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Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration 总被引:1,自引:0,他引:1
Y Murakami H Matsumoto M Roh J Suzuki T Hisatomi Y Ikeda JW Miller DG Vavvas 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(36):14598-14603
Retinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of subsequent nonautonomous cone cell death remain largely unknown. In this study, we show that receptor-interacting protein (RIP) kinase mediates necrotic cone cell death in rd10 mice, a mouse model of retinitis pigmentosa caused by a mutation in a rod-specific gene. The expression of RIP3, a key regulator of programmed necrosis, was elevated in rd10 mouse retinas in the phase of cone but not rod degeneration. Although rd10 mice lacking Rip3 developed comparable rod degeneration to control rd10 mice, they displayed a significant preservation of cone cells. Ultrastructural analysis of rd10 mouse retinas revealed that a substantial fraction of dying cones exhibited necrotic morphology, which was rescued by Rip3 deficiency. Additionally, pharmacologic treatment with a RIP kinase inhibitor attenuated histological and functional deficits of cones in rd10 mice. Thus, necrotic mechanisms involving RIP kinase are crucial in cone cell death in inherited retinal degeneration, suggesting the RIP kinase pathway as a potential target to protect cone-mediated central and peripheral vision loss in patients with retinitis pigementosa. 相似文献
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Tsuji Y Hiraki Y Matsumoto K Mizoguchi A Sadoh S Kobayashi T Sakamoto S Morita K Yukawa E Kamimura H Karube Y 《Scandinavian journal of infectious diseases》2012,44(8):626-629
We evaluated the pharmacokinetics of linezolid in the case of an obese Japanese patient (body weight 116 kg; body mass index 37 kg/m(2)). Linezolid was administered at a dose of 600 mg by intravenous drip infusion for 60-90 min at 12-h intervals. The results showed increased clearance of linezolid and a reduced serum concentration compared to population pharmacokinetic parameters, with trough levels below the 90% minimum inhibitory concentration. However, linezolid was effective for improving lung infection and inflammation in our patient, which may be due to its particularly effective transfer into lung tissues. Linezolid undergoes slow non-enzymatic oxidation in vivo that may be increased in obese patients, and this may account for the greater clearance. Our findings are useful for the planning of linezolid therapy in obese patients. 相似文献
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Masao Araki Naoyuki Matsumoto Kazuya Honda Teruhiko Ishii Hidero Oki Yoshiyuki Yonehara Kazuo Komiyama 《Oral Radiology》2012,28(1):70-73
Ameloblastoma, desmoplastic type, is a rare lesion for which radiographic images are even less common, and such lesions are
sometimes considered to be variant types. It is defined as a variant of ameloblastoma with specific imaging and histological
features. This lesion occurs with the same frequency in the maxilla and mandible, although the predominant site is the anterior-premolar
site in both the mandible and maxilla. For our case of ameloblastoma, desmoplastic type, resected from the right anterior
to premolar maxilla, the radiographic appearance and histopathological findings were compared. Computed tomography images
revealed that the lesion had a multilocular structure with many smaller septa at its periphery. Although expansion toward
the maxillary sinus was suggested radiologically, invasion of the mucosa into the floor of the maxillary sinus was found on
histopathological examination. 相似文献