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101.
102.
T Yoshino M Okano H L Chen J Tsuchiyama E Kondo R Nishiuchi N Teramoto K Nishizaki T Akagi 《Cellular immunology》1999,197(1):39-45
Cutaneous lymphocyte antigen (CLA) is expressed on a subpopulation of human memory T cells and is involved in the primary step of their skin homing. T cells and some B cells in the peripheral blood express CLA, but the pathophysiologic roles of CLA(+) B cells have not yet been clarified. We examined the relationships among CLA expression in B cells and immunoglobulin heavy chain subtype, the localization of CLA(+) B cells in the peripheral lymphoid tissues, and their functional binding to E-selectin. CLA was expressed on class-switched, memory B cells in the peripheral blood and tonsils as revealed by flow cytometry. Immunohistochemical staining of the lymph nodes with various types of inflammation or reactive hyperplasia showed CLA on the monocytoid B cells, which correspond to memory cells. The functional study revealed that CLA on B cells bound to E-selectin transfectants. E-selectin was detected on some of the high endothelial venules in the monocytoid B-cell-rich lymph nodes. These findings suggest that CLA is also expressed on a subset of memory/effector B cells, in addition to a subset of memory T cells. Such B cells were located in the lymph nodes or tonsils and rarely in chronic dermatitis. Therefore, CLA seems to be related to memory/effector B-cell trafficking to the lymph nodes or tonsils. According to the multistep theory, mechanisms involved in the second or third step might be different between CLA(+) B and T cells. 相似文献
103.
104.
Nabe T Hosokawa F Matsuya K Morishita T Ikedo A Fujii M Mizutani N Yoshino S Chaplin DD 《Life sciences》2011,88(25-26):1127-1135
AimsNeutrophils have been found increasingly in the lungs of patients with severe asthma; however, it is unclear whether the neutrophils contribute to the induction of the airway obstruction. We determined using a murine model whether neutrophils are involved in the late asthmatic response (LAR), and analyzed mechanisms underlying the antigen-induced airway neutrophilia.Main methodsBALB/c mice sensitized by ovalbumin (OVA) + Al(OH)3 were challenged 4 times by intratracheal administration of OVA. Airway mechanics were measured as specific airway resistance.Key findingsInduction of the LAR after the 4th challenge coincided with airway neutrophilia. In contrast, eosinophil infiltration was established prior to the 4th challenge. A treatment with an anti-Gr-1 monoclonal antibody (mAb) before the 4th challenge selectively suppressed increases in the neutrophil number and myeloperoxidase (MPO) level in bronchoalveolar lavage fluid (BALF), and attenuated the magnitude of LAR by 60–70%. Selective suppression of eosinophilia by anti-IL-5 mAb had little effect on the LAR. The increases in neutrophil number and MPO level were partially inhibited by an anti-CD4 mAb treatment. The CD4+ cell depletion also significantly inhibited increases in neutrophil chemoattractants, IL-17A, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-2 in BALF. However, blockade of FcγRII/III failed to suppress the neutrophilia.SignificanceThese data suggest that neutrophils are key inducers of the LAR, and that the antigen-induced neutrophilia is partially dependent on activated CD4+ cells that are involved in the production of IL-17A, KC and MIP-2. 相似文献
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Ryunosuke Yoshino Nobuaki Yasuo Daniel Ken Inaoka Yohsuke Hagiwara Kazuki Ohno Masaya Orita Masayuki Inoue Tomoo Shiba Shigeharu Harada Teruki Honma Emmanuel Oluwadare Balogun Josmar Rodrigues da Rocha Carlos Alberto Montanari Kiyoshi Kita Masakazu Sekijima 《PloS one》2015,10(5)
BackgroundChagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease that causes severe human health problems. To develop a new chemotherapeutic agent for the treatment of Chagas disease, we predicted a pharmacophore model for T. cruzi dihydroorotate dehydrogenase (TcDHODH) by fragment molecular orbital (FMO) calculation for orotate, oxonate, and 43 orotate derivatives.Conclusions/SignificanceFMO-based interaction energy analyses revealed a pharmacophore model for TcDHODH inhibitor. Hydrogen bond acceptor pharmacophores correspond to Lys43 and Lys214, hydrogen bond donor and acceptor pharmacophores correspond to Asn67 and Asn194, and the aromatic ring pharmacophore corresponds to FMN, which shows important characteristics of compounds that inhibit TcDHODH. In addition, the Lys214 residue is not conserved between TcDHODH and human DHODH. Our analysis suggests that these orotate derivatives should preferentially bind to TcDHODH, increasing their selectivity. Our results obtained by pharmacophore modeling provides insight into the structural requirements for the design of TcDHODH inhibitors and their development as new anti-Chagas drugs. 相似文献
107.
