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Tsutomu Takeuchi

Publications and source records attributed to Tsutomu Takeuchi.

At least 37 records · Page 2Linked to original sources
PubMed2005

Global parasite control initiative of Japan (Hashimoto Initiative).

The Asian Centre of International Parasite Control (ACIPAC) was established in Bangkok in March 2000 as a JICA technical cooperation project in collaboration with the Mahidol University and the Ministry of Public Health, Thailand. Since then, ACIPAC carried out its activities with emphasis on the establishment of the concept of school health-based parasite control in the Great Mekong sub-region countries. In addition to contributing human resource development through its training courses on school-based malaria and STH control for programme managers and also through small-scale pilot projects implemented in partner countries, ACIPAC proposed that schoolchildren should be considered as health partners rather than simple recipients of health services including deworming programmes.

Adolescent↗
PubMed2005

Relation between plasma adenosine and serum TSH levels in women with hyperemesis gravidarum.

INTRODUCTION: This study investigated the relation between adenosine and thyroid function associated with hyperemesis gravidarum. METHODS: We examined 84 Japanese singleton pregnant women with an average age of 33.0+/-5.8 years at 9-12 weeks gestation being managed at our hospital. The patients were divided into three groups according to the severity of emesis: (1) those with hyperemesis gravidarum (nausea and vomiting with weight loss >5%, n=13), (2) those with emesis (nausea and vomiting with weight loss <5%, n=31), and (3) those with no symptoms as a control (n=40). RESULTS: The average serum TSH levels in the emesis and hyperemesis groups were significantly higher than that in the control group (P<0.05). The average plasma adenosine level in the hyperemesis group was significantly higher than those in the control pregnant and emesis groups (P<0.05). There were no significant differences in plasma adenosine levels between the control pregnant and emesis groups. The serum TSH level showed significant correlations with weight loss (%) and plasma adenosine levels (P<0.05). CONCLUSIONS: Our findings support the possible role of adenosine in counteracting the further progression of hyperemesis gravidarum associated with gestational thyrotoxicosis.

Adenosine↗
PubMed2005

Characterization of protein geranylgeranyltransferase I from the enteric protist Entamoeba histolytica.

Entamoeba histolytica is a unique protozoan parasite possessing both protein farnesyltransferase and geranylgeranyltrasferase I (GGT-I) for isoprenylation of small GTPases. In this study, we demonstrated unique enzymological properties of the amebic GGT-I (EhGGT-I), including substrate specificity and insensitivity to known mammalian inhibitors. Some of important residues of the catalytic beta subunit implicated in the specificity for GTPase acceptors and prenyl donors are substituted in EhGGT-I. Recombinant alpha and beta subunits of EhGGT-I, co-expressed in Escherichia coli, showed activity to transfer geranylgeranyl to both human wild-type (CVLS) and mutant (CVLL) H-Ras, while the mammalian GGT-I geranylgeranylated, but not farnesylated, only mutant H-Ras. All the representative amebic Ras and Rho/Rac small GTPases with phenylalanine, leucine, methionine, or alanine terminus were preferentially geranylgeranylated by EhGGT-I. This indicates that the acceptor specificity of the amebic GGT-I is remarkably broader than that of its mammalian counterpart. In contrast to EhFT, which farnesylates but not geranylgeranlylates solely EhRas4-CVVA, EhGGT-I also showed significant farnesyltransferase activity against Ras GTPase acceptors. EhGGT-I showed remarkable resistance to peptidomimetics known to inhibit mammalian GGT-I. Together with our previous observation that this parasite does not appear to depend on farnesylation for a majority of Ras and Rho/Rac, these data indicate that biological and biochemical advantages leading to the evolutional selection of this isoprenyl modification must exist uniquely in this parasitic protist. Finally, remarkable biochemical differences in binding to substrates and inhibitors between amebic and mammalian GGT-I highlight this enzyme as an attractive target for the development of new chemotherapeutics against amebiasis.

Alkyl and Aryl Transferases↗
PubMed2005

HbA1C levels in Japanese women during early pregnancy.

