Pub Date : 2020-02-01Epub Date: 2019-12-09DOI: 10.1161/HYPERTENSIONAHA.119.13754
Tomohisa Yamashita, Sarfaraz Ahmad, Kendra N Wright, Drew J Roberts, Jessica L VonCannon, Hao Wang, Leanne Groban, Louis J Dell'Italia, Carlos M Ferrario
Bone marrow (BM) Ang II (angiotensin II) is a major participant in the regulation of hematopoiesis and immunity. The novel tissue substrate Ang-(1-12) [angiotensin-(1-12)] and its cleaving enzyme chymase are an essential source of Ang II production in cardiac tissue. We hypothesized this noncanonical chymase-mediated Ang II-producing mechanism exists in the BM tissue. Immunohistostaining and flow cytometry confirmed the presence of Ang-(1-12) immunoreaction in the BM of SD (Sprague Dawley) rats. Chymase-mediated Ang II-producing activity in BM was ≈1000-fold higher than ACE (angiotensin-converting enzyme)-mediated Ang II-producing activity (4531±137 and 4.2±0.3 fmol/min per mg, respectively; n=6; P<0.001) and 280-fold higher than chymase activity in the left ventricle of 16.3±1.7 fmol/min per mg (P<0.001). Adding a selective chymase inhibitor, TEI-F00806, eliminated almost all 125I-Ang II production. Flow cytometry demonstrated that delta median fluorescence intensity of chymase in cluster of differentiation 68 positive cells was significantly higher than that in cluster of differentiation 68 negative cells (1546±157 and 222±48 arbitrary units, respectively; P=0.0021). Cluster of differentiation 68 positive and side scatter low subsets, considered to be myeloid progenitors, express the highest chymase fluorescence intensity in rat BM. Chymase activity and cellular expression was similar in both male and female rats. In conclusion, myeloid lineage cells, especially myeloid progenitors, have an extraordinary Ang II-producing activity by chymase in the BM.
骨髓(BM)Ang II(血管紧张素 II)是造血和免疫调节的主要参与者。新型组织底物 Ang-(1-12) [血管紧张素-(1-12)] 及其裂解酶糜蛋白酶是心脏组织产生 Ang II 的重要来源。我们假设这种由糜蛋白酶介导的非经典 Ang II 生成机制存在于 BM 组织中。免疫组化染色和流式细胞术证实,SD(Sprague Dawley)大鼠的BM中存在Ang-(1-12)免疫反应。乳腺组织中消融酶介导的 Ang II 生成活性比 ACE(血管紧张素转换酶)介导的 Ang II 生成活性高出≈1000 倍(分别为 4531±137 和 4.2±0.3 fmol/min/mg;n=6;PP125I-Ang II 生成)。流式细胞术显示,分化 68 群阳性细胞中糜蛋白酶的δ中值荧光强度明显高于分化 68 群阴性细胞(分别为 1546±157 和 222±48 任意单位;P=0.0021)。分化簇 68 阳性和侧散射低亚群被认为是骨髓祖细胞,在大鼠 BM 中表达最高的糜蛋白酶荧光强度。雌雄大鼠的糜蛋白酶活性和细胞表达相似。总之,髓系细胞,尤其是髓系祖细胞,在生化组织中具有通过糜蛋白酶产生 Ang II 的非凡活性。
{"title":"Noncanonical Mechanisms for Direct Bone Marrow Generating Ang II (Angiotensin II) Predominate in CD68 Positive Myeloid Lineage Cells.","authors":"Tomohisa Yamashita, Sarfaraz Ahmad, Kendra N Wright, Drew J Roberts, Jessica L VonCannon, Hao Wang, Leanne Groban, Louis J Dell'Italia, Carlos M Ferrario","doi":"10.1161/HYPERTENSIONAHA.119.13754","DOIUrl":"10.1161/HYPERTENSIONAHA.119.13754","url":null,"abstract":"<p><p>Bone marrow (BM) Ang II (angiotensin II) is a major participant in the regulation of hematopoiesis and immunity. The novel tissue substrate Ang-(1-12) [angiotensin-(1-12)] and its cleaving enzyme chymase are an essential source of Ang II production in cardiac tissue. We hypothesized this noncanonical chymase-mediated Ang II-producing mechanism exists in the BM tissue. Immunohistostaining and flow cytometry confirmed the presence of Ang-(1-12) immunoreaction in the BM of SD (Sprague Dawley) rats. Chymase-mediated Ang II-producing activity in BM was ≈1000-fold higher than ACE (angiotensin-converting enzyme)-mediated Ang II-producing activity (4531±137 and 4.2±0.3 fmol/min per mg, respectively; n=6; <i>P</i><0.001) and 280-fold higher than chymase activity in the left ventricle of 16.3±1.7 fmol/min per mg (<i>P</i><0.001). Adding a selective chymase inhibitor, TEI-F00806, eliminated almost all <sup>125</sup>I-Ang II production. Flow cytometry demonstrated that delta median fluorescence intensity of chymase in cluster of differentiation 68 positive cells was significantly higher than that in cluster of differentiation 68 negative cells (1546±157 and 222±48 arbitrary units, respectively; <i>P</i>=0.0021). Cluster of differentiation 68 positive and side scatter low subsets, considered to be myeloid progenitors, express the highest chymase fluorescence intensity in rat BM. Chymase activity and cellular expression was similar in both male and female rats. In conclusion, myeloid lineage cells, especially myeloid progenitors, have an extraordinary Ang II-producing activity by chymase in the BM.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"94 1","pages":"500-509"},"PeriodicalIF":6.9,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79608093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-10Epub Date: 2019-11-25DOI: 10.1098/rsta.2019.0240
