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N Takamura

Publications and source records attributed to N Takamura.

At least 19 recordsLinked to original sources
PubMed2006

Kazakhstan: a folate-deficient area?

OBJECTIVE: In the Republic of Kazakhstan, located in central Asia, the traditional diet consists mainly of meat, and vegetable intake tends to be deficient. This eating lifestyle may contribute to folate deficiency, which is closely linked to abnormal homocysteine (HCY) metabolism. SUBJECTS AND METHODS: In order to evaluate current folate status in the healthy Kazakh population, we screened serum folate and plasma HCY in 50 healthy Kazakh adults aged 20-65 years (KZH) and 60 healthy Japanese control subjects aged 27-65 years (JPN). RESULTS: Serum levels of folate were significantly lower in KZH than in JPN (3.1 vs 10.0 ng/ml, P<0.01). Fifty of 61 (82.0%) subjects in KZH but none in JPN showed low concentrations of folate (<3.6 ng/ml). Plasma levels of HCY were significantly higher in KZH than in JPN (13.2 vs 7.8 nmol/ml, P<0.01). CONCLUSIONS: Our findings strongly suggest that owing to the insufficient intake of vegetables, folate deficiency exists in Kazakhstan. Furthermore, hyperhomocysteinemia was observed in this group, probably owing to the secondary effects of folate deficiency.

Adult↗
PubMed2005

Adenovirus-mediated gene delivery of interleukin-10, but not transforming growth factor beta, ameliorates the induction of Graves' hyperthyroidism in BALB/c mice.

Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) are well known anti-inflammatory cytokines. We have studied the effect of adenovirus-mediated IL-10 and TGF-beta gene delivery on the induction of Graves' hyperthyroidism in our mouse model that involves repeated injections of adenovirus expressing the thyrotropin receptor A subunit (AdTSHR). We first constructed adenoviruses encoding the two cytokines (AdIL10 and AdTGF(beta)) and confirmed expression by in vitro infection of COS cells. Susceptible BALB/c mice were injected twice with AdTSHR alone or together with AdIL10 or AdTGF(beta), and bled two weeks after the second immunization. Significantly elevated serum thyroxine levels were seen in 26% of mice immunized with AdTSHR and AdIL10 versus 61% with AdTSHR alone. Levels of thyroid stimulating antibody, but not nonstimulating antibody, were also decreased, and TSHR-specific splenocyte secretion of interferon-gamma in recall assays was impaired in mice treated with AdIL10. In contrast, AdTGF(beta) had little effect on hyperthyroidism. Overall, our findings demonstrate that gene delivery of IL-10, but not TGF-beta, suppresses the induction of Graves' hyperthyroidism in a mouse model. However, the effect of IL-10 is less powerful than we observed previously with T helper type 2-inducers including adenovirus expressing IL-4, Shistosoma mansoni infection or alpha-galactosylceramide.

Adenoviridae↗
PubMed2003

Effects of fish introduction on the length of the tail of cryptomonads in mesocosm experiments.

Two different morphs of the small cryptomonad, Plagioselmis prolonga var. nordica with a posterior tail, were observed during summer and fall in the hypertrophic lake, Lake Kasumigaura, Japan. The tail shortened in mesocosms stocked with planktivorous silver carp ( Hypophthalmichthys molitrix Val.) and elongated by more than 50% in mesocosms from which silver carp were removed. The density of Plagioselmis cells increased significantly upon fish stocking and decreased upon fish removal. The tail length was negatively correlated with algal abundance and positively correlated with crustacean densities, but there was no correlation with nutrient levels or physical environmental parameters in the mesocosms. The variation in tail length was induced by the presence/absence of fish, but was not related to their density. However, silver carp manipulation strongly affected the density of the majority of zooplankters and, interestingly, there was a strong correlation between zooplankton density and tail-length change in Plagioselmis. We propose a possible herbivore-induced defense mechanism triggered by the top predator, silver carp.

Adaptation, Biological↗
PubMed2002

Intracellular cytokine analysis of CD4-positive T cells predictive of sustained response to interferon therapy for patients with chronic hepatitis C.

