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101.
Urokinase-type plasminogen activator is a preferred substrate of the human epithelium serine protease tryptase epsilon/PRSS22 总被引:1,自引:0,他引:1
Yasuda S Morokawa N Wong GW Rossi A Madhusudhan MS Sali A Askew YS Adachi R Silverman GA Krilis SA Stevens RL 《Blood》2005,105(10):3893-3901
Tryptase epsilon is a member of the chromosome 16p13.3 family of human serine proteases that is preferentially expressed by epithelial cells. Recombinant pro-tryptase epsilon was generated to understand how the exocytosed zymogen might be activated outside of the epithelial cell, as well as to address its possible role in normal and diseased states. Using expression/site-directed mutagenesis approaches, we now show that Lys20, Cys90, and Asp92 in the protease's substrate-binding cleft regulate its enzymatic activity. We also show that Arg(-1) in the propeptide domain controls its ability to autoactivate. In vitro studies revealed that recombinant tryptase epsilon possesses a restricted substrate specificity. Once activated, tryptase epsilon cannot be inhibited effectively by the diverse array of protease inhibitors present in normal human plasma. Moreover, this epithelium protease is not highly susceptible to alpha1-antitrypsin or secretory leukocyte protease inhibitor, which are present in the lung. Recombinant tryptase epsilon could not cleave fibronectin, vitronectin, laminin, single-chain tissue-type plasminogen activator, plasminogen, or any prominent serum protein. Nevertheless, tryptase epsilon readily converted single-chain pro-urokinase-type plasminogen activator (pro-uPA/scuPA) into its mature, enzymatically active protease. Tryptase epsilon also was able to induce pro-uPA-expressing smooth muscle cells to increase their migration through a basement membrane-like extracellular matrix. The ability to activate uPA in the presence of varied protease inhibitors suggests that tryptase epsilon plays a prominent role in fibrinolysis and other uPA-dependent reactions in the lung. 相似文献
102.
Masaki Suzuki Minoru Fukuchi Shinji Sakurai Hiroshi Naitoh Shinsuke Kiriyama Takaharu Fukasawa Yuichi Tabe Hayato Yamauchi Tomonori Yoshida Hiroyuki Kuwano 《International surgery》2014,99(1):48-51
We herein describe a 60-year-old Japanese man with a giant retroperitoneal liposarcoma undergoing leiomyosarcomatous differentiation. He was admitted to our hospital because of a 5-month history of dysphagia and abdominal distention. Abdominal computed tomography showed a giant tumor that occupied the entire retroperitoneal space. The majority of the mass was lipomatous and low density; both a heterogenous and solid mass were also present. A giant retroperitoneal liposarcoma was diagnosed, and tumor resection was performed. At surgery, the tumor was mostly isolated from the retroperitoneum and other organs. Histopathologically, the tumor comprised well-differentiated and dedifferentiated liposarcoma with heterologous differentiation of the leiomyosarcomatous components, which is a rare phenomenon in liposarcoma. The patient was alive 3 years after the first treatment, although he has had 3 local recurrences (approximately one recurrence yearly) and has been treated by repeated resection and radiotherapy.Key words: Retroperitoneum, Liposarcoma, Leiomyosarcomatous differentiationDedifferentiated liposarcoma (DL) is one of the most frequent sarcomas of the retroperitoneum. It is defined by the association of an atypical lipomatous tumor, namely, areas of well-differentiated liposarcoma (WDL), with a dedifferentiated component. WDL is composed of mature adipocytes and atypical stromal cells with an enlarged, hyperchromatic nucleus. Usually, the dedifferentiated part of the liposarcoma is composed of either a spindle/pleomorphic high-grade sarcoma or a mixoid/spindle cell low-grade sarcoma. The WDL component may be easily overlooked, and DL may thus be mistaken for another high-grade sarcoma. It has been reported in one study that approximately 5% of the dedifferentiated component showed heterologous differentiation, such as leiomyosarcoma, rhabdomyosarcoma, osteosarcoma, and angiosarcoma.1 A less common phenomenon is the occurrence of WDL with leiomyosarcomatous (LMS) differentiation.2 Limited to the retroperitoneum, only 8 cases of liposarcoma with LMS components have been reported.3–7 We herein report a case of retroperitoneal liposarcoma comprising WDL and DL, with LMS components, treated by surgical resection. 相似文献
103.
