University. Owing to the small electron-beam size in the storage ring, an energy resolution E/dE of >5000 can be obtained.

Journal Article↗
PubMed1998

Improvement of spectrometer energy resolution for high-resolution photoelectron spectroscopy.

For high-energy-resolution photoelectron spectroscopy using synchrotron radiation, the energy resolution of a commercial compact photoelectron spectrometer (hemispherical concentric spectrometer) was improved by reducing the size of the entrance and detector slits and optimizing the operation conditions of the lens voltage. Under the optimized conditions, ray-tracing simulations show that severe spectral intensity decreases can be avoided. An energy resolution of 6.2 meV and a resolving power of 8100 at a kinetic energy of 50 eV were experimentally obtained.

Journal Article↗
PubMed1998

Identification of sirm, a novel insulin-regulated SH3 binding protein that associates with Grb-2 and FYN.

We have previously developed a mouse model of insulin-resistant diabetes by targeted inactivation of the insulin receptor gene. During studies of gene expression in livers of insulin receptor-deficient mice, we identified a novel cDNA, which we have termed sirm (Son of Insulin Receptor Mutant mice). sirm is largely, albeit not exclusively, expressed in insulin-responsive tissues. Insulin is a potent modulator of sirm expression, and sirm mRNA levels correlate with tissue sensitivity to insulin. The product of the sirm gene is a serine/threonine-rich protein with several proline-rich motifs and an NPNY motif, conforming to the consensus sequence recognized by the phosphotyrosine binding domains of insulin receptor substrate and Shc proteins. However, Sirm bears no extended homologies with other known proteins. Based on the sequences of the proline-rich domains, we sought to determine whether Sirm binds to the SH3 domains of FYN and Grb-2. We demonstrate here that Sirm binds to FYN and Grb-2 in 3T3-L1 adipocytes and that insulin treatment results in the dissociation of the Sirm.FYN and Sirm.Grb-2 complexes. We also show that Sirm is a substrate for the kinase activity of FYN in vitro. Based on the patterns of expression of sirm, its regulation by insulin, and the interactions with molecules in the insulin signaling pathway, we surmise that Sirm plays a role in modulating tissue sensitivity to insulin.

3T3 Cells↗