We investigated whether the measurement of serum interleukin 18 (IL-18) and intracellular cytokine analysis of peripheral blood CD4-positive T cells (ICA-CD4+ Tc) of chronic hepatitis C (CH-C) patients before and two weeks after interferon (IFN) administration are useful for predicting sustained response to IFN. Twenty-nine CH-C patients received IFN every day for two weeks and three times a week for 22 weeks. Patients were divided into two groups: responders, in whom serum HCV-RNA was undetectable at the end of the follow-up (week 48), and nonresponders, in whom any other patterns were seen. Before and two weeks after IFN administration, serum IL-18 and ICA-CD4+ Tc as described by Jung et al were measured. Serum IL-18 and the relative prevalence of IFN-gamma+ and IL-4+, IFN-gamma+ and IL-4 (Th-1), and IFN-gamma- and IL-4+ cells in the responders were significantly increased, but only the relative prevalence of Th-1 cells in the nonresponders was increased two weeks after IFN therapy. In conclusion, ICA-CD4+ Tc and the measurement of serum IL-18 might be useful for predicting IFN therapy by comparing the results between before and two weeks after IFN.

CD4-Positive T-Lymphocytes↗
PubMed2001

IL-7 prevents both caspase-dependent and -independent pathways that lead to the spontaneous apoptosis of i-IEL.

Intestinal intraepithelial lymphocytes (i-IEL) readily undergo spontaneous apoptosis in vitro through an unclear mechanism. Here we examined the relationship between caspases, which plays a major role in apoptosis, and IL-7 in the spontaneous apoptosis of i-IEL in vitro. We demonstrated that IL-7 and zVAD prevented the spontaneous apoptosis of i-IEL by approximately 50% and 25% respectively with no additive protection seen when both are used. IL-7 preferentially prevented the apoptosis of gammadelta i-IEL, while zVAD equally prevented the apoptosis of gammadelta and alphabeta i-IEL. Lastly, we demonstrated that the spontaneous apoptosis of i-IEL is associated with a marked increase in caspase activity. Caspase activity was completely inhibited by zVAD, but only slightly by IL-7. Overall these results suggest that two pathways lead to the spontaneous apoptosis of i-IEL, one which is caspase dependent and the other which is caspase independent. IL-7 appears to exert its effect on i-IEL undergoing spontaneous by partially inhibiting both apoptotic pathways.

Amino Acid Chloromethyl Ketones↗
PubMed2001

p53-dependent radiation-induced crypt intestinal epithelial cells apoptosis is mediated in part through TNF-TNFR1 system.

Radiation induces apoptosis of crypt intestinal epithelial cells (IEC) through a pathway that is largely dependent on p53. However, exactly how p53 mediates IEC apoptosis is unclear. Studies in vitro suggest that one mechanism by which p53 mediates apoptosis is through its ability to transactivate members of the TNF receptor family of 'Death Receptors'. Here, we examined the role of one of its member, TNF receptor type 1 (TNFR1), in an in vivo model of p53-dependent radiation-induced IEC apoptosis. We demonstrate that mice genetically engineered to be deficient in TNF receptor type 1 (TNFR1(-/-)) and mice injected with TNFR1-fusion chimeric protein (TNFR1-Fc; a competitive inhibitor of TNFR1) were partially protected (30-40%) from p53-dependent radiation-induced IEC apoptosis. However, we found no evidence to support the possibility p53 transcriptionally regulates the expression of TNFR1 nor increases the susceptibility of IEC to TNF-mediated apoptosis. Interestingly, we found that injection of TNF readily induced IEC apoptosis and that radiation induced a p53-dependent increase in the intestinal level of TNF. Furthermore, injection of a neutralizing anti-TNF mAb reduced p53-dependent radiation-induced IEC apoptosis by approximately 60%. Overall, these results suggest that p53-dependent radiation-induced IEC apoptosis is mediated in part through ability of p53 to regulate TNF, which subsequently induces IEC apoptosis through TNFR1.

Animals↗
PubMed2001

Nutrient dynamics and the eutrophication of shallow lakes Kasumigaura (Japan), Donghu (PR China), and Okeechobee (USA).