Lorenzo Morini, Zafer Gökay Tetik, Gal Shmuel, Massimiliano Gei
The dynamical properties of periodic two-component phononic rods, whose elementary cells are generated adopting the Fibonacci substitution rules, are studied through the recently introduced method of the toroidal manifold. The method allows all band gaps and pass bands featuring the frequency spectrum to be represented in a compact form with a frequency-dependent flow line on the surface describing their ordered sequence. The flow lines on the torus can be either closed or open: in the former case, (i) the frequency spectrum is periodic and the elementary cell corresponds to a canonical configuration, (ii) the band gap density depends on the lengths of the two phases; in the latter, the flow lines cover ergodically the torus and the band gap density is independent of those lengths. It is then shown how the proposed compact description of the spectrum can be exploited (i) to find the widest band gap for a given configuration and (ii) to optimize the layout of the elementary cell in order to maximize the low-frequency band gap. The scaling property of the frequency spectrum, that is a distinctive feature of quasicrystalline-generated phononic media, is also confirmed by inspecting band-gap/pass-band regions on the torus for the elementary cells of different Fibonacci orders. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 2)'.
{"title":"On the universality of the frequency spectrum and band-gap optimization of quasicrystalline-generated structured rods.","authors":"Lorenzo Morini, Zafer Gökay Tetik, Gal Shmuel, Massimiliano Gei","doi":"10.1098/rsta.2019.0240","DOIUrl":"10.1098/rsta.2019.0240","url":null,"abstract":"<p><p>The dynamical properties of periodic two-component phononic rods, whose elementary cells are generated adopting the Fibonacci substitution rules, are studied through the recently introduced method of the toroidal manifold. The method allows all band gaps and pass bands featuring the frequency spectrum to be represented in a compact form with a frequency-dependent flow line on the surface describing their ordered sequence. The flow lines on the torus can be either closed or open: in the former case, (i) the frequency spectrum is periodic and the elementary cell corresponds to a canonical configuration, (ii) the band gap density depends on the lengths of the two phases; in the latter, the flow lines cover ergodically the torus and the band gap density is independent of those lengths. It is then shown how the proposed compact description of the spectrum can be exploited (i) to find the widest band gap for a given configuration and (ii) to optimize the layout of the elementary cell in order to maximize the low-frequency band gap. The scaling property of the frequency spectrum, that is a distinctive feature of quasicrystalline-generated phononic media, is also confirmed by inspecting band-gap/pass-band regions on the torus for the elementary cells of different Fibonacci orders. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 2)'.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"97 1","pages":"20190240"},"PeriodicalIF":0.0,"publicationDate":"2020-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80231095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-09DOI: 10.1002/essoar.10501544.1
P. Terra, F. Vargas, C. Brum, E. Miller
We employ in this work the first airglow dataset registered at the Remote Optical Facility (ROF) in Culebra, Puerto Rico, during the descending phase of the solar cycle #24. From November 4, 2015, ...
