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Biomedical subjects

H Ohmori

Publications and source records attributed to H Ohmori.

At least 19 recordsLinked to original sources
PubMed2006

Effects of exercise on adiponectin and adiponectin receptor levels in rats.

Adiponectin reportedly reduces insulin-resistance. Exercise has also been shown to lessen insulin-resistance, though it is not known whether exercise increases levels of adiponectin and/or its receptors or whether its effects are dependent on exercise intensity and/or frequency. Catecholamine levels have been shown to increase during exercise and to fluctuate based on exercise intensity and duration. In light of this information, we examined the effects of exercise on catecholamine, adiponectin, and adiponectin receptor levels in rats. Our data showed that blood adiponectin levels increased by 150% in animals that exercised at a rate of 30 m/min for 60 min 2 days per week, but not 5 days, per week; no such increase was observed in rats that exercised at a rate of 25 m/min for 30 min. The effects of exercise on adiponectin receptor mRNA were variable, with adiponectin receptor 1 (AdipoR1) levels in muscle increasing up to 4 times while adiponectin receptor 2 (AdipoR2) levels in liver fell to below half in response to exercise at a rate of 25 m/min for 30 min 5 days per week. We also observed that urinary epinephrine levels and plasma lipids were elevated by exercise at a rate of 25 m/min for 30 min 2 days per week. Exercise frequency at a rate of 25 m/min for 30 min correlated with AdipoR1 and AdipoR2 mRNA expression in the muscle and liver, respectively (r=0.640, p<0.05 and r=-0.808, p<0.0005, respectively). Urinary epinephrine levels correlated with AdipoR2 mRNA expression in liver tissues (r=-0.664, p<0.05) in rats that exercised at a rate of 25 m/min for 30 min. Thus, exercise may regulate adiponectin receptor mRNA expression in tissues, which might cause increases in glucose uptake and fatty acid oxidation in the muscle. The effect of exercise on adiponectin levels depends on the specific conditions of the exercise.

Adiponectin↗
PubMed2006

Determinants for prediction of malignant potential by metalloproteinase:E-cadherin ratio in prostate core needle biopsy.

According to a good correlation between in situ hybridization-based metalloproteinase-2/9:E-cadherin ratio (MER) and the pathological stage of prostate cancer, we set the cutoff line of MER at 6.0 (MER>6) to distinguish between organ-confined (pT2) and advanced diseases (pT3a-b/N1). In this study, we looked at the factors affecting MER and leading to a misprediction of the pathological stage. We examined MER in 39 paired specimens of prostate core needle biopsy and prostatectomy from the same patient and compared these MERs. In 34 (87%) of 39 cases, the MER of biopsy was correlated with the final pathological stage (pT2 vs. pT3a-b/N1). MER ranges in pT3a-b/N1 cancer were significantly wider than those in pT2 cancer (p < 0.01). The number of MER>6 fields in Gleason score 8-9 cancer was larger than that in Gleason score 7 cancer (p < 0.0001). In 5 cases where there was a failure to distinguish pT2 from pT3a-b/N1, the misdiagnosis was significantly associated with a small number of biopsies (4 or 6 specimens; p = 0.0469), a small amount of tumor tissue in biopsy specimens (less than 5 mm; p = 0.0492), and a wide MER range (more than 5.0; high intratumoral heterogeneity; p = 0.0202). Considering these factors increases the usefulness of preoperative prediction of the final pathological stage by MER in prostate cancer.

Biomarkers, Tumor↗
PubMed2004

Repression of MLH1 and MGMT genes in colon mucosa adjacent to implanted cancer in athymic mouse.

Hyperplastic mucosa adjacent to colon cancer, being a reactive change, accelerates cancer progression and its metastasis through expression of angiogenic factors. We investigated promoter methylation in hyperplastic mucosa adjacent to orthotopic KM12SM colon cancer in mice. In the hyperplastic mucosa adjacent to KM12SM tumors in the cecum of athymic mice, reductions in the levels of the mutL homologue 1 (MLH1) and O6-methylguanine-DNA methyltransferase (MGMT) proteins were detected by immunohistochemistry and immunoblotting. To examine the effects of growth factors and cytokines on promoter methylation and repressed expression of the MLH1 and MGMT genes, a rat intestinal epithelial cell line, IEC6, was treated with epidermal growth factor (EGF) and interleukin (IL)-15 for 35 days. Protein levels of MLH1 and MGMT were reduced in EGF- and IL-15-treated IEC6 cells. A methylation-sensitive restriction enzyme assay revealed that CpG methylation was present in the promoter regions of the MLH1 and MGMT genes in DNAs extracted from hyperplastic mucosa adjacent to KM12SM tumors. These findings suggest that promoter CpG methylation affects expression of MLH1 MGMT genes in hyperplastic mucosa adjacent to colon cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Exercise training improves ageing-induced decrease in eNOS expression of the aorta.

