Biomedical subjects

Takashi Yamamoto

Publications and source records attributed to Takashi Yamamoto.

At least 19 recordsLinked to original sources

PubMed2007

Mtf-1 lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice after gamma-irradiation.

Mouse strains exhibit different susceptibilities to gamma-ray-induced thymic lymphomas. Our previous study identified Mtf-1 (metal responsive transcription factor-1) as a candidate susceptibility gene, which is involved in the radiation-induced signaling pathway that regulates the cellular reactive oxygen species (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf-1 locus, we examined early effects of gamma-ray on ROS levels in vivo and its difference between Mtf-1 susceptible and resistant congenic mice. Here, we show the detection of clonally growing thymocytes at 4 weeks after irradiation, indicating the start of clonal expansion at a very early stage. We also show that large thymocytes with higher ROS levels and a proliferation capacity were more numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7 days after irradiation, although such tendency was not found in mice lacking one allele of Bcl11b tumor suppressor gene. This high retention of the large thymocytes, at a high risk for ROS-induced mutation, is a compensatory proliferation and regeneration response to depletion of the thymocytes after irradiation and the response is likely to augment the development of prelymphoma cells leading to thymic lymphomas.

Animals↗

PubMed2007

Multidetector-row computed tomography coronary angiography: optimization of image reconstruction phase according to the heart rate.

BACKGROUND: To optimize the image reconstruction phase of multidetector-row computed tomography (MDCT) coronary angiography according to the heart rate is crucial. METHODS AND RESULTS: Scan data were reconstructed for 10 different phases in 58 sequential patients who underwent 8-row cardiac MDCT. The obtained images were scored and compared in terms of motion artifacts and visibility of the vessels, and moreover, ECG record-based evaluations were added for clarification of the temporal relationships among these 10 phases. In the cases with lower heart rates (<65 beats/min), the best quality images were obtained when the end of the image reconstruction phase was positioned at the peak of the P wave. In some cases with higher heart rates (>65 beats/min), they were obtained in the late systolic period. CONCLUSION: As the heart rate increased, the optimal image reconstruction phase changed from mid diastole to late systole. However, it is recommended to try to decrease the heart rate of patients before data acquisition.

Aged↗

PubMed2006

PCB decomposition and formation in thermal treatment plant equipment.

In this study we investigated both the decomposition and unintentional formation of polychlorinated biphenyl congeners during combustion experiments of refuse-derived fuel (RDF) and automobile shredder residue (ASR) at several stages in thermal treatment plant equipment composed of a primary combustion chamber, a secondary combustion chamber, and other equipments for flue gas treatment. In both experiments, the unintentional formation of PCB occurred in the primary combustion chamber at the same time as the decomposition of PCB in input samples. By combusting RDF, non-ortho-PCB predominantly formed, whereas ortho-PCB and symmetric chlorinated biphenyls (e.g., #52/69, #87/108, and #151) tended to be decomposed. ASR formed the higher chlorinated biphenyls more than RDF. These by-products from ASR had no structural relation with ortho-chlorine. Lower chlorinated biphenyls appeared as predominant homologues at the final exit site, while all congeners from lower to higher chlorinated PCB were unintentionally formed as by-products in the primary combustion chamber. This result showed that the flue gas treatment equipments effectively removed higher chlorinated PCB. Input marker congeners of RDF were #11, #39, and #68, while those for ASR were #11, #101, #110/120, and #118. Otherwise, combustion marker congeners of RDF were #13/12, #35, #77, and #126, while those for ASR were #170, #194, #206, and #209. While the concentration of PCB increased significantly in the primary combustion chamber, the value of toxicity equivalency quantity for dioxin-like PCB decreased in the secondary combustion chamber and the flue gas treatment equipments.

Adsorption↗

PubMed2006

Brain regions responsible for the expression of conditioned taste aversion in rats.

Conditioned taste aversion (CTA) is acquired when the ingestion of a food is followed by malaise. CTA is a kind of fear learning making animals avoid subsequent intake of the food and show aversive behavior to the taste of the food. To elucidate the brain regions responsible for the expression of CTA, our previous electrophysiological and recent c-fos immunohistochemical studies have been reviewed. Among a variety of brain regions including the parabrachial nucleus, amygdala, insular cortex, supramammillary nucleus, nucleus accumbens, and ventral pallidum that are involved in different phases of CTA expression, the enhanced taste sensitivity to facilitate detection of the conditioned stimulus may originate in the central nucleus of the amygdala and the hedonic shift, from positive to negative, may originate in the basolateral nucleus of the amygdala.

