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Biomedical subjects

H Eguchi

Publications and source records attributed to H Eguchi.

At least 19 recordsLinked to original sources
PubMed1996

Treatment of high-risk acute lymphoblastic leukemia in children using the AL851 and ALHR88 protocols: a report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan.

A total of 125 children, who were diagnosed as having high-risk acute lymphoblastic leukemia (ALL), were treated with two consecutive protocols designated as AL851 (1985-1988) and ALHR88 (1988-1990). All patients received induction therapy consisting of vincristine (VCR), prednisolone (PSL), daunorubicin (DNR), and I-asparaginase (I-Asp). In the ALHR88 protocol, the patients whose blasts in the bone marrow (BM) were > or = 25% on day 14 of induction therapy and who were classified into T-cell type received additional cytosine arabinoside (AraC). After consolidation with intermediate-dose methotrexate (MTX), reinduction therapy including VCR, dexamethasone, and adriamycin followed by high-dose AraC was done for all patients. Intrathecal MTX and 24Gy of cranial irradiation were used to prevent central nervous system leukemia. A maintenance therapy consisting of 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR, and AraC was administered for 3 years after achieving a complete remission (CR). CR was achieved in 51/55 (92.7%) for AL851 and 68/70 (97.1%) for ALHR88. The 5-year event-free survival rates were 49.1 +/- 6.7% in AL851 and 62.5 +/- 6.1% in ALHR88. The factors related to a poor prognosis were a high initial leukocyte count of greater than 50 x 10(9)/L (P < 0.001), an L2 morphology of leukemic cells by FAB classification (P = 0.009), the chromosomal abnormality (P = 0.004) and high residual leukemic cells in BM (> or = 25%) on day 14 of induction therapy (P < 0.001). Taking these factors into consideration, more intensive protocols were started in 1990 for the patients with high-risk ALL.

Adolescent↗
PubMed1995

Sandwich immunoassay specific for the N-terminal sequence of osteocalcin.

A monoclonal antibody (10B) against the N-terminal sequence of human osteocalcin was selected to characterize its epitope and species specificity. The cross-reactivity of 10B with human and rat osteocalcin demonstrated that the reactivities of 10B with both human and rat osteocalcins were very similar. The pin technology method was used to determine the epitope and clearly demonstrated that the epitope recognized by 10B was localized to residues 12-16, the sequence of which is identical in rat and human osteocalcin molecules. This monoclonal antibody was found to be useful for designing region-specific sandwich immunoassay systems for human and rat N-terminal osteocalcin (N-OC) molecules using rabbit anti-hN20 and anti-rN20 polyclonal antibodies, respectively. The osteocalcin levels in serum determined by this N-OC method were stable during prolonged storage at 25 degrees C and the method could be usefully applied in the development of immunoassay systems for many osteocalcin molecules from many other species.

Amino Acid Sequence↗
PubMed1995

Characterization of orphan nuclear receptor binding elements in sex-differentiated members of the CYP2C gene family expressed in rat liver.

The HepG2-specific P450 2C factor motif (HPF1-motif) is conserved in many hepatic cytochrome P450 genes (CYP). Its functional importance for rabbit CYP2C genes has led to the proposal that the HPF1 motif acts as a common regulator for the liver-specific expression of CYP2 genes with hepatic nuclear factor (HNF)-4 being the corresponding trans-activator. The HPF1-like elements in the rat CYP2C genes 2C7, 2C11, 2C12, and 2C13 have been studied with regard to functional importance and binding of the orphan receptors HNF-4, apoAI regulatory protein-1 (ARP-1), and v-erbA-related receptors (EAR) 3 and 2. Binding activity in rat liver nuclear extracts includes these orphan receptors as judged from electromobility supershift experiments and from results obtained with expressed receptors, although the element in CYP2C11 did not bind HNF-4. Mutations of the HPF1-like elements in the CYP2C7, CYP2C11, and CYP2C12 promoters had marginal effects on the expression of luciferase reporter gene constructs transiently transfected into HepG2 cells, whereas for CYP2C13 the activity was reduced to 60% of the wild type construct. Coexpression of HNF-4 in COS-7 cells had limited effect on the luciferase activity generated from the 2C promoters, maximally 3-fold. Our data indicate that the HPF1 elements in the rat CYP2C genes have limited functional importance and that HNF-4 is not a major trans-activator for any of these genes.