{"title":"Geomagnetic and Solar dependency of MSTIDs occurrence rate: A climatology based on airglow observations from the Arecibo Observatory Remote Optical Facility (ROF)","authors":"P. Terra, F. Vargas, C. Brum, E. Miller","doi":"10.1002/essoar.10501544.1","DOIUrl":"https://doi.org/10.1002/essoar.10501544.1","url":null,"abstract":"We employ in this work the first airglow dataset registered at the Remote Optical Facility (ROF) in Culebra, Puerto Rico, during the descending phase of the solar cycle #24. From November 4, 2015, ...","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/essoar.10501544.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43828697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01Epub Date: 2019-11-21DOI: 10.1007/s00018-019-03366-0
Travis Eisemann, John M Pascal
DNA damage response (DDR) relies on swift and accurate signaling to rapidly identify DNA lesions and initiate repair. A critical DDR signaling and regulatory molecule is the posttranslational modification poly(ADP-ribose) (PAR). PAR is synthesized by a family of structurally and functionally diverse proteins called poly(ADP-ribose) polymerases (PARPs). Although PARPs share a conserved catalytic domain, unique regulatory domains of individual family members endow PARPs with unique properties and cellular functions. Family members PARP-1, PARP-2, and PARP-3 (DDR-PARPs) are catalytically activated in the presence of damaged DNA and act as damage sensors. Family members tankyrase-1 and closely related tankyrase-2 possess SAM and ankyrin repeat domains that regulate their diverse cellular functions. Recent studies have shown that the tankyrases share some overlapping functions with the DDR-PARPs, and even perform novel functions that help preserve genomic integrity. In this review, we briefly touch on DDR-PARP functions, and focus on the emerging roles of tankyrases in genome maintenance. Preservation of genomic integrity thus appears to be a common function of several PARP family members, depicting PAR as a multifaceted guardian of the genome.
DNA 损伤应答(DDR)依赖于迅速而准确的信号传递,以快速识别 DNA 病变并启动修复。DDR 的一个关键信号和调控分子是翻译后修饰聚(ADP-核糖)(PAR)。聚(ADP-核糖)聚合酶(PARPs)是由一系列结构和功能各异的蛋白质合成的。尽管 PARPs 共享一个保守的催化结构域,但各个家族成员独特的调控结构域赋予了 PARPs 独特的性质和细胞功能。PARP-1、PARP-2 和 PARP-3(DDR-PARPs)家族成员在 DNA 受损时催化激活,并充当损伤传感器。家族成员tankyrase-1和与之密切相关的tankyrase-2具有SAM和ankyrin重复结构域,可调节其多种细胞功能。最近的研究表明,tankyrase 与 DDR-PARPs 有一些重叠的功能,甚至还能执行有助于保持基因组完整性的新功能。在这篇综述中,我们将简要介绍 DDR-PARP 的功能,并重点讨论 tankyrases 在基因组维护中的新作用。因此,保持基因组的完整性似乎是 PARP 家族多个成员的共同功能,这说明 PAR 是基因组的多面守护者。
{"title":"Poly(ADP-ribose) polymerase enzymes and the maintenance of genome integrity.","authors":"Travis Eisemann, John M Pascal","doi":"10.1007/s00018-019-03366-0","DOIUrl":"10.1007/s00018-019-03366-0","url":null,"abstract":"<p><p>DNA damage response (DDR) relies on swift and accurate signaling to rapidly identify DNA lesions and initiate repair. A critical DDR signaling and regulatory molecule is the posttranslational modification poly(ADP-ribose) (PAR). PAR is synthesized by a family of structurally and functionally diverse proteins called poly(ADP-ribose) polymerases (PARPs). Although PARPs share a conserved catalytic domain, unique regulatory domains of individual family members endow PARPs with unique properties and cellular functions. Family members PARP-1, PARP-2, and PARP-3 (DDR-PARPs) are catalytically activated in the presence of damaged DNA and act as damage sensors. Family members tankyrase-1 and closely related tankyrase-2 possess SAM and ankyrin repeat domains that regulate their diverse cellular functions. Recent studies have shown that the tankyrases share some overlapping functions with the DDR-PARPs, and even perform novel functions that help preserve genomic integrity. In this review, we briefly touch on DDR-PARP functions, and focus on the emerging roles of tankyrases in genome maintenance. Preservation of genomic integrity thus appears to be a common function of several PARP family members, depicting PAR as a multifaceted guardian of the genome.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"116 1","pages":"19-33"},"PeriodicalIF":8.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11104942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79594471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01Epub Date: 2020-05-25DOI: 10.1007/s41403-020-00103-z
Suryasnata Tripathy, Shiv Govind Singh
This paper presents label-free electrochemical transduction as a suitable scheme for COVID-19-specific viral RNA/c-DNA detection, with an aim to facilitate point of care diagnosis. In lieu of this, we discuss the proposed electrochemical biosensing scheme, based on electrodeposited gold nanoparticles as the transducing elements. Specific to this approach, here, the protocols associated with the immobilization of the single-stranded probe nucleotide on to the biosensor, have also been laid out. This paper also discusses the methods of electrochemical analysis, to be used for data acquisition and subsequent calibration, in relation to target analyte detection. Towards facilitating portable diagnosis, development of miniaturized sensors and their integration with readout units have also been discussed.
