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H Oda

Publications and source records attributed to H Oda.

At least 199 records · Page 11Linked to original sources
PubMed1997

Mutations of the Ki-ras, p53 and APC genes in adenocarcinomas of the human small intestine.

In contrast to the origins of colorectal carcinomas, the mechanisms of carcinogenesis in the small intestine remain unclear. We therefore analyzed the mutational status of the Ki-ras, p53, and adenomatous polyposis coli (APC) genes in primary carcinomas of the small intestine and compared the mutation patterns with those established for colorectal cancers. DNA was extracted from 15 formalin-fixed, paraffin-embedded lesions. Codons 12, 13 and 61 of the Ki-ras gene, exons 5-8 of the p53 gene, and codons 1268-1569, which contain the mutation cluster region (MCR) of the APC gene, were amplified by means of PCR, subcloned and sequenced. Mutations of the Ki-ras and p53 genes were observed in 8 (53.3%) and 4 lesions (26.7%), respectively. The mutational frequency of the Ki-ras gene in the present series of small intestinal carcinomas was similar, while that of the p53 gene was slightly lower than the reported frequencies for colorectal carcinomas. Only one case showed a mutation of the APC gene, involving an insertional mutation of an adenine at codons 1554-1556 with formation of a stop codon immediately downstream. Since the occurrence of an APC mutation is considered an early event in colorectal carcinogenesis, our findings indicating an extremely low frequency of such changes in and around the MCR suggest that carcinomas of the small intestine arise via a genetic pathway distinct from that involved in the development of carcinomas of the colorectum.

Adult↗
PubMed1997

Endothelin-converting enzyme expression in the rat vascular injury model and human coronary atherosclerosis.

BACKGROUND: Endothelin 1 has been implicated in various human diseases, including atherosclerosis. In this study, we examined the expression and localization of endothelin-converting enzyme-1 (ECE-1), the final key enzyme of endothelin 1 processing, in rat carotid arteries after balloon injury and in human coronary atherosclerotic lesions. METHODS AND RESULTS: ECE-1 mRNA levels and ECE activity in rat balloon-injured arteries started to increase between 2 and 5 days after injury. The endothelin 1 content of tissue in injured arteries was concomitantly increased. Immunohistochemical staining located ECE-1 signals in endothelial cells in uninjured arteries, whereas ECE-1 immunoreactivity was detected in neointimal smooth muscle cells in injured arteries 5 to 14 days after balloon denudation. The size of the neointima was effectively reduced by phosphoramidon, an inhibitor of neutral metalloproteases, including ECE-1. In human coronary atherosclerotic lesions, intense ECE-1 immunoreactivity was detected in subsets of cells embedded in atheromatous plaque that correspond to smooth muscle cells and macrophages, as identified by staining for smooth muscle alpha-actin and CD68 surface marker, respectively. CONCLUSIONS: The present study ascertained that ECE-1 is expressed in neointimal smooth muscle cells in rat balloon-injured arteries and in both smooth muscle cells and macrophages in human coronary atherosclerotic lesions. Blockade of ECE-1 was effective in reducing neointimal formation after balloon injury. Thus, ECE-1 may contribute to the process of injury-induced neointimal formation and atherosclerosis through the autocrine/paracrine effects of endothelin 1.

Aged↗
PubMed1997

Inhibition of protein kinase C-dependent noradrenaline release by wortmannin in PC12 cells.

Wortmannin is a specific phosphatidylinositol 3-kinase inhibitor, and it inhibits secretion in many cell types. Previously we reported that high K+ and external ATP stimulated a Ca2+ influx and [3H]-noradrenaline ([3H]NA) release from rat pheochromocytoma cell line 12 (PC12) cells in the presence of extracellular CaCl2. Addition of phorbol 12-myristate 13-acetate (PMA) stimulated [3H]NA release by itself and enhanced the maximal responses of high K+ and ATP. In this study, we investigated the effects of wortmannin on NA release from PC12 cells. Wortmannin inhibited the [3H]NA release induced by high K+ and ATP, and the stimulatory effects of PMA, in a dose-dependent manner. Wortmannin caused 50% inhibition of high K+-induced [3H]NA release at a concentration of 2.78+/-0.68 microM (n = 5). The increased cytosolic free Ca2+ concentrations ([Ca2+]i), induced by ATP, were not inhibited by wortmannin. Wortmannin inhibited PMA-induced phosphorylation of a 80-kDa protein in the cytosol fraction of PC12 cells. Calphostin C, a specific protein kinase C inhibitor, also inhibited high K+-, ATP-, and PMA-induced NA release, and the phosphorylation of the 80-kDa protein induced by PMA. Mastoparan, an amphiphilic tetradecapeptide from wasp venom, stimulated NA release in the presence or absence of extracellular CaCl2. Neither wortmannin nor calphostin C inhibited the NA release induced by mastoparan. These findings suggest that wortmannin inhibits the PKC-dependent pathway, not [Ca2+]i mobilization, resulting in the inhibition of NA release from PC12 cells.

