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21.
KATP channel interaction with adenine nucleotides 总被引:5,自引:0,他引:5
ATP-sensitive potassium (K(ATP)) channels are regulated by adenine nucleotides to convert changes in cellular metabolic levels into membrane excitability. Hence, elucidation of interaction of SUR and Kir6.x with adenine nucleotides is an important issue to understand the molecular mechanisms underlying the metabolic regulation of the K(ATP) channels. We analyzed direct interactions with adenine nucleotides of each subunit of K(ATP) channels. Kir6.2 binds adenine nucleotides in a Mg(2+)-independent manner. SUR has two NBFs which are not equivalent: NBF1 is a Mg(2+)-independent high affinity nucleotide binding site, whereas NBF2 is a Mg-dependent low affinity site. Although SUR has ATPase activity at NBF2, it is not used to transport substrates against the concentration gradient unlike other ABC proteins. The ATPase cycle at NBF2 serves as a sensor of cellular metabolism. This may explain the low ATP hydrolysis rate compared to other ABC proteins. Based on studies of photoaffinity labeling, a model of K(ATP) channel regulation is proposed, in which K(ATP) channel activity is regulated by SUR via monitoring the intracellular MgADP concentration. K(ATP) channel activation is expected to be induced by the cooperative interaction of ATP binding at NBF1 and MgADP binding at NBF2. 相似文献
22.
CD7+ and CD56+ Myeloid/Natural Killer Cell Precursor Acute Leukemia: A Distinct Hematolymphoid Disease Entity 总被引:11,自引:0,他引:11
23.
Ken Yasukawa Michio Takido Mieko Takeuchi Michinori Akasu Shigeki Nakagawa 《Journal of cancer research and clinical oncology》1991,117(5):421-424
Summary Cepharanthine, isolated fromStephania cepharantha, is one of the bisbenzylisoquinoline-type alka-loids. We have found that it inhibits tumor promotion after topical application in two-stage carcinogenesis in mouse skin. Epidermal ornithine decarboxylase activities inhibited by topical application of cepharanthine, with an 5 g/mouse) and mezerein (5 g/mouse) were found to be inhibited by topical application of cepharanthine, with a ED50 of 1.2 mol and 1.4 mol respectively. These inhibitory effects of cepharanthine are considered to be related to its antitumor activity in two-stage carcinogenesis in mouse skin. Cell-mediated immunosuppression by TPA was unaffected by topical application of cepharanthine. A diet containing 0.005% cepharanthine (about 0.5 mg mouse– day–) slightly suppressed the two-stage promotion of skin tumors by twice-weekly applications of 2.5 g TPA for 2 weeks (first stage) followed by twice-weekly applications of 2.5 g mezerein for 23 weeks (second stage) in ICR mice following initiation by 50 g 7,12-dimethylbenz[a]anthracene. Oral administration of cepharanthine inhibits the tumor promotion in two-stage carcinogenesis in mouse skin.Abbreviations DMBA
7,12-dimethylbenz[a]anthracene
- DTH
delayed-type hypersensitivity
- ODC
ornithine decarboxylase
- TPA
12-O-tetradecanoylphorbol 13-acetate 相似文献
24.
Tomohiro Aoki Koji Izutsu Ritsuro Suzuki Chiaki Nakaseko Hiroshi Arima Kazuyuki Shimada Akihiro Tomita Makoto Sasaki Jun Takizawa Kinuko Mitani Tadahiko Igarashi Yoshinobu Maeda Noriko Fukuhara Fumihiro Ishida Nozomi Niitsu Ken Ohmachi Hirotaka Takasaki Naoya Nakamura Tomohiro Kinoshita Shigeo Nakamura Michinori Ogura 《Haematologica》2014,99(12):1817-1825
The prognosis of patients with primary mediastinal large B-cell lymphoma has improved over recent years. However, the optimal treatment strategy including the role of radiotherapy remains unknown. We retrospectively analyzed the clinical outcomes of 345 patients with newly diagnosed primary mediastinal large B-cell lymphoma in Japan. With a median follow up of 48 months, the overall survival at four years for patients treated with R-CHOP (n=187), CHOP (n=44), DA-EPOCH-R (n=9), 2nd- or 3rd-generation regimens, and chemotherapy followed by autologous stem cell transplantation were 90%, 67%, 100%, 91% and 92%, respectively. Focusing on patients treated with R-CHOP, a higher International Prognostic Index score and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival in patients treated with R-CHOP without consolidative radiotherapy (IPI: hazard ratio 4.23, 95% confidence interval 1.48–12.13, P=0.007; effusion: hazard ratio 4.93, 95% confidence interval 1.37–17.69, P=0.015). Combined with the International Prognostic Index score and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without radiotherapy, patients with lower International Prognostic Index score and the absence of effusion comprised approximately one-half of these patients and could be identified as curable patients (95% overall survival at 4 years). The DA-EPOCH-R regimen might overcome the effect of these adverse prognostic factors. Our simple indicators of International Prognostic Index score and the presence of pleural or pericardial effusion could stratify patients with primary mediastinal large B-cell lymphoma and help guide selection of treatment. 相似文献
25.
