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991.
Wanaporn Yimchuen Tetsuya Kadonosono Yumi Ota Shinichi Sato Maika Kitazawa Tadashi Shiozawa Takahiro Kuchimaru Masumi Taki Yuji Ito Hiroyuki Nakamura Shinae Kizaka-Kondoh 《RSC advances》2020,10(26):15154
Tumor-binding peptides such as human epidermal growth factor receptor 2 (HER2)-binding peptides are attractive therapeutic and diagnostic options for cancer. However, the HER2-binding peptides (HBPs) developed thus far are susceptible to proteolysis and lose their affinity to HER2 in vivo. In this report, a method to create a HER2-binding fluctuation-regulated affinity protein (HBP-FLAP) consisting of a fibronectin type III domain (FN3) scaffold with a structurally immobilized HBP is presented. HBPs were selected by phage-library screening and grafted onto FN3 to create FN3-HBPs, and the HBP-FLAP with the highest affinity (HBP sequence: YCAHNM) was identified after affinity maturation of the grafted HBP. HBP-FLAP containing the YCAHNM peptide showed increased proteolysis-resistance, binding to HER2 with a dissociation constant (KD) of 58 nM in ELISA and 287 nM in biolayer interferometry and specifically detects HER2-expressing cancer cells. In addition, HBP-FLAP clearly delineated HER2-expressing tumors with a half-life of 6 h after intravenous injection into tumor-bearing mice. FN3-based FLAP is an excellent platform for developing target-binding small proteins for clinical applications.A HER2-binding protein, HBP-FLAP, developed by peptide immobilization specifically binds to HER2 and has improved resistance to proteases. 相似文献
992.
This research presents the first example of the formation of a triplex via hydrogen bonding of a synthetic cyanuryl nucleoside (Cn) composed of a 6-membered ring compound (triazine-2,4,6-trione) which functions as a pyrimidine base. The Cn was able to form the triad via hydrogen bonding in two directions with two adenines, one in the antisense and one in the parallel chain. The thermal stability of the duplex between the antisense and sense chains was evaluated via its UV melting temperature. The melting curves of triplexes possessing the cyanuryl nucleoside (sense chain) and two adenines (antisense and parallel chains) were biphasic. To prove the formation of hydrogen bonding between the cyanuryl nucleoside and the adenine base toward the major groove, structural analysis via NMR was undertaken. A cyanuryl nucleoside containing three 15N in triazine-2,4,6-trione was synthesized first, and then the 15N cyanuryl nucleoside was incorporated into target sequences. The triplex containing the A·Cn A triad was analyzed via1H NMR, coupled and decoupled with 15N. This triad has two imino proton signals derived from the cyanuryl nucleoside, split according to the 15N coupling condition, at low field. These results are evidence of the formation of hydrogen bonds between the Cn and adenosine. The solution structure of the triplex was analyzed via NOE information from the imino proton. The cyanuryl nucleoside-containing triplex forms a right-handed helical structure similar to natural triplex DNA, albeit DNA having an enhanced pyrimidine analog in the sense chain capable of bidirectional hydrogen bonding with high sequence selectivity.The triplex formation ability of a sense chain containing a cyanuryl nucleoside was evaluated and the tertiary structure of the triplex was calculated using the NOE in 1H NMR by incorporating a 15N into the base moiety. 相似文献
993.
Hiroaki Nakashima Yasutsugu Yukawa Shiro Imagama Keigo Ito Testuro Hida Masaaki Machino Shunsuke Kanbara Daigo Morita Nobuyuki Hamajima Naoki Ishiguro Fumihiko Kato 《European spine journal》2013,22(7):1526-1532
Purpose
There have been few reports on the risk factors for tracheostomy and the possibility of patients for decannulation. The purpose of this study was to identify factors necessitating tracheostomy after cervical spinal cord injury (SCI) and detect features predictive of successful decannulation in tracheostomy patients.Methods
One hundred and sixty four patients with cervical fracture/dislocation were retrospectively reviewed. The patients comprised 142 men and 22 women with a mean age of 44.9 years. The clinical records were reviewed for patients’ demographic data, smoking history, level of cervical spine injury, injury patterns, neurological status, evidence of direct thoracic trauma and head injury, tracheostomy placement, and decannulation. Risk factors necessitating tracheostomy and factors predicting decannulation were statistically analysed.Results
Twenty-five patients (15.2 %) required tracheostomy. Twenty-one patients were successfully decannulated. Smoking history (relative risk [RR], 3.05; p = 0.03) and complete SCI irrespective of injury level (C1–4 complete SCI: RR, 67.55; p < 0.001, C5–7 complete SCI: RR, 57.88; p < 0.001) were significant risk factors necessitating tracheostomy. C1–4 complete SCI was more frequent among those who could not be decannulated. However, even in patients with high cervical complete SCI at the time of injury, patients regaining sufficient movement to shrug their shoulders within 3 weeks after injury could later be decannulated.Conclusions
The risk factors for tracheostomy after complete SCI were a history of smoking and complete paralysis irrespective of the level of injury. High cervical level complete SCI was found to be a risk factor for the failure of decannulation in patients without shoulder shrug within 3 weeks after injury. 相似文献994.
