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T Koda

Publications and source records attributed to T Koda.

At least 19 recordsLinked to original sources
PubMed2005

Estrogenic activity of 37 components of commercial sunscreen lotions evaluated by in vitro assays.

Thirty-seven chemical components of commercial sunscreen lotions were evaluated for estrogen agonistic and/or antagonistic activity using two in vitro assays, (1) an ELISA-based estrogen receptor competitive binding assay (ER-ELISA) and (2) a modified yeast two-hybrid estrogen assay, with and without addition of a rat liver preparation, S9 mix. Eleven compounds, most of which were benzophenone derivatives and parabens, showed binding affinity to ER by ER-ELISA without S9 mix. Although the activities of almost all of the compounds were attenuated by addition of S9 mix, 4-octylphenylsalicylate and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone acquired estrogenic activity, suggesting metabolic activation of these compounds. Two benzophenones showed agonistic activity in the yeast two-hybrid assay without S9 mix. The activity of one of these was reduced by S9 treatment and a further two benzophenones was activated. Eight parabens were active in this assay without S9 exposure, but their activities were eliminated by S9 treatment. Benzophenones with para-phenolic hydroxyl groups and parabens with branched and/or longer linear chains were generally more potent in both bioassays. In addition, weak antagonistic activity of 4-t-butylphenyl-salicylate, 2-ethylhexyl 4-dimethylaminobenzoate and (+/-)-alpha-tocopherolacetate was observed with S9 treatment. In vivo testing of the compounds reported here to have estrogen agonistic and antagonistic activities is required to confirm their effects at an organismal level.

Animals↗
PubMed2004

Monitoring of the generation of non-mutagenic benzoic acid compounds during the manufacture of erythrosine.

The generation of 2-(2',4'-dihydroxybenzoyl) benzoic acid (DHBBA) and 2-(2',4'-dihydroxy-3',5'-diiodobenzoyl) benzoic acid (DHDIBBA) during the manufacture of erythrosine (Food Red No. 3) was examined. DHBBA is formed as an intermediate during the synthesis of fluorescein, and as fluorescein is produced, it is gradually consumed. However, under inappropriate reaction conditions, it remains in the resulting fluorescein at the termination of synthesis. DHDIBBA is easily obtained by the iodination of DHBBA. These compounds are also found when erythrosine is heated in excessive alkali. The results of the Ames test using DHBBA and DHDIBBA showed they did not possess mutagenic activity. The results clearly demonstrated that establishment of an upper limit for DHBBA and DHDIBBA is important in the quality control of fluorescein and erythrosine.

Benzoic Acid↗
PubMed2003

A thirteen-week oral toxicity study of annatto extract (norbixin), a natural food color extracted from the seed coat of annatto (Bixa orellana L.), in Sprague-Dawley rats.

A subchronic oral toxicity study of annatto extract (norbixin), a natural food color, was conducted. Groups of 10 male and 10 female Sprague-Dawley rats were fed annatto extract at dietary levels of 0, 0.1, 0.3 and 0.9% for 13 weeks. There were no treatment-related adverse effects on body weight, food and water consumption, ophthalmology and hematology data. Blood biochemical analysis revealed changes in rats of both sexes confined to the 0.9% and 0.3% groups, including increased alkaline phosphatase, phospholipid, total protein, albumin and albumin/globulin ratio. Marked elevation in absolute and relative liver weights was also found in both sexes of the 0.9% and 0.3% groups, but not the 0.1% group. Hepatocyte hypertrophy was evident and an additional electron microscopic examination demonstrated this to be linked to abundant mitochondria after exposure to a dietary level of 0.9% annatto extract for 2 weeks. Thus, the No-Observed-Adverse-Effect-Level (NOAEL) was judged to be a dietary level of 0.1% (69 mg/kg body weight/day for males, 76 mg/kg body weight/day for females) of annatto extract (norbixin) under the present experimental conditions.

Administration, Oral↗
PubMed2001

Identification of rabaptin-5, rabex-5, and GM130 as putative effectors of rab33b, a regulator of retrograde traffic between the Golgi apparatus and ER.