Animals↗

PubMed2006

Substrate specificity analysis and inhibitor design of homoisocitrate dehydrogenase.

Homoisocitrate dehydrogenase is involved in the alpha-aminoadipate pathway of biosynthesis of l-lysine in fungi, yeast, some prokaryotic bacteria, and archaea. This enzyme catalyzes the oxidative decarboxylation of (2R,3S)-homoisocitrate into 2-oxoadipate using NAD(+) as a coenzyme. Substrate specificity of two homoisocitrate dehydrogenases derived from Deinococcus radiodurans and Saccharomyces cerevisiae was analyzed using a series of synthetic substrate analogs, which indicated a relatively broad substrate specificity of these enzymes. Based on the substrate specificity, 3-hydroxyalkylidene- and 3-carboxyalkylidenemalate derivatives were designed as a specific inhibitor for homoisocitrate dehydrogenase. The synthetic inhibitors showed a moderate competitive inhibitory activity and (R,Z)-3-carboxypropylidenemalate was the most inhibitory among the synthesized inhibitors. Therefore, homoisocitrate dehydrogenase appeared to recognize preferentially an extended conformation of homoisocitrate.

Alcohol Oxidoreductases↗

PubMed2006

Ribavirin uptake by cultured human choriocarcinoma (BeWo) cells and Xenopus laevis oocytes expressing recombinant plasma membrane human nucleoside transporters.

We investigated the mechanism of the transport of ribavirin (1-beta-D-ribofuranosyl-1,2,4-trizole-3-carboxamide) into placental epithelial cells using human choriocarcinoma (BeWo) cells and Xenopus oocytes expressing human nucleoside transporters. In BeWo cells, when a relatively low concentration (123 nM) of ribavirin was used, both Na(+)-dependent uptake and -independent uptake of ribavirin were observed. On the other hand, when a higher concentration (100 microM) of ribavirin was used, Na(+)-independent uptake was observed, but there was only a slight Na(+)-dependent uptake. In Xenopus oocytes, influxes of ribavirin mediated by hCNT2 (concentrative nucleoside transporter 2), hCNT3 (concentrative nucleoside transporter 3), hENT1 (equilibrative nucleoside transporter 1) and hENT2 (equilibrative nucleoside transporter 2) were saturable, and apparent K(m) values were 18.0 microM, 14.2 microM, 3.46 mM and 3.71 mM, respectively. These data indicate that hCNT2 and hCNT3 have higher affinity for ribavirin than do hENT1 and hENT2. Moreover, analysis by RT-PCR showed that BeWo cells express mRNA of hCNT3, hENT1 and hENT2. These results suggest that ribavirin is taken up by BeWo cells via both the high-affinity Na(+)-dependent transporter hCNT3 and the low-affinity Na(+)-independent transporters hENT1 and hENT2.

Animals↗

PubMed2006

Cortical representation of taste-modifying action of miracle fruit in humans.

Red berries of a tropical plant called miracle fruit, Richadella dulcifica, reduce the sour and aversive taste of acids and add sweet and palatable taste. To elucidate the brain mechanism of this unique action of miracle fruit, we recorded taste-elicited magnetic fields of the human cerebral cortex. The initial taste responses were localized in the fronto-parietal opercular/insular cortex reported as the primary taste area. The mean latency of the response to citric acid after chewing miracle fruit was essentially the same as that for sucrose and was 250-300 ms longer than that for citric acid. Since it is known that stimulation with acids after the action of miracle fruit induces both sweetness and sourness responses in the primate taste nerves, the present results suggest that the sourness component of citric acid is greatly diminished at the level of subcortical relays, and mostly sweetness information reaches the cortical primary taste area. We propose the idea that the qualitative aspect of taste is processed in the primary taste area and the affective aspect is represented by the pattern of activation among the different cortical areas.

Adult↗

PubMed2006

Involvement of specific orexigenic neuropeptides in sweetener-induced overconsumption in rats.

