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41.
42.
Allergic rhinitis is an inflammatory disease characterized by nasal wall remodeling with intense infiltration of eosinophils and mast cells/basophils. Matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are the major proteolytic enzymes that induce airway remodeling. These enzymes are also important in the migration of inflammatory cells through basement membrane components. We evaluated whether tranilast (TR) could inhibit MMP production from nasal fibroblasts in response to tumor necrosis factor-alpha (TNF-alpha) stimulation in vitro. Nasal fibroblasts (NF) were established from nasal polyp tissues taken from patients with allergic rhinitis. NF (2 x 10(5) cells/mL) were stimulated with TNF-alpha in the presence of various concentrations of TR. After 24 hours, the culture supernatants were obtained and assayed for MMP-2, MMP-9, TIMP-1, and TIMP-2 levels by ELISA. The influence of TR on mRNA expression of MMPs and TIMPs in cells cultured for 12 hours was also evaluated by RT-PCR. TR at more than 5 x 10(-5) M inhibited the production of MMP-2 and MMP-9 from NF in response to TNF-alpha stimulation, whereas TIMP-1 and TIMP-2 production was scarcely affected. TR also inhibited MMP mRNA expression in NF after TNF-alpha stimulation. The present data suggest that the attenuating effect of TR on MMP-2 and MMP-9 production from NF induced by inflammatory stimulation may underlie the therapeutic mode of action of the agent in patients with allergic diseases, including allergic rhinitis. 相似文献
43.
In social insects, caste-specific characters develop in the postembryonic differentiation processes. However, the mechanisms
of caste-specific organ development have yet to be elucidated. In order to obtain insights into the relationship between caste
differentiation and the regulation of organ development, we determined the caste-developmental pathway and observed compound-eye
development accompanying alate differentiation in the dry-wood termite, Neotermes koshunensis. As previously reported in other Neotermes, this species has a linear caste-developmental pathway, comprising six larval- and two nymphal-instar stages. Although the
apparent eye formation occurs during the last nymphal stages, just prior to the imaginal molt, individuals possess eye primordia
from the first larval-instar stage. The outer morphological structure of the eye was observed from the third larval-instar
stage. The detailed differentiation of cells constituting ommatidia appeared to occur in relatively young larval instars (fourth
stage), although the pigmentation of pigment cells and detailed structural formation of ommatidia occurred during the final
stage of alate development, i.e., during the late second nymphal-instar stage. This suggests that eye development is arrested
in the larval stages, and then resumed during the late nymphal stage to complete functional eye formation, which is required
for nuptial flight. In comparison to major hemimetabolous insects, which possess functional compound eyes even at the first
instar larva, this termite species shows the heterochronic shift in terms of compound-eye development.
Received 20 March 2006; revised 24 September 2006; accepted 4 October 2006. 相似文献
44.
Gram‐negative bacteria cause many types of infections in animals from fish and shrimps to humans. Bacteria use Type III secretion systems (TTSSs) to translocate their toxins directly into eukaryotic cells. The V‐antigen is a multifunctional protein required for the TTSS in Yersinia and Pseudomonas aeruginosa. V‐antigen vaccines and anti‐V‐antigen antisera confer protection against Yersinia or P. aeruginosa infections in animal models. The V‐antigen forms a pentameric cap structure at the tip of the Type III secretory needle; this structure, which has evolved from the bacterial flagellar cap structure, is indispensable for toxin translocation. Various pathogenic gram‐negative bacteria such as Photorhabdus luminescens, Vibrio spp., and Aeromonas spp. encode homologs of the V‐antigen. Because the V‐antigens of pathogenic gram‐negative bacteria play a key role in toxin translocation, they are potential therapeutic targets for combatting bacterial virulence. In the USA and Europe, these vaccines and specific antibodies against V‐antigens are in clinical trials investigating the treatment of Yersinia or P. aeruginosa infections. Pathogenic gram‐negative bacteria are of great interest because of their ability to infect fish and shrimp farms, their potential for exploitation in biological terrorism attacks, and their ability to cause opportunistic infections in humans. Thus, elucidation of the roles of the V‐antigen in the TTSS and mechanisms by which these functions can be blocked is critical to facilitating the development of improved anti‐V‐antigen strategies. 相似文献
45.
Yusuke?YamanoueEmail author Masaki?Miya Keiichi?Matsuura Masaya?Katoh Harumi?Sakai Mutsumi?Nishida 《Ichthyological Research》2004,51(3):269-273
We determined the complete nucleotide sequences of the mitochondrial genomes for the three currently recognized species of ocean sunfish: Mola mola, Masturus lanceolatus, and Ranzania laevis (Tetraodontiformes: Molidae). Each genome contained the 37 genes as found in teleosts, with the typical gene order in teleosts. Bayesian, maximum-likelihood, and maximum-parsimony analyses were conducted with the data set comprising concatenated nucleotide sequences from 36 genes (excluding the ND6 gene) of three molids and four outgroups (three tetraodontiforms plus a caproid). The resultant trees supported monophyly of the Molidae and its intrarelationships ((Mola, Masturus), Ranzania), which were congruent with previous morphology-based hypotheses. 相似文献
46.
The reaction centers (RCs) from several species of a purple photosynthetic bacterium, Rhodopseudomonas palustris, were first isolated by ammonium-sulfate fractionation of the isolated core complexes, and were successfully purified by anion-exchange and gel-filtration chromatography as well as sucrose-density gradient centrifugation. The RCs were characterized by spectroscopic and biochemical analyses, indicating that they were sufficiently pure and had conserved their redox activity. The pigment composition of the purified RCs was carefully analyzed by LCMS. Significant accumulation of both bacteriochlorophyll(BChl)-a and bacteriopheophytin(BPhe)-a esterified with various isoprenoid alcohols in the 17-propionate groups was shown in RCs for the first time. Moreover, a drastic decrease in BPhe-a with the most dehydrogenated and rigid geranylgeranyl(GG) ester was observed, indicating that BPhe-a in RC preferably took partially hydrogenated and flexible ester groups, i.e. dihydro-GG and tetrahydro-GG in addition to phytyl. Based on the reported X-ray crystal structures of purple bacterial RCs, the meaning of flexibility of the ester groups in BChl-a and BPhe-a as the cofactors of RCs is proposed. 相似文献
47.
