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11.
Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation. 总被引:7,自引:0,他引:7
Kazunori Inabe Masamichi Ishiai Andrew M Scharenberg Norman Freshney Julian Downward Tomohiro Kurosaki 《The Journal of experimental medicine》2002,195(2):189-200
To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here we report that Vav3 influences phosphoinositide 3-kinase (PI3K) function through Rac1 in that phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation was attenuated by loss of Vav3 or by expression of a dominant negative form of Rac1. The functional interaction between PI3K and Rac1 was also demonstrated by increased PI3K activity in the presence of GTP-bound Rac1. In addition, we show that defects of calcium mobilization and c-Jun NH2-terminal kinase (JNK) activation in Vav3-deficient cells are relieved by deletion of a PIP3 hydrolyzing enzyme, SH2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP). Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux. 相似文献
12.
Isao Kurosaki Kazuhiro Tsukada Hidenori Ueki Akira Ohya Katsuyoshi Hatakeyama 《Journal of Hepato-Biliary-Pancreatic Surgery》1997,4(1):131-134
We report a case of advanced gallbladder cancer in a 37-year-old man who presented in June 1993 with malignant obstructive jaundice. After percutaneous transhepatic biliary drainage and several diagnostic imaging examinations, the patient underwent laparotomy under a diagnosis of extremely advanced gallbladder cancer involving the confluence of the hepatic ducts. The tumor, however, was judged to be unresectable because of its massive spread into the liver along Glisson's sheath, and because of histologically proven peritoneal dissemination. After exploratory laparotomy, one course of anticancer chemotherapy (cisplatin, 100 mg/body IV, on day 1, and 5-fluorouracil, 1000 mg/body, on days 1–5, by continuous infusion) was administered and the completely obstructed hepatic duct was dramatically re-canalized. Four courses of chemotherapy were administered over a 16-month period until jaundice recurred. For these 16 months, the patient's quality of life was well maintained without biliary drainage. He died of increased peritoneal dissemination approximately 2 years after the first course of anticancer chemotherapy. 相似文献
13.
Takashi Takata Yong Lu Ikuko Ogawa Ming Zhao Zhi Yu Zhou David Mock Hiromasa Nikai 《Pathology international》1998,48(11):877-881
The calcifying odontogenic cyst (COC) presents with diverse hlstologlcal features; thus, several subclasslfl-cations have been proposed. To evaluate the slgnlficance of the various histological features and subtypes of COC from the perspectlve of proliferative activity, the proliferating cell nuclear antigen (PCNA) labellng index (LI; the percentage of positive nuclei) was assessed immunohistochemlcally in 25 cases of COC (21 benign and four malignant). All of the benign cases were of the cystic variety and further subclas-sified into non-proliferative subtype (NPS; four cases); proliferative subtype (PS; eight cases); and COC associated with odontoma (COCaO, nlne cases). The PCNA U of the mallgnant COC (65.2 ± 5.6) was slgnlflcantly higher than that of the benlgn COC (11.6 ± 9.0; P = 0.002). Non-proliferative subtype (6.8 ± 2.8) showed the lowest PCNA LI and PS (17.2 ± 11.2) the highest of among the three subtypes of benign cystic COC (P = 0.028). In nine cases of COCaO, six showed epithelial lining of the non-proliferative type as NPS and the other three had lining wlth proliferative features as PS. The PCNA LI of the latter COCaO group (14.3 ± 6.6) was significantly higher than that of the former (6.1 ± 4.3; P = 0.05), as Seen between PS and NPS. These results demonstrate that PCNA LI is a possible parameter for differentiating mallgnant COC from benign COC and, whatever the subtypes, the proliferative features In the lining are the main factor influencing the prollferatlng actlvity of COC. 相似文献
14.