INTRODUCTION: The maternal glycosylated hemoglobin (HbA1C) level in early pregnancy has been observed to be lower than the prepregnant value. In Japan, the average body mass index (BMI) shows a very slight change during early pregnancy, which has been thought to be associated with the incidence of hyperemesis gravidarum. METHODS: We examined the relation between HbA1C and changes in BMI levels of 274 pregnant Japanese women managed at our hospital during early pregnancy. RESULTS: The average HbA1C in early pregnancy was 5.1 +/- 0.4%, which did not differ markedly from that of nonpregnancy (5.0 +/- 0.5%). The HbA1C level showed a negative correlation with the increasing value of BMI during early pregnancy (r2 = 0.26, p < 0.05). CONCLUSIONS: In this study, we could not identify a significant decrease in HbA1C in Japanese women during early pregnancy. This finding may be associated with the incidence of hyperemesis gravidarum in Japanese women.

Adult↗
PubMed2005

Critical role of the fifth domain of E-cadherin for heterophilic adhesion with alpha E beta 7, but not for homophilic adhesion.

The integrin alpha(E)beta(7) is expressed on intestinal intraepithelial T lymphocytes and CD8(+) T lymphocytes in inflammatory lesions near epithelial cells. Adhesion between alpha(E)beta(7)(+) T and epithelial cells is mediated by the adhesive interaction of alpha(E)beta(7) and E-cadherin; this interaction plays a key role in the damage of target epithelia. To explore the structure-function relationship of the heterophilic adhesive interaction between E-cadherin and alpha(E)beta(7), we performed cell aggregation assays using L cells transfected with an extracellular domain-deletion mutant of E-cadherin. In homophilic adhesion assays, L cells transfected with wild-type or a domain 5-deficient mutant formed aggregates, whereas transfectants with domain 1-, 2-, 3-, or 4-deficient mutants did not. These results indicate that not only domain 1, but domains 2, 3, and 4 are involved in homophilic adhesion. When alpha(E)beta(7)(+) K562 cells were incubated with L cells expressing the wild type, 23% of the resulting cell aggregates consisted of alpha(E)beta(7)(+) K562 cells. In contrast, the binding of alpha(E)beta(7)(+) K562 cells to L cells expressing a domain 5-deficient mutant was significantly decreased, with alpha(E)beta(7)(+) K562 cells accounting for only 4% of the cell aggregates, while homophilic adhesion was completely preserved. These results suggest that domain 5 is involved in heterophilic adhesion with alpha(E)beta(7), but not in homophilic adhesion, leading to the hypothesis that the fifth domain of E-cadherin may play a critical role in the regulation of heterophilic adhesion to alpha(E)beta(7) and may be a potential target for treatments altering the adhesion of alpha(E)beta(7)(+) T cells to epithelial cells in inflammatory epithelial diseases.

Animals↗
PubMed2005

A splice variant of the TCR zeta mRNA lacking exon 7 leads to the down-regulation of TCR zeta, the TCR/CD3 complex, and IL-2 production in systemic lupus erythematosus T cells.

The reduction or absence of TCR zeta-chain (zeta) expression in patients with systemic lupus erythematosus (SLE) is thought to be a factor in the pathogenesis of SLE. We previously reported a splice variant of zeta mRNA that lacks the 36-bp exon 7 (zeta mRNA/exon 7(-)) and is accompanied by the down-regulation of zeta protein in T cells from SLE patients. In this study, we show that EX7- mutants (MA5.8 cells deficient in zeta protein that have been transfected with zeta mRNA/exon 7(-)) exhibit a reduction in the expression of TCR/CD3 complex and zeta protein on their cell surface as well as a reduction in the production of IL-2 after stimulation with anti-CD3 Ab, compared with that in wild-type (WT) mutants (MA5.8 cells transfected with the WT zeta mRNA). Furthermore, real-time PCR analyses demonstrated that zeta mRNA/exon 7(-) in EX7- mutants was easily degraded compared with zeta mRNA by the WT mutants. Pulse-chase experiment showed zeta protein produced by this EX7- mutants was more rapidly decreased compared with the WT mutants. Thus, the lower stability of zeta mRNA/exon 7(-) might also be responsible for the reduced expression of the TCR/CD3 complex, including zeta protein, in SLE T cells.

