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81.
Ryo Kodama Masayoshi Kato Shuichi Furuta Shouta Ueno Yugen Zhang Kuniharu Matsuno Chihiro Yabe‐Nishimura Eiji Tanaka Tohru Kamata 《Genes to cells : devoted to molecular & cellular mechanisms》2013,18(1):32-41
Activated oncogenes induce premature cellular senescence, a permanent state of proliferative arrest in primary rodent and human fibroblasts. Recent studies suggest that generation of reactive oxygen species (ROS) is involved in oncogenic Ras‐induced premature senescence. However, the signaling mechanism controlling this oxidant‐mediated irreversible growth arrest is not fully understood. Here, we show that through the Ras/MEK pathway, Ras oncogene up‐regulated the expression of superoxide‐generating oxidases, Nox1 in rat REF52 cells and Nox4 in primary human lung TIG‐3 cells, leading to an increase in intracellular level of ROS. Ablation of Nox1 and Nox4 by small interfering RNAs (siRNAs) blocked the RasV12 senescent phenotype including β‐galactosidase activity, growth arrest and accumulation of tumor suppressors such as p53 and p16Ink4a. This suggests that Nox‐generated ROS transduce senescence signals by activating the p53 and p16Ink4a pathway. Furthermore, Nox1 and Nox4 siRNAs inhibited both Ras‐induced DNA damage response and p38MAPK activation, whereas overexpression of Nox1 and Nox4 alone was able to induce senescence. The involvement of Nox1 in Ras‐induced senescence was also confirmed with embryonic fibroblasts derived from Nox1 knockout mice. Together, these findings suggest that Nox1‐ and Nox4‐generated ROS play an important role in Ras‐induced premature senescence, which may involve DNA damage response and p38MAPK signaling pathways. 相似文献
82.
Ryohei Kishi Masaki Yamane Ryosuke Sugiura Wataru Yoshida Yosuke Shimizu Masayoshi Nakano 《RSC advances》2020,10(43):25736
In this study, we theoretically investigate the aromatic and open-shell characteristics of carbon nanobelts (CNBs) composed of five- and six-membered rings. We have designed nanobelts composed of indeno[1,2-b]fluorene ([1,2-b]IF) units, which are referred to as [N]IF-CNB (N: the number of five-membered rings). The number of π-electrons, nπ, in neutral [N]IF-CNB is 7N, and thus depending on N and charge states, nπ can be 4n + 2 and 4n. Quantum chemical calculations on neutral [6]IF-CNB and [8]IF-CNB and dicationic [8]IF-CNB2+ have revealed that they are expected to exhibit unique aromatic and open-shell characteristics depending on nπ, there are several analogies of the electronic structures in [N]IF-CNB to those in [N]annulene. Delocalized and intermediate open-shell electronic structures of [N]IF-CNB are also useful to drastically change the third-order nonlinear optical properties. These results suggest that theoretically designed [N]IF-CNB can be attractive and challenging targets of organic synthesis for realizing novel open-shell functional conjugated macrocycles.Dependence of aromatic and open-shell characteristics on the number of units and charged states was theoretically investigated for carbon nanobelts composed of indeno[1,2-b]fluorene units by using quantum chemical calculations. 相似文献
83.
84.