The role of rab33b, a Golgi-specific rab protein, was investigated. Microinjection of rab33b mutants stabilised in the GTP-specific state resulted in a marked inhibition of anterograde transport within the Golgi and in the recycling of glycosyltransferases from the Golgi to the ER, respectively. A GST-rab33b fusion protein stabilised in its GTP form was found to interact by Western blotting or mass spectroscopy with Golgi protein GM130 and rabaptin-5 and rabex-5, two rab effector molecules thought to function exclusively in the endocytic pathway. A similar binding was seen to rab1 but not to rab6, both Golgi rabs. In contrast, rab5 was as expected, shown to bind rabaptin-5 and rabex-5 as well as the endosomal effector protein EEA1 but not GM130. No binding of EEA1 was seen to any of the Golgi rabs.

Animals↗
PubMed2001

Th1 cytokine-conditioned bone marrow-derived dendritic cells can bypass the requirement for Th functions during the generation of CD8+ CTL.

Bone marrow-derived dendritic cell (BMDC) subsets have distinct immunoregulatory functions. Th1 cytokine-induced BMDC (BMDC1), compared with Th2 cytokine-induced BMDC2, have superior activities for the differentiation and expansion of CTL. To evaluate the cellular interactions between dendritic cells and CD8+ T cells for the induction of CTL, BALB/c-derived BMDC subsets were cocultured with purified CD8+ T cells from C57BL/6 mice. Our results demonstrate that BMDC1 support the generation of allogeneic CD8+ CTL in the absence of CD4+ Th cells. In contrast, BMDC0 (GM-CSF- plus IL-3-induced BMDC) and BMDC2 failed to promote the differentiation of CD8+ CTL. Using Ab-blocking experiments and studies with gene knockout mice, IL-2 and LFA-1 are demonstrated to be critical for BMDC1-induced CTL differentiation. Unexpectedly, BMDC1 were able to induce CTL from CD8+ T cells isolated from IFN-gamma-/- and IFN-gamma receptor-/- mice. However, BMDC1 produced higher levels of IFN-beta than other BMDC subsets, and anti-IFN-beta mAb blocked BMDC1-dependent CTL generation. These results indicated an indispensable role of IFN-beta, but not IFN-gamma, during BMDC1-induced CTL differentiation. We conclude that Th1-cytokine-conditioned BMDC1 can bypass Th cell function for the differentiation of naive CD8+ T cells into CTL.

Animals↗
PubMed2001

Pronounced inhibition by a natural anthocyanin, purple corn color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in male F344 rats pretreated with 1,2-dimethylhydrazine.

The potential of purple corn color (PCC), a natural anthocyanin, to modify colorectal carcinogenesis was investigated in male F344/DuCrj rats, initially treated with 1,2-dimethylhydrazine (DMH), receiving 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the diet. After DMH initiation, PCC was given at a dietary level of 5.0% in combination with 0.02% PhIP until week 36. No PCC-treatment-related changes in clinical signs, body weight and food consumption were found. Incidences and multiplicities of colorectal adenomas and carcinomas in rats initiated with DMH were clearly increased by PhIP. In contrast, lesion development was suppressed by PCC administration. Furthermore, in the non-DMH initiation groups, induction of aberrant crypt foci by PhIP tended to be decreased by the PCC supplementation. The results thus demonstrate that while PhIP clearly exerts promoting effects on DMH-induced colorectal carcinogenesis, these can be reduced by 5.0% PCC in the diet, under the present experimental conditions.

1,2-Dimethylhydrazine↗
PubMed2001

Cloning, chromosomal mapping, and characteristic 5'-UTR sequence of murine cytosolic sialidase.

We have totally sequenced a cytosolic sialidase [EC 3.2.1.18] by RT-PCR from the murine thymus (murine thymic sialidase, MTS) which has a 1844-base length (encoding 385 amino acids including two sialidase motifs) and is the longest cytosolic sialidase ever reported. MTS has high and relatively low homologies with those of mammalian cytosolic sialidases from the mouse brain (99%), rat (91%), and human skeletal muscle (75%), and those of the mouse lysosomal (47%) and membrane-bound (51%) sialidases, respectively. Chromosomal mapping, being the first report of mouse cytosolic sialidase gene, showed that the MTS gene is localized to the distal part of mouse chromosome 1D and to rat chromosome 9q36. RT-PCR with the site-specific primers revealed that the coding region was expressed in all organs tested, but expressions including the 5'-UTR were barely detectable except for in the upper-thymic fraction. Also, soluble sialidase activity in the thymus was the highest of these organs. There were mRNA instability signals and AT-rich regions in 143 bp of MTS 5'-end.