AIMS: Ageing impairs endothelial function such as the regulation of vascular tone. The release of nitric oxide (NO), which has a potent vasodilator effect and antiatherosclerotic property, is decreased in the aorta of aged rats. Exercise training, however, has been reported to increase the expression of endothelial NO synthase (eNOS) in the aorta of young rats. In aged rats, it is not known whether the expression of eNOS is altered by exercise training. We hypothesized that exercise training would improve the ageing-induced decrease in eNOS expression in vessels, and examined the messenger RNA (mRNA) and protein expression of eNOS in the aorta of sedentary-young rats (sedentary-young group; 4 months old), sedentary-aged rats (sedentary-aged group; 23 months old), and swim-trained aged rats (training-aged group; 23 months old, swimming training for 8 weeks, 5 days week(-1), 90 min day(-1)). RESULTS: Body weight was significantly lower, and citrate synthase activity in the epitrochlearis muscle was significantly higher in the training-aged group compared with the sedentary-aged group. The mRNA expression of eNOS in the aorta was significantly higher in the training-aged group than in the sedentary-aged group, while it was significantly lower in both the sedentary-aged and training-aged groups than in the sedentary-young group. The expression of eNOS protein in the aorta was also significantly higher in the training-aged group than in the sedentary-aged group, while it was also significantly lower in the sedentary-aged group, but not in the training-aged group, than in the sedentary-young group. CONCLUSION: The present results revealed that the production of eNOS in the aorta decreases with ageing, and that the decreased production is increased by exercise training in aged rats, which may produce beneficial effects on the impaired cardiovascular system caused by ageing.

Aging↗
PubMed2002

Acute gliclazide administration enhances glucose and ketone body utilization in the perfused hind limb of normal and streptozotocin-diabetic rats.

Sulfonylureas are the most commonly used oral hypoglycemic agents. Their hypoglycemic actions are produced not only by stimulating insulin secretion but also by extrapancreatic mechanisms. Some groups have already demonstrated the extrapancreatic actions of sulfonylureas on carbohydrate metabolism in the liver, fat and muscle. In this study, we showed in an in situ perfused hind limb preparation of STZ-diabetic rats that gliclazide has an acute effect on ketone body and glucose utilization.

Animals↗
PubMed2001

Translesional synthesis past acetylaminofluorene-derived DNA adducts catalyzed by human DNA polymerase kappa and Escherichia coli DNA polymerase IV.

Human DNA polymerase kappa (pol kappa) has a sequence significantly homologous with that of Escherichia coli DNA polymerase IV (pol IV). We used a truncated form of human pol kappa (pol kappaDeltaC) and full-length pol IV to explore the miscoding properties of these enzymes. Oligodeoxynucleotides, modified site-specifically with N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) and N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-AF), were used as DNA templates in primer extension reactions that included all four dNTPs. Reactions catalyzed by pol kappaDeltaC were partially blocked one base prior to dG-AAF or dG-AF, and also opposite both lesions. At higher enzyme concentrations, a significant fraction of primer was extended. Analysis of the fully extended reaction product revealed incorporation of dTMP opposite dG-AAF, accompanied by much smaller amounts of dCMP, dAMP, and dGMP and some one- and two-base deletions. The product terminating 3' to the adduct site contained AMP misincorporated opposite dC. On templates containing dG-AF, dAMP, dTMP, and dCMP were incorporated opposite the lesion in approximately equal amounts, together with some one-base and two-base deletions. Steady-state kinetics analysis confirmed the results obtained from primer extension reactions catalyzed by pol kappa. In contract, primer extension reactions catalyzed by pol IV were blocked effectively by dG-AAF and dG-AF. At high concentrations of pol IV, full-length products were formed containing primarily one- or two-base deletions with dCMP, the correct base, incorporated opposite dG-AF. The miscoding properties of pol kappa observed in this study are consistent with mutational spectra observed when plasmid vectors containing dG-AAF or dG-AF are introduced into simian kidney cells [Shibutani, S., et al. (2001) Biochemistry 40, 3717-3722], supporting a model in which pol kappa plays a role in translesion synthesis past acetylaminofluorene-derived lesions in mammalian cells.