Animals↗
PubMed1995

Up-regulation of ICAM-1 expression on human dermal fibroblasts by IFN-beta in the presence of TNF-alpha.

Unstimulated human fibroblasts show low or undetectable ICAM-1 expression. Interferon-beta (IFN-beta) at concentrations of 10, 100, and 1000 IU/ml in the presence of tumor necrosis factor-alpha (TNF-alpha) significantly increased the ICAM-1 expression of fibroblasts in a dose-dependent manner. Treatment with IFN-beta alone, however, did not up-regulate the ICAM-1 expression. Furthermore the attachment of peripheral blood mononuclear cells (PBMCs) to cytokine-treated fibroblasts was increased. This augmented attachment was partly inhibited by anti-ICAM-1 antibody. These results suggest that IFN-beta and TNF-alpha may cooperatively modulate the attachment of PBMCs in the dermis.

Cell Adhesion↗
PubMed1995

Polymorphisms of human Ah receptor gene are not involved in lung cancer.

The Ah receptor (Ahr) is a ligand-dependent transcription factor that positively regulates inducible expression of the CYP1A1 gene. Based on the sequence information of the human Ahr and the intron-exon junctions of the mouse counterpart, an analysis of single-strand conformational polymorphism (SSCP) was carried out to detect subtle base differences in the coding region of the gene among individuals. We found that the Ahr protein has at least two forms of variants in a Japanese gene pool, and that these variants can be ascribed to one amino acid replacement of Arg by Lys at codon 554. The frequencies of Arg-coded and Lys-coded alleles were 0.57 and 0.43, respectively. We found, however, that this germ line polymorphism of the Ahr gene did not show a significant association with aryl hydrocarbon hydroxylase (AHH) inducibility nor with lung cancer incidence.

Animals↗
PubMed1995

Genetic polymorphisms of drug-metabolizing enzymes and lung cancer susceptibility.

A close association of smoking-associated lung cancer incidence with the Msp 1 and 1le-Val polymorphisms of CYP1A1 gene was found in a Japanese population in terms of genotype frequency comparison and cigarette dose response. A synergistic increase in susceptibility to lung cancer was observed when the susceptible genotypes of CYP1A1 were combined with a deficient GSTM1 genotype. Individual difference in expression levels of Ahr and Arnt mRNAs was observed, and the expression levels of CYP1A1 appeared to associate with those of transcriptional factors. The Ahr protein has two different structures, ascribed to one amino acid replacement at codon 554 of Arg by Lys. However, this germ line polymorphism did not show a significant association with AHH inducibility nor lung cancer incidence. The p53 gene alterations in lung cancer tissues were more frequently observed among the patients with a susceptible allele of CYP1A1 gene.

Chromosome Aberrations↗
PubMed1995

An Rsa I polymorphism in the CYP2E1 gene does not affect lung cancer risk in a Japanese population.

CYP2E1 catalyzes the metabolic activation of tobacco-specific N-nitrosamines, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. An Rsa I polymorphism, which is located in the 5'-flanking region of the CYP2E1 gene, has been found to affect the transcriptional regulation of the gene, resulting in different expression levels of the mRNA among individuals. In order to investigate an association between the Rsa I polymorphism and lung cancer susceptibility, the genotype distribution among 316 lung cancer patients was compared with that in 503 healthy controls. No statistically significant association was found between the Rsa I polymorphism and an increased risk of lung cancer, even though histological types of lung cancer, cigarette smoking and alcohol consumption were taken into account.

Cytochrome P-450 CYP2E1↗
PubMed1995

Clonal and non-clonal karyotypically abnormal cells in haemophagocytic lymphohistiocytosis.

We studied chromosomes in bone marrow (BM) or peripheral blood cells of nine patients with haemophagocytic lymphohistiocytosis (HLH); three of them had a family history of HLH and four others underwent concurrent Epstein-Barr virus (EBV) infection. In addition to a large population of normal mitotic cells, karyotypically abnormal clonal cells were found in two patients, abnormal clonal cells and a nonclonal (single) abnormal cell in one, and nonclonal abnormal cells in three. All the six patients with chromosome abnormalities died of progressive disease; one of them also had EBV infection and EBV-associated clonal proliferation. Two of three patients with EBV infection and only normal mitotic cells in BM completely recovered from the disease. Although HLH did not show histological and/or haematological evidence of a neoplastic disease, clonal chromosome abnormalities and the fatal clinical outcome found in some of the patients suggest that the disease may be heterogenous and include malignancy. HLH patients with karyotypically abnormal clonal cells in BM should warrant more intensive chemotherapy than that presently being applied to them and should be considered as candidates for BM transplantation.