Tatsuya Ishigaki Shinsuke Akita Hiroyuki Suzuki Akikazu Udagawa Nobuyuki Mitsukawa 《Auris, nasus, larynx》2021,48(2):288-294
ObjectiveCervical chondrocutaneous branchial remnants (CCBRs) are rare masses located in the anterior region of the neck. Though the basic characteristics of these rare masses were first described by Atlan in 1997, a critical amount of information about these masses remains unknown. This study aimed to further clarify the characteristics of these rare masses.MethodsWe retrospectively reviewed the clinical records of patients with CCBRs in our facility during a 32-year period ranging from 1988 to 2019. We then compared our clinical records with other case reports.ResultsThere were 29 patients with CCBRs in our facility, including 19 males and ten females, Three patients were involved bilaterally (among patients involved unilaterally, the right side included 11 patients, and the left side was 15 patients), eight patients also had associated abnormalities. We submitted CCBRs from 18 patients to pathology, and all of them contained elastic cartilages. Among all the surgical data could be confirmed, cartilages did not reach beyond the musculature of the neck.We could confirm a similar tendency with Atlan regarding sex, the location of CCBRs (involvement side, localization in the neck), and the depth of CCBRs. Among the cases contained in this study, there was a disparity in the rate of associated abnormalities and pathology of contained cartilages.ConclusionSome critical characteristics of CCBRs included, a male predominance, scarcity of bilateral cases and common left side involvement among unilateral involved cases, a common location of CCBRs in the inferior third of the neck and anterior to the sternocleidomastoid muscle, and an involvement of cartilage in CCBRs which has no connections to deep underlying structure of the neck. Further investigations are required to determine the origin of CCBRs and the precise incidence of the associated abnormalities. Systemic examination in patients with CCBRs is recommended because many associated abnormalities have been reported. 相似文献
104.
Takehito Ito Daw-An Wu Toshiyuki Marutani Manami Yamamoto Hidenori Suzuki Shinsuke Shimojo Tetsuya Matsuda 《Social cognitive and affective neuroscience》2014,9(10):1546-1551
Changes in preference are inherently subjective and internal psychological events. We have identified brain events that presage ultimate (rather than intervening) choices, and signal the finality of a choice. At the first exposure to a pair of faces, caudate activity reflected the face of final choice, even if an initial choice was different. Furthermore, the orbitofrontal cortex and hippocampus exhibited correlations only when the subject had made a choice that would not change. 相似文献
105.
106.
Olga Amengual Tetsuya Horita Walter Binder Gary L. Norman Zakera Shums Masaru Kato Kotaro Otomo Yuichiro Fujieda Kenji Oku Toshiyuki Bohgaki Shinsuke Yasuda Tatsuya Atsumi 《Rheumatology international》2014,34(9):1225-1230
Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) were strongly correlated with the presence of lupus anticoagulant showing a high specificity for the diagnosis of antiphospholipid syndrome. However, the main criticism for the clinical applicability of aPS/PT testing is the lack of reproducibility of the results among laboratories. In this study, we measured IgG and IgM aPS/PT using our original in-house enzyme-linked immunosorbent assays (ELISA) and commercial ELISA kits to assess the assay performance and to evaluate the accuracy of aPS/PT results. The study included 111 plasma samples collected from patients and stored at our laboratory for aPS/PT assessment. Sixty-one samples were tested for IgG aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgG ELISA kit (INOVA Diagnostics, Inc., USA). Fifty samples were evaluated for IgM aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgM ELISA kit (INOVA Diagnostics). Ninety-eight percent of samples yielded concordant results for IgG aPS/PT and 82 % for IgM aPS/PT. There was an excellent agreement between the IgG aPS/PT assays (Cohen κ = 0.962) and moderate agreement between the IgM aPS/PT assays (κ = 0.597). Statistically significant correlations in the aPS/PT results were obtained from both IgG and IgM aPS/PT assays (r = 0.749, r = 0.622, p < 0.001, respectively). In conclusion, IgG and IgM detection by ELISA is accurate. The performance of aPS/PT is reliable, and concordant results can be obtained using different ELISA methods. 相似文献
107.
Yasuhiro Izumiya Shinsuke HanataniYuichi Kimura MD Seiji TakashioEiichiro Yamamoto MD PhD Hiroaki KusakaTakanori Tokitsu MD Taku RokutandaSatoshi Araki MD PhD Kenichi TsujitaTomoko Tanaka MD PhD Megumi YamamuroSunao Kojima MD PhD Shinji TayamaKoichi Kaikita MD PhD Seiji HokimotoHisao Ogawa MD PhD 《The Canadian journal of cardiology》2014
Background
Circulating growth differentiation factor 15 (GDF-15) levels correlate with heart mass and fibrosis; however, little is known about its value in predicting the prognosis of patients with heart failure with preserved ejection fraction (HFpEF).Methods
We measured serum GDF-15 levels in 149 consecutive patients with left ventricular diastolic dysfunction (LVDD) and normal LV ejection fraction (>50%) and followed them for cardiovascular events. LVDD was defined according to the European Society of Cardiology guidelines.Results
The New York Heart Association functional class and circulating B-type natriuretic peptide (BNP) levels were significantly higher in the high–GDF-15 group (n = 75; greater than or equal to the median value [3694 pg/mL]) than in the low–GDF-15 group (n = 74). Patients were divided into HFpEF and LVDD groups according to the presence or absence of HF. Serum GDF-15 levels were significantly higher in the HFpEF group (n = 73) than in the LVDD group (n = 76) (median, 4215 [interquartile range, 3382-5287] vs 3091 [interquartile range, 2487-4217 pg/mL]; P < 0.0001). Kaplan-Meier curve analysis showed a significantly higher probability of cardiovascular events in the high–GDF-15 group than in the low–GDF-15 group for data of all patients (log-rank test P = 0.006) and data of patients in the HFpEF group only (P = 0.014). Multivariate Cox hazard analysis identified age (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.87-0.98; P = 0.008), atrial fibrillation (HR, 7.95; 95% CI, 1.98-31.85, P = 0.003), lnBNP (HR, 3.37; 95% CI, 1.73-6.55; P < 0.0001), and GDF-15 (ln[GDF-15]) (HR, 4.74; 95% CI, 1.26-17.88, P = 0.022) as independent predictors of primary end points.Conclusions
GDF-15 is a potentially useful prognostic biomarker in patients with HFpEF. 相似文献108.