5' Untranslated Regions↗
PubMed2001

A critical role for mouse CXC chemokine(s) in pulmonary neutrophilia during Th type 1-dependent airway inflammation.

Ag-specific Th1 and Th2 cells have been demonstrated to play a critical role in the induction of allergic diseases. Here we have investigated the precise mechanisms of Th1-induced airway inflammation. Airway inflammation was induced in BALB/c mice by transfer of freshly induced OVA-specific Th1 or Th2 cells followed by OVA inhalation. In this model, both Th1 and Th2 cells induced airway inflammation. The former induced neutrophilia in airways, whereas the latter induced eosinophilia. Moreover, we found that Th1 cells induced more severe airway hyperresponsiveness (AHR) than Th2 cells. The eosinophilia induced by Th2 cell infusion was almost completely blocked by administration of anti-IL-5 mAb, but not anti-IL-4 mAb. In contrast, Th1-induced AHR and pulmonary neutrophilia were inhibited by the administration of anti-human IL-8R Ab, which blocks the function of mouse CXC chemokine(s). These findings reveal a critical role of mouse CXC chemokine(s) in Th1-dependent pulmonary neutrophilia and AHR.

Administration, Inhalation↗
PubMed2001

Preliminary study of fortnightly irinotecan hydrochloride plus cisplatin therapy in patients with advanced gastric and colorectal cancer.

PURPOSE: Irinotecan hydrochloride shows a strong activity against gastric cancer and colorectal cancer, while combined therapy with irinotecan and cisplatin is useful for gastric cancer. However, myelosuppression and diarrhea are still dose-limiting factors. To reduce such toxicities to enable therapy to be performed on an outpatient basis, we tested the effect of divided administration of cisplatin. METHODS: Irinotecan (60 mg/m2) plus cisplatin (30 mg/m2) were administered on days 1 and 15 every 4 weeks to 13 patients with advanced gastric cancer and 13 with advanced colorectal cancer. Treatment was continued if a leukocyte count > or = 3000/mm3, a platelet count > or = 100,000/mm3, and grade 0 diarrhea were confirmed. Doses were reduced if grade 3-4 hematological toxicity and grade 2 or higher nonhematological toxicity occurred. RESULTS: The major toxicity was leukopenia (neutropenia), but grade 3-4 nonhematological toxicity was not observed. The response rate was 41.7% for gastric cancer (5/12 evaluable patients) and 36.7% for colorectal cancer (4/11 evaluable patients). The median survival time was 313 days (range 29-920 days) for gastric cancer patients and 490 days (range 83-1184 + days) for colorectal cancer patients. CONCLUSION: Fortnightly administration of irinotecan and cisplatin (with a divided cisplatin dose) seems to be a useful regimen for gastrointestinal cancer. It reduces toxicity while maintaining a good antitumor effect.

Adult↗
PubMed2001

Antidepressant drug treatments induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells.

Modulation of neurotrophic factors to protect neurons from damage is proposed as a novel mechanism for the action of antidepressants. However, the effect of antidepressants on modulation of glial cell line-derived neurotrophic factor (GDNF), which has potent and widespread effects, remains unknown. Here, we demonstrated that long-term use of antidepressant treatment significantly increased GDNF mRNA expression and GDNF release in time- and concentration-dependent manners in rat C6 glioblastoma cells. Amitriptyline treatment also increased GDNF mRNA expression in rat astrocytes. GDNF release continued for 24 h following withdrawal of amitriptyline. Furthermore, following treatment with antidepressants belonging to several different classes (amitriptyline, clomipramine, mianserin, fluoxetine and paroxetine) significantly increased GDNF release, but which did not occur after treatment with non-antidepressant psychotropic drugs (haloperidol, diazepam and diphenhydramine). Amitriptyline-induced GDNF release was inhibited by U0126 (10 microM), a mitogen-activated protein kinase (MAPK)-extracellular signal-related kinase (ERK) kinase (MEK) inhibitor, but was not inhibited by H-89 (1 microM), a protein kinase A inhibitor, calphostin C (100 nM), a protein kinase C inhibitor and PD 169316 (10 microM), a p38 mitogen-activated protein kinase inhibitor. These results suggested that amitriptyline-induced GDNF synthesis and release occurred at the transcriptional level, and may be regulated by MEK/MAPK signalling. The enhanced and prolonged induction of GDNF by antidepressants could promote neuronal survival, and protect neurons from the damaging effects of stress. This may contribute to explain therapeutic action of antidepressants and suggest new strategies of pharmacological intervention.

