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Colonization of Helicobacter pylori in the stomach leads to chronic gastritis with massive infiltration by Th1 cells. To assess a role played by those T cells in the remodeling of gastric epithelium, we activated gastric T cells utilizing mice with CD4 T cells bearing transgenic TCR with or without deficiency in either IL-4 or IFN-γ or IL-12. Mice developed gastritis upon injection of an antigen into gastric mucosa. While neutrophil infiltration occurred even with a control antigen, infiltration by transgenic T cells was dependent on the specific antigen. The numbers of epithelial cells undergoing apoptosis and regeneration were increased in the mice with infiltrating T cells producing IFN-γ and the alignment of those cells in the glands was markedly dysregulated. In contrast, mice deficient in Th1 response showed no increase in cell division and apoptosis of epithelial cells. Thus, Th1 type T cells infiltrating into gastric mucosa play an independent role in controlling turnover of epithelial cells.

This paper proposes to apply machine learning techniques to the task of combining outputs of multiple LVCSR models. The proposed technique has advantages over that by voting schemes such as ROVER, especially when the majority of participating models are not reliable. In this machine learning framework, as features of machine learning, information such as the model IDs which output the hypothesized word are useful for improving the word recognition rate. Experimental results show that the combination results achieve a relative word error reduction of up to 39% against the best performing single model and that of up to 23% against ROVER. We further empirically show that it performs better when LVCSR models to be combined are chosen so as to cover as many correctly recognized words as possible, rather than choosing models in descending order of their word correct rates.

Administration of an antigen (Ag) per oral route leads to apoptosis of Ag-specific CD4(+) T cells and to development of Th2 cells expressing Fas ligand (FasL) in the liver. We determined whether presentation of an ingested Ag in the liver alone was enough to select these FasL(+)Th2 cells and explored how this selection was achieved in the liver. Ovalbumin (OVA) administered orally was colocalized with class II(+) cells in the periportal and parenchymal area of the liver. On coculture with naive OVA-specific CD4(+) T cells, hepatic CD11c(+) cells from mice fed OVA generated Ag-specific Th2 cells. This was achieved by apoptosis of CD4(+) T cells, decrease of interleukin 12 (IL-12) secretion, and increase of IL-18 secretion by the CD11c(+) cells. Addition of IL-12 to this coculture prevented apoptosis of the CD4(+) T cells, which was associated with up-modulation of IL-2 receptor beta chain expression. Administration of IL-12 to mice fed OVA prevented apoptosis of OVA-specific CD4(+) T cells in the liver. Moreover, adoptive transfer of hepatic CD11c(+) cells from mice fed OVA together with OVA-specific CD4(+) T cells led to development of Th2 cells as well as apoptosis of the transferred CD4(+) T cells in the lymph nodes of the recipient mice on immunization with OVA. In conclusion, presentation of an ingested Ag by hepatic CD11c(+) cells selects Th2 cells resistant to apoptosis in the liver, which is mediated in part by down-regulation of IL-12 secretion by the former cells.

Background: Although T-cell responses to food antigens are normally inhibited either by deletion, active suppression, or both of antigen-specific T cells, T helper cells for IgE response to a food antigen still develop by unknown mechanisms in a genetically susceptible host. Objective: We determined the site at which those IgE helper T cells develop. Methods: We administered ovalbumin (OVA) orally to DO11.10 mice and studied CD4 + T cells in Peyer's patches, the spleen, and the liver. Helper activity for IgE response was assessed by adoptively transferring those CD4 + T cells to naive BALB/c mice, followed by systemic immunization with OVA. Results: OVA-specific CD4 + T cells were deleted by cell death in the liver and Peyer's patches of DO11.10 mice fed OVA. OVA-specific CD4 + T cells that survived apoptosis in the liver expressed Fas ligand and secreted IL-4, IL-10, and transforming growth factor β 1 . CD4 + T cells producing IFN-γ were deleted in the liver by repeated feeding of OVA. On transfer of CD4 + T cells to naive mice and systemic immunization with OVA, a marked increase in OVA-specific IgE response developed only in the mice that received hepatic CD4 + T cells from OVA-fed mice, the effect of which was not observed in the recipients of hepatic CD4 + T cells deficient in IL-4. In addition, significant suppression of delayed-type hypersensitivity and IgG 1 /IgG 2a responses to OVA was observed in the recipients of hepatic CD4 + T cells, and this suppression required Fas/Fas ligand interaction. Conclusion: Together, these results suggested that a food antigen might negatively select helper T cells for IgE response to the antigen by preferential deletion of T H 1 cells in the liver. (J Allergy Clin Immunol 2003;111:1375-85.)

