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61.
Elevated Fibroblast Growth Factor 23 Exerts Its Effects on Placenta and Regulates Vitamin D Metabolism in Pregnancy of Hyp Mice 下载免费PDF全文
Yasuhisa Ohata Miwa Yamazaki Masanobu Kawai Naoko Tsugawa Kanako Tachikawa Tomoko Koinuma Kazuaki Miyagawa Akihito Kimoto Masahiro Nakayama Noriyuki Namba Hironori Yamamoto Toshio Okano Keiichi Ozono Toshimi Michigami 《Journal of bone and mineral research》2014,29(7):1627-1638
Fibroblast growth factor 23 (FGF23) functions in an endocrine fashion and requires α‐Klotho to exert its effects on the target organs. We have recently demonstrated that the human placenta also expresses α‐Klotho, which led us to hypothesize that FGF23 may exert effects on the placenta. Immunohistochemical analysis demonstrated the expression of FGF receptor 1 (FGFR1) as well as that of α‐Klotho in the feto‐maternal interface of both mouse and human normal‐term placentas, which suggested that these areas might be receptive to FGF23. Therefore, we next investigated whether FGF23 has some roles in the placenta using Hyp mice with high levels of circulating FGF23. Hyp and wild‐type (WT) females were mated with WT males, and the mothers and their male fetuses were analyzed. FGF23 levels in Hyp mothers were elevated. FGF23 levels were about 20‐fold higher in Hyp fetuses than in Hyp mothers, whereas WT fetuses from Hyp mothers exhibited low levels of FGF23, as did fetuses from WT mothers. We analyzed the placental gene expression and found that the expression of Cyp24a1 encoding 25OHD‐24‐hydroxylase, a target gene for FGF23 in the kidney, was increased in the placentas of fetuses from Hyp mothers compared with fetuses from WT mothers. In an organ culture of WT placentas, treatment with plasma from Hyp mothers markedly increased the expression of Cyp24a1, which was abolished by the simultaneous addition of anti‐FGF23 neutralizing antibody. The direct injection of recombinant FGF23 into WT placentas induced the expression of Cyp24a1. The increase in the placental expression of Cyp24a1 in fetuses from Hyp mothers resulted in decreased plasma 25‐hydroxyvitamin D levels. These results suggest that increased levels of circulating FGF23 in pathological conditions such as Hyp mice exerts direct effects on the placenta and affects fetal vitamin D metabolism via the regulation of Cyp24a1 expression. © 2014 American Society for Bone and Mineral Research. 相似文献
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Jun Teishima Daiki Murata Shogo Inoue Tetsutaro Hayashi Koji Mita Yasuhisa Hasegawa Masao Kato Mitsuru Kajiwara Masanobu Shigeta Satoshi Maruyama Hiroyuki Moriyama Seiji Fujiwara Akio Matsubara 《Current Urology》2021,15(4):187
Background:There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI.Materials and methods:A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed.Results:Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively.Conclusions:Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients. 相似文献
66.
Takeshi Nagashima Ken Yamaguchi Kenichi Urakami Yuji Shimoda Sumiko Ohnami Keiichi Ohshima Tomoe Tanabe Akane Naruoka Fukumi Kamada Masakuni Serizawa Keiichi Hatakeyama Kenya Matsumura Shumpei Ohnami Koji Maruyama Tohru Mochizuki Masatoshi Kusuhara Akio Shiomi Yasuhisa Ohde Masanori Terashima Katsuhiko Uesaka Tetsuro Onitsuka Seiichiro Nishimura Yasuyuki Hirashima Nakamasa Hayashi Yoshio Kiyohara Yasuhiro Tsubosa Hirohisa Katagiri Masashi Niwakawa Kaoru Takahashi Hiroya Kashiwagi Masahiro Nakagawa Yuji Ishida Takashi Sugino Mitsuru Takahashi Yasuto Akiyama 《Cancer science》2020,111(2):687-699
This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients. 相似文献
67.