Fujii Hiroyuki Tsuji Taisuke Yuba Tatsuya Tanaka Shunya Suga Yoshifumi Matsuyama Aosa Omura Ayaka Shiotsu Shinsuke Takumi Chieko Ono Seiko Horiguchi Masahito Hiraoka Noriya 《Clinical rheumatology》2020,39(11):3171-3175
Clinical Rheumatology - We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither... 相似文献
109.
Yoshiko Oshiro Toshiyuki Okumura Koichi Kurishima Shinsuke Homma Masashi Mizumoto Hitoshi Ishikawa Masataka Onizuka Mitsuaki Sakai Yukinobu Goto Nobuyuki Hizawa Yukio Sato Hideyuki Sakurai 《Journal of radiation research》2014,55(5):959-965
The aim of this report is to present the preliminary results of a Phase II study of high-dose (74 Gy RBE) proton beam therapy (PBT) with concurrent chemotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients were treated with PBT and chemotherapy with monthly cisplatin (on Day 1) and vinorelbine (on Days 1 and 8). The treatment doses were 74 Gy RBE for the primary site and 66 Gy RBE for the lymph nodes without elective lymph nodes. Adapted planning was made during the treatment. A total of 15 patients with Stage III NSCLC (IIIA: 4, IIIB: 11) were evaluated in this study. The median follow-up period was 21.7 months. None of the patients experienced Grade 4 or 5 non-hematologic toxicities. Acute pneumonitis was observed in three patients (Grade 1 in one, and Grade 3 in two), but Grade 3 pneumonitis was considered to be non-proton-related. Grade 3 acute esophagitis and dermatitis were observed in one and two patients, respectively. Severe ( ≥ Grade 3) leukocytopenia, neutropenia and thrombocytopenia were observed in 10 patients, seven patients and one patient, respectively. Late radiation Grades 2 and 3 pneumonitis was observed in one patient each. Six patients (40%) experienced local recurrence at the primary site and were treated with 74 Gy RBE. Disease progression was observed in 11 patients. The mean survival time was 26.7 months. We concluded that high-dose PBT with concurrent chemotherapy is safe to use in the treatment of unresectable Stage III NSCLC. 相似文献
110.
Kazuyoshi Uchihashi Toshiyuki Tsuruta Hiroko Mine Shigehisa Aoki Aki Nishijima‐Matsunobu Mihoko Yamamoto Akio Kuraoka Shuji Toda 《Pathology international》2014,64(6):276-282
Stenosing flexor tenosynovitis, trigger finger, is a common clinical disorder causing painful locking or contracture of the involved digits, and most instances are idiopathic. This problem is generally caused by a size mismatch between the swollen flexor tendon and the thickened first annular pulley. Although hypertrophic pulleys have been histologically and ultrasonographically detected, little is known about the histopathology of the tenosynovium covering the tendons of trigger fingers. We identified chondrocytoid cells that produced hyaluronic acid in 23 (61%) fingers and hypocellular collagen matrix in 32 (84%) fingers around the tenosynovium among 38 specimens of tenosynovium from patients with trigger fingers. These chondrocytoid cells expressed the synovial B cell marker CD44, but not the chondrocyte marker S‐100 protein. The incidence of these findings was much higher than that of conventional findings of synovitis, such as inflammatory infiltrate (37%), increased vascularity (37%), hyperplasia of synovial lining cells (21%), or fibrin exudation (5%). We discovered the following distinctive histopathological features of trigger finger: hyaluronic acid‐producing chondrocytoid cells originated from fibroblastic synovial B cells, and a hypocellular collagen matrix surrounding the tenosynovium. Thus, an edematous extracellular matrix with active hyaluronic acid synthesis might increase pressure under the pulley and contribute to the progression of stenosis. 相似文献