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991.
992.
993.
Nakai M Hashikura Y Ohkouchi M Yamamura M Akiyama T Shiba K Kajimoto N Tsukamoto Y Hao H Isozaki K Hirai T Hirota S 《Laboratory investigation; a journal of technical methods and pathology》2012,92(3):451-457
We found a novel type germline mutation at exon 11 of the c-kit gene, which results in a substitution of Tyr to Cys at codon 553 of the c-kit gene product (KIT-Tyr553Cys), in a 68-year-old female patient with multiple gastrointestinal stromal tumors (GISTs). In the present study, we carried out mutational analysis in her family members to determine the carriers and characterized the mutation by introducing the corresponding mutation (murine KIT-Tyr552Cys) into expression vector possessing murine c-kit cDNA. Mutational analysis of peripheral blood leukocytes of her family members revealed that a 44-year-old son had the same mutation, but at present he had neither apparent symptoms nor images of multiple GISTs. By transfection with the expression vector possessing the murine mutant c-kit cDNA, interleukin-3-dependent Ba/F3 murine lymphoid cells started growing autonomously without any growth factors, indicating that the mutation was considered to be of gain-of-function. Imatinib, a small molecule of tyrosine kinase inhibitor, effectively inhibited autophosphorylation of KIT-Tyr552Cys. Nilotinib, another small molecule of the KIT inhibitor, also effectively inhibited autophosphorylation of KIT-Tyr552Cys. In fact, proliferation of Ba/F3 cells expressing KIT-Tyr552Cys was effectively inhibited by both imatinib and nilotinib. These findings indicate that the novel type human KIT-Tyr553Cys mutation is the cause of the present familial and multiple GISTs, and that both imatinib and nilotinib might effectively inhibit the growth of GISTs developing in the patients of this family. 相似文献
994.
The area postrema is one of the circumventricular organs, lacks a blood-brain barrier, and is well known as the chemoreceptor trigger zone for emesis. Area postrema neurons are sensitive to emetic chemical substances carried in the blood plasma. Our previous study demonstrated the presence of 3 types of neurons characterized by different ion channels expressed in each cell type, but the type or types of area postrema neurons involved in the induction of nausea and/or emesis have remained unclear. To clarify the role of the most populous cells, which express the hyperpolarization-activated cation channel (H-channel), in induction of nausea and/or emesis, we investigated the effects of ZD7288 (an H-channel inhibitor) on apomorphine-induced conditioned taste aversion (CTA) to saccharin and c-Fos expression in the area postrema. We found that ZD7288 inhibited the acquisition of CTA and reduced apomorphine-induced c-Fos expression in the area postrema, indicating the involvement of the cells expressing H-channels in the induction of nausea and/or emesis. Finally, we discuss the role of cells expressing H-channels in the mechanism of nausea and/or vomiting. 相似文献
995.
996.
Fujita K Akasaka Y Kuwabara T Wang B Tanaka K Kamata I Yokoo T Kinoshita T Iuchi A Akishima-Fukasawa Y Ishikawa Y Kondo M Ishii T 《Immunology letters》2012,144(1-2):1-6
Toll-like receptors appear to play an important role in the pathogenesis of lupus-like nephritis in mice. In human and mouse, CD180 is a homologue of TLR4. In SLE patients, the number of CD180-negative B cells in peripheral blood changes in parallel with disease activity. In the present study using NZBWF1 mice, the population of splenic CD180-negative B cells increased with progression of renal lesions and aging. These cells produced both anti-dsDNA and histone antibodies; the peripheral blood levels of anti-dsDNA antibody increased markedly with aging. B cells infiltrating into renal lesions were CD180-negative and produced anti-dsDNA antibody. Considered together, these findings indicate that CD180-negative B cells contribute significantly to development of SLE-like morbidity in NZBWF1 mice by autoantibody production. 相似文献
997.
Iyoda M Shibata T Hirai Y Kuno Y Akizawa T 《Journal of the American Society of Nephrology : JASN》2011,22(8):1486-1496
The tyrosine kinase inhibitor imatinib is beneficial in experimental renal diseases, but the effect of the new tyrosine kinase inhibitor nilotinib on the progression of renal failure is unknown. We administered either nilotinib or vehicle to Sprague-Dawley rats beginning 2 weeks after 5/6 nephrectomy (Nx) or laparotomy and continuing for 8 weeks. Serum creatinine levels were significantly lower in the nilotinib group after 6 and 8 weeks of treatment. Furthermore, nilotinib-treated rats had less proteinuria, attenuated glomerulosclerosis and tubulointerstitial damage, and reduced macrophage infiltration into the tubulointerstitium. Treatment with nilotinib also significantly decreased renal cortical expression of profibrogenic genes, such as IL-1β and monocyte chemotactic protein-1, which correlated closely with the tubulointerstitial damage score and ED1-positive macrophages score. In addition, nilotinib treatment significantly prolonged survival. Taken together, these results suggest that nilotinib may limit the progression of chronic kidney disease. 相似文献
998.
Morisaki A Hosono M Sasaki Y Hirai H Sakaguchi M Nakahira A Seo H Suehiro S Shibata T 《General thoracic and cardiovascular surgery》2011,59(4):261-267
Purpose
Poststernotomy mediastinitis (PSM) following cardiovascular surgery remains an intractable complication associated with considerable mortality. It is therefore necessary to assess the risk factors associated with hospital mortality and evaluate the surgical treatment options for PSM. 相似文献999.
Hirai M Kadowaki N Kitawaki T Fujita H Takaori-Kondo A Fukui R Miyake K Maeda T Kamihira S Miyachi Y Uchiyama T 《Blood》2011,117(2):500-509
1000.
Sugioka K Matsumura Y Hozumi T Fujita S Ito A Kataoka T Takagi M Mizutani K Naruko T Hosono M Hirai H Sasaki Y Ueda M Suehiro S Yoshiyama M 《The American journal of cardiology》2011,(7):1002-1007
Aortic stenosis (AS) and systemic atherosclerosis have been shown to be closely related. We evaluated the prevalence of aortic arch plaques and their possible association with the risk of cerebral infarction in patients with severe AS. Transesophageal echocardiography was performed in 116 patients with severe AS (55 men, mean age 71 ± 7 years, mean aortic valve area 0.68 ± 0.15 cm(2)) who were scheduled for aortic valve replacement. The presence, thickness, and morphology of the aortic arch plaques were evaluated using transesophageal echocardiography. Cerebral infarcts (chronic cerebral infarction and cerebral infarction after cardiac catheterization and aortic valve replacement) were assessed in all patients. Compared to age- and gender-matched control subjects, the patients with severe AS had a significantly greater prevalence of aortic arch plaques (74% vs 41%; p <0.0001) and complex arch plaques such as large plaques (≥4 mm), ulcerated plaques, or mobile plaques (30% vs 10%; p = 0.004). Multivariate logistic analyses showed that the presence of complex arch plaques was independently associated with cerebral infarction in patients with AS after adjusting for traditional atherosclerotic risk factors and coronary artery disease (odds ratio 8.46, 95% confidence interval 2.38 to 30.12; p = 0.001). In conclusion, the results from the present study showed that there is a greater prevalence of aortic arch plaques in patients with AS and that the presence of complex plaques is independently associated with cerebral infarction in these patients. Therefore, the identification of complex arch plaques using transesophageal echocardiography is important for risk stratification of cerebrovascular events in patients with severe AS. 相似文献