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S Chiba

Publications and source records attributed to S Chiba.

At least 163 records · Page 9Linked to original sources

Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods.

The Delta/Serrate/LAG-2 (DSL) domain containing proteins are considered to be ligands for Notch receptors. However, the physical interaction between DSL proteins and Notch receptors is poorly understood. In this study, we cloned a cDNA for mouse Jagged1 (mJagged1). To identify the receptor interacting with mJagged1 and to gain insight into its binding characteristics, we established two experimental systems using fusion proteins comprising various extracellular parts of mJagged1, a "cell" binding assay and a "solid-phase" binding assay. mJagged1 physically bound to mouse Notch2 (mNotch2) on the cell surface and to a purified extracellular portion of mNotch2, respectively, in a Ca(2+)-dependent manner. Scatchard analysis of mJagged1 binding to BaF3 cells and to the soluble Notch2 protein demonstrated dissociation constants of 0.4 and 0.7 nM, respectively, and that the number of mJagged1-binding sites on BaF3 is 5,548 per cell. Furthermore, deletion mutant analyses showed that the DSL domain of mJagged1 is a minimal binding unit and is indispensable for binding to mNotch2. The epidermal growth factor-like repeats of mJagged1 modulate the affinity of the interaction, with the first and second repeats playing a major role. Finally, solid-phase binding assay showed that Jagged1 binds to Notch1 and Notch3 in addition to Notch2, suggesting that mJagged1 is a ligand for multiple Notch receptors.

Amino Acid Sequence↗

Dissociation of inhibitory effects of guanethidine on adrenergic and on purinergic transmission in isolated canine splenic artery.

The aim of this study was both to investigate the effects of progressive inhibition of adrenergic neurons by increasing concentrations of guanethidine (0.1-10 microM) on the double-peaked vasoconstrictor responses to electrical periarterial nerve stimulation in the isolated and perfused canine splenic artery, and to clarify whether release of noradrenaline is presynaptically separate from release of adenosine 5'-triphosphate (ATP). Double-peaked vasoconstrictions (biphases of vasoconstrictions) were consistently observed under the conditions of 30-s trains of pulses at 1-10 Hz frequencies. Guanethidine, at a lower concentration (0.1 microM) did not modify the first (1st) phase vasoconstriction at low frequencies (1-2 Hz), but markedly inhibited the second (2nd) responses. On the other hand, it slightly but significantly inhibited the double-peaked vasoconstrictor responses at high frequencies (6-10 Hz). Furthermore, a 10-fold increase of concentration of guanethidine (1 microM) almost completely inhibited the 2nd phase responses at any frequencies used but did not completely inhibit the 1st phase response. A further increased concentration of guanethidine (10 microM) failed to enhance the 1 microM guanethidine-induced inhibition. The 1 microM guanethidine-resistant 1st phase responses at any frequencies used (1-10 Hz) were sensitive to tetrodotoxin (30 nM). Treatment with 0.1 microM prazosin did not modify the 1st phase response at any frequencies used in the 1 microM guanethidine-treated preparation. The responses remaining after 1 microM guanethidine and 0.1 microM prazosin were completely suppressed by a subsequent application of 1 microM alpha,beta-methylene ATP at any frequencies used. The results indicated that guanethidine, an adrenergic neuron blocker, may exert a dominant inhibitory effect on adrenergic rather than on purinergic components of sympathetic nerve co-transmission, indicating that guanethidine-sensitive mechanisms may mainly contribute to determine noradrenaline secretion from neurosecretory vesicles rather than ATP secretion.

Adenosine Triphosphate↗

Up-regulation of uterine UCP2 and UCP3 in pregnant rats.

Pregnancy produces profound changes in hormone dynamics, thermoregulation and energy metabolism. Uncoupling proteins (UCPs) have been identified in a variety of tissues and UCP1 is known to play important roles in energy homeostasis, while the regulation of UCP2 and UCP3 is still unclear. The present study aimed to investigate the effects of the changes during pregnancy on UCP gene expression in the uterus, as well as in brown adipose tissue (BAT), white adipose tissue (WAT), soleus muscle (Muscle), and liver, throughout the estrus and metestrus periods, at early, middle and late stages in pregnancy, and during post-gestational stages. The expression of uterine UCP2 and UCP3 were up-regulated by 3.2- and 1. 5-fold, respectively, during the late stage of pregnancy with an increase of WAT leptin mRNA expression and exogenous administration of leptin resulted in induction of the uterine UCP2 and UCP3 levels. Contrary to uterine UCPs, UCP1 mRNA expression in BAT was down-regulated by 0.5-fold and there were no remarkable changes in WAT or liver UCP2, or Muscle UCP3 expression throughout the periods. These results indicate that UCP gene expressions during pregnancy are regulated tissue-dependently, and up-regulation of uterine UCP2 and UCP3 mRNA may be due to increased leptin levels.