Amitriptyline↗
PubMed2001

Effect of fudosteine, a new cysteine derivative, on mucociliary transport.

We examined the effect of fudosteine ((-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid) on the mucociliary transport (MCT) rate in quails. The MCT rate was estimated by ash transport velocity on the tracheal mucosa of quails. Fudosteine (500 mg kg(-1), p.o.) did not affect the normal MCT rate. However, topical application of fudosteine to the tracheal mucosa dose-dependently protected the impairment of the MCT rate caused by exposure to cigarette smoke. The results suggest that fudosteine may participate in the defence mechanism in the respiratory tract against irritant gases.

Administration, Oral↗
PubMed2001

Analytical method for Buddleja colorants in foods.

Buddleja yellow colorant derived from Buddleja officinalis Maxim. has recently been approved for use as a new kind of natural colorant for food additives in China. In order to distinguish Buddleja yellow colorant from other yellow colorants, two known phenylpropanoid glycosides, acteoside (= verbascoside) and poliumoside, were isolated from the colorant as marker substances for Buddleja yellow colorant. Poliumoside has not been detected in B. officinalis Maxim. previously. These phenylpropanoid glycosides were not detected in the fruits of Gardenia jasminoides Ellis or in the stamens of the flowers of Crocus sativus L., which also contain crocetin derivatives as coloring components, using a photodiode array and mass chromatograms. Thus, an analytical HPLC method was developed to distinguish foods that have been colored with yellow colorants containing crocetin derivatives, using phenylpropanoid glycosides as markers.

Food Analysis↗
PubMed2000

Indispensable role for TNF-alpha and IFN-gamma at the effector phase of liver injury mediated by Th1 cells specific to hepatitis B virus surface antigen.

We report the development and characterization of a novel model of severe hepatitis induced against hepatitis B virus surface Ag (HBsAg). HBsAg was successfully targeted into the liver in soluble form. Using this unique property of HBsAg, we established a liver injury model induced by HBsAg-specific Th1 cells. Severe liver injury was induced in C57BL/6 mice by injection of HBsAg together with HBsAg-specific Th1 cells. Histochemical examination demonstrated extensive necroinflammatory hepatic lesions in these animals. Application of this liver injury model to mutant or gene knockout mice enabled us to define the effector mechanisms of Th1 cells in fulminant hepatitis. When Fas-deficient lpr mice were used as recipients, a similar degree of liver injury was induced as in wild-type mice. Moreover, HBsAg-specific Th1 cells obtained from perforin-/- mice could induce severe liver injury in both wild-type and lpr mice. These results indicated that neither Fas ligand nor perforin are essential for Th1-mediated liver injury in this model. Pretreatment with anti-TNF-alpha mAb prevented liver injury, whereas severe liver injury was induced in TNF-alpha-/- mice. Moreover, IFN-gamma receptor-deficient mice were resistant to Th1-mediated liver injury. Therefore, TNF-alpha and IFN-gamma, which were produced by HBsAg-specific Th1 cells during the effector phase, appeared to be indispensable in the pathogenesis of fulminant hepatitis.

Animals↗
PubMed2000

Interleukin-4-dependent induction of preproenkephalin in antigen-specific T helper-type 2 (Th2) cells.