{"title":"Label-Free Electrochemical Detection of DNA Hybridization: A Method for COVID-19 Diagnosis.","authors":"Suryasnata Tripathy, Shiv Govind Singh","doi":"10.1007/s41403-020-00103-z","DOIUrl":"10.1007/s41403-020-00103-z","url":null,"abstract":"<p><p>This paper presents label-free electrochemical transduction as a suitable scheme for COVID-19-specific viral RNA/c-DNA detection, with an aim to facilitate point of care diagnosis. In lieu of this, we discuss the proposed electrochemical biosensing scheme, based on electrodeposited gold nanoparticles as the transducing elements. Specific to this approach, here, the protocols associated with the immobilization of the single-stranded probe nucleotide on to the biosensor, have also been laid out. This paper also discusses the methods of electrochemical analysis, to be used for data acquisition and subsequent calibration, in relation to target analyte detection. Towards facilitating portable diagnosis, development of miniaturized sensors and their integration with readout units have also been discussed.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"93 1","pages":"205-209"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79582554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-11-29Print Date: 2020-03-01DOI: 10.3171/2019.9.SPINE19887
Benedikt W Burkhardt, Andreas Simgen, Gudrun Wagenpfeil, Philipp Hendrix, Matthias Dehnen, Wolfgang Reith, Joachim M Oertel
Objective: There is currently no consensus on whether adjacent-segment degeneration (ASD), loss of disc height (DH), and loss of sagittal segmental angle (SSA) are due to anterior cervical discectomy and fusion (ACDF). The purpose of the present study was to assess the grade of segmental degeneration after ACDF and to analyze if there is a difference with respect to clinical outcome, diagnosis, and number of operated levels.
Methods: A total of 102 patients who underwent ACDF with a minimum follow-up of 18 years were retrospectively identified. At final follow-up, the clinical outcome according to Odom's criteria, the Neck Disability Index (NDI), and reoperation for symptomatic ASD (sASD) was assessed. MRI was performed, and DH, SSA, and the segmental degeneration index (SDI, a 5-step grading system that includes disc signal intensity, anterior and posterior disc protrusion, narrowing of the disc space, and foraminal stenosis) were assessed for evaluation of the 2 adjacent and 4 adjoining segments to the ACDF. MRI findings were compared with respect to clinical outcome (NDI: 0%-20% vs > 20%; Odom's criteria: success vs no success), reoperation for sASD, initial diagnosis (cervical disc herniation [CDH] vs cervical spondylotic myelopathy [CSM] and spondylosis), and the number of operated levels (1 vs 2-4 levels).
Results: The mean follow-up was 25 years (range 18-45 years), and the diagnosis was CDH in 74.5% of patients and CSM/spondylosis in 25.5%. At follow-up, the mean NDI was 12.4% (range 0%-36%), the clinical success rate was 87.3%, and the reoperation rate for sASD was 15.7%. For SDI, no significant differences were seen with respect to NDI, Odom's criteria, and sASD. Patients diagnosed with CDH had significantly more degeneration at the adjacent segments (cranial, p = 0.015; caudal, p = 0.017). Patients with a 2- to 4-level procedure had less degeneration at the caudal adjacent (p = 0.011) and proximal adjoining (p = 0.019) segments. Aside from a significantly lower DH at the proximal cranial adjoining segment in cases of CSM/spondylosis and without clinical success, no further differences were noted. The degree of SSA was not significantly different with respect to clinical outcome.
Conclusions: No significant differences were seen in the SDI grade and SSA with respect to clinical outcome. The SDI is higher after single-level ACDF and with the diagnosis of CDH. The DH was negligibly different with respect to clinical outcome, diagnosis, and number of operated levels.
