Biomedical subjects

Toshi Nagata

Publications and source records attributed to Toshi Nagata.

23 records · Page 2Linked to original sources

PubMed2002

Endosomal/lysosomal targeting of a single helper T-cell epitope of an intracellular bacterium by DNA immunisation induces a specific T-cell subset and partial protective immunity in vivo.

We evaluated here the effect of the intracellular targeting of a helper T-cell (Th) epitope, literiolysin O 215-226 derived from Listeria monocytogenes, on induction of a specific Th by gene gun immunisation. Immunisation of C3H/He mice with pE215LAMP plasmid encoding the Th epitope fused with the endosomal/lysosomal targeting signal of lysosome-associated membrane protein (LAMP)-1 gave the epitope-specific proliferative responses of CD4(+) T lymphocytes. In addition, specific interferon-gamma production from the splenocytes was observed. Concomitantly, pE215LAMP-immunised mice showed moderate, but significant protective immunity against listerial challenge. These results suggest that the intracellular targeting of a Th epitope to endosomal/lysosomal compartments by DNA immunisation is useful for eliciting a specific Th subset in vivo.

Animals↗

PubMed2002

Curcumin prevents and ameliorates trinitrobenzene sulfonic acid-induced colitis in mice.

BACKGROUND & AIMS: Curcumin is known to have a variety of pharmacologic effects, including antitumor, anti-inflammatory, and anti-infectious activities. The pleiotropic effects of curcumin are attributable at least in part to inhibition of transcriptional factor nuclear factor kappaB (NF-kappaB). However, the effect of curcumin on intestinal inflammation has hitherto not been evaluated. The aim of this study was to determine whether treatment with curcumin prevents and ameliorates colonic inflammation in a mouse model of inflammatory bowel disease. METHODS: Mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis were treated with 0.5%, 2.0%, or 5.0% curcumin in the diet, and changes in body weight together with histologic scores were evaluated. Colonic T-cell subsets were characterized, and NF-kappaB in colonic mucosa was detected by immunohistochemistry. NF-kappaB activity in the colonic mucosa was evaluated using electrophoretic mobility shift assay. Cytokine messenger RNA expression in colonic tissue was assessed by semiquantitative reverse-transcription polymerase chain reaction. RESULTS: Treatment of mice with curcumin prevented and improved both wasting and histopathologic signs of TNBS-induced colonic inflammation. Consistent with these findings, CD4(+) T-cell infiltration and NF-kappaB activation in colonic mucosa were suppressed in the curcumin-treated group. Suppression of proinflammatory cytokine messenger RNA expression in colonic mucosa was also observed. CONCLUSIONS: This study has shown for the first time that treatment with curcumin can prevent and improve murine experimental colitis. This finding suggests that curcumin could be a potential therapeutic agent for the treatment of patients with inflammatory bowel disease.

Animals↗

PubMed2002

Induction of protective immunity to Listeria monocytogenes by immunization with plasmid DNA expressing a helper T-cell epitope that replaces the class II-associated invariant chain peptide of the invariant chain.

Listeria epitope-specific helper T (Th) cells were able to be primed and induced in vivo by immunization with a plasmid carrying an invariant chain (Ii) gene whose class II-associated invariant chain peptide (CLIP) region was replaced by a Listeria Th epitope. Immunization of C3H/He mice with an Ii-LLO 215-226 plasmid induced specific interferon-gamma- and interleukin 2-producing Th cells and conferred significant protective immunity against listerial infection.

Animals↗

PubMed1998

Structural Variation in Manganase Complexes: Synthesis and Characterization of Manganese Complexes from Carboxylate-containing Chelating Ligands.