Michinori Funato Osamu Uemura Katsumi Ushijima Hidenori Ohnishi Kenji Orii Zenichiro Kato Satoshi Yamakawa Takuhito Nagai Osamu Ohara Hideo Kaneko Naomi Kondo 《Journal of clinical immunology》2014,34(6):691-695
Purpose
Gain-of-function mutations in complement factor B (CFB) were recently identified in patients with atypical hemolytic uremic syndrome (aHUS), but are extremely rare. Our purpose is to describe a large kindred with aHUS associated with a CFB mutation and to further understand CFB-mutated aHUS patients.Methods and Results
We report a large kindred in which 3 members had aHUS. This kindred revealed that 9 of 12 members, including 2 affected patients, had persistent activation of the alternative pathway with low complement component 3 and that those 9 members showed a CFB mutation (c.1050G?>?C, p.Lys350Asn) in exon 8. This missense mutation was heterozygous in 8 of them and homozygous in only one. From structural studies, this mutation is shown to be located in close proximity to the Mg2-binding site within a von Willebrand factor type A domain of CFB, resulting in a gain-of-function effect of CFB and predisposition to aHUS. At present, 2 of the 3 members with aHUS have maintained normal renal function for a long-term period.Conclusions
This kindred illustrates that a CFB mutation (c.1050G?>?C, p.Lys350Asn) can result in aHUS. In the future, phenotype-genotype correlations and outcome in CFB-mutated aHUS patients need to be further investigated by accumulation of a number of cases. 相似文献26.
Kumiko Shoji Michinori Shirano Mitsuru Konishi Yuko Toyoshima Miyuki Matsumoto Tetsushi Goto Yu Kasamatsu Yuji Ichida Yasuo Kagawa Terue Kawabata Hiromitsu Ogata Daiki Habu 《Nutrients》2022,14(3)
Maintenance of the cluster of differentiation 4 (CD4) positive lymphocyte count (CD4 count) is important for human immunodeficiency virus (HIV) positive individuals. Although a higher body mass index (BMI) is shown to be associated with a higher CD4 count, BMI itself does not reflect body composition. Therefore, we examined the association of body weight, body composition and the CD4 count, and determined the optimal ranges of CD4 count associated factors in Japanese HIV positive individuals. This cross-sectional study included 338 male patients treated with antiretroviral therapy for ≥12 months. Multiple logistic regression analysis was used to identify factors significantly associated with a CD4 count of ≥500 cells (mm3)−1. The cutoff values of factors for a CD4 ≥ 500 cells (mm3)−1 and cardiovascular disease risk were obtained by receiver operating characteristic curves. Age, body fat percentage (BF%), nadir CD4 count, duration of antiretroviral therapy (ART), years since the HIV-positive diagnosis and cholesterol intake showed significant associations with the CD4 count. The cutoff value of BF% for a CD4 ≥ 500 cells (mm3)−1 and lower cardiovascular disease risk were ≥25.1% and ≤25.5%, respectively. The BF%, but not the BMI, was associated with CD4 count. For the management of HIV positive individuals, 25% appears to be the optimal BF% when considering the balance between CD4 count management and cardiovascular disease risk. 相似文献
27.
Takenori Okada Yasuhiko Hayashi Mamoru Toyofuku Michinori Imazu Masaya Otsuka Tadamichi Sakuma Hironori Ueda Hideya Yamamoto Nobuoki Kohno 《Circulation journal》2008,72(9):1430-1435
Background The efficacy of sirolimus-eluting stents (SESs) has not been established in dialysis patients. Methods and Results This study was a non-randomized observational single-center registry in a community hospital: data for 80 consecutive dialysis patients who underwent percutaneous coronary intervention (PCI) with SES were compared with those of a historical group of consecutive 124 dialysis patients treated with bare-metal stents (BMS). After 1 year, the cumulative incidence of major adverse cardiac events (MACE), comprising cardiac death, nonfatal myocardial infarction, stent thrombosis, or target lesion revascularization (TLR), was 25.2% in the SES group and 38.2% in the BMS group (p=0.048). In multivariate analysis, use of SES remained an independent predictor of MACE at 1 year after PCI (risk ratio 0.70, 95% confidence interval 0.52-0.93, p=0.015). Rates of TLR were 21.7% in the SES group and 30.9% in the BMS group and (p=0.15). Subgroup analysis showed that use of SES was effective in patients with small vessels, non-diabetic patients, and patients without highly calcified lesions. Conclusions In dialysis patients, the implantation of SES was moderately effective in reducing MACE at 1 year after PCI as compared with BMS. However, the TLR rate at 1 year was relatively higher than previously reported. (Circ J 2008; 72: 1430 - 1435). 相似文献
28.