Background & Aims: Clonal expansion of T cells is associated with inflammatory bowel diseases, which indicates antigenic activation of the T cells. We investigated whether the introduction of CD4 T cells specific to a microflora would initiate colitis and assessed the cytokine requirements for colitogenic CD4 T cells. Methods: Severe combined immunodeficiency disease (SCID) mice were reconstituted with CD4 T cells, which were either deficient in interleukin (IL)-4/interferon (IFN)-γ production or differentiated in vitro to T-helper (Th) 1/Th 2 and bearing a transgenic T-cell receptor (TCR) specific to ovalbumin (OVA), and then inoculated with an Escherichia coli –producing OVA (ECOVA). Clinical and histologic manifestations of colitis were assessed. Results: Mice with ECOVA colonization and OVA-specific CD4 T cells developed colitis with histologic features of focal infiltration by mononuclear cells, destruction of crypts, and loss of goblet cells. Further, infiltration was initiated in pre-existing lymph follicles. Th1- and IL-4 deficient T cells were diffusely localized in the lamina propria and submucosa, whereas Th2- and IFN-γ–deficient T cells were localized preferentially in lymph follicles. Conclusions: A microbe-associated antigen, non–cross-reactive to colonic tissue, can drive antigen-specific CD4 T cells to cause colitis in SCID mice. Although the presence of IFN-γ and IL-4 in the effector CD4 T cells was not an absolute requirement for the development of colitis, they seemed to regulate it in part by modulating migration of the effector T cells. GASTROENTEROLOGY 2002;123:1949-1961

In conclusion, we have developed a 1/spl times/8 star coupler waveguide device with mechanically transferable (MT)-compatible connections, which is easy to fabricate because the assembling process automatically involves adjusting the position of waveguides. In addition to this convenience, the device has low connection losses and good reliability. The device structure is favorable to mass production and can be applied to various waveguide circuits with low cost.

We have successfully developed multifibre push on (MPO)-receptacle waveguide device realizing ultimately easy push-on/pull-off fiber attachment to single mode waveguides without index matching. Connection loss is 0.31 dB on the average and direct core-to-core contact has been achieved.

Pressure equipment in refinery and petrochemical industries in Japan has been getting old, mostly more than 30 years in operation. Accordingly, there are many fitness for service evaluations required for pressure equipment. However, Japanese regulation still requires as the same quality level as the original fabrication for pressure equipment in service. In order to introduce the latest FFS methodologies to Japanese industries, a special task group was established at the High Pressure Institute of Japan and started study of API RP579 from its drafting stage as a member of TG579. And then, FFS handbook for refinery and petrochemical industries has been developed based on API RP579 with several modifications to meet Japanese pressure vessel regulations on April 2001. It is expected that FFS handbook will be introduced as an exemplified standard with Japanese regulations for practical maintenance.Copyright © 2002 by ASME

Although some animal models suggest an involvement of CD4 T cells reactive to luminal microbial antigen(s) for the pathogenesis of inflammatory bowel diseases (IBD), direct linkage between microflora-driven clonal expansion of CD4 T cells and the development of colitis has not been well studied. Here, BALB/c and SCID mice were given CD4 T cells purified from Rag-2(-/-) mice crossed to transgenic mice expressing TCR specific to ovalbumin (OVA) then administered with antibiotic-resistant Escherichia coli producing OVA (ECOVA) or LacZ (ECLacZ) via the rectum. The ECOVA-inoculated BALB/c and SCID mice developed a subacute colitis with microscopic features of distortion of crypt architecture, loss of goblet cells, and focal infiltration by mononuclear cells in the lamina propria (LP) and submucosa. Expanding OVA-specific CD4 T cells were detected in colonic follicles of mice with ECOVA. Early in colitis, OVA-specific CD4 T cells producing IFN-gamma predominate in the LP of the colon, which was followed by an emergence of OVA-specific CD4 T cells producing IL-4 and IL-10 at a later time point. Co-transfer of an IL-10-secreting OVA-specific CD4 T cell line prevented colitis. Thus, an expansion of CD4 T cells monospecific to OVA, an antigen non-cross-reactive to colonic tissue, can mediate both induction and inhibition of the colitis which was associated with hyperplasia of lymph follicles.

