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41.
Inamo Y Okubo T Wada M Fuchigami S Hashimoto K Fuchigami T Takahashi S Sawada S Harada K 《International archives of allergy and immunology》2002,127(1):89-94
BACKGROUND: More effective therapy is needed for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The clinical efficacy of intravenous ulinastatin therapy was investigated in 3 Japanese pediatric patients with SJS or TEN. METHODS: Ulinastatin was given to 1 pediatric SJS patient and 2 pediatric TEN patients within 7 days (patient 1; SJS), 6 days (patient 2; TEN), or 4 days (patient 3; TEN) after the onset of the skin rash. Ulinastatin was administered intravenously at a dose of 7,500 U/kg/day (maximum dose: 300,000 U/day). No corticosteroids were given. After the skin lesions resolved, the ulinastatin dose was reduced to between 2,500 and 5,000 U/kg/day as maintenance therapy and then the drug was withdrawn. RESULTS: Erythema, fatigue, and fever improved within 12-36 h of starting the ulinastatin infusion, and the skin lesions resolved completely after 4-7 days of ulinastatin therapy. None of the patients had cutaneous or ocular sequelae. No patient developed secondary infection or relapse and ulinastatin therapy caused no side effects. CONCLUSION: Ulinastatin dramatically reduced the febrile period with no adverse effects and was very safe in this study. Ulinastatin appears to be a useful and effective therapy for controlling SJS and TEN without sequelae. 相似文献
42.
Characterization of lectin-induced cellular cytotoxicity mediated by mouse spleen cells and the role of lymphotoxin.
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The cellular cytotoxicity mediated by mouse spleen cells in the presence of mitogenic or non-mitogenic lectins was established under serum-free conditions and characterized. Compared with the lectin-induced cellular cytotoxicity (LICC) in the guinea-pig, the activity of lymphotoxin (LT) released into the murine LICC assay cultures was very low. However, a positive correlation was found between the strength of LICC and the LT activity released into the supernatants. Moreover, the addition of puromycin, a potent enhancing reagent of guinea-pig LT activity, markedly promoted the LICC when added 4 h after the initiation of the LICC culture. These data, taken together, suggest that LT acts as an effector molecule in the murine LICC systems as well as in the guinea-pig LICC systems. Properties of the effector cell populations mediating LICC were investigated by depletion of plastic-adherent or nylon-wool adherent cells, by treatment of spleen cells with anti-T-cell sera and complement, and by use of nude mouse spleen cells. The results obtained suggest that both concanavalin A and phytohaemagglutinin-P can induce nylon-wool non-adherent T-cell mediated LICC, phytohaemagglutinin-W was found to be capable of inducing both the nylon-wool non-adherent T-cell mediated LICC and the nylon-wool adherent non-T-cell mediated LICC, the major effector of Bauhinia purpurea agglutinin-LICC was found to be the nylon-adherent non-T-cell population. 相似文献
43.
Acetylcholine (ACh) induces a hyperpolarization during current clamp and an outward current during voltage clamp in tail sensory neurons of Aplysia kurodai. This response was proved to be produced by a specific increase in membrane permeability toward potassium ions, the cholinergic antagonists, d-tubocurarine chloride (d-TC), and atropine mildly reduced the ACh response, while tetraethylammonium (TEA) most effectively blocked this response. These findings provide evidence that tail sensory neurons have the inhibitory ACh receptor in addition to the known receptors for serotonin (5-HT), small cardioactive peptide B (SCPB), and neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide). 相似文献
44.
Hirohata S Yanagida T Nagai T Sawada T Nakamura H Yoshino S Tomita T Ochi T 《Journal of leukocyte biology》2001,70(3):413-421
To assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA), we examined the capacity of CD34(+) cells from bone marrow to generate fibroblast-like type B synoviocytes. CD34(+) cells from the bone marrow of 22 RA patients differentiated into cells with fibroblast-like morphology, which expressed prolyl 4-hydroxylase, in the presence of stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha), much more effectively than CD34(+) cells from bone marrow of 15 control subjects (10 patients with osteoarthritis and 5 healthy individuals). The generation of fibroblast-like cells was not at all observed in cultures with SCF, GM-CSF, and interleukin 4 (IL-4) with or without TNF-alpha. Generation of fibroblast-like cells was correlated with matrix metalloproteinase (MMP)-1 levels in culture supernatants. Thus, MMP-1 levels were significantly higher in TNF-alpha-stimulated cultures of bone marrow CD34(+) cells from patients with RA than in those from the control group. These results indicate that bone marrow CD34(+) cells from patients with RA have abnormal capacities to respond to TNF-alpha and to differentiate into fibroblast-like cells producing MMP-1, suggesting that bone marrow CD34(+) progenitor cells might generate type B synoviocytes and thus could play an important role in the pathogenesis of RA. 相似文献
45.
