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31.
Kanamycin ototoxicity in glutamate transporter knockout mice 总被引:2,自引:0,他引:2
Glutamate-aspartate transporter (GLAST), a powerful glutamate uptake system, removes released glutamate from the synaptic cleft and facilitates the re-use of glutamate as a neurotransmitter recycling system. Aminoglycoside-induced hearing loss is mediated via a glutamate excitotoxic process. We investigated the effect of aminoglycoside ototoxicity in GLAST knockout mice using the recorded auditory brainstem response (ABR) and number of hair cells in the cochlea. Kanamycin (100 mg/mL) was injected directly into the posterior semicircular canal of mice. Before the kanamycin treatment, there was no difference in the ABR threshold average between the wild-type and knockout mice. Kanamycin injection aggravated the ABR threshold in the GLAST knockout mice compared with the wild-type mice, and the IHC degeneration was more severe in the GLAST knockout mice. These findings suggest that GLAST plays an important role in preventing the degeneration of inner hair cells in aminoglycoside ototoxicity. 相似文献
32.
Wakabayashi Y Watanabe H Inoue J Takeda N Sakata J Mishima Y Hitomi J Yamamoto T Utsuyama M Niwa O Aizawa S Kominami R 《Nature immunology》2003,4(6):533-539
The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies. We have generated Bcl11b-deficient mice that show a block at the CD4-CD8- double-negative stage of thymocyte development without any impairment in cells of B- or gammadelta T cell lineages. The Bcl11b-/- thymocytes showed unsuccessful recombination of V(beta) to D(beta) and lacked the pre-T cell receptor (TCR) complex on the cell surface, owing to the absence of Tcrb mRNA expression. In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice. These results suggest that Bcl11b is a key regulator of both differentiation and survival during thymocyte development. 相似文献
33.
Therapeutic effect of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in treatment of corneal alkali burns in mice 总被引:1,自引:0,他引:1 下载免费PDF全文
Saika S Miyamoto T Yamanaka O Kato T Ohnishi Y Flanders KC Ikeda K Nakajima Y Kao WW Sato M Muragaki Y Ooshima A 《The American journal of pathology》2005,166(5):1393-1403
We evaluated the therapeutic efficacy of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in a corneal alkali burn model in mice. An alkali burn was produced with 1 N NaOH in the cornea of C57BL/6 mice under general anesthesia. SN50 (10 microg/microl) or vehicle was topically administered daily for up to 12 days. The eyes were processed for histological or immunohistochemical examination after bromodeoxyuridine labeling or for semi-quantification of cytokine mRNA. Topical SN50 suppressed nuclear factor-kappaB activation in local cells and reduced the incidence of epithelial defects/ulceration in healing corneas. Myofibroblast generation, macrophage invasion, activity of matrix metalloproteinases, basement membrane destruction, and expression of cytokines were all decreased in treated corneas compared with controls. To elucidate the role of tumor necrosis factor (TNF)-alpha in epithelial cell proliferation, we performed organ culture of mouse eyes with TNF-alpha, SN50, or an inhibitor of c-Jun N-terminal kinase (JNK) and examined cell proliferation in healing corneal epithelium in TNF-alpha-/- mice treated with SN50. An acceleration of epithelial cell proliferation by SN50 treatment was found to depend on TNF-alpha/JNK signaling. In conclusion, topical application of SN50 is effective in treating corneal alkali burns in mice. 相似文献
34.
Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease 总被引:2,自引:0,他引:2 下载免费PDF全文
Hasebe A Yoshimura A Into T Kataoka H Tanaka S Arakawa S Ishikura H Golenbock DT Sugaya T Tsuchida N Kawanami M Hara Y Shibata K 《Infection and immunity》2004,72(3):1318-1325
Bacteroides forsythus is a gram-negative, anaerobic, fusiform bacterium and is considered to be an etiological agent in periodontal disease. A lipoprotein fraction prepared from B. forsythus cells by Triton X-114 phase separation (BfLP) activated human gingival fibroblasts and a human monocytic cell line, THP-1, to induce interleukin-6 production and tumor necrosis factor alpha production. BfLP was found to be capable of inducing nuclear factor-kappaB translocation in human gingival fibroblasts and THP-1 cells. By using Chinese hamster ovary K1 cells transfected with Toll-like receptor genes together with a nuclear factor-kappaB-dependent CD25 reporter plasmid, it was found that signaling by BfLP was mediated by Toll-like receptor 2 but not by CD14 or Toll-like receptor 4. BfLP induced apoptotic cell death in human gingival fibroblasts, KB cells (an oral epithelial cell line), HL-60 cells (a human myeloid leukemia cell line), and THP-1 cells but not in MOLT4 cells (a T-cell leukemia cell line). Caspase-8, an initiator caspase in apoptosis, was found to be activated in these cells in response to BfLP stimulation. Thus, this study suggested that BfLP plays some etiological roles in oral infections, especially periodontal disease, by induction of cell activation or apoptosis. 相似文献
35.
Inhibition of p38MAP kinase suppresses fibrotic reaction of retinal pigment epithelial cells 总被引:3,自引:0,他引:3
36.
Koyama C Matsumoto H Sakai T Wakabayashi K Ito A Couch EF Inoue K 《Endocrine pathology》1995,6(1):67-75
A new cell line (TtT/GF) established from a murine pituitary thyrotropic tumor having characteristics similar to those of
pituitary folliculo-stellate cell (FS cell) was implanted into nude mice together with cells from a rat pituitary somatotrophic
tumor cell line (MtT/S) to determine whether the former enhances pituitary tumor growth. For as long as 2-3 mo after implantation,
MtT/S cells implanted either alone or together with fibroblasts formed either no tumors or only very small tumors in the nude
mice. In contrast all of the nude mice that had received MtT/S cells implanted together with TtT/GF cells developed large
tumors. Furthermore, the mice bearing the MtT/S and TtT/GF implants showed a significantly higher body weight and serum growth
hormone level than those bearing only MtT/S cells or a combination of MtT/S cells and fibroblasts. The TtT/GF cell line itself
had no tumorigenicity during the experimental period. Therefore, the TtT/GF cell line as a model of FS cells enhanced pituitary
endocrine cell tumor formation. Additionally, immunocytochemistry showed that TtT/GF cells positive for glial fibrillary acidic
protein (GFAP) or S-100 protein were present in the parenchymatous tissue elements or connective tissue surrounding the tumor
nests. In the parenchymatous tissue, the TtT/GF cells exhibited a stellate appearance and surrounded neighboring tumor cells
with their long cell processes. These results suggest that TtT/GF cells can serve as a model for pituitary FS cells, and are
capable of stimulating pituitary tumor growth either by modifying the microenvironment or producing growth factors. 相似文献
37.
Kayo Adachi Michihiko Momota Yoshiki Teranishi Reiko Ueki Masatoshi Hagiwara Takashi Wakabayashi Jerzy Popinigis 《Pathology international》1992,42(8):549-557
The physicochemical properties of mitochondria in liver tissue obtained from rats given 32% ethanol, 32% propanol or 6.9% butanol in drinking water for up to 3 months were investigated using differential scanning calo-rimetry and fluorescence polarization measurements. The results obtained were as follows: 1) Phospholipids extracted from mitochondria showed increases in the relative amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylserine, and a decrease in the relative amount of phosphatidylethanolamine. An increase in the unsatu-rated/saturated fatty acid ratio of phospholipids was also observed. 2) Elevation of the thermotropic lipid phase transition temperature with a decrease in the enthalpy value (δ H ) was revealed by differential scanning calo-rimetry. 3) The elevation of the lipid phase transition temperature was detected also by fluorescence polarization measurements using 1,6 diphenyl 1, 3, 5 hexatriene (DPH) as a probe. Elevation of mitochondrial membrane fluidity was found in some of the experimental animals, but most showed no changes in comparison with the control. A possible role of membrane fusion in the mechanism of formation of ethanol-, propanol- and butanol induced hepatic megamitochondria is discussed on the basis of these results. Acta Pathol Jpn 42: 549–557, 1992. 相似文献
38.