Naive Th cells obtained from OVA(323-339)-specific DO11.10 TCR-Tg mice did not express preproenkephalin (PPE) mRNA. However, culture of naive Th cells with OVA(323-339) peptide (OVA-pep) plus IL-2 under Th2-inducing conditions for 7 days resulted in an induction of PPE mRNA. The PPE mRNA was also induced by culturing with OVA-pep plus IL-2 (neutral condition). However, PPE mRNA induction under neutral conditions was totally abrogated by addition of anti-IL-4 mAb. The existence of methionine-enkephalin was also demonstrated in peptidase-digested peptides derived from Th2 cell lysate. These results demonstrate that IL-4 is a critical factor for the induction of PPE mRNA in freshly expanded antigen-specific Th2 cells.

Animals↗
PubMed2000

alpha-galactosylceramide induces early B-cell activation through IL-4 production by NKT cells.

alpha-Galactosylceramide (alpha-GalCer), a glycolipid antigen, specifically activates natural killer T (NKT) cells by a CD1d-restricted mechanism. In this work, we found that in vivo administration of alpha-GalCer resulted in the activation of B cells in addition to NKT cells, namely, alpha-GalCer administration caused upregulation of the early activation marker, CD69, on both NKT and B cells. In addition, expression of B7.2 and I-A(b) on B cells was greatly upregulated by alpha-GalCer. However, serum levels of IgE, IgG1, and IgG2a were not significantly changed within 48 h. In the present experiments, it was also demonstrated that the upregulation of CD69 expression by alpha-GalCer was strongly blocked by anti-IL-4 monoclonal antibody. Moreover, B-cell activation by alpha-GalCer was not observed in NKT-deficient mice. These results suggested that antigen-stimulated NKT cells might play a critical role not only in early defense mechanisms but also in early B-cell activation through IL-4 production.

Animals↗
PubMed2000

The critical role of Th1-dominant immunity in tumor immunology.

To investigate the precise role of antigen-specific Th1 and Th2 cells in tumor immunity, we developed a novel adoptive tumor-immunotherapy model using OVA-specific Th1 and Th2 cells and an OVA gene-transfected tumor. This therapeutic model demonstrated that both antigen-specific Th1 and Th2 cells had strong antitumor activity in vivo with distinct mechanisms. However, immunological memory suitable for the generation of tumor-specific cytotoxic T lymphocytes was induced only when tumor-bearing mice received Th1 cell therapy, but not Th2 cell therapy. Thus it was strongly suggested that Th1-dominant immunity is critically important for the induction of antitumor cellular immunity in vivo. We also proposed that several immunomodulating protocols using interleukin (IL)-12, IL-12 gene, the natural killer T cell ligand alpha-galactosylceramide, or Th1 cytokine-conditioned dendritic cells might be useful strategies for the induction of Th1-dominant immunity essential for the development of tumor-specific immunotherapy.

Animals↗
PubMed2000

Potentiation of antitumor effect of NKT cell ligand, alpha-galactosylceramide by combination with IL-12 on lung metastasis of malignant melanoma cells.

The combined therapeutic effect of natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer) and IL-12 against highly metastatic B16-BL6-HM melanoma cells was investigated. In comparison with a single administration of alpha-GalCer or IL-12, the combined treatment of tumor-bearing mice with alpha-GalCer plus IL-12 caused a super-induction of serum IFN-gamma levels, though alpha-GalCer-induced IL-4 production was rather inhibited. In parallel with the augmented IFN-gamma production, the natural killing activity against YAC-1 cells and syngeneic B16-BL6-HM melanoma was greatly augmented by the combined therapy. The major effector cells responsible for natural killing activity induced by alpha-GalCer plus IL-12 were enriched in both NK1.1+ TCRalphabeta+ NKT cells and NK1.1+ TCRalphabeta- NK cells. The preventing effect of alpha-GalCer or IL-12 alone against lung metastasis of B16-BL6-HM was also enhanced by the combination therapy. The antitumor activity of alpha-GalCer was totally abolished in NKT-deficient mice. However, IL-12-induced antitumor activity was not eliminated in NKT-deficient mice though it was inhibited by anti-asialo GM1 Ab treatment. These findings suggested that alpha-GalCer synergistically act with IL-12 to activate both NKT cells and NK cells, which may play a critical role in the strong prevention of distant tumor metastasis at early stages of tumor-bearing. These data will provide a novel tool for the prevention of tumor metastasis using NKT-specific ligands alpha-GalCer and IL-12.

Animals↗