Alternative Splicing↗
PubMed2005

Resting oxygen consumption in patients with twin pregnancy.

OBJECTIVE: This study examined the resting oxygen consumption in patients with a twin pregnancy and compared the results with those of singleton pregnancies. METHODS: In 15 patients with a twin and 26 patients with a singleton pregnancy, the resting oxygen consumption was measured using an open-circuit ventilatory system during the third trimester of pregnancy. RESULTS: The average resting oxygen consumption in patients with a twin pregnancy was 231+/-25 ml/min, significantly higher than that in patients with a singleton pregnancy (209+/-24 ml/min, P<0.05). CONCLUSION: Our results indicate an estimated increase in metabolic rate in patients during the third trimester of a twin pregnancy compared with those with a singleton pregnancy.

Adult↗
PubMed2005

Proposed [corrected] Japanese guidelines for the use of infliximab for rheumatoid arthritis.

Differences in ethnic backgrounds as well as in medical and socioeconomic status often affect both the efficacy and adverse effects of medications. Recent data suggest an increased risk of opportunistic infections, especially tuberculosis (TB), among rheumatoid arthritis (RA) patients receiving infliximab, a chimeric monoclonal anti-tumor necrosis factor alpha (TNF-alpha) antibody. In this regard, the annual incidence of TB is approximately five times higher in Japan than in the United States. Furthermore, since Bacillus Calmette-Guérin vaccination is mandatory in childhood when the skin test for purified protein derivative (PPD) is negative, a high incidence of false-positive PPD skin tests is observed among the Japanese population. In addition, the upper limit of methotrexate dosage to be used for RA is lower in Japan. We have therefore established official guidelines for the proper use of infliximab in Japanese RA patients. In this review, an algorithm for the diagnosis and management of TB in RA is presented in an evidenced-based form.

Journal Article↗
PubMed2005

Isolation and functional analysis of a chk2 homologue from Entamoeba histolytica.

Mammalian Chk2 is a Ser/Thr kinase required for cell-division arrest induced by DNA damage. We found six new kinase genes of Entamoeba histolytica by analysis in silico. One of the kinase genes was a homologue of human chk2 gene. The chk2 homologue gene (Eh chk2) was expected to encode 398 amino acids and showed nearly 50% homology to human Chk2 in amino acid sequence. Eh chk2 had a catalytic domain of Ser/Thr kinase and a fork head-associated (FHA) domain that is highly conserved among Chk2 homologues in vertebrates. To examine the biological functions of Eh chk2, we synthesized Eh chk2 mRNA in vitro and injected it into immature frog eggs (Xenopus laevis oocytes) as a model system of cell division. Eh chk2 markedly delayed the cell division of frog eggs by disrupting transition of G2 phase to M phase. Eh chk2 also inhibited the activation of p42 MAPK and Cdc2 kinase which are representative events induced by cell division. These results suggest that Eh chk2 gene should be a cell-division regulator in E. histolytica.

Amino Acid Sequence↗
PubMed2005

T cell abnormalities in systemic lupus erythematosus.

Because of the consensus that T cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE), we explored the molecular basis of the defective function of SLE T cells for expression of signal transduction molecules, as well as surface structures such as adhesion molecules, by extensively testing peripheral blood T cells from SLE patients. Upregulated expression and function of adhesion molecules was observed in T cells from patients with active SLE who had specific clinical manifestations such as vasculitis, epithelitis and arthritis, but proximal signal transduction was defective. Comprehensive analysis to identify the molecules responsible for the defects showed the expression of the TCR zeta chain was attenuated, or absent in more than half of SLE patients. Moreover, the aberrant transcripts of the TCR zeta chain, including spliced variants lacking exon 7 and with a short 3' UTR, were detected in SLE T cells. Although attenuated expression of the TCR zeta chain is also observed in patients with cancers, infections and other autoimmune diseases, sustained attenuation of TCR zeta expression and aberrant transcripts are only observed in SLE. In this review we discuss the unique features of the TCR zeta defects in SLE.