Motonori Kurosumi Yoshino Nishio Satoko Osawa Hisayoshi Kobayashi Takeshi Iwatsubo Taisuke Tomita Hiroyuki Miyachi 《Bioorganic & medicinal chemistry letters》2010,20(17):5282-5285
Screening of our library of peroxisome proliferator-activated receptor (PPAR) agonists yielded several phenylpropanoic acid-derived γ-secretase inhibitors (GSIs). Structure–activity relationship studies indicated that (R)-configuration of α-substituted phenylpropanoic acid structure and cinnamic acid structure is favorable to prepare Notch-sparing GSIs. 相似文献
108.
Freshly dissociated myocytes from nonpregnant, pregnant, and postpartum rat uteri have been studied with the tight-seal patch-clamp method. The inward current contains both INa and ICa that are vastly different from those in tissue-cultured material. INa is abolished by Na+-free medium and by 1 μM tetrodotoxin. It first appears at ∼−40 mV, reaches maximum at 0 mV, and reverses at 84 mV. It activates with a voltage-dependent τ of 0.2 ms at 20 mV, and inactivates as a single exponential with a τ of 0.4 ms. Na+ conductance is half activated at −21.5 mV, and half inactivated at −59 mV. INa reactivates with a τ of 20 ms. ICa is abolished by Ca2+-free medium, Co2+ (5 mM), or nisoldipine (2 μM), and enhanced in 30 mM Ca2+, Ba2+, or BAY-K 8644. It first appears at ∼−30 mV and reaches maximum at +10 mV. It activates with a voltage-dependent τ of 1.5 ms at 20 mV, and inactivates in two exponential phases, with τ''s of 33 and 133 ms. Ca2+ conductance is half activated at −7.4 mV, and half inactivated at −34 mV. ICa reactivates with τ''s of 27 and 374 ms. INa and ICa are seen in myocytes from nonpregnant estrus uteri and throughout pregnancy, exhibiting complex changes. The ratio of densities of peak INa/ICa changes from 0.5 in the nonpregnant state to 1.6 at term. The enhanced role of INa, with faster kinetics, allows more frequent repetitive spike discharges to facilitate simultaneous excitation of the parturient uterus. In postpartum, both currents decrease markedly, with INa vanishing from most myocytes. Estrogen-enhanced genomic influences may account for the emergence of INa, and increased densities of INa and ICa as pregnancy progresses. Other influences may regulate varied channel expression at different stages of pregnancy. 相似文献
109.
A new terapontid fish, Mesopristes iravi, is described based on 13 specimens collected on Iriomote Island, the Ryukyu Islands, Japan. This species closely resembles
M. argenteus (Cuvier in Cuvier and Valenciennes, 1829) in having dark stripes on the body, but differs from that species in retaining the stripes
even in adults (vs. stripes disappearing ontogenetically in the latter species), having the median stripe passing through
the eye interrupted on the postorbital region (vs. continuous when the stripe present), a shorter fifth (longest) dorsal spine
(14.6–19.7% SL vs. 18.0–22.2% SL), and a longer postorbital length (40.0–43.0% HL vs. 37.8–40.7% HL). Mesopristes iravi has been confused with M. argenteus in previous reports, and on the basis of the literature it may extend from the Ryukyu Islands, Japan, southward to Borneo,
Indonesia, and New Guinea.
Received: August 6, 2001 / Revised: February 24, 2002 / Accepted: March 7, 2002 相似文献
110.