Adenosine Triphosphate↗
PubMed1997

Cytochrome P450-dependent drug oxidation activities in liver microsomes of various animal species including rats, guinea pigs, dogs, monkeys, and humans.

Levels of cytochrome P450 (P450 or CYP) proteins immunoreactive to antibodies raised against human CYP1A2, 2A6, 2C9, 2E1, and 3A4, monkey CYP2B17, and rat CYP2D1 were determined in liver microsomes of rats, guinea pigs, dogs, monkeys, and humans. We also examined several drug oxidation activities catalyzed by liver microsomes of these animal species using eleven P450 substrates such as phenacetin, coumarin, pentoxyresorufin, phenytoin, S-mephenytoin, bufuralol, aniline, benzphetamine, ethylmorphine, erythromycin, and nifedipine; the activities were compared with the levels of individual P450 enzymes. Monkey liver P450 proteins were found to have relatively similar immunochemical properties by immunoblotting analysis to the human enzymes, which belong to the same P450 gene families. Mean catalytic activities (on basis of mg microsomal protein) of P450-dependent drug oxidations with eleven substrates were higher in liver microsomes of monkeys than of humans, except that humans showed much higher activities for aniline p-hydroxylation than those catalyzed by monkeys. However, when the catalytic activities of liver microsomes of monkeys and humans were compared on the basis of nmol of P450, both species gave relatively similar rates towards the oxidation of phenacetin, coumarin, pentoxyresorufin, phenytoin, mephenytoin, benzphetamine, ethylmorphine, erythromycin, and nifedipine, while the aniline p-hydroxylation was higher and bufuralol 1'-hydroxylation was lower in humans than monkeys. On the other hand, the immunochemical properties of P450 proteins and the activities of P450-dependent drug oxidation reactions in dogs, guinea pigs, and rats were somewhat different from those of monkeys and humans; the differences in these animal species varied with the P450 enzymes examined and the substrates used. The results presented in this study provide useful information towards species-related differences in susceptibilities of various animal species regarding actions and toxicities of drugs and xenobiotic chemicals.

Adrenergic beta-Antagonists↗
PubMed1997

Effect of lipoproteins on cultured human mesangial cells.

It was recently reported that low-density lipoprotein (LDL) promotes mesangial cell proliferation, and oxidized LDL is cytotoxic for mesangial cells. However, there have been few studies about the effects of other lipoproteins on mesangial cells. Accordingly, we investigated the effect of various lipoproteins on cultured human mesangial cells using 3H-thymidine (3H-TdR) incorporation and cell counting assays. We also investigated the levels of several cytokines in mesangial cell culture supernatants after stimulation by the lipoproteins. Addition of very-low-density lipoprotein (VLDL) at concentrations up to 100 micrograms/mL, intermediate-density lipoprotein (IDL) at up to 50 micrograms/mL, and LDL at up to 50 micrograms/mL induced the proliferation of cultured human mesangial cells, whereas cell growth was inhibited at higher concentrations. Oxidized LDL caused a concentration-dependent decrease of 3H-TdR incorporation. High-density lipoprotein (HDL) had no proliferative effective effect at any concentration. Exposure to VLDL, IDL, LDL, or a high concentration of HDL enhanced the secretion of interleukin-6, platelet-derived growth factor, and transforming growth factor-beta by mesangial cells, whereas tumor necrosis factor-alpha secretion was stimulated by oxidized LDL. These finding indicate that triglyceride (TG)-rich lipoproteins (VLDL and IDL) promote mesangial cell proliferation as well as LDL, whereas oxidized LDL has the reverse effect. These effects of lipoproteins may be related to modulation of various cytokines. Accordingly, TG-rich lipoproteins, LDL, and oxidized LDL may be involved in mesangial cell proliferation and injury in patients with mesangial proliferative glomerulonephritis.