Palatability is one of the factors that regulates food and fluid intake and contributes to overconsumption in turn contributing to obesity. To elucidate the brain mechanisms of the palatability-induced ingestion, we explored the roles of six hypothalamic orexigenic neuropeptides, orexin, melanin-concentrating hormone (MCH), neuropeptide Y (NPY), agouti-related protein (AgRP), ghrelin and dynorphin, in the intake of a palatable solution, saccharin. Of the six peptides, intracerebroventricular (i.c.v.) administrations of orexin, MCH and NPY increased the intake of saccharin. Drinking of saccharin in turn elevated the mRNA levels of orexin and NPY, but not MCH. Pre-treatments of naloxone, an opioid antagonist, blocked the orexigenic effects of orexin and NPY. Specific gastric motor responses induced by central orexin-A and NPY are well known, however, MCH did not induce such responses. The i.c.v. administration of orexin-A facilitated gastric emptying. These results suggest that the overconsumption promoted by sweet and palatable tastes is attributed to the activation of orexigenic neuropeptides, such as orexin and NPY, and a downstream opioid system together with enhanced digestive functions.

Agouti-Related Protein↗

PubMed2006

Crystallization of helical oligomers with chirality selection. I. A molecular dynamics simulation for bare helix.

Helical polymers often exhibit pronounced chirality recognition during crystallization. By molecular dynamics simulation, we have already shown that the helical polymers crystallize with or without marked chirality selection depending on structural details of the polymer molecules. We have there classified the helical polymers into two categories: the bare helices made of only backbone atoms which show rather tolerant chirality selection, and the general helices with large side groups showing strict chirality recognition. Polymer crystallization is in general largely hampered and retarded by slow dynamics of the entangled chains, and therefore short helical oligomers are very suitable models for studying the chiral crystallization. We here report on molecular simulations of crystallization in the bare helical oligomer molecules by the use of Monte Carlo and molecular dynamics simulations. First we confirm the low temperature chiral crystal phase and the reversible order-disorder transition. We also observe frequent inversions of the helical sense, and the helix reversal defects propagating along the chains. Then we investigate crystallization from the melt into the chiral crystal phase. We find that the crystallization rate depends very sensitively on the degree of undercooling. The crystallization is found to be the first order transition that conforms well to the traditional picture of crystal growth in small molecules. Even when the crystallization directly into the chiral crystal phase is conducted, marked chirality selections are not observed at the early stage of crystallization; the chains adhere to the crystal surfaces selecting their helical senses rather at random resulting in racemic crystallites. The isothermal crystallization for a sufficiently long time, however, yields lamellar crystals composed of well-developed chiral domains, the growth of which seems to be accomplished through the transition back into the ordered chiral crystal phase.

Journal Article↗

PubMed2006

Formation of bromo-substituted triclosan during chlorination by chlorine in the presence of trace levels of bromide.

The side reactions of triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether, TC) and chlorine in the presence of sodium chloride were investigated. In the absence of sodium chloride, three chloro-derivatives of TC, 2',3,4,4'-tetrachloro-2-hydroxydiphenyl ether (3-Cl-TC), 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether (5-Cl-TC), and 2',3,4,4',5-pentachloro-2-hydroxydiphenyl ether (3,5-Cl(2)-TC) were formed, whereas in the presence of sodium chloride, 3-bromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (3-Br-TC), 5-bromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (5-Br-TC), (3 or 5)-bromo-2',4,4',(5 or 3)-chloro-2-hydroxydiphenyl ether ((3,5)-(BrCl)-TC), and 3,5-dibromo-2',4,4'-trichloro-2-hydroxydiphenyl ether (3,5-Br(2)-TC) were additionally formed. Radiochemical neutron activation analysis indicated that 1g of commercially available sodium chloride contained 73 microg of bromide and the bromide ion was determined to be the source of the side reactions. The rate of decrease of TC due to reaction with chlorine was greatly accelerated by the presence of bromide ion in the system: the rate with only 1 x 10(-5) M bromide ion was three times the rate in the absence of bromide.

Bromides↗

PubMed2006

Activity related to the carcinogenicity of plastic additives in the benzophenone group.

This study examines the activities relating to the carcinogenicity of six types of benzophenone derivatives (benzophenone, 2-hydroxy-4-octyloxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2,4-dihydroxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone) currently used in plastic products as additives to serve as ultraviolet absorbing agents. The evaluation of the initiation activity used a light absorption umu-test, a luminescent umu-test and the Ames test. The promotion activity was examined by a Bhas assay, a method that uses Bhas 42 cells for the formation of transformation foci. The luminescent umu-test indicated positive initiation activity of 2-hydroxy-4-methoxybenzophenone, and pseudo-positive activity of 2,4-dihydroxybenzophenone and 2,2'-dihydroxy-4-methoxybenzophenone. In the Ames test, 2-hydroxy-4-octyloxybenzophenone showed pseudo-positive initiation activity. Conversely, 2,4-dihydroxybenzophenone indicated weak promotion activity at 10 microg/ml concentration.