2-Acetylaminofluorene↗
PubMed2001

[Effects of smoking on pulmonary function: a cross-sectional and longitudinal study].

Cross-sectional and longitudinal studies were done to investigate the influence that a change in smoking habit can have on the pulmonary function. Seventeen hundred and thirty nine people (698 men, 1,041 women), 39 years of age or older, from the population of a farming village located in the central part of Miyazaki Prefecture were examined. A population-based cohort study with a 4-time observation was done over an interval of 12 years. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1.0) were used as the index of respiratory function, and adjusted annual change of FVC and adjusted annual change of FEV1.0 were used as a pulmonary function inspection index. There was a statistical significance in both %FVC and %FEV1.0 to the predicted values between smokers and non-smokers at the beginning of observation. The adjusted annual change of FVC both of male- and female-smokers and the adjusted annual change of FEV1.0 of male-smokers was higher than those of non-smokers in the longitudinal study. Percent FVC, %FEV1.0 and the adjusted FEV1.0 change of former male-smokers were lower than those of continuing smokers. In addition to %FVC and %FEV1.0, annual change of FVC and annual change of FEV1.0 were important predictors of pulmonary function related to cigarette smoking.

Adult↗
PubMed2001

Determinants of activation kinetics in mammalian hyperpolarization-activated cation channels.

1. The structural basis for the different activation kinetics of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels was investigated with the whole-cell patch clamp technique by using HCN1, HCN4, chimeric channels and mutants in a mammalian expression system (COS-7). 2. The activation time constant of HCN4 was about 40-fold longer than that of HCN1 when compared at -100 mV. 3. In chimeras between HCN1 and HCN4, the region of the S1 transmembrane domain and the exoplasmic S1-S2 linker markedly affected the activation kinetics. The cytoplasmic region between S6 and the cyclic nucleotide-binding domain (CNBD) also significantly affected the activation kinetics. 4. The S1 domain and S1-S2 linker of HCN1 differ from those of HCN4 at eight amino acid residues, and each single point mutation of them changed the activation kinetics less than 2-fold. However, the effects of those mutations were additive and the substitution of the whole S1 and S1-S2 region of HCN1 by that of HCN4 resulted in a 10- to 20-fold slowing. 5. The results indicate that S1 and S1-S2, and S6-CNBD are the crucial components for the activation gating of HCN channels.

Animals↗
PubMed2001

DNA polymerase kappa, implicated in spontaneous and DNA damage-induced mutagenesis, is overexpressed in lung cancer.

DNA polymerase kappa (Pol kappa) is a newly identified low-fidelity polymerase implicated in spontaneous and DNA damage-induced mutagenesis. As an initial study to investigate its possible involvement in tumorigenesis, we compared the expression level of Pol kappa in tumors and adjacent nontumorous tissues by Northern blot, semiquantitative RT-PCR, and Western blot analyses. In this study, paired tumor and normal specimens from 29 patients with stages I to IIIb non-small cell lung cancer (NSCLC), including 13 adenocarcinomas, 15 squamous cell cancers, and 1 adenosquamous carcinoma, were analyzed, among which different levels of tumor-associated Pol kappa overexpression were observed in 21 of 29 matched specimens. In addition, five matched specimens exhibited elevated Pol kappa expression in both tumor and control tissues, whereas only one nontumorous tissue expressed a higher level of Pol kappa than its tumor counterpart. The preferential up-regulation of Pol kappa expression in tumors was highly significant (P < 0.001). There was no apparent correlation of Pol kappa expression levels with tumor histology, grade, and stage or with smoking history. Southern blot analysis did not show amplification of the Pol kappa gene, indicating that the elevated Pol kappa expression is likely attributable to dysregulated transcription. Our data suggest that Pol kappa may contribute to lung tumor development by accelerating the accumulation of mutations.

Aged↗
PubMed2001

Use of secondarily revised VH genes in IgE antibodies produced in mice infected with the nematode Nippostrongylus brasiliensis.

