Do neutrophil extracellular traps implicate in atheromatous plaques from carotid endarterectomy? Re-analyzes of cDNA microarray data by surgeons

BackgroundCarotid artery stenosis is the cause of 15% of strokes. Neutrophil extracellular traps (NETs) and peptidyl arginine deiminase 4 (PAD4) are believed to be involved in thrombosis. This pilot study described the differential expression profile of NETs between atheromatous plaques and surrounding tissues.MethodsMicroarray datasets of carotid plaques were obtained from Gene Expression Omnibus. The normalized data were processed into comma-separated value matrix files using spreadsheet software. Analyzes of microarray data were conducted using integrated differential expression and pathway analysis.ResultThe clustering results illustrated that the classifications of plaque and control had reasonable biological validity. Pathway analysis revealed the relevance of immune response, cell signaling, and other pathways. Differentially expressed genes were detected between carotid plaques and control specimens. However, enrichment analyzes did not reveal a difference in PAD4 expression between the groups and that NET implication was only found in one cDNA microarray dataset.DiscussionThis pilot study does not necessarily dismiss the possibility of a relationship between NETs and atherothrombotic stroke. Gene expression could differ between endothelial cells and atheromas, and further studies are needed

Recent trend of research on the nongenotoxic mechanisms of chemical carcinogenesis

本総説は,筆者らが進めている｢低線量放射線の健康への影響と医療への応用｣に関する研究に資するために調査した,化学発がんの非遺伝毒性的メカニズムの解明に関する最近の動向の概要についてまとめたものである｡即ち,非遺伝毒性的発がんにおける細胞増殖,シトクロムP450誘導,酸化的ストレス,および遺伝子発現のそれぞれの役割,並びに量的な応答性について言及した｡また,後成的発がんにおけるアポトーシス,およびギャップ結合による情報伝達のそれぞれの役割についても触れた｡その結果,非遺伝毒性的な発がん物質の作用の様式とメカニズムやこれによる後成的な影響などについては解明さ れつつあり,特に,これらの発がん物質がゲノムDNAに対し直接的な相互作用,突然変異,修飾などを行う発がん物質とは機能的に異なった作用をすることが明らかになった｡また,これらは放射線発がんなど低線量放射線の健康への影響などについて研究する上で,重要な知見となっていることもわかった。To elucidate the health effects by low dose radiation, we reviewed the recent trend of research on the epigenetic mechanisms of chemical carcinogenesis. The following view were obtained. It has become apparent that chemical and physical agents that induce cancer may do so through different cellular and molecular mechanisms. Investigators, recognizing the apparent differences in the ways compounds participate in the carcinogenesis process, coined the phrases "genotoxic" and "epigenetic" in describing activities of chemicals and physical agents that induced cancer. The term "nongenotoxic" has to some extent replaced "epigenetic" and thus, classification of chemical carcinogens has been frequently delegated to either the genotoxic or nongenotoxic categories. Moreover, while much work remains in the understanding of the modes and mechanisms of action of nongenotoxic carcinogens and the epigenetic effects of these agents, it is apparent that this category of chemicals are functionally different than those compounds which directly interact, mutate, and modify genomic DNA

Three-dimensional 4K resolution video microscope in an orbitozygomatic approach for skull base tumor

Background: The authors propose that the newly developed three-dimensional 4K resolution (3D-4K) video microscope, Orbeye™, can be a user-friendly alternative tool for performing orbitozygomatic craniotomy and tumor removal. It was officially approved in Japan in October 2017.Case description: A 38-year-old, otherwise healthy, woman presented with left impaired visual acuity, motor aphasia, headache, and vomiting. Magnetic resonance imaging (MRI) revealed the presence of a large left sphenoid ridge meningioma with marked perifocal edema and mass effect. Using Orbeye™, en bloc orbitozygomatic craniotomy and skull base tumor removal were safely performed. It enabled us to perform the procedure, and to share the operative image owing to the realistic 3D perception of the operative field, its excellent illumination, and viewing angle. Especially, the lower viewing angle appeared to be extremely difficult to obtain using conventional methods. The patient resumed her daily life, and a postoperative MRI showed total removal of the tumor.Conclusions: Orbeye™ has overcome shortcomings of the operative microscope. It has a user-friendly design, and surgeons’ intraoperative fatigue and stress appear to be decreased. It is useful for observers to understand the skull base technical nuances using the 3D-4K image

MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells

Background: Esophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC. Methods: Total RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR. Results: Based on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC. Conclusions: These results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.Kayoko Matsushima... Gregory J Goodall... et al

