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Biomedical subjects

E Noguchi

Publications and source records attributed to E Noguchi.

At least 19 recordsLinked to original sources
PubMed2000

Extent and distribution of linkage disequilibrium in three genomic regions.

The positional cloning of genes underlying common complex diseases relies on the identification of linkage disequilibrium (LD) between genetic markers and disease. We have examined 127 polymorphisms in three genomic regions in a sample of 575 chromosomes from unrelated individuals of British ancestry. To establish phase, 800 individuals were genotyped in 160 families. The fine structure of LD was found to be highly irregular. Forty-five percent of the variation in disequilibrium measures could be explained by physical distance. Additional factors, such as allele frequency, type of polymorphism, and genomic location, explained <5% of the variation. Nevertheless, disequilibrium was occasionally detectable at 500 kb and was present for over one-half of marker pairs separated by <50 kb. Although these findings are encouraging for the prospects of a genomewide LD map, they suggest caution in interpreting localization due to allelic association.

Computer Simulation↗
PubMed2000

Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families.

Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, we conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed significant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MLS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups.

Adolescent↗
PubMed2000

Electro-acupuncture stimulation to a hindpaw and a hind leg produces different reflex responses in sympathoadrenal medullary function in anesthetized rats.

The effects of electro-acupuncture stimulation (EAS) of two different areas of a hindlimb with different stimulus intensities on sympathoadrenal medullary functions were examined in anesthetized artificially ventilated rats. Two needles of 160 microm diameter and about 5 mm apart were inserted about 5 mm deep into a hindpaw (Chungyang, S42) or a hind leg (Tsusanli, S36) and current of various intensities passed to excite various afferent nerve fiber groups at a repetition rate of 20 Hz and pulse duration of 0.5 ms for 30-60 s. Fiber groups of afferent nerves stimulated in a hindlimb were monitored by recording evoked action potentials from the afferents innervating the areas stimulated. The sympathoadrenal medullary functions were monitored by recording adrenal sympathetic efferent nerve activity and secretion rates of catecholamines from the adrenal medulla. EAS of a hindpaw at a stimulus strength sufficient to excite the group III and IV somatic afferent fibers produced reflex increases in both adrenal sympathetic efferent nerve activity and the secretion rate of catecholamines. EAS of a hind leg at a stimulus strength sufficient to excite the group III and IV afferent fibers produced reflex responses of either increases or decreases in sympathoadrenal medullary functions. All responses of adrenal sympathetic efferent nerve activity were lost after cutting the afferent nerves ipsilateral to the stimulated areas, indicating that the responses are the reflexes whose afferents nerve pathway is composed of hindlimb somatic nerves. It is concluded that electro-acupuncture stimulation of a hindpaw causes an excitatory reflex, while that of a hind leg causes either excitatory or inhibitory reflex of sympathoadrenal medullary functions, even if both group III and IV somatic afferent fibers are stimulated.

Action Potentials↗
PubMed2000

Lack of substantial effect of the H(3)-antagonist thioperamide and of the non-selective mixed H(3)-antagonist/H(1)-agonist betahistine on amygdaloid kindled seizures.

We investigated whether some histamine H(3)-antagonists would attenuate amygdaloid kindled seizures in rats. Thioperamide, a standard H(3)-antagonist, did not significantly reduce either seizure ranks or afterdischarge duration (ADD). Betahistine which has both H(3)-antagonistic activity and H(1)-agonistic activity significantly reduced ADD, albeit mild at a toxic dose, though seizure ranks were not affected. In addition, L-histidine, the precursor of histamine, affected neither seizure ranks, nor ADD. It was shown that H(3)-antagonists have no significant inhibitory action against amygdaloid kindled seizures, probably because released histamine was unable to inhibit those seizures.

Amygdala↗
PubMed2000

Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthma.

BACKGROUND: IL-4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL-4 gene cluster and asthma and/or asthma-related traits. Interferon regulatory factor 1 (IRF-1) is located approximately 300 kb telomeric to IL-4 and recent study reveals that IRF-1 deficiency results in an elevated production of Th2-related cytokines and a compensatory decrease in the expression of native cell- and Th1-related cytokines. OBJECTIVE: To determine if there are any mutations associated with the development of atopy and asthma present in the coding exons and 5' flanking region of the IRF-1 gene. METHODS AND RESULTS: We have screened the promoter and coding regions of the IRF-1 gene in atopic asthmatics and controls by SSCP method. We found three novel nuclear variants (the -300G/T and 4396 A/G polymorphisms and the 6355G > A rare variant) in the IRF-1 gene. No variants causing amino acid alterations of IRF-1 were detected. The -300G/T polymorphism was in nearly complete linkage disequilibrium with the 4396 A/G polymorphism. An association between the 4396 A > G polymorphism and atopy/asthma was examined by transmission disequilibrium test in 81 asthmatic families. Either of 4396 A or 4396G alleles was not significantly preferentially transmitted to atopy- or asthma-affected children. CONCLUSION: The IRF-1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population.

Adolescent↗
PubMed2000

Sequential changes of arterial oxygen tension in the supine position during one-lung ventilation.

UNLABELLED: To investigate how surgical positions affect the severity and progress of hypoxemia during one-lung ventilation (OLV), we studied 33 adult patients undergoing right thoracotomy with left OLV. The patients were divided into three groups according to the positions during surgery as follows: the supine position (SP) group (n = 11), the left semilateral decubitus position (LSD) group (n = 9), and the left lateral decubitus position (LLD) group (n = 13). Analysis of arterial blood gases was sequentially determined every 5 min for 30 min during OLV (fractional ratio of inspiratory oxygen = 1.0) in each position. OLV was promptly terminated and switched to bi-lung ventilation if Spo2 declined to 90%. Pao2 progressively decreased with time in all three groups (P < 0.01). The incidence of termination of OLV within 30 min was higher in the SP group (82%), compared with that in the LSD (11%) and LLD (8%) groups (P < 0.01). Final Pao2 (65+/-12 mm Hg, mean +/- SD, P < 0.01 versus LLD, P < 0.05 versus LSD) and SaO2 (91%+/-4%, P < 0.01 versus LLD and LSD) at the termination of OLV in the SP group were the lowest. There was no difference between these values in the LSD and LLD groups (128+/-54 mm Hg, 96%+/-2%, and 167+/-69 mm Hg, 97%+/-4%, respectively) 30 min after the start of OLV. The time for Pao2 to decrease to 200 mm Hg calculated from each regression curve was 354 s in the SP group, 583 s in the LSD group, and 798 s in the LLD group. The time for Pao2 to decline to 100 mm Hg was 794 s in the SP group. In the regression curves of the LSD and LLD groups, the Pao2 did not decrease to 100 mm Hg. Heart rate was slow at baseline in the SP group (P < 0.05 versus LSD), but other hemodynamic variables did not differ among the three groups throughout this study. The LSD was as effective as the LLD in avoiding life-threatening hypoxemia during OLV. IMPLICATIONS: Close observation and prompt counteractions including termination of one-lung ventilation (OLV) are crucial for patients under OLV in the supine position, because life-threatening hypoxemia frequently occurs approximately 10 min after starting OLV, even under 100% oxygen inhalation. The left semilateral decubitus position was as effective as the left lateral decubitus position in avoiding life-threatening hypoxemia during OLV.

Blood Gas Analysis↗
PubMed1999

The effect of electro-acupuncture stimulation on the muscle blood flow of the hindlimb in anesthetized rats.

The effect of electro-acupuncture stimulation (EAS) on blood flow in the muscle biceps femoris (MBF) and on mean arterial pressure (MAP) was investigated in anesthetized, artificially ventilated rats. EAS was applied to a hindpaw for 30 s at intensities of 0.1-10.0 mA and at frequencies of 1-20 Hz, and MBF was measured by laser Doppler flowmetry. EAS at less than 1.0 mA, which excited group II fibers maximally and III fibers partially in a saphenous nerve, had no significant effect on MBF or MAP, although both revealed variable responses. EAS at 1.5 mA, which additionally excited group III fibers almost maximally and was subthreshold for group IV fibers, produced a small but significant increase in MBF and MAP. These responses were further increased at 2.0 mA or more, which was suprathreshold for group IV fibers. The increased response of MBF at 10.0 mA was followed by a small decrease in MBF. EAS at 1.5 mA or more also elicited a decrease in renal blood flow (RBF) and an arterial pressor response. Following severance of the bilateral splanchnic nerves, EAS at 10.0 mA induced only a slight increase in MAP and a decrease in MBF. The decrease in MBF was abolished following further severance of the bilateral lumbar sympathetic trunks (LSTs). In conclusion, EAS to a hindpaw at a stimulus strength sufficient to excite group III and IV afferent fibers, particularly group IV afferent fibers, can produce a reflex decrease in MBF via a reflex activation of muscle sympathetic activity, although this decrease in MBF is overridden by an increase in MBF caused passively by a reflex MAP pressor response elicited by a reflex increase, at least in splanchnic sympathetic activity.