Hiroko Sasahara Susumu Sueyoshi Toshiaki Tanaka Hiromasa Fujita Kazuo Shirouzu 《The Japanese Journal of Thoracic and Cardiovascular Surgery》2004,52(5):231-239
Objective: The purpose of this experimental study was to investigate whether aortic stent grafting can be applied to the treatment of
an esophageal cancer involving the thoracic aorta. Methods: The canine thoracic aorta was partially resected without aorta being clamped after emplacement of an endovascular stent graft.
Study I; The aortic whole layer of 1 cm in length and 1/4 of the circumference was resected and was covered by a free fascia
patch of the abdominal rectal muscle immediately after stent graft placement. Study II; The aortic adventitia and the outer
half of the media of the same size was resected on day 3, 7,14, 21, and on day 28, after the stent graft placement. The resected
portion was covered by the free fascia patch in half experimental dogs, and was uncovered in the others. Study III; The aortic
adventitia and the outer half of the media of 1 cm in length and 1/2 of the circumference was resected and was uncovered on
day 7 after stent graft placement. Histological examinations were performed on day 28 and at one year after aortic resection.
Results: The aortic wall could be resected in all cases with no complication, except in resection of 1/2 the circumference where the
aorta had become narrow. There was no difference in healing of the resected portion of the aorta between with and without
fascia covering. Conclusion: An aortic endovascular stent graft could be applied to surgery for an esophageal cancer involving the aorta. 相似文献
15.
Hiromasa Yanagi Jiro Kondo Keiji Uchida Michio Tobe Shin-ichi Suzuki Yoshimi Yano 《General thoracic and cardiovascular surgery》1998,46(10):1014-1019
We experienced a case with acute mitral regurgitation caused by complete posterior papillary muscle rupture as complication of acute inferior myocardial infarction, who underwent successfully emergency operation of mital valve replacement and coronary revascularization in acute stage. A 64-year-old woman developed sudden cardiogenic shock shortly after the onset of acute inferior myocardial infarction. The diagnosis of acute inferior myocardial infarction was based on the electrocardiographic findings. Under IABP support, preoperative coronary angiography visualized total occlusion of segment 3 of the right coronary artery, and preoperative left ventriculography showed akinesis of inferior wall and severe mitral regurgitation. At 6 hours after onset of papillary muscle rupture, emergency operation was performed. At operation, posterior papillary muscle was found to be totally ruptured. Coronary artery revascularization and mitral valve replacement were performed. Postoperative course was uneventful, with 4 days of IABP and 5 days of ventilatory support. She was discharged on the twentieth postoperative day in NYHA class I. Reports of successful emergency operation for total papillary muscle rupture following acute myocardial infarction are rare. Early diagnosis and surgical treatment are mandatory to save this group of patients. 相似文献
16.
Hong-Guo Jin Hiroshi Yamashita Takeshi Nakamura Hiromasa Fukuba Tetsuya Takahashi Masanori Hiji Tatsuo Kohriyama Masayasu Matsumoto 《Neuroscience letters》2008
Synphilin-1 represents a cytoplasmic protein that interacts with α-synuclein and localizes close to synaptic vesicles. The interaction of synphilin-1 with several proteins involved in Parkinson's disease suggests that it might be involved in the pathogenesis of the disease. Nonetheless, the function of synphilin-1 remains unclear. In the present study, we generated transgenic mice expressing human synphilin-1 under the prion protein promoter. Synphilin-1 was widely expressed in neurons in the brain including the substantia nigra, where massive loss of dopamine neurons was not observed. In the transgenic mouse brain, synphilin-1 protein was polyubiquitinated, and partially insoluble. Although modified-SHIRPA revealed no significant difference in behavior and morphology, the reduced rotarod performance and step length were observed in transgenic mice as compared with non-transgenic littermates. Synphilin-1 might be involved in motor function, and its accumulation in the central nervous system can cause motor impairments. 相似文献
17.