Takeshita M Yamamoto M Kikuchi M Kimura N Nakayama J Uike N Daimaru H Sawada H Okamura T 《American journal of clinical pathology》2000,113(2):201-211
We compared the expression of cell adhesion molecules (CAMs), cytotoxic granule proteins, and apoptosis-related proteins by immunohistology and in situ terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick end labeling (TUNEL) of 10 cases of cutaneous CD56+ NK/T cell lymphoma with and 6 cases without angiodestruction. Lymphoma cells in cases with angiodestruction frequently expressed CAMs CD2, CD11a, and CD49d and their ligands CD58, CD54, and CD106 and were positive for CD122 and cytotoxic granule proteins TIA1, perforin, and granzyme B. Lymphoma cells in cases without angiodestruction mostly were negative for CD2, CD58, CD54, CD106, and TIA1 and weakly positive for perforin and granzyme B. In the TUNEL method, mean apoptotic indices (AI) for cases with angiodestruction showed a higher percentage than those without angiodestruction. CD95L, CD95, apoptosis-induced cysteine protease CPP32, apoptosis-promoting protein Bax, and proliferating marker (MIB1) frequently were positive in the lymphoma cells of cases with angiodestruction, but there was no expression of apoptosis-inhibitor protein Bcl2. In most cases without angiodestruction, lymphoma cells were positive for CD95L and Bax and negative for CD95, CPP32, and MIB1. CAMs and the 3 cytotoxic granule proteins and an apoptosis pathway might be important factors in the paracrine and autocrine mechanisms of tissue necrosis in cutaneous CD56+ NK/T cell lymphoma. 相似文献
46.
Adhesion polypeptides are useful for the prevention of peritoneal dissemination of gastric cancer 总被引:3,自引:0,他引:3
Tasuku Matsuoka Kosei Hirakawa-YS Chung Masakazu Yashiro Shigehiko Nishimura Tetsuji Sawada Ikuo Saiki Michio Sowa 《Clinical & experimental metastasis》1998,16(4):381-388
We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. We previously reported the establishment of an extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both 21 and 31 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD, and two RGD derivatives significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination given YIGSR sequenc e intraperitoneally was obviously longer than that of untreated mice. The survival of mice treated with RGD was also improved, and this effect was increased using the RGD derivatives, poly(CEMA-RGDS) and CM-chitin RGDS. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM, and consequently inhibit peritoneal implantation. The peritoneal injection of adhe-sion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients. © Rapid Science Ltd. 相似文献
47.
Suzuki K Kokai Y Sawada N Takakuwa R Kuwahara K Isogai E Isogai H Mori M 《Virchows Archiv : an international journal of pathology》2002,440(3):318-324
Helicobacter pylori induces severe neutrophilic infiltration in the lamina propria of the stomach, which leads to gastritis in humans. The possible involvement of a paracellular route for bacterial nutrients and etiologic agents that may play an important role in colonization of the bacteria and cause gastritis has been suggested. To study the functions of the paracellular barrier of gastric surface epithelium, SS1, a strain of H. pylori adapted to the murine stomach, was inoculated into the stomachs of C57BL/6 mice. At 4 months after inoculation, SS1 had achieved a high level of colonization (10(6)-10(7) colony-forming units/g tissue) associated with neutrophilic infiltration in the lamina propria of the junctional zone. Disruption of the paracellular barrier was observed in the SS1-infected stomachs, as revealed by the invasion of a lanthanum tracer into the paracellular space of the surface epithelium. Only 2% of junctions were permeable in control stomachs, whereas 72% of the paracellular barrier was disrupted in the SS1-infected gastric epithelia. Furthermore, distribution of tight junction-related molecules such as 7H6 antigen, occludin, and cortical actin was affected in the surface epithelium by SS1 infection. The linear expression pattern of occludin was disrupted and became irregular or punctuated. The 7H6 antigen accumulated as aggregates in the apical portion of the surface epithelium and cortical actin became irregular and punctuated. Taken together, these results indicate that infection by SS1 directly or indirectly caused an increase in paracellular permeability and altered the localization of tight junction-related molecules of the gastric surface epithelium. This observation suggests that the paracellular pathway may play a significant role in establishing H. pylori-induced gastritis in the clinical setting. 相似文献
48.