The Long-Evans Cinnamon (LEC) rats, due to a genetic defect, accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease and spontaneously develop acute hepatitis with severe jaundice. In this study we examined the protective effect of DL-alpha-Lipoic acid (LA) against acute hepatitis in LEC rats. LA was administered to LEC rats by gavage in doses of 10, 30 and 100 mg/kg five times per week, starting at 8-weeks-old and continuing till 12-weeks-old. Although LA had little effect against the increases in serum transaminase activities, it suppressed the loss of body weight and prevented severe jaundice in a dose-dependent manner. Antioxidant system analyses in liver showed that LA treatment significantly suppressed the inactivations of catalase and glutathione peroxidase, and the induction of heme oxygenase-1, an enzyme which is inducible under oxidative stress. Furthermore, LA showed dose-dependent suppressive effect against increase in nonheme iron contents of both cytosolic and crude mitochondrial fractions in a dose-dependent manner. Although at the highest dose, LA slightly suppressed the accumulation of Cu in crude mitochondrial fraction, it had no effect on the accumulation of Cu in cytosolic fraction. While LA completely suppressed the increase in lipid peroxidation (LPO) in the microsomal fraction at the highest dose, the suppressive effect against LPO in crude mitochondrial fractions was slight. From these results, it is concluded that LA has antioxidant effects at the molecular level against the development of Cu-induced hepatitis in LEC rats. Moreover, mitochondrial oxidative damage might be involved in the development of acute hepatitis in LEC rats.

The Long-Evans Cinnamon (LEC) rats accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease (WD) and spontaneously develop acute hepatitis with severe jaundice. Although hydroxyl radicals (*OH) have been proposed to be a cause of hepatitis by the accumulation of Cu, it is not clear whether or not *OH can be produced in the liver of hepatitic LEC rats in vivo and also can be involved in the onset of hepatitis. In the present study, *OH production in plasma and liver of hepatitic LEC rats was quantified by trapping *OH with salicylic acid (SA) as 2, 3-dihydroxybenzoic acid (2, 3-DHBA). The ratios of 2, 3-DHBA/SA were significantly higher in plasma and liver of hepatitic LEC rats than those of Wistar rats and LEC rats showing no signs of hepatitis. Furthermore, the ratios of 2, 3-DHBA/SA in plasma and liver of hepatitic LEC rats were almost the same as those of Wistar rats treated orally with CuSO(4) (0.5 mmol/kg) 2 h before acetylsalicylic acid (ASA) injection. We also evaluated the protective effects of D-mannitol (a *OH scavenger) treatment against acute hepatitis in LEC rats. D-mannitol (500 mg/kg) was administered intraperitoneally to 10-week-old LEC rats for 3 weeks. D-mannitol treatment suppressed the increases in serum aspartate aminotransferase activity and total bilirubin concentration. In addition, D-mannitol treatment significantly reduced hepatic mitochondrial lipid peroxidation, which is thought to be important in the pathogenesis of Cu-induced hepatotoxicity. These observations suggest that accelerated generation of *OH catalyzed by free Cu in the liver may, at least in part, play a role in the pathogenesis of acute hepatitis in LEC rats.

A patient with massive rectal bleeding due to ileal tuberculosis is reported. Technetium-99m labelled red blood cell scintigraphy indicated hemorrhage from the ileum, and laparotomy was then carried out. A 70-cm segment of ileum containing ulcers and erosions was resected, and epitheloid granuloma with Langhans-type giant cell was found in the resected specimen. Massive rectal bleeding is considered a rare presenting symptom of intestinal tuberculosis. Intestinal tuberculosis, including small intestinal tuberculosis, although uncommon, should be taken into consideration as a cause of rectal bleeding.

