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91.
Chen L Kawano T Bajic S Kaziro Y Itoh H Art JJ Nakajima Y Nakajima S 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(12):8430-8435
G protein-coupled inward rectifiers (GIRKs) are activated directly by G protein betagamma subunits, whereas classical inward rectifiers (IRKs) are constitutively active. We found that a glutamate residue of GIRK2 (E315), located on a hydrophobic domain of the C terminus, is crucial for the channel activation. This glutamate (or aspartate) residue is conserved in all members of the Kir family. Substitution of alanine for the glutamate on GIRK1, GIRK2, and IRK2, expressed in HEK293 cells, greatly reduced the whole-cell currents. The whole-cell current of GIRK channels with a constitutively active gate, GIRK2(V188A), [Yi, B. A., Lin, Y. F., Jan, Y. N. & Jan, L. Y. (2001) Neuron 29, 657-667] was also reduced by the same glutamate mutation. Mean open time and conductance of single channels in GIRK2 and IRK2 were not affected by the mutation, indicating that the reduced whole-cell current resulted from a lowered probability of channel activation. The mutated GIRK and IRK showed normal trafficking to the cell membrane. The mutated GIRK2 retained the ability to interact with G protein betagamma subunits, and it showed almost the same inwardly rectifying property as the wild type. The mutated GIRK1 and GIRK2 retained ion selectivity to K(+) ions. This glutamate residue corresponds to one of the residues causing Andersen's syndrome [Plaster, N. M., Tawil, R., Tristani-Firouzi, M., Canun, S., Bendahhou, S., Tsunoda, A., Donaldson, M. R., Iannaccone, S. T., Brunt, E., Barohn, R., et al. (2001) Cell 105, 511-519]. Our interpretation is that this region of the glutamate residue is crucial in relaying the activating message from the ligand sensor region to the gate. 相似文献
92.
Isolated brain-retrocerebral neurohemal complex of the silkworm of Bombyx mori was stimulated electrically and the released bombyxin (an insulin-like neuropeptide) was measured using time-resolved fluoroimmunoassay. The amount of bombyxin release depended on the number of stimulus pulses delivered to the axonal tract of the bombyxin-producing (BP) neurosecretory cells, and 17 fg of bombyxin per pulse was released from a cell. The titer of bombyxin in the hemolymph of bombyxin-II injected pupae decreased exponentially, the half-life being 170 min. To relate firing activity of a population of BP cells to the hormone titer in the hemolymph, bombyxin titer and its change in the hemolymph were calculated numerically. We assumed that the amount of bombyxin release was proportional to the firing rate of BP cells and the released bombyxin was inactivated with the same time course of injected bombyxin. Our calculations suggested that the hemolymph bombyxin titer may fluctuate dynamically and the mean titer is 380 pg/ml, a level which is close to the actually determined bombyxin titer at middle stages of pupal-adult development. 相似文献
93.
Evaluation of the efficacy of an Helicobacter pylori eradication treatment for idiopathic thrombocytopenic purpura patients] 总被引:1,自引:0,他引:1
Atsunaga Kato Hideaki Kato Noboru Hirashima Tomoyuki Sakamoto Haruhiko Nukaya Kiyoaki Ito Seijiro Matsunaga Hiromu Kondo Yoshito Tanaka Kenji Sakakibara 《Nihon Shokakibyo Gakkai zasshi》2004,101(11):1209-1216
The relationship between Helicobacter pylori (H. pylori) and gastric diseases (e.g. peptic ulcer, MALT lymphoma, and stomach cancer) has been widely accepted. Recent studies have also suggested an association between H. pylori infection and idiopathic thrombocytopenic purpura (ITP). In this study, an H. pylori eradication treatment was administered to 20 ITP patients and elucidated for its effectiveness. Among those 20 patients, H. pylori infection was confirmed in 17 (85%) through a C14 urea breath test, a rapid urease test, or a culture examination of a biopsied sample obtained by gastrointestinal endoscopy. Although the other 3 were negative to H. pylori, the H. pylori eradication treatment was also attempted because no other effective treatments had been established at the time of this study. In the H. pylori eradication treatment, lansoprazole (LPZ) 60 mg bid, amoxicillin (AMPC) 1500 mg bid, and clarithromycin (CAM) 400 mg bid were given to each patient for 7 days. For 4 cases, CAM was replaced with metronidazole (MNZ) 750 mg bid. The patients whose H. pylori infection was not eradicated after the first treatment received the re-eradication treatment with LPZ 60 mg bid, AMPC 1500 mg bid, and MNZ 750 mg bid for 7 days. After the treatments, the success of eradicating H. pylori was confirmed in all 17 H. pylori positive patients. In addition, platelet recovery was obtained in 11/20 patients (55%), which included 2 H. pylori negative patients and 2 patients whose H. pylori eradication was not successful after the first treatment. No relationship was found between the eradication effectiveness and the following clinical parameters: age, gender, previous therapies, disease duration, presence of anti-nucleus antibody, endoscopic atrophic change in the stomach, or kinds of antibiotics used for the treatment. These results support the efficacy of an H. pylori eradication treatment for ITP patients. A noteworthy result of this study was that an increase of platelet count was observed not only in H. pylori positive ITP patients, but also in 2 out of 3 H. pylori negative ITP patients after H. pylori eradication. Further studies are required to elucidate the efficacy of H. pylori eradication therapy in the patients negative for H. pylori. 相似文献
94.