We examined the cellular activity in the rostral cingulate motor area (CMAr) with respect to multiple behavioral factors that ranged from the retrieval and processing of associative visual signals to the planning and execution of instructed actions. We analyzed the neuronal activity in monkeys while they performed a behavioral task in which 2 visual instruction cues were given successively with an intervening delay. One cue instructed the location of the target to be reached; the other cue instructed which arm was to be used. After a second delay, the monkey received a motor-set cue to be prepared to initiate the motor task in accordance with instructions. Finally, after a GO signal, the monkey reached for the instructed target with the instructed arm. We found that the activity of neurons in the CMAr changed profoundly throughout the behavioral task, which suggested that the CMAr participated in each of the behavioral processing steps. However, the neuronal activity was only modestly selective for the spatial location of the visual signal. We also found that selectivity for the instructional information delivered with the signals (target location and arm use) was modest. Furthermore, during the motor-set and movement periods, few CMAr neurons exhibited selectivity for such motor parameters as the location of the target or the arm to be used. The abundance and robustness of the neuronal activity within the CMAr that reflected each step of the behavioral task and the modest selectivity of the same cells for sensorimotor parameters are strikingly different from the preponderance of selectivity that we have observed in other frontal areas. Based on these results, we propose that the CMAr participates in monitoring individual behavioral events to keep track of the progress of required behavioral tasks. On the other hand, CMAr activity during motor planning may reflect the emergence of a general intention for action. 相似文献
18.
19.
Regulation of B cell fates by BCR signaling components 总被引:5,自引:0,他引:5
Kurosaki T 《Current opinion in immunology》2002,14(3):341-347
Recent results obtained in mice harboring cytoplasmic mutations of Igalpha and/or Igbeta have reinforced the concept that the strength of BCR signaling is important for ensuring appropriate developmental outcomes as well as antigen-specific responses. To establish the optimal signaling intensity and duration, the BCR utilizes positive and negative regulatory molecules. Studies are beginning to reveal how these molecules maintain immunological homeostasis and tolerance. 相似文献
20.
Kupffer cell-mediated cytotoxicity against hepatoma cells occurs through production of nitric oxide and adhesion via ICAM-1/CD18 总被引:1,自引:0,他引:1
Saito Hidetsugu; Kurose Iwao; Ebinuma Hirotoshi; Fukumura Dai; Higuchi Hajime; Atsukawa Kazuhiro; Tada Shinichiro; Kimura Hiroyuki; Yonei Yoshikazu; Masuda Tetsuya; Miura Soichiro; Ishii Hiromasa 《International immunology》1996,8(7):1165-1172
Rat Kupffer cell (KC)-mediated cytotoxicity against both thesyngeneic hepatoma cell line AH70 and hepatocytes was evaluatedby changes in mitochondrial function, and the possible roleof ICAM-1/CD18 in the interaction between the cells was studied.Rhodamine 123 fluorescence, a marker of the mitochondrial membranepotential, decreased in AH70 cells after co-culture with KC,while that in hepatocytes was unchanged by co-culture. Thisdecrease was blocked by anti-ICAM-1, anti-CD18 and the Inhibitionof nitric oxide synthesis. Cytometric studies demonstrated thatICAM-1 expression on AH70 cells increased after addition ofIFN-, IL-1ß, tumor necrosis factor (TNF)- or KC, whilein hepatocytes ICAM-1 was not increased. Anti-ICAM-1 pretreatmentinhibited the increase in ICAM-1 expression and the decreasein rhodamine 123 fluorescence on AH70 cells after co-culturewith KC. CD18 on KC was increased only after co-culture withAH70. TNF- but not IFN- was detected in the supernatant of co-culturebetween KC and AH70 cells, and this production was partiallyinhibited by anti-ICAM-1 and anti-CD18. The activity of Induciblenitric oxide synthase in Kupffer cells and the levels of nitritesand nitrates in the co-culture supernatant increased over time,and this increase was attenuated either by addition of NO synthesisinhibitors, anti-ICAM-1 or anti-CD18. These results indicatethat the rat KC causes mitochondrial dysfunction in cancer cellsvia the production of NO and cell-to-cell adhesion via ICAM-1/CD18has an Important role in this cytotoxic process. 相似文献