Tomoko Shimoike Masayoshi Goto Itsuro Nakano Takeaki Sato Yoshikatsu Migita Tetsuhide Ito Toshihiko Yanase Shu-Ichi Sezai Tsunemichi Suzuki Hajime Nawata 《Journal of gastroenterology》1997,32(6):830-835
A case of acinar-islet cell carcinoma presenting as insulinoma is reported. The patient was a 28-year-old man who presented with two convulsive episodes. Fajans' index [immunoreactive insulin (IRI; μU/ml/ glucose mg/dl)] and Turner's [IRI (μU/ml) × 100/glucose (mg/dl)—30] index were high (2.8 and 308, respectively), as were serum proinsulin levels (550pg/ml). Abdominal computed tomography and angiography revealed a highly vascular tumor in the pancreatic tail and several similar tumors in the liver. Histologic features of a biopsy specimen from a hepatic tumor were those of a malignant pancreatic endocrine tumor. Insulin secretion by the liver metastases was confirmed by venous sampling after arterial stimulation with calcium. These findings led us to diagnose malignant insulinoma with liver metastases. Serum levels of α-fetoprotein and trypsin were markedly elevated, to 2234ng/ml (normal <10) and 22000ng/ml (normal<460) respectively, and these levels continued to rise with further growth of the liver metastases. Immunohistochemically, the metastatic liver tumor specimen was positive for α-fetoprotein, α1-antichymotrypsin, chromogranin A, and neuron-specific enolase. These findings of amphicrine features in the tumor were indicative of acinar-islet cell carcinoma that produced α-fetoprotein and trypsin in addition to insulin. 相似文献
85.
Yu Sato Akiomi Yoshihisa Yusuke Kimishima Takatoyo Kiko Yuki Kanno Tetsuro Yokokawa Satoshi Abe Tomofumi Misaka Takamasa Sato Masayoshi Oikawa Atsushi Kobayashi Takayoshi Yamaki Hiroyuki Kunii Kazuhiko Nakazato Yasuchika Takeishi 《Journal of cardiac failure》2019,25(3):195-203
Background
We aimed to clarify the prognosis and pathophysiological parameters of low T3 syndrome in patients with heart failure (HF).Methods and Results
Hospitalized patients with HF and euthyroidism (n?=?911) were divided into 2 groups on the basis of free triiodothyronine (FT3) serum levels: the normal FT3 group (FT3 ≥2.3 pg/mL; n?=?590; 64.8%) and the low FT3 group (FT3 <2.3 pg/mL; n?=?321; 35.2%). We compared post-discharge cardiac and all-cause mortality by means of Kaplan-Meier analysis and Cox proportional hazard analysis, and the parameters of echocardiography and cardiopulmonary exercise testing by means of Student t test. In the follow-up period of median 991 (interquartile range 534-1659) days, there were 193 all-cause deaths, including 88 cardiac deaths. Cardiac and all-cause mortality were higher in the low FT3 group (log-rank P < .01). Low FT3 was a predictor of cardiac death (hazard ratio 1.926, 95% confidence interval [CI] 1.268–2.927; P?=?.002) and all-cause death (hazard ratio 2.304, 95% CI 1.736–3.058; P < .001). Although left ventricular ejection fraction was similar between the groups, the low FT3 group showed lower peak VO2 (13.6 ± 4.6 vs 16.6 ± 4.4 mL·kg?1·min,?one P < .001) and higher VE/VCO2 slope (36.5 ± 8.2 vs 33.0 ± 7.5; P?=?.001).Conclusion
Low T3 syndrome in patients with HF is associated with higher cardiac and all cause-mortality. 相似文献86.
Kosuke Okuwaki Hironori Masutani Hiroshi Imaizumi Tsutomu Yoshida Mitsuhiro Kida Tomohisa Iwai Hiroshi Yamauchi Masayoshi Tadehara Kai Adachi Masafumi Watanabe Takahiro Kurosu Wasaburo Koizumi 《Pancreatology》2019,19(3):419-423
Background/Objectives
A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness has been receiving attention as a novel predictor of anticancer drug sensitivity in PDAC, making the screening of BRCAness paramount.Methods
We conducted the first-ever examination of the feasibility of analyzing BRCAness using multiplex ligation-dependent probe amplification (MLPA). Formalin-fixed paraffin-embedded (FFPE) tissue samples obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) from 20 patients with the highest pancreatic carcinoma cell counts in tissue samples out of 40 consecutive PDAC patients who underwent EUS-FNAB at our hospital were analyzed by MLPA for BRCAness.Results
We were able to accurately analyze BRCAness in 75% of the 20 cases of PDAC using FFPE tissue obtained by EUS-FNAB. BRCAness was observed in one of the 20 cases.Conclusions
In PDAC, analyzing BRCAness by MLPA using FFPE tissue obtained by EUS-FNAB offers the remarkable benefit of yielding results in a short period of time and at a low cost. In addition, this method of BRCAness analysis may prove to be a feasible and effective approach for performing precision medicine. 相似文献87.