Analysis of Variance↗
PubMed1997

Development of DNA diagnostic methods for the detection of new fish iridoviral diseases.

A new disease of epidemic proportions caused by fish viruses within the Iridoviridae family inflicts serious damage on red sea breams (Pagrus major) and striped jack (Caranx delicatissimus) populations grown in aquacultures in Japan. A partial segment of the fish iridoviral DNA was directly amplified using the polymerase chain reaction (PCR) with synthetic primers designed from well conserved nucleotide sequences between the frog virus 3 (Ranavirus) and the silkworm iridescent virus type 6. The deduced amino acid sequence from the nucleotide sequence of the PCR fragment demonstrates a high correlation with a partial sequence from the frog virus 3. Using the PCR method with specific primers, we could detect three of four different known types of fish iridoviruses in diseased fishes. To construct more reliable detection methods specific for this viral family, DNA fragments which can specifically hybridize with all of the four known iridoviridae viral DNAs were screened from the genomic library of one iridoviridae strain. The hybridization assay, using a specific fragment which contains regions which are highly homologous with a characterized partial sequence from the frog virus 3, proved to be a reliable diagnostic tool for fish iridoviral diseases.

Animals↗
PubMed1997

Phenotypic analysis of null mutants for DE-cadherin and Armadillo in Drosophila ovaries reveals distinct aspects of their functions in cell adhesion and cytoskeletal organization.

BACKGROUND: DE-cadherin is an epithelial cadherin in Drosophila, and forms adherens junctions by associating with Armadillo (beta-catenin). To investigate its role in oogenesis, we generated germ-line clones homozygous for a null mutation in shotgun (shg) encoding this molecule, and examined their phenotypes, comparing with those of armadillo (arm) mutants. RESULTS: In the wild-type ovaries, DE-cadherin was expressed by both the germ-line and somatic derivatives, colocalizing with Armadillo. In the shg mutant ovaries in which the mutation was restricted to the germ line, germ cells were rounded, and generated gaps between themselves, suggesting that their surface adhesiveness was reduced or lost. However, the positioning of germ cells in the egg chamber was normal. Two groups of somatic follicle cells--the border cells and centripetal follicle cells--frequently migrated along incorrect pathways, indicating that DE-cadherin is required for their appropriate migration. Notably, the shg phenotypes were distinct from those of arm null mutants. Intercellular adhesion appeared to be less severely affected by arm than by the shg mutation, and the actin-based cytoskeleton and cell arrangement were disorganized only in the arm mutants. CONCLUSIONS: These findings suggest that DE-cadherin is critical for cell-cell adhesion, and functional to a certain extent without Armadillo, whereas Armadillo is required for cytoskeletal organization and for the control of cell positioning. We therefore propose that the molecular complex of DE-cadherin and Armadillo which is present in normal cells is endowed with multiple functions derived from each molecule.

Actins↗
PubMed1997

Inhibition of inducible nitric oxide synthase expression by endothelin in rat glial cells prepared from the neonatal rat brain.

In primary cultured rat glial cells, a combination of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) stimulates production of nitrite via expression of the inducible form of nitric oxide synthase (iNOS). In these cells, simultaneous addition of endothelin (ET) decreased iNOS expression and nitrite accumulation induced by TNF-alpha/IL-1beta. The inhibitory effect of ET on TNF-alpha/IL-1beta-stimulated iNOS expression appears to be mediated by ET(B) receptors, because (1) both ET-1 and ET-3 inhibited the effects of TNF-alpha/IL-1beta on iNOS expression and nitrite accumulation, (2) a selective ET(B) receptor agonist, Suc-[Glu(9),Ala(11,15)]-ET-1 (8-21) (IRL1620), decreased the effects of TNF-alpha/IL-1beta, and (3) a selective ET(B) receptor antagonist, N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D- 1-methoxycarbonyltryptophanyl-D-norleucine, abolished the inhibitory effects of ETs and IRL1620. Incubation of glial cells with lipopolysaccharide (LPS) caused an increase in iNOS expression. Simultaneous addition of ET-3 decreased the effects of LPS (10 and 100 ng/ml) on iNOS expression. Furthermore, cyclic AMP-elevating agents (dibutyryl cyclic AMP and forskolin) inhibited TNF-alpha/IL-1beta-induced and LPS-induced iNOS expression and nitrite accumulation. These findings suggest that ETs can decrease TNF-alpha/IL-1beta-induced and LPS-induced iNOS expression via ET(B) receptors and that cyclic AMP may be involved in this process.