Animals↗
PubMed2005

[Evaluation of a nested-pCR to detect 18S rDNA for the diagnosis of toxoplasmic meningoencephalitis].

To detect an 18S ribosomal DNA fragment of Toxoplasma gondii Nested-PCR was used to detect an 18S ribosomal DNA fragment of Toxoplasma gondii in the CSF of 13 patients at 6 facilities in whom Toxoplasma meningoencephalitis had been suspected between January 2001 and Feburary 2005. Based on the diagnostic criteria of the CDC, all patients were treated with the anti-toxoplasmic chemotherapy based on the clinical diagnosis. Clinical improvement was observed in 11 patients, and the final diagnosis was toxoplasmosis, but the conditions of 2 patients deteriorated, and they were ultimately diagnosed with malignant lymphoma. Based on the results of the clinical diagnosis, we assessed the effectiveness of the nested-PCR method of examining the CSF for making the diagnosis of Toxoplasma meningoenephalitis. The results of the nested-PCR were positive in 8 of the 13 cases, and all 8 cases had been diagnosed with Toxoplasma encephalitis clinically. The results were negative in 5 of the 13 cases, but 3 of the 5 negative cases had been clinically diagnosed as toxoplasmosis, indicating that the test was false-negative in some cases (27.3%; 3/11). Toxoplasma meningoencephalitis is so difficult to diagnose that the development of the new, high-specificity diagnostic methods is being eagerly awaited.

Adult↗
PubMed2005

Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection.

In order to develop CD8+-T-cell-mediated immunotherapy against intracellular infectious agents, vaccination using recombinant virus vectors has become a promising strategy. In this study, we generated recombinant adenoviral and vaccinia virus vectors expressing a single CD8+-T-cell epitope, ANYNFTLV, which is derived from a Trypanosoma cruzi antigen. Immunogenicity of these two recombinant virus vectors was confirmed by the detection of ANYNFTLV-specific CD8+ T cells in the spleens of immunized mice. Priming/boosting immunization using combinations of these two recombinant virus vectors revealed that the adenovirus vector was efficient for priming and the vaccinia virus vector was effective for boosting the CD8+-T-cell responses. Moreover, we also demonstrated that the ANYNFTLV-specific CD8+-T-cell responses were further augmented by coadministration of recombinant vaccinia virus vector expressing the receptor activator of NFkappaB (RANK) ligand as an adjuvant. By priming with the adenovirus vector expressing ANYNFTLV and boosting with the vaccinia virus vectors expressing ANYNFTLV and RANK ligand, the immunized mice were efficiently protected from subsequent challenge with lethal doses of T. cruzi. These results indicated, for the first time, that the induction of immune responses against a single CD8+-T-cell epitope derived from an intrinsic T. cruzi antigen was sufficient to control lethal T. cruzi infection.

Adenoviridae↗
PubMed2005

Plasma adenosine levels in peri-menopausal women having frequent hot flushes.

BACKGROUND: The effect of hormone replacement therapy (HRT) on plasma adenosine levels was investigated in climacteric women experiencing hot flushes. METHODS AND RESULTS: Plasma adenosine levels were measured in 13 peri-menopausal women with frequent hot flushes (>5 per day) before and 3-4 months after initiating HRT. Thirteen healthy pre-menopausal, 9 peri-menopausal women with few hot flushes (<1 or 2 per day) and 10 healthy postmenopausal women were enrolled as controls. The average plasma adenosine level in the peri-menopausal women was 0.20+/-0.09 micromol/L, which was significantly higher than in the pre-menopausal (0.12+/-0.07 micromol/L, p<0.05), peri-menopausal with few hot flushes (0.10+/-0.09 micromol/L, p<0.05) and postmenopausal women (0.13+/-0.06 micromol/L, p<0.05). Both the increased adenosine level and the hot flushes were decreased by HRT (plasma adenosine: 0.13+/-0.06 micromol/L). CONCLUSIONS: Increased plasma adenosine in peri-menopausal women may be associated with frequent hot flushes.