Characteristic of GAFCHROMIC XR TYPE T dosimetry film

医療の高度化に伴い,近年では長時間のⅩ線透視を行うInterventional Radiology(IVR)手技が頻繁に行われ,副作用としての難治性放射線皮膚障害例の報告が増加している｡確定的影響である放射線皮膚障害はしきい値を超えると発症し,線量に依存して障害の程度が重篤となるため,患者被曝線量の測定が重要である｡しかし,IVRでは照射部位が多彩で,焦点-皮膚間距離が不安定なため,その測定方法は確立されていない｡本研究では,近年IVR等低エネルギー線量測定用フイルムとして開発されたCAFCHROMIC XR TYPE T について性能評価を行い,患者皮膚入射面の被曝線量測定への応用の可能性について検討した｡その結果,線量特性,線質特性,ネット値の安定性に良好な特性を示し,臨床に使用可能であったので報告する｡In recent years, interventional radiology (IVR) using which uses prolomged fluoroscopy has been performed frequently in clinical radiology. Also, reports of radiation skin injuries whose symptoms occur after IVR has been also increasing. These symptoms will become worse if the radiation induced skin injuries are caused by doses which are above the designated threshold, and the grade of injuries are dependent on dose. Therefore, it is important that patient skin dose is measured correctly. But when perfoming IVR, irradiation is complex pricedure, and there is a measurement error with an unfixed source-to-skin distance. So. in this paper, characteristics of GAFCHROMIC XR TYPE T (which are film for low energy X-rays) are performed. Then, they are decided whether the application to the skin surface incidence dose measurement whoud be posible. From these results usefull data can be obtainned; for exanmpe film characteristics, energy factors and stability of sensivility

Progressive perianeurysmal edema preceding the rupture of a small basilar artery aneurysm.

We herein report the first case of progressive perianeurysmal edema preceding the rupture of a small saccular aneurysm, without any intervention or intraluminal thrombosis. A 71-year-old woman was incidentally noted to have a cerebral aneurysm (5mm in diameter) at the lower basilar artery. Twelve months later, magnetic resonance (MR) imaging showed a T2-elongated area around a dome of the aneurysm buried in the brain stem, suggesting perianeurysmal edema formation. Interestingly, the edema progressed with the formation of a bleb, in addition to an increase in size of the aneurysm over the following 3-year period. The aneurysm eventually ruptured as a brain stem hemorrhage without any subarachnoid clots 3 days after the final check-up with MR imaging, by which a significant increase of edema formation with an increase in size of the aneurysm and a marked expansion of the bleb was observed. These findings raise the possibility that bleb formation and an enlargement of a small cerebral aneurysm might also be associated with perianeurysmal edema and a subsequent aneurysmal rupture. In addition to the pulsatile flow and/or compression from the expanded aneurysm, local inflammation in the aneurysm wall may play an important role in such edema formation

Identification of Novel SNPs in Glioblastoma Using Targeted Resequencing

High-throughput sequencing opens avenues to find genetic variations that may be indicative of an increased risk for certain diseases. Linking these genomic data to other “omics” approaches bears the potential to deepen our understanding of pathogenic processes at the molecular level. To detect novel single nucleotide polymorphisms (SNPs) for glioblastoma multiforme (GBM), we used a combination of specific target selection and next generation sequencing (NGS). We generated a microarray covering the exonic regions of 132 GBM associated genes to enrich target sequences in two GBM tissues and corresponding leukocytes of the patients. Enriched target genes were sequenced with Illumina and the resulting reads were mapped to the human genome. With this approach we identified over 6000 SNPs, including over 1300 SNPs located in the targeted genes. Integrating the genome-wide association study (GWAS) catalog and known disease associated SNPs, we found that several of the detected SNPs were previously associated with smoking behavior, body mass index, breast cancer and high-grade glioma. Particularly, the breast cancer associated allele of rs660118 SNP in the gene SART1 showed a near doubled frequency in glioblastoma patients, as verified in an independent control cohort by Sanger sequencing. In addition, we identified SNPs in 20 of 21 GBM associated antigens providing further evidence that genetic variations are significantly associated with the immunogenicity of antigens

miR-196a Downregulation Increases the Expression of Type I and III Collagens in Keloid Fibroblasts

Keloids are a fibroproliferative disease due to abnormal wound healing process after skin injury. They are characterized by overproduction of extracellular matrix (ECM) such as collagens. MicroRNAs (miRNAs) are noncoding small RNAs and negatively regulate protein expression. Several miRNAs that have critical roles in tissue fibrosis and ECM metabolism have been reported. However, regulation and function of miRNAs in keloid remain to be explored. The purpose of this study was to identify miRNAs involved in keloid pathogenesis. We performed miRNA microarray analysis to compare miRNA expression profiles between keloid-derived fibroblasts (KFs) and normal fibroblasts (NFs). In all, 7 upregulated and 20 downregulated miRNAs were identified. Among these, we focused on miR-196a, which showed the highest fold change. Overexpression or knockdown of miR-196a led to a decreased or increased level of secreted type I/III collagens, respectively. Reporter analysis showed direct binding of miR-196a to the 3′ untranslated region (UTR) of COL1A1 and COL3A1. In conclusion, we demonstrate for the first time that miRNA expression profile is altered in KFs compared with NFs. Downregulation of miR-196a may be one of the mechanisms by which collagens are highly deposited in keloid tissues. Our findings suggest that miR-196a could be a new therapeutic target for keloid lesions

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd