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131.
Kosuke Izumi Avni B. Santani Matthew A. Deardorff Holly A. Feret Tanya Tischler Brian D. Thiel Surabhi Mulchandani Catherine A. Stolle Nancy B. Spinner Elaine H. Zackai Laura K. Conlin 《American journal of medical genetics. Part A》2013,161(1):166-171
Prader–Willi syndrome is caused by the loss of paternal gene expression on 15q11.2–q13.2, and one of the mechanisms resulting in Prader–Willi syndrome phenotype is maternal uniparental disomy of chromosome 15. Various mechanisms including trisomy rescue, monosomy rescue, and post fertilization errors can lead to uniparental disomy, and its mechanism can be inferred from the pattern of uniparental hetero and isodisomy. Detection of a mosaic cell line provides a unique opportunity to understand the mechanism of uniparental disomy; however, mosaic uniparental disomy is a rare finding in patients with Prader–Willi syndrome. We report on two infants with Prader–Willi syndrome caused by mosaic maternal uniparental disomy 15. Patient 1 has mosaic uniparental isodisomy of the entire chromosome 15, and Patient 2 has mosaic uniparental mixed iso/heterodisomy 15. Genome‐wide single‐nucleotide polymorphism array was able to demonstrate the presence of chromosomally normal cell line in the Patient 1 and trisomic cell line in Patient 2, and provide the evidence that post‐fertilization error and trisomy rescue as a mechanism of uniparental disomy in each case, respectively. Given its ability of detecting small percent mosaicism as well as its capability of identifying the loss of heterozygosity of chromosomal regions, genome‐wide single‐nucleotide polymorphism array should be utilized as an adjunct to the standard methylation analysis in the evaluation of Prader–Willi syndrome. © 2012 Wiley Periodicals, Inc. 相似文献
132.
Aberrant activation of receptor tyrosine kinases (RTKs) is a common feature of many cancer cells. It was previously suggested that the mechanisms of kinase activation in cancer might be linked to transitions between active and inactive states. Here, we estimate the effects of single and double cancer mutations on the stability of active and inactive states of the kinase domains from different RTKs. We show that singleton cancer mutations destabilize active and inactive states; however, inactive states are destabilized more than the active ones, leading to kinase activation. We show that there exists a relationship between the estimate of oncogenic potential of cancer mutation and kinase activation. Namely, more frequent mutations have a higher activating effect, which might allow us to predict the activating effect of the mutations from the mutation spectra. Independent evolutionary analysis of mutation spectra complements this observation and finds the same frequency threshold defining mutation hotspots. We analyze double mutations and report a positive epistasis and additional advantage of doublets with respect to cancer cell fitness. The activation mechanisms of double mutations differ from those of single mutations and double mutation spectrum is found to be dissimilar to the mutation spectrum of singletons. Hum Mutat 33:1566–1575, 2012. Published 2012 Wiley Periodicals, Inc.* 相似文献
133.
Chika Nishizawa Sarah Cajusay-Velasco Masato Mashima Nobuhiro Mori Keiji Hayashi Hiroyuki Kubo Ryuichi Shimono Kosuke Koyano Toshiyuki Hata 《Journal of Medical Ultrasonics》2014,41(4):511-514
Enteric duplication cysts are rare congenital anomalies, but their antenatal diagnosis is becoming more common because of advances in ultrasonography. With the latest state-of-the-art technology, HDlive facilitates a more realistic anatomical visualization of different fetal organ structures, making diagnosis more precise. We present a case of antenatal HDlive imaging of an enteric duplication cyst. A 26-year-old pregnant Japanese woman was referred to our ultrasound clinic because of a fetal intra-abdominal cyst at 27 weeks of gestation. Two-dimensional (2D) ultrasound revealed a sonolucent, ellipsoid structure in the subhepatic area. Magnetic resonance imaging yielded the same findings. However, irregular internal echoes appeared at 33 weeks of gestation. There was no vascularity on color Doppler. HDlive clearly depicted a more realistic image of the circular mass, which was thick walled, with a large amount of debris inside, and showed no communication with adjacent structures. Careful monitoring was conducted for these unusual findings. A day after delivery, an emergency operation was performed because the infant had sudden signs and symptoms of obstruction. Intra-operative findings were ileus and a necrotic ileal duplication cyst confirmed by histopathologic studies. Complications of enteric duplication cyst can arise at any time of life, and so thorough monitoring may be recommended. The findings of irregular internal echoes and a large amount of debris inside the cyst are relatively characteristic features of a complicated cyst. HDlive gives us additional information on the actual appearance of a complicated cyst that may be difficult to obtain using conventional 2D sonography alone. HDlive can be very useful in the antenatal surveillance of enteric duplication cysts. 相似文献
134.