Animals↗
PubMed1997

bor1-1, an Arabidopsis thaliana mutant that requires a high level of boron.

bor1-1 (high boron requiring), an Arabidopsis thaliana mutant that requires a high level of B, was isolated. When the B concentration in the medium was reduced to 3 microM, the expansion of rosette leaves was severely affected in bor1-1 but not in wild-type plants. In a medium containing 30 microM B the mutant grew normally but showed female sterility, whereas the wild type was able to set seeds. These defects of the bor1-1 mutant were not detected with supplementation of 100 microM B. In vivo concentrations of B in bor1-1 mutants were lower than those of the wild type, especially in the inflorescence stems. Tracer experiments using 10B suggested that the mutant has defects in uptake and/or translocation of B. The mutation was mapped on the lower arm of chromosome 2.

Arabidopsis↗
PubMed1997

p16INK4 gene mutations are relatively frequent in ampullary carcinomas.

A high incidence of gene mutations or deletions of p16INK4, a cell cycle regulator which inhibits the activity of cyclin-dependent kinase 4/cyclin D complex and blocks the G1-to-S transition, has been reported in pancreato-biliary tract cancers. In order to investigate p16INK4 gene alterations in sporadic ampullary carcinomas, 17 sporadic ampullary carcinomas were examined. After histological diagnosis, DNA samples extracted separately from both cancerous and normal paraffin-embedded tissues were investigated. Loss of heterozygosity (LOH) was investigated utilizing 3 microsatellite markers on 9p21-22, and a mutational analysis was performed by cloning and sequencing. LOH was observed in 3 cases (17.6%) and somatic mutations with retention of heterozygosity were found in 7 cases (41.2%). Of note was that two mutations resulted in truncated incomplete proteins and one was a point mutation at the consensus site in the conserved ankyrin repeats, which would be crucial for function. Although two-hit inactivation was not evident in any of the mutation cases and further investigation would be needed to elucidate the role of altered p16INK4, these results suggest that the p16INK4 gene mutations are relatively frequent and its inactivation might be important in ampullary carcinogenesis.

Aged↗
PubMed1997

Frequent somatic mutations of the APC and p53 genes in sporadic ampullary carcinomas.

Although a close relation of somatic mutations of the adenomatous polyposis coli gene with ampullary carcinomas in familial adenomatous polyposis patients has been reported, the possible association with sporadic ampullary neoplasms has not been fully examined. We have therefore investigated loss of heterozygosity at the adenomatous polyposis coli locus and the mutational status of a portion of the adenomatous polyposis coli gene, including the mutation cluster region, in 17 ampullary carcinomas of non-familial adenomatous polyposis patients. Alteration of the adenomatous polyposis coli gene was found in 8 of 17 (47.1%) cases, as missense or insertion mutations, with or without loss of heterozygosity. Additional investigation of p53 (exons 5-8) and K-ras (codons 12 and 13) gene mutations revealed a striking mutational pattern of the p53 gene. Nine of the 17 cases demonstrated a total of 12 mutations, 6 clustered at codon 189 and 3 at codon 166. Furthermore, 5 of the 12 mutations were nonsense mutations. Regarding the K-ras gene, 4 of the 17 (23.5%) cases had mutations in codon 12, 3 of the 4 cases being derived from the intraduodenal bile duct. The findings indicate that alterations of the adenomatous polyposis coli and the p53 genes are relatively frequent in sporadic ampullary carcinomas. In particular, the clustering at specific p53 codons might offer an etiological clue to clarify ampullary carcinogenesis. Mutations of the K-ras gene, on the other hand, might be characteristic of intraduodenal bile duct origin.

Adenomatous Polyposis Coli↗
PubMed1997

Cystic teratoma of the greater omentum: a case report and review of the literature.