Benzophenones↗

PubMed2006

Acute suppression, but not chronic genetic deficiency, of c-fos gene expression impairs long-term memory in aversive taste learning.

Several lines of evidence have indicated that the establishment of long-term memory requires protein synthesis, including the synthesis of immediate-early gene products. Although the anatomical expression patterns of the c-fos gene, a transcription factor-encoding immediate-early gene, in conditioned taste aversion (CTA) are well documented, the functional roles of c-fos gene expression and Fos-mediated transcription remain to be clarified. Using the antisense oligodeoxynucleotide (AS-ODN) method in rats and gene-targeting knockout techniques in mice (c-fos(-/-) mice), we examined the roles of c-fos gene expression in the acquisition, retrieval, and retention of CTA. Preconditioning microinfusion of AS-ODN directed against c-fos mRNA (c-fos AS-ODN) into the parabrachial nucleus (PBN) impaired the acquisition, whereas infusion of control ODNs consisting of a randomized or inverted base order had no effect. Microinfusion of c-fos AS-ODN into either the amygdala or insular cortex did not impair the acquisition, whereas it attenuated the retention. Retrieval and subsequent retention of an acquired CTA were not disrupted by c-fos AS-ODN infusion into the PBN or amygdala. Microinfusion of another AS-ODN directed against zif268 (egr-1, krox-24, NGFI-A) mRNA into the PBN or amygdala did not affect the acquisition and retention. The genetic deficiency in c-fos(-/-) mice caused normal acquisition and retention. The present results suggest that the Fos-mediated gene transcription in the PBN, amygdala, or insular cortex plays critical roles in the acquisition and/or consolidation, but not the retrieval, of long-term taste memory; nevertheless, some other factors could compensate CTA mechanism when Fos-mediated transcription is not available.

Animals↗

PubMed2006

Discovery, structure-activity relationship study, and oral analgesic efficacy of cyproheptadine derivatives possessing N-type calcium channel inhibitory activity.

Antiallergic drug cyproheptadine (Cyp) is known to have inhibitory activities for L-type calcium channels in addition to histamine and serotonin receptors. Since we found that Cyp had an inhibitory activity against N-type calcium channel, Cyp was optimized to obtain more selective N-type calcium channel blocker with analgesic action. As a consequence of the optimization, we found 13 with potent N-type calcium channel inhibitory activity which had lower inhibitory activities against L-type calcium channel, histamine (H1), and serotonin (5-HT2A) receptors than those of Cyp. 13 showed an oral analgesic activity in rat formalin-induced pain model.

Administration, Oral↗

PubMed2006

Formation and control of toxic polychlorinated compounds during incineration of wastes containing polychlorinated naphthalenes.

To estimate the potential impact on municipal solid waste (MSW) incinerator toxic equivalent (TEQ) emissions of treating wastes containing polychlorinated naphthalenes (PCNs), pilot-scale thermal treatment experiments were conducted. MSW (run 1) and MSW fortified with synthetic rubber belts containing PCNs (runs 2 and 3) were incinerated. Flue-gas and ash samples were analyzed for polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), coplanar polychlorinated biphenyls (co-PCBs), and PCNs. Final exhaust-gas WHO-TEQ emissions were all less than 0.1 ng/Nm3. Flue-gas TEQs were mainly from PCDFs (58-74%). When 2,3,7,8-tetrachlorodibenzo-p-dioxin relative potency factors (REPs) of specific PCN congeners from previous reports were used as estimated toxic equivalency factors to compute estimated PCN TEQs and total TEQs along with PCDDs, PCDFs, and co-PCBs, the contributions of PCNs to the total TEQs were small in ash samples and up to 28% in final exhaust gas. The TEQs in primary combustion flue gases increased through the formation of dioxins and PCNs and then decreased via secondary combustion, fabric filtration, and activated carbon adsorption. From this pilot-scale study, the incremental impact of incinerating PCN-containing wastes on annual TEQ emissions in Japan is estimated as 0.27 g of total TEQ.

Hydrocarbons, Chlorinated↗

PubMed2006

Developmental expression of HpNanos, the Hemicentrotus pulcherrimus homologue of nanos.