Publisher Summary A 48-amino-acid peptide, named “ω-agatoxin-TK” (ω-Aga-TK), has been isolated that has been found to be a potent blocker of the P-type calcium channels in rat cerebellar Purkinje neurons. The peptide has a unique structural profile, including a high density disulfide core structure with four disulfide bonds and a d -form amino acid, d -Ser. Interestingly, ω-Aga-TK contains two serine residues of which only Ser 46 is in the d -form (ω-[ d -Ser 46 ]Aga-TK). It has very low solubility under neutral conditions, which precluded detailed studies of its tertiary structure by nuclear magnetic resonance (NMR) spectroscopy. In the chapter, the structure–function relationship studies of ω-[ d -Ser 46 ]Aga-TK describes that ω-[ l -Ser 46 ]Aga-TK has 80- to 90-fold less potency toward the P-type calcium channels compared with ω-[ d -Ser 46 ] Aga-TK. Two proteolytic fragments of ω-[ d -Ser 46 ]Aga-TK—namely, ω-Aga-TK and a carboxyl-terminal peptide fragment, ω-Aga-TK, do not exert any significant inhibition of P-type calcium channels or interfere with the blockade of the channels elicited by native ω-Aga-TK. Furthermore, molecular dynamics calculations have shown that the carboxyl-terminal sixamino-acid peptide of ω-Aga-TK containing d -Ser 46 assumes a different conformation from that containing l -Ser 46 . These data suggests that the specific conformation of the carboxyl-terminal tail generated by the d -Ser 46 residue, together with the triple-stranded antiparallel β-sheet, might be essential for the blockade of the P-type calcium channels. In this study, the conformations of ω-[ d -Ser 46 ]Aga-TK and ω-[ l -Ser 46 ]Aga-TK are investigated by the combination of size-exclusion chromatography, circular dichroism (CD) measurement, and fluorescence spectroscopy to elucidate the structural and functional effects of the configuration of the Ser 46 residue in ω-Aga-TK. It has been found that ω-[ d -Ser 46 ]Aga-TK has a particularly compact molecular shape involving β-sheet structure, whereas ω-[ l -Ser 46 ]Aga-TK has a relatively unfolded or extended structure at physiological pH and ionic strength. These data are discussed in terms of the possible role of the configuration of the Ser 46 residue in determining the molecular conformation of ω-Aga-TK.

A novel peptide isomerase was purified from the venom of funnel web spider, Agelenopsis aperta. The complete primary structure of the isomerase has been established by sequence analyses of polypeptide chains, assignments of disulfide bridges, carbohydrate analyses, and mass spectrometry of sugar chains. The isomerase was found to be a 29-kDa polypeptide that consists of an 18-residue light chain and a 243-residue heavy chain connected by a single disulfide bridge. The heavy chain contains three intramolecular disulfide bridges and one N-linked oligosaccharide chain with a simple trimannosyl core structure. A sequence homology search showed a significant similarity of the enzyme with serine proteases, particularly around a putative catalytic triad of the isomerase. The isomerase specifically interconverts the configuration of Ser46 of a 48-amino-acid peptide, omega-agatoxin-TK, and the conversion rate from L-Ser to D-Ser was approximately two times faster than the reverse reaction.

HES-3 is a cerebellar Purkinje cell-specific helix-loop-helix factor structurally related to the products of the Drosophila hairy and Enhancer of split genes. Here, we report the nucleotide sequence and chromosomal locus of the mouse Hes-3 gene. This gene consists of four exons and the exon-intron boundaries are well conserved when compared with those of the mouse Hes-1 and Drosophila hairy genes. Southern blot and interspecies backcross analyses show that the mouse Hes-3 gene is a single-copy gene and is located around position 80 on chromosome 4. Further analysis indicates that this locus is close to the Hes-5 locus, which is different from the Hes-1 locus (position 26 on chromosome 16). These results suggest that the Hes-3 and Hes-5 genes may be clustered on chromosome 4 while the Hes-1 gene is not.

The electron paramagnetic resonance signals attributed to the triplet state of the positive-hole pairs on oxide ions are observed in (100−x) Bi2O3·x Li2O glass (x = 25, 30, 35 mol%). So far as we know, this is the first experimental observation of the triplet oxygen hole center in oxide glasses.

Organic ferroelectric gate field-effect transistor (FET) memories have been fabricated using pentacene as the semiconductor and a poly(vinylidene fluoride–tetrafluoroethylene) [P(VDF–TeFE)] thin film as the ferroelectric gate. The P(VDF–TeFE) film is prepared by spin coating and annealing at 170 °C for 2.5 h, and pentacene is prepared by vacuum evaporation. The polarization–electric field (P–E) hysteresis of the P(VDF–TeFE) thin film is observed and enhanced by poling treatment. The obtained P r of 4 µC/cm2 is sufficient for controlling pentacene surface potential. Good memory characteristics are obtained in the P(VDF–TeFE) gate FET. For such a FET, the ON/OFF ratio of drain current is 830, the carrier mobility is 0.11 cm2 V-1 s-1, and the memory retention is over 16 h.