Adipose Tissue↗

Expression cloning of an ascidian syndecan suggests its role in embryonic cell adhesion and morphogenesis.

Expression cloning of maternally expressed genes of the ascidian Ciona savignyi demonstrated that the overexpression of syndecan, a member of a multigene family of integral membrane heparan sulfate proteoglycans, resulted in a disturbance of cell adhesion and morphogenesis. The Ciona syndecan gene was expressed both maternally and zygotically. The maternal transcript was distributed evenly in fertilized eggs and early embryos up to the 32-cell stage without any special localization and then became barely detectable in the 64-cell and gastrula stages. The zygotic transcription became evident during neurulation, mainly in cells of epidermis, the central nervous system, and mesenchyme. Embryos with syndecan overexpression via RNA injection cleaved as did normal embryos, but showed loose blastomere adhesion after the 32-cell stage. Gastrulation occurred, but the closure of the blastopore was markedly delayed, resulting in larvae without normal morphology. About half of the syndecan-overexpressing embryos hatched, and differentiation of epidermis, endoderm, muscle, and notochord was evident. However, the formation of pigment cells of the sensory organs was markedly disturbed. These results indicate that an appropriate level of syndecan expression is required for normal cell adhesion and morphogenesis of the ascidian embryo.

Amino Acid Sequence↗

Frequent false-positive results of Aspergillus latex agglutination test: transient Aspergillus antigenemia during neutropenia.

BACKGROUND: Two serologic assays, Aspergillus latex agglutination testing (LA) and plasma (1-->3)-beta-D-glucan (BDG) measurement, are used when invasive pulmonary aspergillosis (IPA) is suspected. Despite the high specificity of these assays, false-positive results are frequent for neutropenic patients. This study was conducted to evaluate the efficacy of LA and BDG and to investigate the cause of the false-positive results. METHODS: Eighty-eight consecutive patients with hematologic malignancies who underwent intensive chemotherapy were tested weekly with LA and BDG. RESULTS: Sixteen of 88 patients were diagnosed as having IPA. The sensitivity, specificity, and positive predictive values were 23%, 98%, and 64% for LA and 27%, 88%, and 52% for BDG, respectively. Of 11 patients who became positive for LA only during neutropenic periods, 2 patients developed IPA. In contrast, six of eight patients who became positive for LA during nonneutropenic periods developed IPA. Transient Aspergillus antigenemia was more frequently encountered during neutropenia (2.9%) than during nonneutropenic periods (0.2%). The plasma BDG concentration increased at the nadir of neutropenia in 36 of 45 patients who had no signs of IPA, and it exceeded the level of 20 pg/mL in 2 patients. CONCLUSIONS: Both BDG and LA have a low sensitivity and a high specificity for IPA. However, the false-positive rate of LA increases during neutropenic periods. Caution should be exercised in interpreting the results of these blood tests, especially when patients are neutropenic.

Adolescent↗

TT virus in bone marrow transplant recipients.

TT virus (TTV) is a newly discovered transfusion-transmissible DNA virus, which may cause posttransfusion hepatitis. The virus was detected in 12% of Japanese blood donors. The aim of the study is to investigate the prevalence and clinical influence of TTV in bone marrow transplant (BMT) recipients. Sera from 25 BMT recipients obtained 6 to 12 weeks after the transplant were examined for TTV-DNA by the seminested polymerase chain reaction. Serial samples were additionally analyzed in patients with TTV-DNA. Fifteen of 25 recipients (60%) were positive for TTV-DNA after transplant, whereas it was detected in only two of 20 BMT donors (10%). In patients positive for TTV-DNA before BMT, the amount of TTV-DNA decreased to an undetectable level during the myelosuppressed period after BMT. We also found that there was a novel group of TTV, G3, classified by the nucleotide sequences. The median peak alanine aminotransferase (ALT) levels were 135.0 IU/L and 116.5 IU/L (normal range, 4 to 36 IU/L) in TTV-positive and TTV-negative recipients, respectively. In one of the seven TTV-positive patients who developed hepatic injury (ALT > 150 IU/L), a serial change in the serum TTV titer showed a good correlation with the ALT level. We concluded that (1) the prevalence of TTV is high in BMT recipients, (2) TTV might be replicated mainly in hematopoietic cells, (3) transfusion-transmitted TTV may cause persistent infection, (4) a novel genetic group of TTV, G3, was discovered, and (5) TTV does not seem to frequently cause hepatic injury, although one patient was strongly suggested to have TTV-induced hepatitis.