The Hemicentrotus pulcherrimus homologue of nanos (HpNanos), that encodes a protein containing two CCHC zinc finger motifs, was isolated from a gastrula cDNA library. The accumulation of HpNanos mRNA during embryonic development and the spatial expression pattern are reported. Developmental northern blot analysis revealed that HpNanos mRNA markedly accumulated during the blastula stages, and then decreased in abundance at the mesenchyme blastula stage. The second phase of HpNanos mRNA expression occurred during gastrulation, after which the expression returned to a low level. Whole-mount in situ hybridization showed that the HpNanos was exclusively expressed in four to six small micromere-descendant cells at the blastula stage. The expression of HpNanos was restricted to the coelomic pouch, which gives rise to the mesoderm of the ventral surface of the adult rudiment, at the prism stage. These results suggest that HpNanos expression will be instrumental for future analyses of the function of small micromere-descendant cells and of the origin of germ cells during sea urchin development.

Amino Acid Sequence↗

PubMed2006

Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure.

OBJECTIVES: This study sought to evaluate the relationship between brain natriuretic peptide (BNP), renal function, and the severity of congestive heart failure (CHF). BACKGROUND: Both BNP and renal function are prognostic predictors in CHF patients. METHODS: We measured the plasma BNP level in the aortic root and coronary sinus in 366 consecutive patients with CHF. Estimated glomerular filtration rate (eGFR) by the Cockcroft-Gault equation was used as an indicator of renal function. RESULTS: By stepwise multivariate analyses, hemodynamic parameters such as left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP) but not eGFR were independent predictors of a transcardiac increase (coronary sinus-aortic root) in BNP. Regarding the plasma level of BNP in the aortic root, not only LVEF (p < 0.0001) and LVEDP (p < 0.0001) but also eGFR (p < 0.0001) were independent predictors. Patients were divided into two groups, patients with an eGFR > or =60 ml/min (group 1, n = 229) and patients with an eGFR <60 ml/min (group 2, n = 137). There was no difference in LVEF, LVEDP, or the transcardiac gradient of BNP between the two groups, but the plasma level of BNP in the aortic root was approximately two-fold greater in group 2 than in the group 1. CONCLUSIONS: These findings suggest that decreased clearance from the kidney contributes to the elevated BNP in CHF patients with renal dysfunction, especially in patients with an eGFR <60 ml/min.

Aged↗

PubMed2006

Proteomic analysis reveals significant alternations of cardiac small heat shock protein expression in congestive heart failure.

BACKGROUND: Because congestive heart failure (CHF) is a complex syndrome with many different underlying mechanisms of worsening of heart function, it is important to recognize the global alternations in protein expression associated with the processes of CHF. METHODS AND RESULTS: The purpose of our study was to use a proteomic approach to investigate global alternations in protein expression in tachycardia induced CHF dogs. We compared the 2-dimensional electrophoresis protein patterns of left ventricular samples from the normal with those from failing myocardium. Differentially expressed cardiac proteins showed approximately 500 cardiac protein spots. A total of 20 spots (14 increased, 6 decreased) was altered in CHF, whereas the more distinguishably increased spots in CHF were identified by using mass spectrometry as alpha B crystallin, heat shock protein (HSP) 27, and HSP20, which maintain both the morphologic and functional integrity of the cardiomyocytes and increase tolerance against various types of stress. Because phosphorylation is one of the most important posttranslational modifications, we evaluated whether or not the overexpressed small HSPs were phosphorylated in CHF. Phosphoprotein staining and Western blotting demonstrated that the phosphorylation of alpha B crystallin at serine (Ser)-59 site and of HSP27 at both Ser-78 and Ser-82 sites increased in CHF. CONCLUSION: Proteomics studies can provide new insights into molecular mechanisms in CHF and phosphorylated small HSPs may be involved in preventing cardiac dysfunction.

Animals↗

PubMed2006

Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice.

Granuphilin is a crucial component of the docking machinery of insulin-containing vesicles to the plasma membrane. Here, we show that the granuphilin promoter is a target of SREBP-1c, a transcription factor that controls fatty acid synthesis, and MafA, a beta cell differentiation factor. Potassium-stimulated insulin secretion (KSIS) was suppressed in islets with adenoviral-mediated overexpression of granuphilin and enhanced in islets with knockdown of granuphilin (in which granuphilin had been knocked down). SREBP-1c and granuphilin were activated in islets from beta cell-specific SREBP-1c transgenic mice, as well as in several diabetic mouse models and normal islets treated with palmitate, accompanied by a corresponding reduction in insulin secretion. Knockdown- or knockout-mediated ablation of granuphilin or SREBP-1c restored KSIS in these islets. Collectively, our data provide evidence that activation of the SREBP-1c/granuphilin pathway is a potential mechanism for impaired insulin secretion in diabetes, contributing to beta cell lipotoxicity.

Animals↗