Although a high level of IgE is produced after primary infection with Nippostrongylus brasiliensis (Nb), most of the IgE antibodies (Abs) are not specific to the worm. Analyses with Western blotting and enzyme-linked immunosorbent assay (ELISA) revealed that the IgE Abs from Nb-infected BALB/c mice did not show reactivity with Nb-derived excretory-secretory proteins (NES) and antigens present in the cell-free extracts of the worm. Monoclonal IgE Abs obtained from the Nb-infected mice were not reactive with these Nb antigen either. To characterize Nb-induced IgE response, we used (QM x C57BL/6)F1 (QBF1) mice that bear the knock-in 17.2.25 VHDJH segment (VHT) encoding a VH region specific to 4-hydroxy-3-nitrophenylacetyl hapten, and express VHT-encoded antigen receptors on 80-85% of their B cells. Consistent with the frequency of VHT-positive B cells, more than 80% of IgE Abs induced in QBF1 B cells that were cultured with LPS plus IL-4 were found to bear VHT-encoded H chains. In contrast, when QBF1 mice were infected with Nb, less than 10% of Nb-induced IgE Abs were found to use VHT. The QBF1-derived IgE did not react with Nb antigens either. Taken together, data suggest that Nb-induced IgE response in mice is not merely the result of polyclonal activation of B cells, but may involve a mechanism that revises Ig genes secondarily.

Animals↗
PubMed2001

Differential development of Ca2+ dynamics in presynaptic terminal and postsynaptic neuron of the rat auditory synapse.

Postnatal development of Ca2+ influx and Ca2+ clearance capacity were investigated in the synapse of medial nucleus of the trapezoid body (MNTB) of rat with fura-2 fluorimetry. In contrast to the presynaptic terminal, Ca2+ dynamics does not basically change in the postsynaptic principal neuron developmentally. This differential development of Ca2+ dynamics between pre- and postsynaptic neurons might be crucial for the organized formation and functional maturation of this synapse.

Animals↗
PubMed2001

Translesion DNA synthesis catalyzed by human pol eta and pol kappa across 1,N6-ethenodeoxyadenosine.

1,N(6)-Ethenodeoxyadenosine, a DNA adduct generated by exogenous and endogenous sources, severely blocks DNA synthesis and induces miscoding events in human cells. To probe the mechanism for in vivo translesion DNA synthesis across this adduct, in vitro primer extension studies were conducted using newly identified human DNA polymerases (pol) eta and kappa, which have been shown to catalyze translesion DNA synthesis past several DNA lesions. Steady-state kinetic analyses and analysis of translesion products have revealed that the synthesis is >100-fold more efficient with pol eta than with pol kappa and that both error-free and error-prone syntheses are observed with these enzymes. The miscoding events include both base substitution and frameshift mutations. These results suggest that both polymerases, particularly pol eta, may contribute to the translesion DNA synthesis events observed for 1,N(6)-ethenodeoxyadenosine in human cells.

Animals↗
PubMed2001

Physical interactions between DinI and RecA nucleoprotein filament for the regulation of SOS mutagenesis.

The Escherichia coli dinI gene is one of the LexA-regulated genes, which are induced upon DNA damage. Its overexpression conferred severe UV sensitivity on wild-type cells and resulted in the inhibition of LexA and UmuD processing, reactions that are normally dependent on activated RecA in a complex with single-stranded (ss)DNA. Here, we study the mechanism by which DinI inhibits the activities of RecA. While DinI neither binds to ssDNA nor prevents the formation of RecA nucleoprotein filament, it binds to active RecA filament, thereby inhibiting its coprotease activity but not the ATPase activity. Furthermore, even under in vitro conditions where UmuD cleavage dependent on RecA-ssDNA-adeno sine-5'-(3-thiotriphosphate) is blocked in the presence of DinI, LexA is cleaved normally. This result, taken together with electron microscopy observations and linear dichroism measurements, indicates that the ternary complex remains intact in the presence of DinI, and that the affinity to the RecA filament decreases in the order LexA, DinI and UmuD. DinI is thus suited to modulating UmuD processing so as to limit SOS mutagenesis.