Toshiro Ito Nobuyoshi Kawaharada Yoshihiko Kurimoto Tetsuya Koyanagi Takeshi Uzuka Mayuko Uehara Takayuki Hagiwara Yohsuke Yanase Toshiyuki Maeda Tetsuya Higami 《Surgery today》2013,43(9):1019-1024
Purpose
To evaluate the association of previous abdominal aortic aneurysm (AAA) graft replacement with infradiaphragmatic malperfusion in patients with acute aortic dissection.Methods
Between November 2006 and June 2011, 133 patients were referred to our hospital for management of acute aortic dissection. Eight (6.0 %) of these patients had undergone AAA graft replacement prior to the acute aortic dissection. We compared the computed tomography (CT) images of these 8 patients with those of the remaining 125 patients without previous AAA graft replacement, in terms of organ ischemia as a complication induced by acute aortic dissection.Results
Infradiaphragmatic malperfusion from acute aortic dissection was confirmed in four of the eight patients who had undergone AAA graft replacement. Contrasted CT scan images indicated that the main cause of infradiaphragmatic malperfusion was collapse of the true lumen from compression by the false lumen into the suprarenal aorta. Although there was no significant difference between the groups in terms of cerebral ischemia and myocardial ischemia, bilateral leg ischemia and visceral ischemia occurred more frequently in the patients who had undergone AAA graft replacement.Conclusion
Previous AAA graft replacement is a risk factor for infradiaphragmatic malperfusion in patients with acute aortic dissection. 相似文献995.
Tomohiro Izumi Toru Hirano Kei Watanabe Atsuki Sano Takui Ito Naoto Endo 《European spine journal》2013,22(11):2569-2574
Background
Two-dimensional imaging is not adequate for evaluating ossification of the posterior longitudinal ligament (OPLL). This study was designed to evaluate the accuracy of a novel computed tomography (CT)-based three-dimensional (3D) analysis method that we had devised to measure volume changes in OPLL.Subjects and methods
Twenty OPLL patients (12 male and 8 female; mean age 63.6 years) who were being followed conservatively were examined twice with an interval of at least 1 year between the two scans. The mean interval was 22 (range 12–45) months. A 3D model was created with DICOM data from CT images, using the MIMICS® software to calculate the volume. The mean ossification volume was determined from two measurements. Since ossification size varies widely, evaluation of change in volume is generally affected by the original size. Therefore, the change in ossification volume between the first and second CT examinations was calculated as the annual rate of progression.Results
The type of OPLL was classified as continuous in 3 patients, segmented in 3, and mixed in 14. The mean ossification volume was 1,831.68 mm3 at the first examination and 1,928.31 mm3 at the second, showing a significant mean increase in ossification volume. The mean annual rate of lesion increase was 3.33 % (range 0.08–7.79 %).Conclusion
The 3D method used allowed detailed OPLL classification and quantification of change in the ossified volume. Thus, this method appears to be very useful for quantitative evaluation of OPLL with only minimal measurement error. 相似文献996.
Jun Takahashi Hirokazu Kobayashi Shinji Wakabayashi Masao Deguchi Hidehiro Ito Yuji Mogami Hirotaka Tanikawa Hiroyuki Nakagawa Hideki Moriya Ryohei Ashizawa Kenji Takahara Hisatoshi Kinoshita Yutaka Tateiwa Hiromichi Misawa Takahiro Tsutsumimoto Taku Nakakohji Yohei Yuzawa Akihito Sawaumi Yohei Hidai Satoshi Matsuda Isao Nakamura Shigeyuki Toba Mikio Kamimura Takeshi Nakane Hiroki Hirabayashi Hiroyuki Hashidate Nobuhide Ogihara Keijiro Mukaiyama Hiroyuki Kato Kuniyoshi Ohtsuka 《Journal of orthopaedic science》2013,18(2):208-215
Background
Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D).Methods
QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0–100).Results
Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5–15, 15–30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group.Conclusion
According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects. 相似文献997.