Adolescent↗

RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease.

In this study we used an in situ approach to identify the oxidized nucleosides 8-hydroxydeoxyguanosine (8OHdG) and 8-hydroxyguanosine (8OHG), markers of oxidative damage to DNA and RNA, respectively, in cases of Alzheimer's disease (AD). The goal was to determine whether nuclear and mitochondrial DNA as well as RNA is damaged in AD. Immunoreactivity with monoclonal antibodies 1F7 or 15A3 recognizing both 8OHdG and 8OHG was prominent in the cytoplasm and to a lesser extent in the nucleolus and nuclear envelope in neurons within the hippocampus, subiculum, and entorhinal cortex as well as frontal, temporal, and occipital neocortex in cases of AD, whereas similar structures were immunolabeled only faintly in controls. Relative density measurement showed that there was a significant increase (p < 0.0001) in 8OHdG and 8OHG immunoreactivity with 1F7 in cases of AD (n = 22) as compared with senile (n = 13), presenile (n = 10), or young controls (n = 4). Surprisingly, the oxidized nucleoside was associated predominantly with RNA because immunoreaction was diminished greatly by preincubation in RNase but only slightly by DNase. This is the first evidence of increased RNA oxidation restricted to vulnerable neurons in AD. The subcellular localization of damaged RNA showing cytoplasmic predominance is consistent with the hypothesis that mitochondria may be a major source of reactive oxygen species that cause oxidative damage in AD.

8-Hydroxy-2'-Deoxyguanosine↗

Tumor necrosis factor-alpha regulates in vivo expression of the rat UCP family differentially.

A family of uncoupling proteins (UCPs), free fatty acid anion transporters, plays a crucial role in energy homeostatic thermoregulation. Tumor necrosis factor-alpha (TNF-alpha), a member of the cytokine family, is well known as an endogenous pyrogen. To evaluate the interaction of TNF-alpha with UCPs in thermogenesis, effects of TNF-alpha on rat UCP gene expression were examined in intrascapular brown adipose tissue (BAT), epididymal white adipose tissue (WAT) and soleus muscle (Muscle). Administration of TNF-alpha elevated rectal temperature by 0.7 degree C as well as serum leptin which peaked at 6 h, compared with saline controls. BAT UCP1 mRNA expression was increased by 1.2-fold at 6 h after the TNF-alpha treatment and decreased by 0.8-fold at 16 h after the treatment. In contrast to UCP1 expression in BAT, UCP2 mRNA expressions in BAT, WAT, and Muscle was increased to reach maximum levels of 1.3-, 1.6- and 1.8-fold, respectively, at 16 h after the treatment. UCP3 mRNA in Muscle, but not in BAT or WAT, was exclusively up-regulated by 1.7-fold at 16 h after the treatment. These results indicate that TNF-alpha up-regulates UCP gene expression differentially and tissue dependently, and add novel insights into thermogenesis under conditions of malignancy and inflammation.

Adipose Tissue↗

Epidemiological study of the G serotype distribution of group A rotaviruses in Kenya from 1991 to 1994.

An epidemiological study on the G serotype distribution of group A rotaviruses (GARV) isolated in Kenya was carried out in one urban hospital in Nairobi and in two rural hospitals in Nanyuki and Kitui to clarify the prevalent G serotypes before future introduction of the ready licensed rotavirus vaccine in Kenya. A total of 1,431 stool specimens were collected from children, who were mainly outpatients, aged from 0 to 6 years old with acute gastroenteritis from August 1991 to July 1994. Samples positive for GARV by conventional ELISA were then analyzed by subgrouping and serotyping ELISA and by PAGE. To ascertain the G serotypes of viruses in samples that were unable to be typed by serotyping ELISA, polymerase chain reaction was also attempted. The prevalence of GARV was 28.4% in the urban hospital, 22.5% in Nanyuki, and 13.7% in Kitui. Among rotavirus-positive samples, subgroup II rotaviruses were detected in 63.1%, and subgroup I rotaviruses were 25.9%. Serotype G4 was most prevalent, accounting for 41.6% followed by 23.3% of serotype G1, 17.0% of serotype G2, and serotype G3 was rarely isolated. Seven strains of serotype G8/P1B rotavirus was detected for the first time in Kenya by RT-PCR. Eleven specimens with an unusual composition of subgroup, serotype, and electropherotype were atypical GARV in which the P-serotype was P1A, P1B, or P2. Although uncommon GARV serotype G8/P1B and atypical GARV were detected, the four major GARV serotypes, G1 through G4, should be targeted at this moment for vaccination to control this diarrheal disease in Kenya. Continuous monitoring of the G- and P-serotype distribution of GARV should provide important information about the impact of rotavirus vaccination in Kenya.