Adolescent↗
PubMed1995

Insulin-like growth factor I resistance in peripheral tissue but not in liver in streptozotocin-induced diabetic rats.

The metabolic effect of recombinant human insulin-like growth factor I (IGF-I) was investigated by the glucose clamp technique in normal rats and streptozotocin-induced diabetic rats, a model of insulin-dependent diabetes mellitus (IDDM), and compared with that of insulin. Glucose uptake by peripheral tissues was stimulated by intravenous administration of IGF-I at rates of from 0.369 to 3.690 nmol/kg/min in a dose dependent manner, with a potency of 1/52 that of insulin estimated on the basis of the ED50 molar ratio in normal rats. In streptozotocin-induced diabetic rats, the maximum effects of IGF-I and insulin were reduced to 72% and 70% of those in normal rats, respectively, indicating the presence of both IGF-I and insulin resistance. Hepatic glucose output in normal rats was suppressed by IGF-I in a dose dependent manner with a weaker potency of 1/99 that of insulin assessed on the basis of the ED50 values. In streptozotocin-induced diabetic rats, a dose-response curve of the suppressive effect of insulin on hepatic glucose output shifted to the right, indicating the presence of hepatic insulin resistance, but a leftward shifting of the suppressive effect of IGF-I on hepatic glucose output was observed. We concluded that the IGF-I effect on peripheral tissue was decreased but that on the liver was rather increased in streptozotocin-induced diabetic rats, in contrast to the resistance of both peripheral tissues and liver to insulin.

Animals↗
PubMed1995

[Treatment results of acute nonlymphocytic leukemia in childhood--Kyushu Yamaguchi Children's Cancer Study Group].

Seventy-three children with acute nonlymphocytic leukemia (ANLL) have been treated with ANLL-85 and ANLL-88 protocol at Kyushu-Yamaguchi Children's Cancer Study Group between June, 1985 and February, 1993. Ten boys and 10 girls (0y4m-16ylm) were treated with the ANLL-85 protocol. The complete remission (CR) rate was 75% and the 5-year event free survival (EFS) was 20 +/- 9%. It was terminated because of frequent early relapse (within 6 months after CR). Thirty-four boys and 19 girls (0y3m-17ylm) were treated with the ANLL-88 protocol. The CR rate was 85% and the 5-year EFS was 32 +/- 7%. Early relapse rate with ANLL-88 was lower than that of ANLL-85, however 9 cases relapsed after terminating therapy. Although bone marrow transplantation (BMT) from related donors during the first CR was effective in ANLL-88, EFS was not improved. Recognition of risk factors and appropriate chemotherapy regimens with or without the support of stem cell transplantation may be necessary to cure children with ANLL.

Adolescent↗
PubMed1994

Antagonistic activities of N-3389, a newly synthesized diazabicyclo derivative, at 5-HT3 and 5-HT4 receptors.

The antagonistic activities of compound N-3389 (endo-3,9-dimethyl-3,9- diazabicyclo[3,3,1]non-7-yl 1H-indazole-3-carboxamide dihydrochloride) at 5-HT3 and 5-HT4 receptors were examined using in vitro and in vivo assays. N-3389 showed potent 5-HT3 receptor antagonistic activities in a radioligand binding assay (pKi = 8.77), against 2-methyl-5-HT (2-Me-5-HT)-induced bradycardia in rats (ED50 = 0.73 micrograms/kg i.v., 38 micrograms/kg p.o.) and against 2-Me-5-HT-induced contraction in longitudinal muscle myenteric plexus preparations of guinea-pig ileum (IC50 = 3.2 x 10(-8) M). As a preliminary to investigating the effect of N-3389 on 5-HT4 receptors, we examined the contraction induced by 5-HT in guinea-pig ileum preparations. We confirmed that 5-HT (10(-8)-10(-5) M) induced biphasic contractions in the preparations. Furthermore, 5-HT3 receptor antagonism inhibited the late phase of the contraction induced by high concentrations of 5-HT (3 x 10(-6)-10(-5) M), whereas 5-HT4 receptor antagonism inhibited the early phase of the contraction induced by low concentrations of 5-HT (10(-8)-10(-6) M). N-3389 (10(-7)-10(-5) M) inhibited both phases of contraction induced by 5-HT. In addition, N-3389 (3 x 10(-7)-3 x 10(-6) M) was found to inhibit the increase of electrically stimulated twitch responses induced by 5-HT (10(-8) M) longitudinal muscle myenteric plexus preparation of the guinea-pig ileum. These results suggest that N-3389 acts as a 5-HT3 and 5-HT4 receptor antagonist.