Action Potentials↗
PubMed1999

No association between atopic asthma and a coding variant of Fc epsilon R1 beta in a Japanese population.

Susceptibility to atopic diseases is known to involve genetic factors. The Gly237 allele of a polymorphism (Glu237Gly) of the Fc epsilon R1 beta gene is reportedly associated with atopic asthma in Japanese. To confirm this association, we conducted transmission disequilibrium tests in 76 families identified through atopic asthmatics. A case-control study was also carried out in atopic asthmatic subjects and non-atopic controls. The Gly237 allele was not preferentially transmitted to atopic asthma-affected offspring. Neither the Gly237 allele nor the Gly237/Gly237 + Glu237/Gly237 genotypes were significantly more prevalent in the atopic asthmatics than in the controls. This study failed to confirm a substantial role of the Gly237Glu polymorphism of the Fc epsilon R1 beta gene in the genetic predisposition for atopic asthma in this Japanese population.

Amino Acid Substitution↗
PubMed1999

Lack of association of atopy/asthma and the interleukin-4 receptor alpha gene in Japanese.

BACKGROUND: Susceptibility to the development of atopic diseases is known to involve genetic factors. Several investigators have reported the interleukin-4 (IL-4) receptor alpha gene to be involved in the development of atopy. Recent study has shown that the R allele of a polymorphism in the IL-4 receptor alpha chain gene (Q576R) to be associated with atopy. OBJECTIVE: The objective of this study was to evaluate the possible role of the IL-4 receptor alpha gene in modulating allergic response and asthma in the Japanese population. METHODS: We conducted linkage analysis using microsatellite markers flanking the IL-4 alpha receptor gene in 82 families ascertained through asthmatic children. The IL-4 receptor Q576R polymorphism was also genotyped by PCR-restriction fragment length polymorphism analysis. RESULTS: We did not find evidence for linkage of the asthma and atopy phenotypes with the markers D16S298 and D16S403 (P = 0.10 and P = 0.56, respectively, for the atopy phenotype and P = 0.17 and P = 0.60, respectively, for the asthma phenotype). The IL-4 receptor R576 allele was not preferentially transmitted to atopy- or asthma-affected children (chi2 = 1.67, P = 0.24 for atopy and chi2 = 0.91, P = 0.40 for asthma). In addition, the prevalence of the R576 allele among parents with and without atopy was similar, 20 of 81 (24.7%) parents with atopy and 22 of 77 (28.6%) parents without atopy. CONCLUSION: Our findings indicate that the IL-4 receptor alpha gene does not exert a substantial influence on the inheritance of atopy or asthma in this Japanese population.

Adolescent↗
PubMed1999

Saccharomyces cerevisiae putative G protein, Gtr1p, which forms complexes with itself and a novel protein designated as Gtr2p, negatively regulates the Ran/Gsp1p G protein cycle through Gtr2p.

Prp20p and Rna1p are GDP/GTP exchanging and GTPase-activating factors of Gsp1p, respectively, and their mutations, prp20-1 and rna1-1, can both be suppressed by Saccharomyces cerevisiae gtr1-11. We found that gtr1-11 caused a single amino acid substitution in Gtr1p, forming S20L, which is a putative GDP-bound mutant protein, while Gtr1p has been reported to bind to GTP alone. Consistently, gtr1-S20N, another putative GDP-bound mutant, suppressed both prp20-1 and rna1-1. On the other hand, gtr1-Q65L, a putative GTP-bound mutant, was inhibitory to prp20-1 and rna1-1. Thus, the role that Gtr1p plays in vivo appears to depend upon the nucleotide bound to it. Our data suggested that the GTP-bound Gtr1p, but not the GDP-bound Gtr1p, interacts with itself through its C-terminal tail. S. cerevisiae possesses a novel gene, GTR2, which is homologous to GTR1. Gtr2p interacts with itself in the presence of Gtr1p. The disruption of GTR2 suppressed prp20-1 and abolished the inhibitory effect of gtr1-Q65L on prp20-1. This finding, taken together with the fact that Gtr1p-S20L is a putative, inactive GDP-bound mutant, implies that Gtr1p negatively regulates the Ran/Gsp1p GTPase cycle through Gtr2p.