Hiroshi Kinashi Yasuhiko Ito Masashi Mizuno Yasuhiro Suzuki Takeshi Terabayashi Fumiko Nagura Ryohei Hattori Yoshihisa Matsukawa Tomohiro Mizuno Yukihiro Noda Hayato Nishimura Ryosuke Nishio Shoichi Maruyama Enyu Imai Seiichi Matsuo Yoshifumi Takei 《Journal of the American Society of Nephrology : JASN》2013,24(10):1627-1642
Peritoneal fibrosis (PF) causes ultrafiltration failure (UFF) and is a complicating factor in long-term peritoneal dialysis. Lymphatic reabsorption also may contribute to UFF, but little is known about lymphangiogenesis in patients with UFF and peritonitis. We studied the role of the lymphangiogenesis mediator vascular endothelial growth factor-C (VEGF-C) in human dialysate effluents, peritoneal tissues, and peritoneal mesothelial cells (HPMCs). Dialysate VEGF-C concentration correlated positively with the dialysate-to-plasma ratio of creatinine (D/P Cr) and the dialysate TGF-β1 concentration. Peritoneal tissue from patients with UFF expressed higher levels of VEGF-C, lymphatic endothelial hyaluronan receptor-1 (LYVE-1), and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UFF. Furthermore, mesothelial cell and macrophage expression of VEGF-C increased in the peritoneal membranes of patients with UFF and peritonitis. In cultured mesothelial cells, TGF-β1 upregulated the expression of VEGF-C mRNA and protein, and this upregulation was suppressed by a TGF-β type I receptor (TGFβR-I) inhibitor. TGF-β1–induced upregulation of VEGF-C mRNA expression in cultured HPMCs correlated with the D/P Cr of the patient from whom the HPMCs were derived (P<0.001). Moreover, treatment with a TGFβR-I inhibitor suppressed the enhanced lymphangiogenesis and VEGF-C expression associated with fibrosis in a rat model of PF. These results suggest that lymphangiogenesis associates with fibrosis through the TGF-β–VEGF-C pathway.The decrease in ultrafiltration capacity that is associated with the high peritoneal solute transport that is observed after prolonged peritoneal dialysis (PD) treatment is a major reason for its discontinuation.1–4 Several studies have shown that a higher peritoneal solute transport rate is associated with reduced survival of PD patients.1,2,5 The characteristic features of chronic peritoneal damage in PD treatment are associated with submesothelial fibrosis and neoangiogenesis.6,7 Analyses of the surface peritoneum showed no significant changes in vessel density with duration of PD.6,8 In addition, the vessel density in patients with ultrafiltration failure (UFF) was significantly higher than the vessel density in normal individuals or non-PD patients, but it was not higher than the vessel density in patients undergoing PD.6 These findings suggest that factors other than increased vascular density may be involved in disease states associated with increased transport of peritoneal membranes. In addition, the relationship between peritoneal fibrosis and UFF remains obscure.Blood capillaries have a continuous basal lamina with tight interendothelial junctions and are supported by pericytes and smooth muscle cells. In contrast, lymphatic capillaries are thin-walled with a wide lumen and do not contain pericytes or basement membrane. The structures of lymphatic vessels are suitable for the removal of tissue fluid, cells, and macromolecules from the interstitium.9–11 If lymphangiogenesis develops in the peritoneal membrane, absorption of the PD fluid could be increased and lead to UFF. An increase in the number of lymphatic vessels has recently been reported in several disease conditions, including tumor metastasis,12–15 chronic respiratory inflammatory diseases,16–18 wound healing,19 and renal transplant rejection.20,21 We recently reported that lymphangiogenesis had developed in tubulointerstitial fibrosis of human renal biopsy specimens,22 and we also reported the mechanisms of lymphangiogenesis in rat unilateral ureteral obstruction models.23The lymphatic absorption rate, which is measured by the rate at which intraperitoneally administered radioactive serum albumin or macromolecule dextran 70 disappears, is significantly higher in patients with UFF, and lymphatic reabsorption is considered to be one of the causes of UFF.24–27 However, the results from these clinical approaches have been controversial.28,29 In addition, little is known about the pathology and the process of lymphangiogenesis in patients with UFF and peritonitis.In this study, we investigated lymphangiogenesis and the expression of vascular endothelial growth factor-C (VEGF-C), which is a potentially important mediator of lymphangiogenesis, in human peritoneal tissues, PD effluent, and peritoneal mesothelial cells. We also explored VEGF-C induction by TGF-β1 in the human mesothelial cell line (Met-5A) and cultured human peritoneal mesothelial cells (HPMCs) from the spent PD effluent of patients with varying rates of peritoneal transport. Finally, we explored the relationship between peritoneal fibrosis and lymphangiogenesis in rats that were administered chlorhexidine gluconate (CG) into the abdominal cavity, which provides a model of chemically induced peritoneal inflammation/fibrosis.30–32 This work is the first report to show that lymphangiogenesis is linked to the peritoneal fibrosis that is often associated with a high peritoneal transport rate. 相似文献
998.