Kosuke Saito Nozomi Tanaka Jun Ikari Masaki Suzuki Rie Anazawa Mitsuhiro Abe Yoshiro Saito Koichiro Tatsumi 《Journal of applied toxicology : JAT》2019,39(4):658-671
Drug‐induced lung injury is an adverse effect of drug treatment that can result in respiratory failure. Because lipid profiling could provide cutting‐edge understanding of the pathophysiology of toxicological responses, we performed lipidomic analyses of drug‐induced lung injury. We used a mouse model of bleomycin‐induced lung injury and followed the physiological responses at the acute inflammatory (day 2), inflammatory‐to‐fibrosis (day 7) and fibrosis (day 21) phases. The overall lipid profiles of plasma, lung and bronchoalveolar lavage fluid (BALF) revealed that drastic changes in lipids occurred in the lung and BALF, but not in the plasma, after 7 and 21 days of bleomycin treatment. In the lung, the levels of ether‐type phosphatidylethanolamines decreased, while those of phosphatidylcholines, bismonophosphatidic acids and cholesterol esters increased on days 7 and 21. In BALF, the global lipid levels increased on days 7 and 21, but only those of some lipids, such as phosphatidylglycerols/bismonophosphatidic acids and phosphatidylinositols, increased from day 2. The lung levels of prostaglandins, such as prostaglandin D2, were elevated on day 2, and those of 5‐ and 15‐lipoxygenase metabolites of docosahexaenoic acid were elevated on day 7. In BALF, the levels of 12‐lipoxygenase metabolites of polyunsaturated fatty acids were elevated on day 7. Our comprehensive lipidomics approach suggested anti‐inflammatory responses in the inflammatory phase, phospholipidosis and anti‐inflammatory responses in the inflammatory‐to‐fibrosis phase, and increased oxidative stress and/or cell phenotypic transitions in the fibrosis phase. Understanding these molecular changes and potential mechanisms will help develop novel drugs to prevent or treat drug‐induced lung injury. 相似文献
135.
Takeshi Saraya Kosuke Ohkuma Yayoi Tsukahara Takayasu Watanabe Daisuke Kurai Haruyuki Ishii Hirokazu Kimura Hajime Goto Hajime Takizawa 《Respiratory investigation》2018,56(4):320-325
Background
Mycoplasma pneumoniae (MP) is the primary cause of community-acquired pneumonia. We aimed to evaluate the correlation between clinical features, with special reference to hypoxemia and the total affected area obtained using high-resolution computed tomography (HRCT).Methods
Medical records of MP pneumonia patients > 15 years of age at Kyorin University Hospital between January 2006 and November 2013 were reviewed retrospectively and compared to patients with Streptococcus pneumoniae pneumonia, diagnosed between January 2013 and September 2014.Results
We identified 65 and 32 patients with MP- and S. pneumoniae pneumonia, respectively. HRCT data were available for 42 and 32 patients with MP- and S. pneumoniae pneumonia, respectively. Data were available for all hypoxemic patients. Hypoxemia was significantly higher in patients with S. pneumoniae (14/32, p = 0.008) than those with MP (5/39). Total visual score on HRCT correlated significantly with hypoxemia in both groups, but showed significantly higher scores with MP- than with S pneumoniae pneumonia in hypoxemic patients.MP pneumonia showed significant positive correlation between the total visual score and serum inflammatory markers (C-reaction protein [r = 0.43, p = 0.025] and lactate dehydrogenase [r = 0.466, p = 0.016]). In both groups, individual scores in the middle and lower lung fields were significantly higher than in the upper field, suggesting zonal predominance.Conclusions
This study provides the first evidence that the total affected area on lung HRCT was more with MP compared to S. pneumoniae pneumonia in hypoxemic patients and positively correlated with hypoxemia and serum inflammatory markers. 相似文献136.
Mayu Shiomi Shinya Matsuzaki Satoshi Serada Koji Matsuo Chihiro Mizuta-Odani Mariko Jitsumori Ruriko Nakae Satoko Matsuzaki Satoshi Nakagawa Kosuke Hiramatsu Ai Miyoshi Eiji Kobayashi Toshihiro Kimura Yutaka Ueda Kiyoshi Yoshino Tetsuji Naka Tadashi Kimura 《Cancer science》2021,112(9):3655-3668
This study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody-drug conjugate (CD70-ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock- or nuclear factor (NF)-κB-p65-small interfering RNA. We developed an ADC with an anti-CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P < .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780-NF-κB-p65-silenced cells. CD70-ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70-ADC treated mice was significantly inhibited compared to that in the control-ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm3, P < .01; SKOV3cisR: 232.2 vs 584.9 mm3, P < .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer. 相似文献
137.