Child↗

Effects of lidocaine on isolated, blood-perfused ventricular contractility in the dog.

Direct inotropic effects of lidocaine on ventricular muscle were investigated in isolated canine left ventricular preparations which were perfused with a donor dog's arterial blood. Intravenous administration of lidocaine in doses of less than 1 mg/kg did not cause any significant hemodynamic or cardiac changes in the donor dog and in the isolated ventricular preparation. A large dose of 10mg/kg of lidocaine produced a marked depressor response in the donor and a negative inotropic effect in the isolated ventricle. Direct injection of lidocaine (1-30 micromol) to the isolated preparation induced a dose-related decrease in the ventricular contractile force. Infusion of lidocaine (3 micromol/ml per min) did not influence norepinephrine- or calcium chloride-induced positive inotropic effects. In the frequency-force relationship, lidocaine generally depressed the contractility, exhibiting the positive staircase phenomenon. On the other hand, a calcium entry inhibitor, diltiazem, readily caused the negative staircase. From these results, it is concluded that (1) a large amount of lidocaine has a cardiac depressant property, (2) lidocaine has no antiadrenergic properties, and (3) the action of lidocaine may probably be due to the effect of intracellular calcium movement but not to a modification of Ca inward currents.

Adrenergic alpha-Agonists↗

Successful stenting of congenital bronchial stenosis in infancy.

UNLABELLED: Recently, stent implantation has become the treatment of choice for patients with tracheobronchial stenosis due to malignant tumours, tuberculosis and recurrent stenosis following lung transplant. However, reports on this procedure in infants with congenital bronchial stenosis are extremely rare. We report successful stent implantation in an infant with congenital left bronchial stenosis followed by rapid improvement in his respiratory condition. CONCLUSION: The use of a stent in infants is still controversial because size mismatch will take place with growth. However, we believe that implantation of a metallic stent can be the preferred treatment of congenital bronchial stenosis even in small infants.

Bronchial Diseases↗

Cardiac effects of propofol and its interaction with autonomic nervous system in isolated, cross-circulated canine atria.

PURPOSE: The effects of propofol on sinoatrial pacemaker activity and myocardial contractility and its interaction with the autonomic nervous system were investigated in isolated, cross-circulated right atrial canine preparations. METHODS: An isolated right atrial preparation was perfused with heparinized arterial blood from an anesthetized support dog and changes in atrial rate and atrial contractile force were recorded. RESULTS: Propofol (30-1000 microg) and thiopental (30-1000 microg), injected into the sinus node artery of the isolated atrium, induced dose-dependent decreases in atrial rate and contractile force. The negative chronotropic and inotropic effects of propofol were greater than those of thiopental. The propofol-induced negative chronotropic and inotropic responses were not inhibited by atropine. Propofol had no effects on the cardiac responses to acetylcholine, norepinephrine, and the intracardiac parasympathetic nerve stimulation which activates ganglionic nicotinic acetylcholine receptors. CONCLUSION: These results indicate that: (a) propofol directly depresses sinoatrial pacemaker activity and myocardial contractility, (b) the negative chronotropic and inotropic effects of propofol do not involve activation of muscarinic receptors, and (c) propofol has little interaction with the autonomic nervous system at the effector site.

Journal Article↗

Mutation screening of phenylketonuria in the Far East of Russia.

We analyzed mutant genotypes at the human phenylalanine hydroxylase (PAH) locus among phenylketonuria (PKU) patients in the Far East of Russia. A total of 60 variant alleles from 30 PKU families were analyzed for prevalent Caucasian mutations and restriction fragment length polymorphism/variable number of tandem repeats (RFLP/VNTR) haplotypes. Seventy-eight percent of all variant alleles carried six mutations. The most prevalent mutation was R408W (63%), with a haplotype background of 2.3. It also showed a very high degree of homozygosity (43%). The other five mutations (R158Q, R261Q, R252W, R261X, and IVS12nt-1) accounted for 1.7%-6.7% of all PKU alleles, and a single haplotype was associated with each genotype, except for R261Q. The genetic structure of PKU patients in the Far East of Russia seems to be relatively homogeneous, compared with that in the other Slavic and Oriental populations of surrounding countries. Prediction of a clinical phenotype and carrier detection will be feasible using DNA tests.

Child↗