Animals↗
PubMed1994

Hepatitis C virus antibody and hepatitis C virus replication in chronic hepatitis B patients.

We assessed hepatitis C virus infection in 156 chronic hepatitis B patients using second-generation hepatitis C virus antibody (anti-HCV). Active virus replication was further investigated in anti-HCV-positive cases by means of polymerase chain reaction assay for the detection of serum hepatitis C virus RNA. Anti-HCV prevalence was higher in patients negative for hepatitis B e antigen (HBeAg) (10/48, 21%) than in HBeAg-positive patients (10/108, 9%) (p < 0.05), and the reactivity (cut-off index) in anti-HCV enzyme-linked immunosorbent assay of the positive cases was significantly higher in HBeAg-negative patients (4.1 +/- 0.1) than in -positive ones (3.6 +/- 0.6) (p < 0.05). The prevalence of hepatitis C virus RNA in anti-HCV-positive cases was also higher in the HBeAg-negative group (9/10, 90%) than in the -positive group (3/10, 30%) (p < 0.01). Viremia was found in association with high reactivity in anti-HCV ELISA (cut-off index > 3.5) in both groups. Nine (90%) of 10 such cases were viremic in the HBeAg-negative group compared with three (43%) of seven in the HBeAg-positive group (p < 0.05). These results suggest that hepatitis C virus replication may be influenced by hepatitis B virus replicative states, indicating possible interference between hepatitis B and C viruses.

Adult↗
PubMed1994

Interindividual difference in expression of human Ah receptor and related P450 genes.

The genomic clones of human aryl hydrocarbon receptor (Ahr) and Ahr nuclear translocator (Arnt) were isolated, and the structures of exon-intron junctions of these genes were partially determined. Based on the sequence information, a quantitative RT-PCR analysis was developed, and the expression of these genes was studied in various human tissues. mRNAs for Ahr and Arnt were widely expressed in human tissues and abundantly in lung. Individual difference in expression levels of Ahr and Arnt mRNA was observed in liver, lung and blood. In order to examine whether expression levels of Ahr and Arnt were associated with those of CYP1A1, we studied the expression of these mRNAs in blood among 20 healthy subjects, taking account of individuals' cigarette smoking habits. We found that the expression levels of CYP1A1 appeared to associate with those of Ahr and Arnt mRNAs (P < 0.06), and also that the expression of Ahr and Arnt was influenced by cigarette smoking. The expression of human Ahr and Arnt is reported here for the first time, providing a quantitative RT-PCR analysis as a useful tool for further studies.

Adult↗
PubMed1994

Platelet-activating factor acetylhydrolase in term and preterm human milk: a preliminary report.

Human milk may protect against necrotizing enterocolitis (NEC). Since platelet-activating factor (PAF) may participate in the pathophysiology of NEC, we measured PAF acetylhydrolase (PAF-AH), which metabolizes PAF, in term and preterm human milk. The activity of PAF-AH in term milk collected 2-4 days after delivery (n = 17) was 2.7 +/- 1.2 nmol x min-1 x ml-1. A higher activity was found in milk collected at similar times from mothers who delivered between 33 and 36 weeks of gestation (n = 6, 5.6 +/- 2.1 nmol x min-1 x ml-1, p < 0.01). However, milk from mothers who delivered between 26 and 32 weeks of gestation had a PAF-AH activity similar to that of term milk (n = 6, 3.0 +/- 0.7 nmol x min-1 x ml-1). With advancing lactational age, PAF-AH activity in term milk decreased, whereas the activity of this enzyme in preterm milk remained unchanged. In milk samples collected beyond 14 days after delivery from women who gave birth between 33 and 36 weeks or 26 and 32 weeks of gestation, PAF-AH activity was fivefold higher than that found in milk for women delivering at term (3.7 +/- 1.3 and 3.6 +/- 3.6 nmol x min-1 x ml-1 serum 0.7 +/- 0.4 nmol x min-1 x ml-1, respectively, p < 0.05). We speculate that the presence of PAF-AH in human milk may protect against NEC in preterm newborns.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1992

Occurrence of 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid as an N-acyl substituent in the O-polysaccharide chain of the lipopolysaccharide of Vibrio anguillarum V-123.