Background and Aims; Ahhough CD4+CD25+ T (Treg) cells suppress development of autoimmune disease in animals, little is known as to the mechanism by which Treg cells inhibit the responses of antigen (Ag)-speciflc pathogenic T cells in vivo Recently, we established an ani~nal model of colitis in an Ag-specific manner by inoculating E.coli expressing ovalbumin (Gastroenterology 2002;123:1949-61). In this paper, we investigate the mechanism how Treg cells control Ag-specific colitis by vasualizing the localization of cditogenic T cells Methods; Ovalbumin(OVA)-specific colitis was induced by adoptive transfer of CD4 + CD25T celIs (lxl06/mouse)purified from DO1110 (OVA-TCR-transgenic) mice into SCID mice t0llowed by oraI administration of E coli expressing OVA (ECOVA)or LacZ (ECLACZ) These SCID mice were treated with CD4 + CD25or CD4 + CD25 + T ceils (5x 105/mouse) puritied from BALB/e mice. Results; Adoptive transfer of OVA-specific CD4 + CD25T cells tbllowed by' oral administration of ECOVA, but not ECLACZ, developed coIitis in SCID mice. In these mice, massive monmmdear cell infihmtion and loss of goblet cells were obserced in the proximal colon, which was associated with diffuse localization ot OVA-specific (KJ 1-26 + ) T cells in the submucosa. In contrast, such intlamtnatory changes were hardly seen in the mice treated with Treg cells. Interestingly', KJb26+ T cells were pre~erentiaBy localized in colonic follicles in the mice treated with Treg cells. AlphaEbeta7(aEb7) expression was observed in colonic tollicles of the mice treated with Treg cells. ]:/ow-cytometric analysis revealed significant decrease of the percentage in CD4 + KJ1-26 + T ceils in colon lamnia pmpria lymphocy'tes. Moreover, aEb7 expression in CD4+KJ1-26+CD25T cells stimulated by" anti-CD3 in vitro was enhanced in the presence of Treg cells, whereas CD44 and CD69 expression was suppressed, Conclusion; Treg cells suppress development of Ag-specdic colitis by akering the localization of pathogenic Ag-specihc CD4 + "l cells which is achieved by aEb7 expression m the latter cells.

ヒドロキシラジカル(・OH)による芳香環の水酸化反応を利用するHPLC蛍光定量法を開発した.芳香族化合物としてはフェノールであるp-クマル酸,チラミン,オクトパミン及びシネフリンを用いた.それぞれの水酸化反応により生成するカテコールであるカフェー酸,ドーパミン,ノルエピネフリン及びエピネフリンをイオン交換カートリッジを用いて固相抽出した後,カテコール化合物に特異的な蛍光試薬メゾ-1,2-ジフェニルエチレンジアミンを用いて蛍光ラベルし,HPLC検出する.・OHの発生系としては主にFe2+/ジヒドロキシフマル酸系を用いた.内標準物質としてカフェー酸の定量には3,4-ジヒドロキシフェニル酢酸を用い,他のアミンの場合にはイソプロテレノールを用いた.生成したカテコール類の検出下限(S/N=3)は10～25fmolであった.いずれのフェノールを用いても・OHの定量が可能であった.

Sulfurifustis variabilis and Sulfuricaulis limicola are autotrophic sulfur-oxidizing bacteria belonging to the family Acidiferrobacteraceae in the order Acidiferrobacterales. The type strains of these species, strain skN76(T) and strain HA5(T), were isolated from lakes in Japan. Here we describe the complete genome sequences of Sulfurifustis variabilis skN76T and Sulfuricaulis limicola HA5T. The genome of Sulfurifustis variabilis skN76T consists of one circular chromosome with size of 4.0 Mbp including 3864 protein-coding sequences. The genome of Sulfuricaulis limicola HA5T is 2.9 Mbp chromosome with 2763 protein-coding sequences. In both genomes, 46 transfer RNA-coding genes and one ribosomal RNA operon were identified. In the genomes, redundancies of the genes involved in sulfur oxidation and inorganic carbon fixation pathways were observed. This is the first report to show the complete genome sequences of bacteria belonging to the order Acidiferrobacterales in the class Gammaproteobacteria.