{"title":"Is there a difference in the grade of degeneration at the cervical spine following anterior cervical fusion with respect to clinical outcome, diagnosis, and repeat procedure? An MRI study of 102 patients with a mean follow-up of 25 years.","authors":"Benedikt W Burkhardt, Andreas Simgen, Gudrun Wagenpfeil, Philipp Hendrix, Matthias Dehnen, Wolfgang Reith, Joachim M Oertel","doi":"10.3171/2019.9.SPINE19887","DOIUrl":"10.3171/2019.9.SPINE19887","url":null,"abstract":"<p><strong>Objective: </strong>There is currently no consensus on whether adjacent-segment degeneration (ASD), loss of disc height (DH), and loss of sagittal segmental angle (SSA) are due to anterior cervical discectomy and fusion (ACDF). The purpose of the present study was to assess the grade of segmental degeneration after ACDF and to analyze if there is a difference with respect to clinical outcome, diagnosis, and number of operated levels.</p><p><strong>Methods: </strong>A total of 102 patients who underwent ACDF with a minimum follow-up of 18 years were retrospectively identified. At final follow-up, the clinical outcome according to Odom's criteria, the Neck Disability Index (NDI), and reoperation for symptomatic ASD (sASD) was assessed. MRI was performed, and DH, SSA, and the segmental degeneration index (SDI, a 5-step grading system that includes disc signal intensity, anterior and posterior disc protrusion, narrowing of the disc space, and foraminal stenosis) were assessed for evaluation of the 2 adjacent and 4 adjoining segments to the ACDF. MRI findings were compared with respect to clinical outcome (NDI: 0%-20% vs > 20%; Odom's criteria: success vs no success), reoperation for sASD, initial diagnosis (cervical disc herniation [CDH] vs cervical spondylotic myelopathy [CSM] and spondylosis), and the number of operated levels (1 vs 2-4 levels).</p><p><strong>Results: </strong>The mean follow-up was 25 years (range 18-45 years), and the diagnosis was CDH in 74.5% of patients and CSM/spondylosis in 25.5%. At follow-up, the mean NDI was 12.4% (range 0%-36%), the clinical success rate was 87.3%, and the reoperation rate for sASD was 15.7%. For SDI, no significant differences were seen with respect to NDI, Odom's criteria, and sASD. Patients diagnosed with CDH had significantly more degeneration at the adjacent segments (cranial, p = 0.015; caudal, p = 0.017). Patients with a 2- to 4-level procedure had less degeneration at the caudal adjacent (p = 0.011) and proximal adjoining (p = 0.019) segments. Aside from a significantly lower DH at the proximal cranial adjoining segment in cases of CSM/spondylosis and without clinical success, no further differences were noted. The degree of SSA was not significantly different with respect to clinical outcome.</p><p><strong>Conclusions: </strong>No significant differences were seen in the SDI grade and SSA with respect to clinical outcome. The SDI is higher after single-level ACDF and with the diagnosis of CDH. The DH was negligibly different with respect to clinical outcome, diagnosis, and number of operated levels.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"94 1","pages":"335-343"},"PeriodicalIF":2.9,"publicationDate":"2019-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79216901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-14DOI: 10.3760/cma.j.issn.0253-2727.2019.10.009
J Zhou, J W Zhao, Y C Zheng, J Xiao, C W Li
Objective: To investigate the genetic screening methods for cryptic acute promyelocytic leukemia (APL) to further explore its clinical prognosis. Methods: From June 2016 to November 2018, we collected 373 newly diagnosed APL cases. The patients were retrospected by the results of PML-RARα detections both by RT-PCR and i-FISH, those who harbored positive PML-RARα detection by RT-PCR and negative by i-FISH were chosen. Metaphase FISH and Sanger sequencing were further performed to verify these results. Results: A total of 7 cryptic APL cases were discovered. These cases had tiny fragment of RARα inserted into PML in chromosome 15, formed ins (15;17) . The 7 cryptic APL cases had no PML-RARα gene subtype specificity, involving 5 cases in L subtype, 1 case in S subtype and 1 case in V subtype respectively. After the treatment of retinoic acid and arsenic or anthracyclines, 6 cases achieved complete remission, 1 case died of intracranial hemorrhage on the 6th day of therapy. Conclusion: The size and covering position of PML-RARα probe should be taken into account when PML-RARα was performed by FISH on APL patients. Furthermore, combination with Metaphase FISH could improve the recognition of cryptic APL. There were no differences between the cryptic and common APL patients in terms of clinical features and treatment choices. Cryptic APL patients also had a good response to the therapy of retinoic acid and arsenic or anthracyclines.