Yu Sato Akiomi Yoshihisa Yusuke Kimishima Takatoyo Kiko Shunsuke Watanabe Yuki Kanno Satoshi Abe Makiko Miyata Takamasa Sato Satoshi Suzuki Masayoshi Oikawa Atsushi Kobayashi Takayoshi Yamaki Hiroyuki Kunii Kazuhiko Nakazato Takafumi Ishida Yasuchika Takeishi 《The Canadian journal of cardiology》2018,34(1):80-87
Background
It is widely recognized that overt hyper- as well as hypothyroidism are potential causes of heart failure (HF). Additionally it has been recently reported that subclinical hypothyroidism (sub-hypo) is associated with atherosclerosis, development of HF, and cardiovascular death. We aimed to clarify the effect of sub-hypo on prognosis of HF, and underlying hemodynamics and exercise capacity.Methods
We measured the serum levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4) in 1100 consecutive HF patients. We divided these patients into 5 groups on the basis of plasma levels of TSH and FT4, and focused on euthyroidism (0.4 ≤ TSH ≤ 4 μIU/mL and 0.7 ≤ FT4 ≤ 1.9 ng/dL; n = 911; 82.8%) and sub-hypo groups (TSH > 4 μIU/mL and 0.7 ≤ FT4 ≤ 1.9 ng/dL; n = 132; 12.0%). We compared parameters of echocardiography, cardiopulmonary exercise testing, and cardiac catheterization, and followed up for cardiac event rate and all-cause mortality between the 2 groups.Results
Although left ventricular ejection fraction did not differ between the 2 groups, the sub-hypo group had lower peak breath-by-breath oxygen consumption and higher mean pulmonary arterial pressure than the euthyroidism group (peak breath-by-breath oxygen consumption, 14.0 vs 15.9 mL/min/kg; P = 0.012; mean pulmonary arterial pressure, 26.8 vs 23.5 mm Hg, P = 0.020). In Kaplan-Meier analysis (mean 1098 days), the cardiac event rate and all-cause mortality were significantly higher in the sub-hypo group than those in the euthyroidism group (log rank, P < 0.01, respectively). In Cox proportional hazard analysis, sub-hypo was a predictor of cardiac event rate and all-cause mortality in HF patients (P < 0.05, respectively).Conclusions
Sub-hypo might be associated with adverse prognosis, accompanied by impaired exercise capacity and higher pulmonary arterial pressure, in HF patients. 相似文献88.
Keisuke Nakamura Masayoshi Ohira Yoshiharu Yokokawa Yuya Nagasawa 《Journal of Sports Science and Medicine》2015,14(4):708-715
Sit-to-stand exercise (STS) is a common activity of daily living. The objectives of the present study were: 1) to assess the validity of aerobic fitness measurements based on anaerobic thresholds (ATs), during incremental sit-to-stand exercise (ISTS) with and without arm support compared with an incremental cycle-ergometer (CE) test; and 2) to examine the reproducibility of the AT measured during the ISTSs. Twenty-six healthy individuals randomly performed the ISTS and CE test. Oxygen uptakes at the AT (AT-VO2) and heart rate at the AT (AT-HR) were determined during the ISTSs and CE test, and repeated-measures analyses of variance and Tukey’s post-hoc test were used to evaluate the differences between these variables. Pearson correlation coefficients were used to assess the strength of the relationship between AT-VO2 and AT-HR during the ISTSs and CE test. Data analysis yielded the following correlations: AT-VO2 during the ISTS with arm support and the CE test, r = 0.77 (p < 0.05); AT-VO2 during the ISTS without arm support and the CE test, r = 0.70 (p < 0.05); AT-HR during the ISTS with arm support and the CE test, r = 0.80 (p < 0.05); and AT-HR during the ISTS without arm support and the CE test, r = 0.66 (p < 0.05). The AT-VO2 values during the ISTS with arm support (18.5 ± 1.9 mL·min-1·kg-1) and the CE test (18.4 ± 1.8 mL·min-1·kg-1) were significantly higher than those during the ISTS without arm support (16.6 ± 1.8 mL·min-1·kg-1; p < 0.05). The AT-HR values during the ISTS with arm support (126 ± 10 bpm) and the CE test (126 ± 13 bpm) were significantly higher than those during the ISTS without arm support (119 ± 9 bpm; p < 0.05). The ISTS with arm support may provide a cardiopulmonary function load equivalent to the CE test; therefore, it is a potentially valid test for evaluating AT-VO2 and AT-HR in healthy, young adults.