Amino Acid Sequence↗
PubMed1999

Linkage and association of atopic asthma to markers on chromosome 13 in the Japanese population.

Chromosome 13 contains several candidate genes for asthma and atopy, and markers on this chromosome have been shown to be linked to phenotypes of atopy or asthma in two genome-wide searches. We conducted a linkage study for atopic asthma using markers spanning the whole of chromosome 13 in Japanese families ascertained through asthmatic children and examined associations of atopic asthma with markers where linkage was suggested. Data were analysed using MAPMAKER/SIBS for the multipoint lod score (MLS) analysis and SIB-PAIR for the transmission dis-equilibrium test (TDT). Three peaks which exceeded a lod score of 1.0 were observed (MLS 2.4 between D13S175 and D13S217, MLS 2.0 between D13S153 and D13S156, and MLS 1.4 between D13S285 and D13S293). The global TDT for atopic asthma was significant for the marker D13S153 ( P = 0.0065) and the 96 bp allele of D13S153 was preferentially transmitted to atopic asthma-affected children ( P = 0.0009, Bonferroni correction 5% = 0. 0037, 1% = 0.00072). These findings indicate that genes on chromosome 13 may play an important role in the development of atopy or asthma across various populations.

Adolescent↗
PubMed1999

Disruption of the YRB2 gene retards nuclear protein export, causing a profound mitotic delay, and can be rescued by overexpression of XPO1/CRM1.

Disruption of the YRB2 gene encoding a nuclear Ran-binding protein homologous to Yrb1p/RanBP1 makes Saccharomyces cerevisiae cold sensitive for colony-formation, but not for growth in liquid medium. Schizosaccharomyces pombe Hba1p, which is homologous to Saccharomyces cerevisiae Yrb2p, rescued the cold sensitivity of Deltayrb2 cells. When released from an alpha factor block, Deltayrb2 cells underwent a prolonged delay at the short spindle stage of mitosis with a normal level of Clb/p34(CDC28) kinase activity, but there was no chromosome loss, this being consistent with the finding that Deltayrb2 was synthetic lethal with neither Deltamad1 nor Deltamad3. The cold sensitive colony-formation of Deltayrb2 cells was rescued by both XPO1/CRM1 and GSP1, but not CDC5, carried on a multicopy vector. XPO1/CRM1 rescued Deltayrb2 even in a single copy. Consistent with such a tight functional interaction, Xpo1p/Crm1p directly bound to Yrb2p, but not Yrb1p, and Deltayrb2 cells were found to have a defect in nuclear export signal (NES)-dependent nuclear protein export. From these results together, the ability of Xpo1/Crm1p to export NES-proteins is suggested to be enhanced by both Yrb2p and Gsp1p, and thereby disruption of YRB2 retards nuclear protein export, resulting in the mitotic delay.

Amino Acid Sequence↗
PubMed1999

No association between atopy/asthma and the ILe50Val polymorphism of IL-4 receptor.

Susceptibility to atopic diseases is known to involve genetic factors. The interleukin-4 (IL-4) receptor- alpha gene (IL4R) reportedly is involved in the development of atopy. A recent study has shown the Ile50 allele of a polymorphism (Ile50Val) of IL4R to be associated with atopy. The objective of this study was to replicate this association and confirm the possible role of the Ile50Val polymorphism of IL4R in the etiology of atopic asthma in a Japanese population. We conducted a transmission disequilibrium test in 86 families identified through asthmatic children. A case-control study was also carried out using both atopic and control subjects. The IL4R Ile50Val polymorphism was genotyped by a PCR-restriction fragment length polymorphism method using an intronic upstream primer. The IL4R Ile50 allele was not preferentially transmitted to atopy- or to asthma-affected children. Neither the Ile50 allele nor the Ile50/Ile50 genotype was more prevalent in the atopic subjects than in the control subjects. Our findings indicate that the Ile50Val polymorphism of IL4R does not play a substantial role in genetic predisposition for the etiology of atopy or asthma in this Japanese population.

Adolescent↗
PubMed1998

Evidence for linkage between the development of asthma in childhood and the T-cell receptor beta chain gene in Japanese.

Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components, and several candidate genes have been reported to be linked to atopy and asthma. We have examined a linkage between traits of specific IgE responses to the house dust mite and its purified allergens, high total serum IgE levels and asthma, and the markers at the T-cell receptor (TCR) alpha chain gene (TCR-alpha) and beta chain gene (TCR-beta) in Japanese families ascertained through asthmatic children. Affected sib-pair analyses provided evidence for linkage between TCR-beta and nearby markers (D7S684) on chromosome 7q35 and both IgE and asthmatic phenotypes, but no evidence for linkage of IgE responses nor asthma phenotype to TCR-alpha was detected. The results suggest the presence of major gene(s) controlling atopy and asthma susceptibility in TCR-beta and the nearby region.

Adolescent↗
PubMed1998

Nuclear protein import, but not mRNA export, is defective in all Saccharomyces cerevisiae mutants that produce temperature-sensitive forms of the Ran GTPase homologue Gsp1p.

A series of ts mutations in the GSP1 gene of Saccharomyces cerevisiae was isolated by error-prone PCR. A total of 25 ts gsp1 strains was obtained. Each of these mutants showed between one and seven different amino acid alterations. In several of these ts gsp1 strains, the same amino acid residues in Gsp1p were repeatedly mutated, indicating that our screen for ts gsp1 mutations was saturating. All of the ts gsp1 strains isolated had a defect in nuclear protein import, but only 16 of the 25 ts gsp1 strains had a defect in mRNA export. Thus, Gsp1p is suggested to be directly involved in nuclear protein import, but not in mRNA export. Following release from alpha-factor arrest, 11 of the ts gsp1 mutants arrested in G1; the remainder did not show any specific cell-cycle arrest, at 37 degrees C, the nonpermissive temperature. While the mutants that are defective in both mRNA export and protein import have a tendency to arrest in G1, there was no clear correlation between the cell cycle phenotype and the defects in mRNA export and nuclear protein import. Based on this, we assume that Ran/Gsp1p GTPase regulates the cell cycle and the nucleus/cytosol exchange of macromolecules through interactions with effectors that were independent of each other, and are differentially affected by mutation.

Amino Acid Sequence↗
PubMed1998

Association of asthma and the interleukin-4 promoter gene in Japanese.

BACKGROUND: Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. Several investigator have linked the interleukin-4 (IL-4) gene and nearby markers located on chromosome 5 to atopy and asthma. Recent study has demonstrated that the T allele of a polymorphism in the IL-4 gene promoter region (C-590T) is associated with elevated levels of total serum IgE. OBJECTIVE: The objective of this study was to evaluate the possible role of this IL-4 polymorphism (C-590T) in modulating the allergic response and asthma in Japanese children. METHODS AND RESULTS: The study was conducted in two different populations: families ascertained through asthmatic children (asthmatic group, 306 members) in whom linkage of asthma and atopy to chromosome 5q31-33 is suggested and a random general population (control group, 215 members). The IL-4 C-590T polymorphism was genotyped by PCR-restriction fragment length polymorphism analysis. Frequency of the T allele was 0.73 in the asthmatic group and 0.70 in the control group. No significant difference in the levels of total serum IgE and specific IgE to house dust mite was observed between subjects with homozygote for the C allele, a heterozygote and a homozygote for the T allele by intrafamilial and interfamilial comparisons. Using the transmission disequilibrium test, however, we found a significantly frequent transmission of the T allele to asthmatic children (chi2=5.72, P=0.023). CONCLUSION: Our data suggest that the IL-4 promoter C-590T polymorphism may be associated with the development of asthma in Japanese children, but not through modulating total serum IgE levels.

Adolescent↗
PubMed1998

Human dis3p, which binds to either GTP- or GDP-Ran, complements Saccharomyces cerevisiae dis3.

Saccharomyces cerevisiae Dis3p, which interacts with Ran/Gsp1p, complements Schizosaccharomyces pombe dis3-54. Consistent with the functional conservation of Dis3p in S. cerevisiae and S. pombe, the human ORF (accession number: R27667) was found to be highly homologous to yeast Dis3p. Based on its nucleotide sequence, we cloned a full-sized human DIS3 cDNA. The cloned human cDNA partly but significantly restored the temperature-sensitivity of S. cerevisiae dis3. Thus, Dis3p was found to be structurally and functionally conserved from yeast to mammals. Consistent with the report that S. cerevisiae Dis3p is identical to Rrp44p, which comprises the exosome involved in ribosomal RNA processing, S. cerevisiae Dis3p was found to be localized in the nucleolus. Similar to S. cerevisiae Dis3p, human Dis3p enhanced RCC1-stimulated nucleotide release from Ran, in a dose-dependent manner, and bound to GTP- or GDP-Ran.

Amino Acid Sequence↗