Naoki Horikawa Tomoyuki Suzuki Takaoki Uchiumi Tetsuji Minamimura Kazuhiro Tsukada Noriaki Takeguchi Hideki Sakai 《The Journal of physiology》2005,562(3):885-897
Increased release of thromboxane A2 (TXA2 ) has been shown to be involved in inflammatory bowel diseases. In the present study, we have investigated the effect of a stable TXA2 analogue (STA2 ) on the electrical parameters in isolated human colonic mucosa. In the human mucosa set between Ussing chambers, STA2 stimulated Cl− secretion in a concentration-dependent manner with an EC50 of 0.06 μ m . The STA2 -induced Cl− secretion was significantly inhibited by ONO-3708 (10 μ m ), a specific TXA2 receptor antagonist. The effect of STA2 (0.3 μ m ) was independent of the colonic segment from which the tissue was obtained, from caecum to rectum. Chromanol 293B, an inhibitor of the cAMP-dependent KvLQT1 channel, attenuated the STA2 -induced Cl− secretion in the human colonic mucosa (IC50 value 1.18 μ m ). We found that KvLQT1 mRNA and protein were expressed in all the tested segments of the human colon. The STA2 -induced Cl− secretion was significantly inhibited by 8-bromo-2'-monobutyryladenosine-3',5'-cyclic monophosphorothioate (50 μ m ), a membrane-permeant cAMP antagonist. STA2 (0.3 μ m ) significantly increased the intracellular cAMP levels and the short-circuit current via TXA2 receptor in a human colonic cell line. These results suggest that the TXA2 -induced Cl− secretion in the colon is mediated via the cAMP pathway in addition to the Ca2+ –calmodulin pathway which was previously reported. 相似文献
49.
Takashi Kojima Toshinobu Yamamoto Mengdong Lan Masaki Murata Ken-ichi Takano Mitsuru Go Shingo Ichimiya Hideki Chiba Norimasa Sawada 《Medical Electron Microscopy》2004,37(2):101-113
The signal transduction pathways and activation of the MAP kinase or PI3 kinase signaling cascade regulate a variety of cellular processes, including proliferation and differentiation in hepatocytes. To elucidate the mechanisms of signal transmission required for the regulation of gap and tight junctions during DNA synthesis in rat hepatocytes, we determined changes of expression and function of gap and tight junctions of cells grown in primary culture, using inhibitors of signaling pathways for MAP kinase (PD98059) and PI3 kinase (LY294002). During the stimulation of DNA synthesis induced by epidermal growth factor (EGF), immunoreactivity and mRNAs of gap junction protein Cx32 and of tight junction protein claudin-1 markedly decreased with reduction of gap junctional intercellular communication (GJIC) and the fence function of tight junctions. In Western blots, whole-cell lysate of claudin-1 protein decreased and phosphorylated Cx32 protein in the insoluble fraction of Triton X-100 increased during the stimulation of DNA synthesis. During reinhibition of DNA synthesis, the changes of Cx32 and claudin-1 returned to control levels, as did both functions. In treatment with the inhibitors before DNA synthesis, PD98059 inhibited the changes of expression and function of Cx32, but not claudin-1, without inhibition of cell growth, whereas LY294002 completely inhibited cell growth. These findings indicate that the PI3 kinase pathway rather than the MAP kinase pathway plays an important role for EGF-induced proliferation of rat hepatocytes, and that changes of Cx32 in hepatocytes during the stimulation of DNA synthesis may be in part controlled through MAP kinase. Furthermore, Cx32, but not claudin-1, protein may be a target of activated MAP kinase in hepatocytes. 相似文献
50.
Ishihara A Kawano F Ishioka N Oishi H Higashibata A Shimazu T Ohira Y 《Neuroscience research》2004,48(2):119-127
The effects of hindlimb unloading and recovery with or without running exercise on morphological and metabolic properties of soleus muscle fibers and their spinal motoneurons in rats were investigated. Ten-week-old rats were hindlimb suspended for 2 weeks and thereafter were rehabilitated with or without voluntary running exercise for 2 weeks. A decreased percentage of type I fibers and atrophy of all types of fibers were observed after hindlimb unloading. In addition, decreased oxidative enzyme activity of all types of fibers was observed after hindlimb unloading. In contrast, an improvement in the decreased percentage of type I fibers, decreased fiber cross-sectional area, and decreased fiber oxidative enzyme activity was observed after recovery with running exercise, but not without running exercise. There were no changes in the number, cell body size, or oxidative enzyme activity of motoneurons innervating the soleus muscle after hindlimb unloading or recovery with or without running exercise. These results indicate that running exercise is beneficial for the recovery of the decreased percentage of type I fibers and the atrophy and decreased oxidative enzyme activity of all types of fibers in the soleus muscle induced by hindlimb unloading and that there are no changes in morphological or metabolic properties of spinal motoneurons innervating the soleus muscle following decreased or increased neuromuscular activity. 相似文献