Kato H Nakajima S Saito Y Takahashi S Katoh R Kitamura M 《Cell death and differentiation》2012,19(2):310-320
Mammalian target of rapamycin (mTOR) has a key role in the regulation of an array of cellular function. We found that rapamycin, an inhibitor of mTOR complex 1 (mTORC1), attenuated endoplasmic reticulum (ER) stress-induced apoptosis. Among three major branches of the unfolded protein response, rapamycin selectively suppressed the IRE1-JNK signaling without affecting PERK and ATF6 pathways. ER stress rapidly induced activation of mTORC1, which was responsible for induction of the IRE1-JNK pathway and apoptosis. Activation of mTORC1 reduced Akt phosphorylation, which was an event upstream of IRE-JNK signaling and consequent apoptosis. In vivo, administration with rapamycin significantly suppressed renal tubular injury and apoptosis in tunicamycin-treated mice. It was associated with enhanced phosphorylation of Akt and suppression of JNK activity in the kidney. These results disclosed that, under ER stress conditions, mTORC1 causes apoptosis through suppression of Akt and consequent induction of the IRE1-JNK pathway. 相似文献
48.
Naganawa A Matsui T Saito T Ima M Tatsumi T Yamamoto S Murota M Yamamoto H Maruyama T Ohuchida S Nakai H Kondo K Toda M 《Bioorganic & medicinal chemistry》2006,14(19):6628-6639
4-({2-[Isobutyl(phenylsulfonyl)amino]-5-(trifluoromethyl)phenoxy}methyl)benzoic acid (1) is a functional PGE2 antagonist selective for EP1 receptor subtype. Analogs of 1, in which the phenyl-sulfonyl moiety has been replaced with more hydrophilic heteroarylsulfonyl moieties, exhibited more optimized antagonist activity, while some of them showed in vivo antagonist activity. Structure-activity relationship (SAR) studies are also presented. 相似文献
49.
Shuichiro Ito Tomoko Takayama Hiroyuki Hanzawa Kimihisa Ichikawa Jun Ohsumi Nobufusa Serizawa Tadashi Hata Hideyuki Haruyama 《Journal of biochemistry》2002,131(1):137-143
Binding of Fas ligand to Fas induces apoptosis. The Fas-Fas ligand system plays important roles in many biological processes, including the elimination of autoreactive lymphoid cells. The mouse anti-human Fas monoclonal antibody HFE7A (m-HFE7A), which induces apoptosis, has been humanized based on a structure predicted by homology modeling. A version of humanized HFE7A is currently under development for the treatment of autoimmune diseases such as rheumatoid arthritis. For a deeper understanding of the protein engineering aspect of antibody humanization, for which information on the three-dimensional structure is essential, we determined the crystal structure of the m-HFE7A antigen-binding fragment (Fab) by X-ray crystallography at 2.5 A resolution. The main-chain conformation of the five loops in the six complementarity-determining regions (CDRs) was correctly predicted with root-mean-square deviations of 0.30-1.04 A based on a comparison of the crystal structure with the predicted structure. The CDR-H3 conformation of the crystal structure, which was not classified as one of the canonical structures, was completely different from that of the predicted structure but adopted the conformation which followed the "H3-rules." The results of charge distribution analysis of the antigen-binding site suggest that electrostatic interactions may be important for its binding to Fas. 相似文献
50.
Murata S Mochizuki K Nakazawa T Kondo T Nakamura N Yamashita H Urata Y Ashihara T Katoh R 《Cytometry》2002,49(3):91-95
BACKGROUND: Aspiration biopsy cytology of thyroid tumors has been used more frequently in recent times to differentiate between malignant and benign lesions. Chromatin patterns of the tumor cell nuclei are one of most important factors for cytologic diagnosis. The interpretation of nuclear chromatin patterns is subjective and more difficult than that of nuclear size or shape. In the present report, we investigated how to detect underlying chromatin characteristics of benign and malignant thyroid tumor cells by means of texture and factor analyses. METHODS: We employed a computer-aided system in which light microscopy was combined with an image processor and monochrome camera. Using this system, 100 randomly selected cells in a Papanicolaou stained, aspiration biopsy cytologic smear in each case of 39 benign and malignant thyroid tumor cases were digitized. We applied two-dimensional and higher texture analyses with the use of co-occurrence and run-length matrices to analyze the chromatin patterns. Factor analysis was used to determine whether a large number of independent variables actually measured one or more underlying common variables. RESULTS: According to parameters with high factor-loading values, the morphologic chromatin characters were classified into three categories according to heterogeneity, contrast, and homogeneity of chromatin patterns. On the basis of analyses with these morphologic categories, nuclei of papillary carcinoma showed higher contrast of chromatin patterns than did those of the benign group. Moreover, there was a variety of contrasting chromatin patterns among cells in each papillary carcinoma case in comparison with the benign group. In contrast, follicular carcinomas showed a significant difference in the standard deviation of factor 3, which indicated more monotonous chromatin patterns among cells in each follicular carcinoma case than in each benign case. CONCLUSION: We believe that this technique, using texture and factor analyses, is useful in the detection of underlying characteristics of nuclear chromatin patterns in aspiration biopsy cytology. 相似文献