Adenosine Triphosphate↗
PubMed2001

Mutagenic and nonmutagenic bypass of DNA lesions by Drosophila DNA polymerases dpoleta and dpoliota.

cDNA sequences were identified and isolated that encode Drosophila homologues of human Rad30A and Rad30B called drad30A and drad30B. Here we show that the C-terminal-truncated forms of the drad30A and drad30B gene products, designated dpoletaDeltaC and dpoliotaDeltaC, respectively, exhibit DNA polymerase activity. dpoletaDeltaC and dpoliotaDeltaC efficiently bypass a cis-syn-cyclobutane thymine-thymine (TT) dimer in a mostly error-free manner. dpoletaDeltaC shows limited ability to bypass a 6-4-photoproduct ((6-4)PP) at thymine-thymine (TT-(6-4)PP) or at thymine-cytosine (TC-(6-4)PP) in an error-prone manner. dpoliotaDeltaC scarcely bypasses these lesions. Thus, the fidelity of translesion synthesis depends on the identity of the lesion and on the polymerase. The human XPV gene product, hpoleta, bypasses cis-syn-cyclobutane thymine-thymine dimer efficiently in a mostly error-free manner but does not bypass TT-(6-4)PP, whereas Escherichia coli DNA polymerase V (UmuD'(2)C complex) bypasses both lesions, especially TT-(6-4)PP, in an error-prone manner (Tang, M., Pham, P., Shen, X., Taylor, J. S., O'Donnell, M., Woodgate, R., and Goodman, M. F. (2000) Nature 404, 1014-1018). Both dpoletaDeltaC and DNA polymerase V preferentially incorporate GA opposite TT-(6-4)PP. The chemical structure of the lesions and the similarity in the nucleotides incorporated suggest that structural information in the altered bases contribute to nucleotide selection during incorporation opposite these lesions by these polymerases.

Animals↗
PubMed2001

Synthesis and structure--activity analysis of novel dihydropyridine derivatives to overcome multidrug resistance.

The structure activity relationships were studied on newly synthesized 1,4-dihydropyridine derivatives possessing a 1-pentyl group at the 4-position, and 3-pyridylpropylester was found to be one of the effective fragments for overcoming P-glycoprotein mediated multidrug-resistance (MDR) in cultured human cancer cells, in vitro. 3-Pyridylpropylester was also found to be one of the effective fragments for increasing the life span of P-glycoprotein overexpressing MDR P388 leukemia-bearing mice, in vivo. All compounds had weak calcium antagonistic activities, but there appeared no relationship between MDR reversing effect and calcium antagonistic activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Synchronisation of neurotransmitter release during postnatal development in a calyceal presynaptic terminal of rat.

Mechanisms contributing to the synchronisation of transmitter release during development were studied in synapses of the medial nucleus of the trapezoid body (MNTB) using patch recording and Ca2+ imaging techniques in a rat brainstem slice preparation. Excitatory postsynaptic currents (EPSCs) were generated in an all-or-none manner at immature synapses (postnatal days earlier than P6). Many delayed miniature EPSC (mEPSC)-like currents followed EPSCs at immature synapses, while observations of delayed mEPSC-like currents were rare at mature synapses (later than P9). At immature synapses bath application of either omega-conotoxin GVIA or omega-agatoxin-IVA reduced EPSCs (both to 40% of control), and Ca2+ currents in the presynaptic terminal (both to 70% of control). The frequency of delayed mEPSC-like currents was reduced by omega-conotoxin GVIA, but not by omega-agatoxin IVA. At immature synapses delayed mEPSC-like currents were rare after incubation of the slice with extrinsic Ca2+ buffers (EGTA AM). At mature synapses many mEPSC-like currents followed evoked EPSCs after partial block of Ca2+ channels by bath application of a low concentration of Cd2+ (3 microM) or omega-agatoxin IVA (50 nM) but not by low [Ca2+]o (0.5-1 mM). Ca2+ transients induced by action potentials in presynaptic terminals were monitored by adding a high concentration of fura-2 (200 microM) to the pipette. Their decay time course was slower at immature presynaptic terminals than at mature terminals. Both the Ca2+ extrusion rate and the endogenous Ca2+ binding capacity were estimated to be smaller at immature terminals than at mature terminals. These results suggest that the maturation of synaptic transmission in MNTB progresses with the capacity for Ca2+ clearance from the presynaptic terminal. The possible importance of developmental increases in both Ca2+ clearance capacity and Ca2+ currents is discussed in relation to the synchronisation of transmitter release.

Animals↗