Adenosine↗
PubMed2005

Axenic cultivation of Entamoeba dispar in newly designed yeast extract-iron-gluconic acid-dihydroxyacetone-serum medium.

Yeast extract-iron-gluconic acid-dihydroxyacetone-serum medium that allows axenic cultivation of Entamoeba dispar was designed based on casein-free yeast extract-iron-serum (YI-S) medium, and the usefulness of the medium was assessed. The main differences from YI-S medium are replacement of glucose by gluconic acid, addition of dihydroxyacetone and D-galacturonic acid monohydrate, and sterilization by filtration. This medium promoted the axenic growth of 5 strains of E. dispar (2 strains of nonhuman primate isolates and 3 strains of human isolates). In addition, to clarify the biological basis for the growth of E. dispar in this medium, analyses of relevant enzymes on the glycolytic pathway of the amoebae as well as of the protozoans that are the best culture supplement for amoebae are being performed.

Animals↗
PubMed2005

Therapeutic targets of misguided T cells in systemic lupus erythematosus.

It is widely accepted that T cells with defective function play a central role in the pathogenesis of systemic lupus erythematosus (SLE). The detailed molecular mechanism underlying the aberrant function of SLE T cells is now being revealed. The TCR zeta chain, transcription factor, elf-1, inflammation signal transducer NF-kB, and PKC theta have been identified as the responsible molecules. In contrast to the defective signal transduction molecules, surface structures such as adhesion molecules, and co-stimulators have been reported to increase in their expression and function. Glucocorticoids and immunosuppressive agents have greatly improved the outcome of acute diseases and 5-year survival rate. However, it is suggested that long-term survival and quality of life appears to be unsatisfactory. Although the medical management of SLE is not sufficient to warrant long-term survival of young patients, recent progress in anti-cytokine biologics therapy against rheumatoid arthritis (RA) has facilitated searching for the molecular targets of SLE. In this report, we briefly review the molecular basis of SLE pathogenesis, and discuss possible therapeutic targets in this disease, focusing particularly on signal transduction and adhesion molecules in T cells.

Animals↗
PubMed2005

[Manifestations mimicking relapsing polychondritis in a patient with microscopic polyangiitis].

Microscopic polyangiitis (MPA) is a systemic disorder characterized by inflammation of small vessels mainly affecting the kidneys and lungs. We describe a 72-year-old woman who developed multiple cartilage involvements as well as major manifestations of MPA. The left ear biopsy demonstrated cartilaginous inflammation and small vessel vasculitis. She also had conjunctivitis, hearing impairment, interstitial lung disease, glomerulonephritis with vasculitis and mononeuritis multiplex. Serological examinations revealed a positive antineutrophil cytoplasmic antibody (PR-3 ANCA). Cyclophosphamide and oral corticosteroid therapy was instituted and remission achieved. Due to lacks of nasal and bronchial involvements, as well as the evidence of auricular vasculitis, we concluded that her findings mimicking relapsing polychondritis developed as systemic manifestations of MPA.

Aged↗
PubMed2005

Prevalence of toxocariasis in northeastern Brazil based on serology using recombinant Toxocara canis antigen.

To evaluate the prevalence of toxocariasis in children in Jaboatão dos Guararapes, Pernambuco in northeastern Brazil, 215 serum samples were examined by an enzyme-linked immunosorbent assay (ELISA) using a recombinant Toxocara canis antigen. In the ELISA, 26 (12.1%) of 215 subjects were positive. In a dot-blot assay using 53 of 215 serum samples, the diagnostic results correlated with those obtained by the ELISA. Moreover, it has been confirmed that the recombinant T. canis antigen was highly specific for toxocariasis by ELISA using serum samples positive for antibody to Ascaris lumbricoides. Considering the specificity of the recombinant antigen to toxocariasis, the ELISA or dot-blot assay using the recombinant T. canis antigen is recommended in tropical and sub-tropical regions where various parasitic infections are commonly endemic.

Animals↗