目的:研究隐性急性早幼粒细胞白血病(APL)的基因筛查方法:研究隐性急性早幼粒细胞白血病(APL)的基因筛查方法,进一步探讨其临床预后。方法:从2016年6月至2018年11月,我们收集了373例新诊断的APL病例:2016年6月至2018年11月,我们收集了373例新诊断的APL病例。根据RT-PCR和i-FISH检测PML-RARα的结果对患者进行回顾性分析,选择RT-PCR检测PML-RARα阳性而i-FISH检测阴性的患者。为了验证这些结果,进一步进行了分裂期 FISH 和 Sanger 测序。结果:共发现7例隐性APL病例。这些病例中,RARα的微小片段插入到15号染色体的PML中,形成ins(15;17)。这 7 例隐性 APL 没有 PML-RARα 基因亚型特异性,其中 5 例为 L 亚型,1 例为 S 亚型,1 例为 V 亚型。经过维甲酸和砷或蒽环类药物治疗后,6 例患者病情完全缓解,1 例患者在治疗第 6 天死于颅内出血。结论用 FISH 对 APL 患者进行 PML-RARα 检测时,应注意 PML-RARα 探针的大小和覆盖位置。此外,与 Metaphase FISH 结合使用可提高对隐性 APL 的识别率。在临床特征和治疗选择方面,隐性 APL 患者与普通 APL 患者没有差异。隐性APL患者对维甲酸和砷或蒽环类药物治疗的反应也很好。
{"title":"[Cytogenetic test and clinical study on cryptic acute promyelocytic leukemia with ins (15; 17)].","authors":"J Zhou, J W Zhao, Y C Zheng, J Xiao, C W Li","doi":"10.3760/cma.j.issn.0253-2727.2019.10.009","DOIUrl":"10.3760/cma.j.issn.0253-2727.2019.10.009","url":null,"abstract":"<p><p><b>Objective:</b> To investigate the genetic screening methods for cryptic acute promyelocytic leukemia (APL) to further explore its clinical prognosis. <b>Methods:</b> From June 2016 to November 2018, we collected 373 newly diagnosed APL cases. The patients were retrospected by the results of PML-RARα detections both by RT-PCR and i-FISH, those who harbored positive PML-RARα detection by RT-PCR and negative by i-FISH were chosen. Metaphase FISH and Sanger sequencing were further performed to verify these results. <b>Results:</b> A total of 7 cryptic APL cases were discovered. These cases had tiny fragment of RARα inserted into PML in chromosome 15, formed ins (15;17) . The 7 cryptic APL cases had no PML-RARα gene subtype specificity, involving 5 cases in L subtype, 1 case in S subtype and 1 case in V subtype respectively. After the treatment of retinoic acid and arsenic or anthracyclines, 6 cases achieved complete remission, 1 case died of intracranial hemorrhage on the 6th day of therapy. <b>Conclusion:</b> The size and covering position of PML-RARα probe should be taken into account when PML-RARα was performed by FISH on APL patients. Furthermore, combination with Metaphase FISH could improve the recognition of cryptic APL. There were no differences between the cryptic and common APL patients in terms of clinical features and treatment choices. Cryptic APL patients also had a good response to the therapy of retinoic acid and arsenic or anthracyclines.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"104 1","pages":"843-847"},"PeriodicalIF":0.0,"publicationDate":"2019-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79173931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Nusbaumer, Lucas Marques da Cunha, Claus Wedekind
Sperm cryopreservation is routinely used in reproductive medicine, livestock production and wildlife management. Its effect on offspring performance is often assumed to be negligible, but this still remains to be confirmed in well-controlled within-subject experiments. We use a vertebrate model that allows us to experimentally separate parental and environmental effects to test whether sperm cryopreservation influences offspring phenotype under stress and non-stress conditions, and whether such effects are male-specific. Wild brown trout (Salmo trutta) were stripped for their gametes, and a portion of each male's milt was cryopreserved. Then, 960 eggs were simultaneously fertilized with either non-cryopreserved or frozen-thawed semen and raised singly in the presence or absence of a pathogen. We found no significant effects of cryopreservation on fertilization rates, and no effects on growth, survival nor pathogen resistance during the embryo stage. However, fertilization by cryopreserved sperm led to significantly reduced larval growth after hatching. Males varied in genetic quality as determined from offspring performance, but effects of cryopreservation on larval growth were not male-specific. We conclude that cryopreservation causes a reduction in offspring growth that is easily overlooked because it only manifests itself at later developmental stages, when many other factors affect growth and survival too.