Cystic teratoma in the greater omentum remains one of gynecology's rarest entities. A 28-year-old woman presented with a goose-egg-sized mass in the right lower quadrant. At laparotomy, the mass proved to be a cystic teratoma of the greater omentum. To our knowledge, this report documents the first case where an omental pedicle was torsioned.

Adult↗
PubMed1997

Localization of hepatocyte growth factor and tubulointerstitial lesions in IgA nephropathy.

To investigate the relationship between localization of hepatocyte growth factor (HGF) and tubulointerstitial lesions (TILs) in the cortical area of renal biopsy specimens, a clinicopathological study was performed in 35 patients with IgA nephropathy. HGF was detected by an enzyme-antibody method and TILs were assessed semiquantitatively by light microscopy. HGF was observed mainly on epithelial cells in the tubules, but not in the glomeruli. Fourteen patients had biopsies that were positive for HGF. There was a correlation between HGF positivity and histological damage, the TIL grade, and several clinical parameters determined at biopsy. Thus, HGF is related to TILs in IgA nephropathy, and may be a factor in the exacerbation of this disease.

Adolescent↗
PubMed1997

Remnant-like particle cholesterol may indicate atherogenic risk in patients on chronic hemodialysis.

Recently, involvement of remnant-like particle cholesterol (RLP-C) in atherosclerosis was reported, but this parameter has not been adequately investigated in hemodialysis (HD) patients. The present study investigated the relationship between the RLP-C level and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipid peroxides (malone dialdehyde, MDA), apolipoprotein (Apo) A-I, and ApoB. In addition, the fractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), LDL, and HDL in serum lipoproteins were determined by disk polyacrylamide gel electrophoresis. The relationship between the RLP-C level and three atherogenic indices was also studied. The RLP-C level in HD patients (8.2 +/- 6.7 mg/dl) was significantly higher than that in normal controls (2.7 +/- 1.3 mg/dl). The RLP-C level showed a significant positive correlation with the levels of TC, TG, LDL-C, MDA, ApoB, VLDL(%), and IDL(%), as well as a negative correlation with HDL(%). However, there was no correlation with age or the duration of HD. RLP-C also showed significant positive correlations with the (TC -HDL-C)/HDL-C ratio and the (VLDL + LDL)/HDL ratio, as well as a negative correlation with the ApoA-I/ApoB ratio. These results suggest that RLP-C may be a potential indicator of atherogenic risk in HD patients.

Adult↗
PubMed1997

Cord blood IgE against milk and egg antigens.

The aim of the present study was to reevaluate the prenatal production of specific IgE for eggs and milk and, in those cases, to determine whether there is a relation to the amount of maternal egg and milk intake. Total and specific IgEs from 160 cord blood-samples were determined by immunoassays using a paramagnetic particle solid phase and an enzyme-mediated chemiluminescent reaction for signal detection. The levels of cord blood IgE for total, egg, and milk were 0.63 +/- (SD) 1.10 IU/ml, 0.020 +/- 0.055, and 0.036 +/- 0.053 IU/ml, respectively. IgE levels specific to egg and milk over 0.03 IU/ml were observed in 33 and 70 out of 160 cases, respectively. To address whether the maternal intake of eggs and milk affects the level of cord blood IgEs, all mothers except 9 were interviewed, and the amount of eggs and milk taken during pregnancy was recorded. No correlation was seen between egg and milk intakes and cord blood IgE levels. Our data demonstrate a high incidence of the prenatal production of specific IgE for eggs and milk which is independent of maternal egg and milk intakes.

Adult↗
PubMed1997

Effects of cigarette smoking on the serum concentration of lung surfactant protein A (SP-A).

We have tested the hypothesis that serum surfactant protein A (SP-A) production may be affected by cigarette smoke exposure, and that alterations in serum levels may reflect smoking habits. A total of 52 subjects were divided into the following two groups: active smokers (Group A; n = 23); and nonsmokers (Group B; n = 29). The assessment of smoking habit was determined by self-report, carbon monoxide concentration in expired air, and cotinine concentration in urine. Serum SP-A was compared in both groups and was found to be higher in Group A (active smokers) (p < 0.002). We conclude that surfactant protein A levels are increased in the serum of smokers. However, it was found that this is not a sensitive discriminating factor to separate smokers from nonsmokers.

Adult↗