Yoshiyuki Kojima Norio Takahashi Nobuhiro Haga Masanori Nomiya Tomohiko Yanagida Kei Ishibashi Ken Aikawa David I Lee 《International journal of urology》2013,20(11):1052-1063
Robot‐assisted radical prostatectomy has been shown to have comparable and possibly improved postoperative continent rates compared with retropubic and laparoscopic radical prostatectomy. However, postoperative urinary incontinence has remained one of the most bothersome postoperative complications. The basic concept of the intraoperative technique to improve postoperative urinary continence is to maintain as normal anatomical and functional structure in the pelvis as possible. Therefore, improved knowledge of the normal structure in the pelvis should lead to a greater understanding of the pathophysiology of urinary incontinence, and further development of intraoperative techniques to improve the outcomes of urinary continence. It might be necessary to carry out three steps to realize improvement of the early return of urinary continence after robot‐assisted radical prostatectomy: (i) preservation (bladder neck, neurovascular bundle, puboprostatic ligament, pubovesical complex, and/or urethral length, etc.); (ii) reconstruction (posterior and/or anterior reconstruction, and/or reattachment of the arcus tendineus to the bladder neck, etc.); and (iii) reinforcement (bladder neck plication and/or sling suspension, etc.). On the basis of these steps, further modifications during robot‐assisted radical prostatectomy should be developed to improve urinary continence and quality of life after robot‐assisted radical prostatectomy. 相似文献
999.
Mai Sato Shuichi Ito Masao Ogura Koichi Kamei Isao Miyairi Ippei Miyata Masataka Higuchi Kentaro Matsuoka 《Pediatric nephrology (Berlin, Germany)》2013,28(1):145-149
Background
Rituximab, an anti-CD20 antibody that targets B cells, is a promising agent against steroid-dependent and steroid-resistant nephrotic syndrome in children.Case-Diagnosis/Treatment
We report a 3-year-old boy who presented with atypical Pneumocystis jiroveci pneumonia (PCP) following administration of rituximab for refractory nephrotic syndrome. He had received cyclosporine and daily prednisolone for over 1?year. Following rituximab therapy, a hazy shadow was observed on his chest X-ray. Chest-computed tomography revealed multiple nodular lesions in bilateral lungs, although his clinical symptoms were subtle. PCR analysis demonstrated the presence of Pneumocystis DNA in his bronchoalveolar lavage. Lung wedge resection of the nodular lesion exhibited granulomas containing a few cysts of P. jiroveci that primarily consisted of T cells and histiocytes and lacked B cells. A deficiency of B cells following rituximab treatment suggests a dramatic effect on the immune response and, therefore, could result in granulomatous PCP. Nodular granulomatous lesions of PCP comprise an emerging concept previously reported in adults with hematological disease, bone marrow transplant, or treatment with rituximab. We report the first pediatric case of nodular PCP. Granulomatous PCP can be life-threatening. Moreover, bronchoalveolar lavage often fails to demonstrate the presence of P. jiroveci DNA. Wedge biopsy is warranted for definitive diagnosis. Our patient fully recovered with sulfamethoxazole/trimethoprim treatment because of early detection.Conclusions
The indication of rituximab for refractory nephrotic syndrome has increased recently. Therefore, recognition of the risk of atypical PCP is important. Our findings suggest that PCP prophylaxis should be considered following rituximab therapy. 相似文献1000.
Nanako Nakamura-Taira Yoshimi Muranaka Masako Miwa Seikon Kin Kei Hirai 《International urology and nephrology》2013,45(4):1145-1158