{"title":"Sperm cryopreservation reduces offspring growth.","authors":"David Nusbaumer, Lucas Marques da Cunha, Claus Wedekind","doi":"10.1098/rspb.2019.1644","DOIUrl":"10.1098/rspb.2019.1644","url":null,"abstract":"<p><p>Sperm cryopreservation is routinely used in reproductive medicine, livestock production and wildlife management. Its effect on offspring performance is often assumed to be negligible, but this still remains to be confirmed in well-controlled within-subject experiments. We use a vertebrate model that allows us to experimentally separate parental and environmental effects to test whether sperm cryopreservation influences offspring phenotype under stress and non-stress conditions, and whether such effects are male-specific. Wild brown trout (<i>Salmo trutta</i>) were stripped for their gametes, and a portion of each male's milt was cryopreserved. Then, 960 eggs were simultaneously fertilized with either non-cryopreserved or frozen-thawed semen and raised singly in the presence or absence of a pathogen. We found no significant effects of cryopreservation on fertilization rates, and no effects on growth, survival nor pathogen resistance during the embryo stage. However, fertilization by cryopreserved sperm led to significantly reduced larval growth after hatching. Males varied in genetic quality as determined from offspring performance, but effects of cryopreservation on larval growth were not male-specific. We conclude that cryopreservation causes a reduction in offspring growth that is easily overlooked because it only manifests itself at later developmental stages, when many other factors affect growth and survival too.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"110 1","pages":"20191644"},"PeriodicalIF":0.0,"publicationDate":"2019-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79301224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-17Epub Date: 2019-09-12DOI: 10.1161/JAHA.119.013558
David A Jaques, Edward Pivin, Menno Pruijm, Daniel Ackermann, Idris Guessous, Georg Ehret, Fang-Fei Wei, Jan A Staessen, Antoinette Pechère-Bertschi, Cees Vermeer, Bruno Vogt, Michel Burnier, Pierre-Yves Martin, Murielle Bochud, Belen Ponte
Background Increased renal resistive index (RRI) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (γ-carboxyglutamate) protein (MGP) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho-uncarboxylated MGP [dp-ucMGP]) has been associated with vascular stiffness, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP were associated with increased RRI. Methods and Results We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Levels of dp-ucMGP were measured in plasma by sandwich ELISA. RRI was measured by Doppler ultrasound in 3 segmental arteries in both kidneys. We used mixed regression models to assess the relationship between dp-ucMGP and RRI. We adjusted for common determinants of RRI as well as renal function and cardiovascular risk factors. We included 1006 participants in our analyses: 526 women and 480 men. Mean values were 0.44±0.20 nmol/L for dp-ucMGP and 64±5% for RRI. After multivariable adjustment, dp-ucMGP was positively associated with RRI (P=0.001). In subgroup analysis by age tertiles, this association was not significant in the youngest age group (<38 years; P=0.62), whereas it was significant in older age groups (38-55 and >55 years; P=0.016 and P<0.001, respectively). Conclusions Levels of dp-ucMGP are positively and independently associated with RRI after adjustment for common determinants of RRI, cardiovascular risk factors, and renal function. The stronger association among older adults is probably due, in part, to age-related arterial stiffness. RRI thus seems to reflect the global atherosclerotic burden in a general adult population.
{"title":"Renal Resistive Index Is Associated With Inactive Matrix Gla (γ-Carboxyglutamate) Protein in an Adult Population-Based Study.","authors":"David A Jaques, Edward Pivin, Menno Pruijm, Daniel Ackermann, Idris Guessous, Georg Ehret, Fang-Fei Wei, Jan A Staessen, Antoinette Pechère-Bertschi, Cees Vermeer, Bruno Vogt, Michel Burnier, Pierre-Yves Martin, Murielle Bochud, Belen Ponte","doi":"10.1161/JAHA.119.013558","DOIUrl":"10.1161/JAHA.119.013558","url":null,"abstract":"<p><p>Background Increased renal resistive index (RRI) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (γ-carboxyglutamate) protein (MGP) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho-uncarboxylated MGP [dp-ucMGP]) has been associated with vascular stiffness, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP were associated with increased RRI. Methods and Results We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Levels of dp-ucMGP were measured in plasma by sandwich ELISA. RRI was measured by Doppler ultrasound in 3 segmental arteries in both kidneys. We used mixed regression models to assess the relationship between dp-ucMGP and RRI. We adjusted for common determinants of RRI as well as renal function and cardiovascular risk factors. We included 1006 participants in our analyses: 526 women and 480 men. Mean values were 0.44±0.20 nmol/L for dp-ucMGP and 64±5% for RRI. After multivariable adjustment, dp-ucMGP was positively associated with RRI (<i>P</i>=0.001). In subgroup analysis by age tertiles, this association was not significant in the youngest age group (<38 years; <i>P</i>=0.62), whereas it was significant in older age groups (38-55 and >55 years; <i>P</i>=0.016 and <i>P</i><0.001, respectively). Conclusions Levels of dp-ucMGP are positively and independently associated with RRI after adjustment for common determinants of RRI, cardiovascular risk factors, and renal function. The stronger association among older adults is probably due, in part, to age-related arterial stiffness. RRI thus seems to reflect the global atherosclerotic burden in a general adult population.