Quantitative analysis of the spinal cord motoneuron under chronic compression: an experimental observation in the mouse 总被引:5,自引:0,他引:5
Hisatoshi Baba Yasuhisa Maezawa Shinichi Imura Norio Kawahara Kenji Nakahashi Katsuro Tomita 《Journal of neurology》1996,243(2):109-116
We investigated quantitative changes in spinal cord motoneurons following chronic compression using a mouse model of cervical
cord compression. Twenty-five tiptoe-walking Yoshimura (twy) mice with calcified mass lesions compressing the spinal cord
posterolaterally at the C1–C2 vertebral levels were compared with five Institute of Cancer Research (ICR) mice that served
as controls. Spinal cord motoneurons in the anterior grey horn between the C1 and C3 spinal cord segments were Nissl-stained
and counted topographically and then analysed in relation to the extent of spinal cord compression. The number of motoneurons
in C1–C3 spinal cord segments decreased significantly with a linear correlation with the transverse area of the spinal cord
when the cord was compressed to 50–70% of control values. A significant reduction in the number of motoneurons occurred at
the C2–C3 spinal cord segment compressed at the C1–C2 vertebral level. In contrast, at the level rostral to the C1 vertebra,
the number of motoneurons increased significantly in proportion to the magnitude of compression. The current study demonstrates
that a number of neurons, morphologically consistent with anterior horn cells, were observed at a rostral site absolutely
free of external compression where no such cells normally exist. 相似文献
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Seiichi Himeno Seiichiro Tarui Shuji Kanayama Toshio Kuroshima Vasuhisa Shinomura Chozo Hayashi Kayoko Tateishi Kenichi Imagawa Etsuro Hashimura Tushiyuki Hamaoka 《The American journal of gastroenterology》1983,78(11):703-707
A highly sensitive and precise radioimmunoassay system for plasma cholecystokinin (CCK) was developed with the anli-CCK-8 specific antiserum which raised against N-terminal amino acids residue of sulfated CCK-8 and reacted with CCK-8, CCK-33, and CK-39 but not with gastrin and its related peptides. Mean concentration of the fasting plasma CCK determined with this method using CCK-8 as standard was 12.9 ± 5.9 pg/ml in normal subjects (n = 26), and in patients with hepatic cirrhosis it was significantly higher (36.7 ± 16.9 pg/ml, n = 9, p < 0.01) than in normal subjects. In six young healthy volunteers, intraduodenal infusion of fat caused a significant increase ( p < 0.05) of plasma CCK from a basal level of 8.0 pg/ml to a peak of 43.0 ± 12.0 pg/ml at 20 min after starting of infusion. In the same subjects, a significant increase of plasma CCK was also observed by amino acids infusion, but no elevation of plasma CCK level was found during intraduodenal acidification. 相似文献
70.
Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos) 下载免费PDF全文
Seiki Kiriyama Kazuto Kozaka Tadahiro Takada Steven M. Strasberg Henry A. Pitt Toshifumi Gabata Jiro Hata Kui‐Hin Liau Fumihiko Miura Akihiko Horiguchi Keng‐Hao Liu Cheng‐Hsi Su Keita Wada Palepu Jagannath Takao Itoi Dirk J. Gouma Yasuhisa Mori Shuntaro Mukai Mariano Eduardo Giménez Wayne Shih‐Wei Huang Myung‐Hwan Kim Kohji Okamoto Giulio Belli Christos Dervenis Angus C. W. Chan Wan Yee Lau Itaru Endo Harumi Gomi Masahiro Yoshida Toshihiko Mayumi Todd H. Baron Eduardo de Santibañes Anthony Yuen Bun Teoh Tsann‐Long Hwang Chen‐Guo Ker Miin‐Fu Chen Ho‐Seong Han Yoo‐Seok Yoon In‐Seok Choi Dong‐Sup Yoon Ryota Higuchi Seigo Kitano Masafumi Inomata Daniel J. Deziel Eduard Jonas Koichi Hirata Yoshinobu Sumiyama Kazuo Inui Masakazu Yamamoto 《Journal of hepato-biliary-pancreatic sciences》2018,25(1):17-30
Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large‐scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30‐day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30‐day mortality among patients with Grade I or Grade III AC, but significantly lower 30‐day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included. 相似文献