We compared the nutrient dynamics of three lakes that have been heavily influenced by point and non-point source pollution and other human activities. The lakes, located in Japan (Lake Kasumigaura), People's Republic of China (Lake Donghu), and the USA (Lake Okeechobee), all are relatively large (> 30 km2), very shallow (< 4 m mean depth), and eutrophic. In all three lakes we found strong interactions among the sediments, water column, and human activities. Important processes affecting nutrient dynamics included nitrogen fixation, light limitation due to resuspended sediments, and intense grazing on algae by cultured fish. As a result of these complex interactions, simple empirical models developed to predict in-lake responses of total phosphorus and algal biomass to external nutrient loads must be used with caution. While published models may provide 'good' results, in terms of model output matching actual data, this may not be due to accurate representation of lake processes in the models. The variable nutrient dynamics that we observed among the three study lakes appears to be typical for shallow lake systems. This indicates that a greater reliance on lake-specific research may be required for effective management, and a lesser role of inter-lake generalization than is possible for deeper, dimictic lake systems. Furthermore, accurate predictions of management impacts in shallow eutrophic lakes may require the use of relatively complex deterministic modeling tools.

Conservation of Natural Resources↗
PubMed2001

Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl.

We evaluated the incidence of childhood thyroid diseases and urinary iodine levels in Nagasaki, Japan and in Gomel, Belarus, which was greatly radio-contaminated by the Chernobyl accident, in order to obtain the comparative data of thyroid diseases between iodine-rich (Japan) and -deficient (Belarus) areas. In Nagasaki, the median level of urinary iodine, measured by ammonium persulfate digestion in microplate method, was 362.9 microg/L. In order to evaluate the geographical differences in Japan, other samples were collected in Hamamatsu and in South Kayabe, Hokkaido, where the median levels were 208.4 microg/L and 1015.5 microg/L, respectively. Furthermore, thyroid screening by ultrasound (US) in Nagasaki revealed only four cases that showed goiter (1.6%) and two cases (0.8%) that had cystic degeneration and single thyroid cyst. There was no evidence of thyroid nodule detected by US examination. In contrast, the median of urinary iodine level was 41.3 microg/L in Gomel. The incidences of goiter (13.6%) and echogenic abnormality (1.74%) in Gomel were much higher than in Nagasaki, suggesting the critical involvement of iodine deficiency in increased childhood thyroid abnormality around Chernobyl. Radioactive iodine released just after the Chernobyl accident may have influenced predominantly children residing in iodine-deficient areas. Our results suggest that management of thyroid screening for schoolchildren at ordinary times may be beneficial for monitoring the adverse effects of radioactive iodine from the standpoint of future prospective study.

Adolescent↗
PubMed2001

Heterochronous development of intrahepatic cholangiocellular carcinoma following hepatocellular carcinoma in a hepatitis B virus carrier.

A 68-year-old Japanese woman was admitted to our hospital in September 1995, because of a mass detected by ultrasonography during a follow-up examination for chronic hepatitis B. Hepatocellular carcinoma (HCC) in the right liver lobe was diagnosed based on imaging studies and elevated alpha-fetoprotein (AFP). Percutaneous ethanol injection therapy (PEIT) was performed. PEIT was repeated in November 1998, because the tumor had enlarged and serum AFP was re-elevated. Follow-up ultrasonography (US) demonstrated low echoic mass in the left liver lobe in August 1999; serum AFP was normal, but serum carbohydrate antigen 19-9 (CA19-9) was elevated to 420 U/ml. In October 1999, radiofrequency interstitial tissue ablation (RITA) was performed after tumor biopsy. Pathological findings revealed adenocarcinoma and pathological diagnosis was made as intrahepatic cholangiocellular carcinoma (ICC). Three weeks later, her serum CA19-9 was remarkably decreased (180 U/ml). The patient has been well for 5 months. Her latest AFP and CA19-9 in the serum were 2 ng/ml and 89 U/ml, respectively. The incidence of double cancer in the liver is rare. This is also the first case report to discuss ICC treated with RITA.

Aged↗
PubMed2001

Evaluation of a telemedicine system for supporting thyroid disease diagnosis.