Yukio Kobayashi Kensei Tobinai Akihiro Takeshita Kensuke Naito Osamu Asai Nobuaki Dobashi Shinpei Furusawa Kenji Saito Kinuko Mitani Yasuo Morishima Michinori Ogura Fumiaki Yoshiba Tomomitsu Hotta Masami Bessho Shin Matsuda Jin Takeuchi Shuichi Miyawaki Tomoki Naoe Noriko Usui Ryuzo Ohno 《International journal of hematology》2009,89(4):460-469
The primary objective of this study was to investigate the tolerability, efficacy and pharmacokinetic profile of gemtuzumab
ozogamicin (GO) in patients with relapsed and/or refractory CD33-positive acute myeloid leukemia (AML). Patients received
2-h infusions of GO twice with an interval of approximately 14 days. Tolerability was assessed using the National Cancer Institute
Common Toxicity Criteria Version 2.0. Samples for pharmacokinetics were taken on day 1 and day 8 of the first treatment cycle.
The dose was increased stepwise and, in each cohort, patients were treated at the same dose. Forty patients, median age 58 years
(range 28–68) were treated; 20 and 20 patients were enrolled to the phase I and II parts, respectively. In the phase I part,
dose-limiting toxicities (DLTs) were hepatotoxicities, and the recommended dose was established as 9 mg/m2 given as two intravenous infusions separated by approximately 14 days. The pharmacokinetic study revealed that C
max and AUC were equivalent to those of non-Japanese patients. In the phase II part, complete remission was observed in 5 patients,
and one patient had complete remission without platelet recovery. Four of these 6 in remission and one in the phase I are
long-term survivors (alive for at least 44 months). GO is safe and effective as a single agent among Japanese CD33-positive
AML patients. Remission lasted longer in a subset of patients than in non-Japanese patients in earlier studies. Further studies
of this agent are warranted to establish standard therapy.
S. Furusawa: deceased. 相似文献
29.
One‐year safety and efficacy study of bilastine treatment in Japanese patients with chronic spontaneous urticaria or pruritus associated with skin diseases
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Akiko Yagami Masutaka Furue Michinori Togawa Akihiro Saito Michihiro Hide 《The Journal of dermatology》2017,44(4):375-385
A number of second‐generation non‐sedating antihistamines are used in clinical practices over the world. However, long‐term safety and efficacy have not been proved high level evidence based medicine. We have performed an open‐label, multicenter, phase III study to evaluate the long‐term safety and efficacy of bilastine, a novel non‐sedating H1‐antihistamine for patients with chronic spontaneous urticaria (CSU) or pruritus associated with skin diseases (trial registration no. JapicCTI‐142528). Patients aged 18–74 years were treated with bilastine 20 mg once daily for up to 52 weeks. Safety and tolerability were assessed on the basis of adverse events (AE), bilastine‐related AE, laboratory tests and vital signs. Efficacy was assessed based on rash score, itch score, overall improvement and quality of life. One hundred and ninety‐eight patients enrolled, 122 of whom (61.6%) completed the 52‐week treatment period. AE were reported in 64.5% and bilastine‐related AE in 2.5% of patients throughout the 52‐week treatment period. All AE were mild to moderate in severity. AE associated with the nervous system occurred in 10 patients (5.1%) including seven patients (3.6%) with headache. Somnolence reported in two of these patients (1.0%) was related to bilastine. All efficacy variables improved during treatment with bilastine. In conclusion, long‐term treatment with bilastine 20 mg once daily for 52 weeks is safe and well tolerated in Japanese patients with CSU or pruritus associated with skin diseases. Bilastine improved disease symptoms of both conditions early in treatment, and the efficacy was maintained throughout the treatment. 相似文献
30.
Yoshihiro Saito Sumitaka Kobayashi Atsuko IkedaAraki Sachiko Ito Chihiro Miyashita Takashi Kimura Takumi Hirata Akiko Tamakoshi Michinori Mayama Kiwamu Noshiro Kinuko Nakagawa Takeshi Umazume Kentaro Chiba Satoshi Kawaguchi Mamoru Morikawa Kazutoshi Cho Hidemichi Watari Yoshiya Ito Yasuaki Saijo Reiko Kishi the Japan Environment Children's Study group 《Journal of diabetes investigation.》2022,13(5):889
Aims/IntroductionWe investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre‐pregnancy body mass index (BMI) and/or gestational weight gain (GWG).Materials and MethodsData from the national birth cohort in the Japan Environment and Children''s Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM.ResultsThe OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre‐pregnancy BMI of ≥25.0 kg/m2 and insufficient GWG (<2.75 kg) was 1.78 (1.02–3.12). The OR of having a large for gestational age infant of the same BMI group with excessive GWG (>7.25 kg) was 2.04 (1.56–2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m2 in the GDM group than in the non‐GDM group.ConclusionsLarge for gestational age and hypertensive disorders of pregnancy were associated with pre‐pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m2 are at risk of having small for gestational age and large for gestational age infants depending on GWG. 相似文献