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"115 1","pages":"e013558"},"PeriodicalIF":0.0,"publicationDate":"2019-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1161/JAHA.119.013558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79581121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-03eCollection Date: 2019-01-01DOI: 10.1155/2019/3873928
Thoralf Bernhardt, Marie Luise Semmler, Mirijam Schäfer, Sander Bekeschus, Steffen Emmert, Lars Boeckmann
The ability to produce cold plasma at atmospheric pressure conditions was the basis for the rapid growth of plasma-related application areas in biomedicine. Plasma comprises a multitude of active components such as charged particles, electric current, UV radiation, and reactive gas species which can act synergistically. Anti-itch, antimicrobial, anti-inflammatory, tissue-stimulating, blood flow-enhancing, and proapoptotic effects were demonstrated in in vivo and in vitro experiments, and until now, no resistance of pathogens against plasma treatment was observed. The combination of the different active agents and their broad range of positive effects on various diseases, especially easily accessible skin diseases, renders plasma quite attractive for applications in medicine. For medical applications, two different types of cold plasma appear suitable: indirect (plasma jet) and direct (dielectric barrier discharge-DBD) plasma sources. The DBD device PlasmaDerm® VU-2010 (CINOGY Technologies GmbH), the atmospheric pressure plasma jet (APPJ) kINPen® MED (INP Greifswald/neoplas tools GmbH), and the SteriPlas (Adtec Ltd., London, United Kingdom) are CE-certified as a medical product to treat chronic wounds in humans and showed efficacy and a good tolerability. Recently, the use of plasma in cancer research and oncology is of particular interest. Plasma has been shown to induce proapoptotic effects more efficiently in tumor cells compared with the benign counterparts, leads to cellular senescence, and-as shown in vivo-reduces skin tumors. To this end, a world-wide first Leibniz professorship for plasmabiotechnology in dermatology has been introduced to establish a scientific network for the investigation of the efficacy and safety of cold atmospheric plasma in dermatooncology. Hence, plasma medicine especially in dermatology holds great promise.
{"title":"Plasma Medicine: Applications of Cold Atmospheric Pressure Plasma in Dermatology.","authors":"Thoralf Bernhardt, Marie Luise Semmler, Mirijam Schäfer, Sander Bekeschus, Steffen Emmert, Lars Boeckmann","doi":"10.1155/2019/3873928","DOIUrl":"10.1155/2019/3873928","url":null,"abstract":"<p><p>The ability to produce cold plasma at atmospheric pressure conditions was the basis for the rapid growth of plasma-related application areas in biomedicine. Plasma comprises a multitude of active components such as charged particles, electric current, UV radiation, and reactive gas species which can act synergistically. Anti-itch, antimicrobial, anti-inflammatory, tissue-stimulating, blood flow-enhancing, and proapoptotic effects were demonstrated in <i>in vivo</i> and <i>in vitro</i> experiments, and until now, no resistance of pathogens against plasma treatment was observed. The combination of the different active agents and their broad range of positive effects on various diseases, especially easily accessible skin diseases, renders plasma quite attractive for applications in medicine. For medical applications, two different types of cold plasma appear suitable: indirect (plasma jet) and direct (dielectric barrier discharge-DBD) plasma sources. The DBD device PlasmaDerm® VU-2010 (CINOGY Technologies GmbH), the atmospheric pressure plasma jet (APPJ) kINPen® MED (INP Greifswald/neoplas tools GmbH), and the SteriPlas (Adtec Ltd., London, United Kingdom) are CE-certified as a medical product to treat chronic wounds in humans and showed efficacy and a good tolerability. Recently, the use of plasma in cancer research and oncology is of particular interest. Plasma has been shown to induce proapoptotic effects more efficiently in tumor cells compared with the benign counterparts, leads to cellular senescence, and-as shown <i>in vivo-</i>reduces skin tumors. To this end, a world-wide first Leibniz professorship for plasmabiotechnology in dermatology has been introduced to establish a scientific network for the investigation of the efficacy and safety of cold atmospheric plasma in dermatooncology. Hence, plasma medicine especially in dermatology holds great promise.</p>","PeriodicalId":15836,"journal":{"name":"Journal of Geophysical Research","volume":"101 1","pages":"3873928"},"PeriodicalIF":0.0,"publicationDate":"2019-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79386416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}