Key points
- The ISTS is a simple test that varies only according to the frequency of standing up, and requires only a small space and a chair.
- The ISTS with arm support is valid and reproducible, and is a safe test for evaluating AT in healthy young adults.
- For evaluating the AT, the ISTS may serve as a valid alternative to conventional CPX, using either a cycle ergometer or treadmill, in cases where the latter methods are difficult to implement.
89.
Takai K Nikkuni K Sanada M Shibuya H 《[Rinshō ketsueki] The Japanese journal of clinical hematology》2003,44(7):462-467
A 72-year-old woman was admitted with left cervical lymphadenopathy, high fever, pancytopenia and liver dysfunction. Bone marrow aspiration showed infiltration of large atypical lymphoid cells and hemophagocytic histiocytes, thus suggesting a diagnosis of lymphoma associated hemophagocytic syndrome (LAHS). An abdominal CT scan revealed multiple low-density areas in the liver, and the patient's liver function rapidly deteriorated. Histologically, the cervical biopsy showed lymphoma cell infiltration with prominent necrosis and karyorrhectic debris. The lymphoma cells expressed CD3+, CD4-, CD8+, CD20-, CD56+/-, TIA-1+, granzyme B+, and EBER was positive using in situ hybridization. DNA analysis of the TCR beta and gamma chain gene with the Southern blot showed rearranged bands. These findings were compatible with those of EB-virus associated peripheral T-cell lymphoma. After chemotherapy with the THP-COP regimen, the patient's liver dysfunction improved rapidly, but she died from bacterial peritonitis due to perforation of a recurrent duodenal ulcer. Post-mortem examination of the liver showed multiple irregular massive necroses of the hepatocytes, where no lymphoma cell infiltration was present. Hemophagocytic histiocytosis was remarkable in the bone marrow, spleen, lymph nodes, and liver. Marked elevation of serum levels of cytokines such as TNF-alpha or IFN-gamma suggests that these cytokines played an important role in the pathogenesis of the hepatic cell necrosis. 相似文献
90.
Akira Endo Yoshio Kano Koichiro Mihara Kunzo Orita Masayoshi Namba 《Journal of cancer research and clinical oncology》1993,119(9):522-526
Genetic analysis was carried out in human fibroblasts (KMST-6) immortalized by treatment with60Co gamma rays in order to determine if any genetic change was involved in the immortal transformation of human cells. Analysis by restriction fragment length polymorphism revealed an alteration in chromosome 13q12–14, in which the retinoblastoma (RB) gene locus (13q14) is located. Then the RB gene itself was examined. Structural abnormalities in the RB gene were detected by Southern blot analysis. Furthermore, abnormal RB protein (pRB) was expressed in immortalized KMST-6 cells, as shown by in vitro phosphorylation, whereas normal KMS-6 cells expressed the intact pRB. These findings indicated that inactivation of the RB gene is one of the key events of the immortalization of human cells.Abbreviations RB
retinoblastoma
- pRB
retinoblastoma gene product (protein)
- T
simian virus 40 large T antigen
- E1A
adenovirus E1A protein 相似文献