Yoshitaka Iwasaki Judith Bartlett Kelly MacKay Jennifer Mactavish Janice Ristock 《Journal of community psychology》2008,36(6):702-722
This study reports key findings from a research project, which examined the stress and coping mechanisms of several nondominant groups of individuals. The groups were based in Winnipeg, Manitoba, Canada and included (a) Aboriginal individuals with diabetes, (b) individuals with disabilities, and (c) gays and lesbians. Our analyses of personal narratives and life stories have led to develop an interpretive map of findings that depicts mechanisms of how stress and coping operate. Specifically, the interpretive map consists of personal and structural stressors, meanings of stress, and personal and structural resources, as well as of two constructs termed intersectionality and social exclusion. Not only are nondominant voices and lived experiences recognized and incorporated into an emergent interpretive map, but this map also articulates the complex ways in which multiple identities intersect (i.e., intersectionality) and the realities of being excluded socioeconomically, culturally, and politically among nondominant groups (i.e., social exclusion). © 2008 Wiley Periodicals, Inc. 相似文献
39.
Shigetoshi Horiguchi Yoshitaka Okamoto Shuji Yonekura Toru Okawa Naoki Kunii Heizaburo Yamamoto Daiju Sakurai Toyoyuki Hanazawa 《Arerugī》2008,57(5):558-561
BACKGROUND: Japanese cedar and cypress pollen share a common antigen. The cedar pollen season is followed by the cypress pollen season. However, both the clinical significance and involvement of cypress pollinosis in the treatment of the cedar pollinosis have not yet been clarified. METHODS: The clinical efficacy of sublingual immunotherapy with cedar pollen extract for cedar pollinosis was evaluated during the cypress pollen dispersal season in Japan. In addition, the change in cypress pollen specific IgE antibodies of the patients with cedar pollinosis was examined before and after the pollen season. RESULTS: Sublingual immunotherapy with cedar pollen extract did not improve the clinical symptoms of the cedar pollinosis patients combined with cypress pollinosis in the cypress pollen season. The cypress pollen specific IgE antibodies were found to demonstrate significant seasonal changes. CONCLUSION: The presence of cypress pollinosis should therefore be taken into consideration when planning the optimal treatment for cedar pollinosis. Sublingual immunotherapy with cedar pollen extract may not be effective for cypress pollinosis. 相似文献
40.
Fu J Hato M Ohmae H Matsuoka H Kawabata M Tanabe K Miyamoto Y Leafasia JL Chinzei Y Ohta N 《Parasitology research》2000,86(5):345-351
We analyzed the relationships between levels of antibody specific for merozoite surface glycoprotein-1 (MSP1) of Plasmodium falciparum and clinical manifestations in humans. We prepared recombinant MSP1 proteins representing block 3 (M3), block 6 (M6), blocks
1–6 (M1/6), and block 17. When we divided the slide-positive individuals in Guadalcanal into symptomatic and asymptomatic
groups, the former group showed lower IgG levels against M6 and block 17, but not against M3, than did the asymptomatic group
(P < 0.01). The possibility of nonspecific suppression was unlikely, given that the levels of antibody against poliomyelitis
virus observed in the two groups were almost the same. Among the IgG subclasses tested, production of cytophilic IgG3 seemed to be dominant. When we analyzed epitopes recognized by antibodies against block 17, a peptide (SSSNFLGIS) was preferentially
recognized by sera from asymptomatic individuals. These results suggest that clinical symptoms occurring during falciparum
malaria seem to be associated with the development of levels of antibody against particular epitopes on MSP1, which is under
the control of an immunoregulatory mechanism.
Received: 1 October 1999 / Accepted: 21 October 1999 相似文献