A telemedicine system connecting Japan and Belarus via a communication satellite and the international ISDN has been in use since February, 1999. Two relational databases, which are essentially the same, are set respectively at Nagasaki University School of Medicine and Gomel Regional Specialized Dispensary in Belarus for management of patients' data and for research including epidemiologic studies. The thyroid ultrasonographic images, microscopic images of cytological findings and other information on patients are sent from Gomel to Nagasaki once a week with diagnoses and comments by physicians at Gomel Regional Specialized Dispensary for cases whom they found difficult to diagnose. Thyroid specialists at Nagasaki University School of Medicine correct the diagnoses, if necessary, on the basis of information from Gomel and send their comments and instructions to Gomel for improving diagnosis skills of physicians at Gomel. The findings of 330 cases have been sent from Gomel to Nagasaki by September, 2000 since the commencement of the system in February, 1999. Of the 329 cases, thyroid diagnosis was made at Gomel for 261 cases in whom two or more diagnoses were made for 35 cases. As of the end of October, 2000, the Gomel diagnoses have been reviewed for 217 cases and the remaining 112 cases are under review at Gomel. The diagnoses made at Gomel and Nagasaki were in agreement for 110 (50.7%) of 217 cases. Thyroid cancer was diagnosed in 8 cases in whom 6 had been diagnosed at Gomel while the other 2 were diagnosed anew at Nagasaki. The usefulness of the system for improving thyroid diagnosis in Belarus was indicated.

Databases, Factual↗
PubMed2000

Involvement of cell surface glycans in adhesion of human colon carcinoma cells to liver tissue in a frozen section assay: role of endo-beta-galactosidase-sensitive structures.

Adhesion of human colon carcinoma variant cell lines expressing different levels of the cell surface sialyl Lewis X (sLeX) antigen to frozen sections of mouse liver was examined. KM12-HX cells that bound the monoclonal antibody (mAb) FH6 (anti-sLeX) and thus expressed a high level of sLeX demonstrated a greater degree of adhesion to liver sections than their low-binding counterparts, KM12-LX cells. The adhesion of KM12-HX cells to liver sections was partially blocked by mAb FH6, but not by another anti-sLeX mAb, KM93. The adhesion was Ca2+ dependent but was not inhibited by anti-E-selectin. Endo-beta-galactosidase treatment significantly reduced adhesion and resulted in the loss of cell surface binding sites for mAb FH6. O-linked oligosaccharides from KM12-HX cells incubated in the presence of p-nitrophenyl-N-acetylgalactosaminide were fractionated by a combination of gel filtration, anion exchange chromatography, and normal phase high-performance liquid chromatography. The structure of a mAb FH6-reactive and endo-beta-galactosidase-sensitive glycan was estimated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry in a post source decay mode and by glycosidase digestions to be NeuAc alpha2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc-NAc beta1-3Gal beta1-4(+/-Fuc alpha1-3)GlcNAc beta1-6(NeuAc alpha2-3Gal beta1-3)GalNAc-pNP. Mild detergent lysates of mouse liver surface-labeled with sulfo-NHS biotin were incubated with glutaraldehyde-fixed monolayers of KM12-HX cells, and bound components were isolated after EDTA treatment. A Mr 49,000 component that bound only to KM12-HX cells and not to KM12-LX cells was identified.

Animals↗
PubMed2000

Hormone binding induces rapid proteasome-mediated degradation of thyroid hormone receptors.

The thyroid hormone 3,3',5-triiodo-l-thyronine (T3) is essential for growth, differentiation, and development. Its biological activities are mediated by T3 nuclear receptors (TRs). At present, how T3 regulates TR proteins and the resulting functional consequences are still unknown. Immunofluorescence analyses of endogenous TR in the growth hormone-producing GC cells showed that the T3-induced rapid degradation of TR was specifically blocked by lactacystin, a selective inhibitor of the ubiquitin-proteasome degradation pathway. Immunoblots demonstrated that the transfected TRbeta1 was ubiquitinated and that the ubiquitination was T3 independent. Studies with a series of truncated TRbeta1 showed that the hormone-binding domain was sufficient for the T3-induced rapid degradation of TRbeta1 by the proteasome degradation pathway. T3 also induced rapid degradation of TRbeta2 and TRalpha1. In contrast, the stability of the non-T3-binding TRalpha2 and naturally occurring TRbeta1 mutants that do not bind T3 was not affected by T3 treatment, indicating that hormone binding to receptor was essential for the degradation of the wild-type receptors. In the presence of proteasome protease inhibitors, the levels of both total and ubiquitinated TRbeta1 protein increased, yet T3-dependent transcriptional activation and the expression of the growth hormone gene were diminished, suggesting that proteasome-mediated degradation played a novel role in modulating transcriptional activation by TR. The present study reveals a role of T3 in modulating the functions of TR by regulating its receptor level via the ubiquitin-proteasome degradation pathway.

Animals↗