Three manganese(II) complexes, [Mn(II)(2)L(1)(2)(H(2)O)(4)](ClO(4))(2).H(2)O (1, L(1)H = (bis(2-pyridylmethyl)amino)acetic acid), [Mn(II)(2)L(2)(2)(H(2)O)(2)](BPh(4))(2).2EtOH.2H(2)O (2, L(2)H = 3-(bis(2-pyridylmethyl)amino)propionic acid), {[Mn(II)(2)L(2)(2)(H(2)O)(MeCN)](BPh(4))(2).2MeCN}(infinity) (3), and a manganese(IV) complex [Mn(IV)(2)O(2)L(2)(2)](ClO(4))(2).4H(2)O (4) were synthesized and characterized by X-ray crystallography. The compound 1 was a dinuclear Mn(II)(2) complex which crystallized in the monoclinic crystal system, space group P2(1)/n, with Z = 4, a = 12.19(1) Å, b = 14.623(8) Å, c = 21.72(1) Å, beta = 96.29(6) degrees, V = 3849(4) Å(3). The complex cation had an approximate C(2) symmtery. The two manganeses were both seven-coordinate and doubly bridged by one oxygen atom of carboxylate groups in &mgr;(2),eta(1)-mode. The compound 2 was also a dinuclear Mn(II)(2) complex which crystallized in the monoclinic crystal system, space group P2(1)/n, with Z = 2, a = 16.760(2) Å, b = 9.643(2) Å, c = 23.533(2) Å, beta = 92.984(8) degrees, V = 3798.4(7) Å(3). The complex cation of 2 also had two seven-coordinate manganese ions, but unlike 1 the nonbridging carboxylate oxygens weakly coordinate to the manganese ions. The compound 3 crystallized in the orthorhombic crystal system, space group P2(1)2(1)2(1), with Z = 4, a = 27.888(3) Å, b = 29.054(2) Å, c = 9.428(2) Å, V = 7638(2) Å(3). The cationic portion of 3 consisted of infinite chains of Mn(II) (two Mn(II) ions per an asymmetric unit) bridged by carboxylates in bidentate syn/anti mode. The compound 4 was a dinuclear bis(&mgr;-oxo) Mn(IV)(2) complex which crystallized in the trigonal crystal system, space group R&thremacr;, with Z = 8, a = 23.962(4) Å, c = 17.190(3) Å, V = 8547(3) Å(3). All these structures are made up from a common fragment "L(n)()Mn" assembling in various topologies. Variable-temperature magnetic susceptibility measurements revealed that the Mn(II) ions in 1-3 were weakly antiferromagnetically coupled (J = -0.631(6), -0.655(5), and -0.20(1) cm(-)(1) for 1-3), and that the Mn(IV) ions in 4 were strongly antiferromagnetically coupled (J = -97.5(5) cm(-)(1)). The cyclic voltammogram of 4 showed two reduction waves with E(1/2) values of -0.52 and 0.28 V (vs ferrocene). These E(1/2) values are more negative by 0.1 V than those of the closely related complex [Mn(III)Mn(IV)O(2)L(1)(2)](ClO(4)).

Journal Article↗

PubMed1997

Polyoxoanion-Supported Organometallic Complexes: Carbonyls of Rhenium(I), Iridium(I), and Rhodium(I) That Are Soluble Analogs of Solid-Oxide-Supported M(CO)(n)()(+) and That Exhibit Novel M(CO)(n)()(+) Mobility.

The Dawson-type P(2)W(15)Nb(3)O(62)(9)(-) polyoxoanion-supported Re(CO)(3)(+) complex, [Re(CO)(3).P(2)W(15)Nb(3)O(62)](8)(-) (1), has been synthesized and characterized in two different counter-cation compositions. The [(n-C(4)H(9))(4)N](8)(8+) complex provides a highly soluble compound which exists as a single isomer in solution. The carbonyl stretching infrared frequencies suggest that the P(2)W(15)Nb(3)O(62)(9)(-) ligand serves as a strong electron donor to the Re(CO)(3)(+) fragment. The P(2)W(15)Nb(3)O(62)(9)(-) polyoxoanion-supported Ir(CO)(2)(+) complex [Ir(CO)(2).P(2)W(15)Nb(3)O(62)](8)(-) (2) has also been synthesized and characterized as its octakis(tetrabutylammonium), [(n-C(4)H(9))(4)N](8)(8+), salt. This compound was characterized by NMR and IR, results which demonstrate that 2 also exists as a single isomer in solution. The [Ir(CO)(2).P(2)W(15)Nb(3)O(62)](8)(-) complex is stable in the absence of water, but decomposes quickly in the presence of even 1 equiv of water. Attempted preparation of the analogous P(2)W(15)Nb(3)O(62)(9)(-) -supported Rh(CO)(2)(+) complex (3), while monitoring by (31)P NMR, revealed that this compound is unstable in solution at room temperature. In addition, we have discovered that added Na(+) can induce the formation of non-C(3)(v)() symmetry isomers of supported Re(CO)(3)(+) and Ir(CO)(2)(+) and, by inference, supported Ir(1,5-COD)(+). When Na(+) is removed from these systems by addition of Kryptofix[2.2.2], the non-C(3)(v)() isomers convert back to the single, C(3)(v)() isomer with heating, thereby providing a model system for the little studied mobility of M(CO)(n)()(+) cations across a soluble-oxide surface. When [Rh(CO)(2).P(2)W(15)Nb(3)O(62)](8)(-) is irradiated in the presence of hydrogen and cyclohexene a novel polyoxoanion-stabilized Rh(0)(n)() nanocluster is formed, results that bear a strong analogy to Yates' work studying atomically-dispersed Rh(CO)(2)(+) on solid Al(2)O(3).(10e) Yates and co-workers observe that Rh(CO)(+).Al(2)O(3) loses a CO upon photolysis, and that the resultant Rh(CO)(1)(+).Al(2)O(3) is reduced under H(2) to form Rh(0), which in turn yields Rh(0)(n)() clusters on Al(2)O(3)-a process that, intriguingly, is largely reversible if CO is readded. Also briefly discussed is other relevant literature of solid-oxide-supported Re(CO)(3)(+) and M(CO)(2)(+) (M = Ir, Rh), literature that makes apparent the potential significance of these complexes as EXAFS and other spectroscopic models of solid-oxide-supported M(CO)(n)()(+).

Journal Article↗