Kentaro Kajino Tetsuhisa Kitamura Kosuke Kiyohara Taku Iwami Mohamud Daya Marcus Eng Hock Ong 《Prehospital emergency care》2016,20(4):477-484
Objective: Survival after out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical service (EMS) personnel has been insufficiently understood. The aim of this study was to evaluate temporal trends in survival after EMS-witnessed OHCAs in Japan. Methods: A nationwide, population-based, observational cohort study of consecutive adult OHCA patients with emergency responder resuscitation attempts from January 2005 to December 2012 in Japan. We assessed the trends in annual incidence, characteristics, and outcomes of OHCA patients witnessed by EMS personnel. Multiple logistic regression analysis was used to assess factors that were potentially associated with neurologically favorable outcome defined as cerebral performance category scale 1or 2. Results: During the study period, a total of 66,760 EMS-witnessed OHCAs were documented. The annual incidence rates per 100,000 persons of EMS-witnessed OHCA patients increased from 4.6 (n = 7219) in 2005 to 4.9 (n = 9256) in 2012 (p for trend = 0.035). The proportion of one-month survival with neurologically favorable outcome improved from 5.9% in 2005 to 8.6% in 2012 (p for trend < 0.001), and the proportion increased from 22.1% in 2005 to 30.2% in 2012 in cases with shockable rhythm (p for trend < 0.001). In a multivariate analysis, adults, male gender, shockable rhythm, presumed cardiac origin, and year were associated with a better neurological outcome. Conclusions: In this population, the proportion of one-month survival with neurologically favorable outcome among OHCA patients witnessed by EMS personnel significantly improved during the study period. 相似文献
138.
Kosuke Takahashi Hiroshi Saito Yoshinori Hasegawa Masahiko Ando Masashi Yamamoto Eiji Kojima Yasuteru Sugino Tomoki Kimura Fumio Nomura Tomohiko Ogasawara Joe Shindoh Norio Yoshida Ryujiro Suzuki 《Cancer chemotherapy and pharmacology》2014,73(4):721-727
Purpose
Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability.Methods
Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10).Results
Plasma concentration of Icotinib reached peak at a median Tmax of 0.75–3.5 h after single dose and then declined with a mean t1/2β of 6.02–7.83 h. Over the dose range of 100–600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported.Conclusion
The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100–600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects. 相似文献139.
Hitoshi Tajiri M.D Kosuke Kozaiwa M.D Tokuzo Harada M.D Yoshikazu Ozaki M.D Kazunori Miki M.D Kazuo Shimizu M.D Shintaro Okada M.D. 《Pediatrics international》1991,33(3):323-326
We assessed the efficacy of a government-sponsored mass protection program in Osaka, Japan, for perinatal HBV infection in infants born to HBeAg positive HBV carrier mothers. We also evaluated the impact of optional follow-up procedures in such infants, including an evaluation of anti-HBs response and a booster dose of HBV vaccine for poor responders. The results demonstrated that this mass protection program protected 94.4% of the infants from perinatal HBV infection in the Osaka area. However, the proportion of infants with an unprotective level of anti-HBs was higher in the standard group than in the follow-up group both at 1.0 and 1.5 years of age, which was also the case for HBV events. Furthermore, the present study showed that a booster dose of vaccine in poor responders was very effective in promoting an anti-HBs response. In conclusion, we recommend that a follow-up blood test to confirm a response of anti-HBs to HBV vaccine should be performed at 4–8 weeks after the third injection of HBV vaccine in infants born to HBeAg positive HBV carrier mothers. We also recommend that a booster injection of HBV vaccine should be immediately given to poor responding infants who otherwise are at a considerable risk of developing HBV infection in late infancy. 相似文献
140.
Susumu Yagome Takehiro Sugiyama Kosuke Inoue Ataru Igarashi Ryotaro Bouchi Mitsuru Ohsugi Kohjiro Ueki Atsushi Goto 《Journal of epidemiology / Japan Epidemiological Association》2022,32(10):476
BackgroundRegular visits with healthcare professionals are important for preventing serious complications in patients with diabetes. The purpose of this retrospective cohort study was to clarify whether there was any suppression of physician visits among patients with diabetes during the spread of the novel coronavirus 2019 (COVID-19) in Japan and to assess whether telemedicine contributed to continued visits.MethodsWe used the JMDC Claims database, which contains the monthly claims reported from July 2018 to May 2020 and included 4,595 (type 1) and 123,686 (type 2) patients with diabetes. Using a difference-in-differences analysis, we estimated the changes in the monthly numbers of physician visits or telemedicine per 100 patients in April and May 2020 compared with the same months in 2019.ResultsFor patients with type 1 diabetes, the estimates for total overall physician visits were −2.53 (95% confidence interval [CI], −4.63 to 0.44) in April and −8.80 (95% CI, −10.85 to −6.74) in May; those for telemedicine visits were 0.71 (95% CI, 0.47–0.96) in April and 0.54 (95% CI, 0.32–0.76) in May. For patients with type 2 diabetes, the estimates for overall physician visits were −2.50 (95% CI, −2.95 to −2.04) in April and −3.74 (95% CI, −4.16 to −3.32) in May; those for telemedicine visits were 1.13 (95% CI, 1.07–1.20) in April and 0.73 (95% CI, 0.68–0.78) in May.ConclusionThe COVID-19 pandemic was associated with suppression of physician visits and a slight increase in the utilization of telemedicine among patients with diabetes during April and May 2020.Key words: COVID-19, telemedicine, outpatient, diabetes 相似文献