A new and highly branched amino acid was found as an N-acyl substituent of the O-polysaccharide chain obtained from the lipopolysaccharide of Vibrio anguillarum V-123 (serogroup JO-2) and evidence is presented to support the structure as 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. Acid hydrolysis of the O-polysaccharide gave the lactone of 2,4-dihydroxy-3,3,4-trimethylglutamic acid, together with 2-amino-2-deoxy-D-galacturonic acid, 2-amino-2,6-dideoxy-D-glucose (D-quinovosamine), and 4-amino-4,6-dideoxy-D-glucose (D-viosamine). Degradation of the O-polysaccharide with hydrogen fluoride yielded a fragment (H1) that was indicated by the 1H-NMR data to be 4-amino-4,6-dideoxy-D-glucose N-acetylated with 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. The configuration of the amino acid was not determined.

Amino Acids↗
PubMed1992

Structure of the O-polysaccharide chain of the lipopolysaccharide of Vibrio anguillarum V-123.

The O-polysaccharide chain (PS-1), released by mild acidic treatment of the LPS of V. anguillarum V-123 (serogroup JO-2), a pathogenic bacterium of marine and estuarine fish, consists of 2-amino-2-deoxy-D-galacturonic acid, 2-amino-2,6-dideoxy-D-glucose (D-quinovosamine), and 4-amino-4,6-dideoxy-D-glucose (D-viosamine) N-acylated with 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. Strong-acid hydrolysis of PS-1 afforded alpha-GalNA-(1----4)-alpha-GalNA-(1----3)-QuiN (A1) and alpha-GalNA-(1----3)-QuiN (A2), and hydrolysis with hydrogen fluoride gave N-acetylated A1 and 4-amino-4,6-dideoxy-D-glucose N-acylated by 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. Mild treatment of PS-1 with alkali removed the N-formyl substituents and Smith degradation of the product gave alpha-QuiNAc-(1----3)-beta-VioNAcyl-(1----3)-alpha-GalNAc A-(1----3)-2,3,4- trihydroxybutanoic acid (S1) and S2 in which the carboxyl group of the GalNAcA residue was amidated. Thus, the repeating unit of the O-polysaccharide is----3)-alpha-GalNAcA(amino)-(1----4)-alpha-GalNFoA-(1----3 )- alpha-QuiNAc-(1----3)-beta-VioNAcyl-(1----in which the N-Acyl group is 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid and Fo is formyl.

Carbohydrate Conformation↗
PubMed1992

Insulin antibody does not cause insulin resistance during glucose clamping in rats.

Although it has often been stated that insulin antibodies cause insulin resistance, this concept is still controversial. The effect of insulin antibody GP30, commonly used in insulin radioimmunoassay, on insulin action was investigated in Wistar rats in vivo by the euglycemic glucose clamp technique. As a preliminary experiment, the equilibrium time required for insulin antibody to bind with endogenous insulin was examined. One hundred microliters/kg insulin antibody took 60 min or more to attain equilibrium, but 10 microliters/kg insulin antibody almost immediately equilibrated with endogenous insulin. During a 60-min glucose clamp study, 2 mU/kg/min porcine insulin was infused with 100 microliters/kg insulin antibody. At steady state, during the last 20-min period, the mean glucose infusion rate was 2.10 +/- 0.85 mg/kg/min (n = 5, mean +/- SD), significantly lower than the 5.77 +/- 1.61 mg/kg/min of the control, indicating insulin resistance before equilibrium was reached. However, the glucose infusion rates during the clamp with 10 microliters/kg insulin antibody and 100 microliters/kg insulin antibody infused 75 min before the insulin were 6.10 +/- 1.44 and 7.12 +/- 1.19 mg/kg/min, respectively, no different from the control. In these instances, free insulin levels measured by radioimmunoassay using the polyethyleneglycol method were 43.8 +/- 20.4 and 15.4 +/- 6.1 microU/ml, respectively, lower than the control (77.0 +/- 16.1 microM/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