Yasuhiro Mizoguchi M.D. Hiroshi Kuboi Hiroko Tsutsui Shuichi Seki Kenzo Kobayashi Sukeo Yamamoto Seiji Morisawa Ikuya Yano 《Journal of gastroenterology》1989,24(5):519-522
When BALB/cAJcl mice are intravenously injected with heat-killedPropionibacterium acnes (P. acnes) followed by an intravenous injection of lipopolysaccharide (LPS) 7 days later, massive necrosis is induced in the liver tissue
and most of the mice die within 24 hours of LPS injection. Using this experimental model, acute hepatic failure was induced
in various strains of mice and the difference in the response was studied. As a result, as in BALB/cAJcl mice, acut hepatic
failure was also induced in BALB/ cAJcl-nu, AKR/J, C3H/HeNJcl, C57BL/6NJcl and DDy mice. However, as an exception, hepatic
cell necrosis was hardly seen and the survival rate was remarkable high in C3H/HeJ mice, which genetically do not respond
to LPS stimulation. These results indicate that for this experimental induction of acute hepatic failure, macrophages must
be activated by the two-step stimulation ofP. acnes and LPS. 相似文献
95.
96.
Naoto Okada Momoyo Azuma Masaki Imanishi Yoshito Zamami Yasushi Kirino Toshimi Nakamura Kazuhiko Teraoka Masahiro Abe Keisuke Ishizawa 《Clinical therapeutics》2018,40(2):252-260
Purpose
Liposomal amphotericin B (L-AMB) is an essential antifungal agent for patients with hematologic diseases; however, the drug causes severe hypokalemia at a high frequency. Meanwhile, there is little evidence regarding the risk factors for L-AMB–induced severe hypokalemia, and the prevention protocol has not been established. The goal of this study was to identify the risk factors related to severe hypokalemia induced by L-AMB in hematologic patients.Methods
Seventy-eight hematologic patients with a first administration of L-AMB were enrolled in the study. Eleven patients who had serum potassium levels <3.0 mmol/L before L-AMB administration and 12 patients who received L-AMB administration within 3 days were excluded. Patients who had a serum potassium level <3.0 mmol/L during L-AMB administration were classified into a hypokalemia group (n = 26), and those who had a serum potassium level ≥3.0 mmol/L were classified into a non-hypokalemia group (n = 29). The patient characteristics were analyzed retrospectively. In addition, the usefulness of potassium supplementation was analyzed for those patients who received potassium formulations (non-hypokalemia group, n = 15; hypokalemia group, n = 24).Findings
Twenty-six patients had hypolalemia after L-AMB administration. Hypokalemia with serum potassium levels <3.0 mmol/L was observed ~7 days after starting L-AMB administration. The patient characteristics, L-AMB dose, and L-AMB administration period did not differ between the 2 groups. In the patients who received potassium formulations, the period between starting L-AMB administration and starting potassium supplementation was significantly shorter in the non-hypokalemia group than in the hypokalemia group (median, 0 vs 4 days, respectively; P < 0.01); the potassium dose was not different between the 2 groups. A receiver-operating characteristic curve revealed that the cutoff time for the start of potassium supplementation to reduce the incidence of L-AMB–induced hypokalemia was 3 days. Multivariate logistic regression analysis revealed that beginning potassium supplementation within 2 days from the start of L-AMB administration was an independent factor reducing the risk of L-AMB–induced hypokalemia (odds ratio, 0.094 [95% CI, 0.019–0.47]).Implications
This study showed that starting administration of a potassium formulation within 2 days from the start of L-AMB administration was a risk reduction factor for L-AMB–induced hypokalemia. This finding indicates that early potassium supplementation should be incorporated into the regimen of hypokalemia management when L-AMB is used. 相似文献97.
98.
Tahata Yuki Hikita Hayato Mochida Satoshi Enomoto Nobuyuki Kawada Norifumi Kurosaki Masayuki Ido Akio Miki Daiki Yoshiji Hitoshi Takikawa Yasuhiro Sakamori Ryotaro Hiasa Yoichi Nakao Kazuhiko Kato Naoya Ueno Yoshiyuki Yatsuhashi Hiroshi Itoh Yoshito Tateishi Ryosuke Suda Goki Takami Taro Nakamoto Yasunari Asahina Yasuhiro Matsuura Kentaro Yamashita Taro Kanto Tatsuya Akuta Norio Terai Shuji Shimizu Masahito Sobue Satoshi Miyaki Tomokatsu Moriuchi Akihiro Yamada Ryoko Kodama Takahiro Tatsumi Tomohide Yamada Tomomi Takehara Tetsuo 《Journal of gastroenterology》2022,57(2):120-132
Journal of Gastroenterology - Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the... 相似文献
99.
100.