Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.

The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking

ステロイド治療が奏功した猫ひっかき病の１女児例

京都府立医科大学附属北部医療センター小児科Department of Pediatrics, North Medical Center, Kyoto Prefectural University of Medicine猫ひっかき病 (Cat Scratch Disease: CSD) は、猫やノミを媒介して感染する人畜共通感染症で、基本的に自然治癒する。しかし、全身性の症状を呈する場合は、治療に難渋し、ステロイド治療が施行されることがある。本症例は局所のリンパ節腫脹と発熱を主訴とした典型的なCSDであったが、抗生剤の反応が乏しく、発熱が遷延するためプレドニゾロンを使用し著効した。発熱が遷延するCSDにおいては、全身性炎症を考慮し、ステロイドの使用が考慮される

低マグネシウム血症のないGitelman症候群の小児同胞例

京都府立医科大学附属北部医療センター　小児科Department of Pediatrics, North Medical Center, Kyoto Prefectural University of MedicineGitelman症候群(GS、MIM#263800)は腎遠位尿細管のサイアザイド感受性Na-Cl共輸送体(NCCT、責任遺伝子SLC12A3)の機能異常に由来する常染色体劣性遺伝病である。今回我々は頭痛・全身倦怠感・嘔気嘔吐・テタニーを契機に診断されたGSの小児同胞例を経験した。9歳の女児(姉)が夏季運動部活動の練習中に頭痛、全身倦怠感、嘔吐を訴え当科を紹介となった。右前腕にテタニーを認め、血液検査では低カリウム(K)血症(血清K、3.1mmol/L)を伴う代謝性アルカローシスを認めた。低マグネシウム(Mg)血症はなかった。高レニン血症および血清アルドステロンの高値を認めた。次世代シーケンサーを用いた遺伝子解析でSLC12A3 exon 22にc.2573T>A(p.Leu858His)ヘテロ接合性バリアントを認めた。塩化カリウムの経口補充で頭痛・倦怠感・テタニーの症状はなくなった。4歳の弟には慢性頭痛、全身倦怠感、嘔吐の主訴があり精査を実施した。低K血症、代謝性アルカローシス、高レニン性高アルドステロン血症の存在が明らかとなった。低Mg血症はなかった。姉と同様に遺伝子解析でSLC12A3 p.Leu858Hisバリアントを認め、GSの診断となった。低K血症は全身倦怠感の原因やテタニー・慢性頭痛・嘔気嘔吐の増悪因子として重要であり、GSを含む腎尿細管異常症を視野に積極的に精査する価値は高い。自験例では低Mg血症の存在はなく、GSとしては非典型例だったが、次世代シーケンサーを用いた網羅的な遺伝学的解析が確定診断に有用であった。(著者抄録

Calpain Inhibition Restores Autophagy and Prevents Mitochondrial Fragmentation in a Human iPSC Model of Diabetic Endotheliopathy

The relationship between diabetes and endothelial dysfunction remains unclear, particularly the association with pathological activation of calpain, an intracellular cysteine protease. Here, we used human induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) to investigate the effects of diabetes on vascular health. Our results indicate that iPSC-ECs exposed to hyperglycemia had impaired autophagy, increased mitochondria fragmentation, and was associated with increased calpain activity. In addition, hyperglycemic iPSC-ECs had increased susceptibility to cell death when subjected to a secondary insult-simulated ischemia-reperfusion injury (sIRI). Importantly, calpain inhibition restored autophagy and reduced mitochondrial fragmentation, concurrent with maintenance of ATP production, normalized reactive oxygen species levels and reduced susceptibility to sIRI. Using a human iPSC model of diabetic endotheliopathy, we demonstrated that restoration of autophagy and prevention of mitochondrial fragmentation via calpain inhibition improves vascular integrity. Our human iPSC-EC model thus represents a valuable platform to explore biological mechanisms and new treatments for diabetes-induced endothelial dysfunction.Singapore Ministry of Health's National Medical Research Council Open Fund-Young Individual Research Grant [NMRC/OFYIRG/0021/2016]; Khoo Postdoctoral Fellowship Award [Duke-NUS-KPFA/2016/0010]; Hitachi Scholarship Research Support Grant from the Hitachi Global Foundation, Japan [RS-13, H-1]; American Heart Association Scientist Development Grant [16SDG27560003]; Stanford Diabetes Research Center under NIH [P30DK116074]; Frontier Research Grant 2017 from the Frontier Science Research Cluster (FSRC), Universiti Malaya, Malaysia [FG021-17AFR]; NIH [R01HL126516, R00HL130416]; Samsung Biomedical Research Institute [OTC 1180261]; National Research Foundation of Korea [NRF-2016R1A2B4008235]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Multi wavelength injection-seeded THz parametric generator

Recently, we have succeeded in the development of high power and high sensitivity THz wave spectral imaging system using injection-seeded THz parametric generation (is-TPG) and detection. A dynamic range of 100 dB has been obtained, and the peak output power of is-TPG approached 50 kW by introducing a microchip YAG laser with shorter pulse width of 420ps. Now we can detect drugs under much thicker obstacles than before using is-TPG spectroscopic imaging system

THz techniques using metal mesh sensor for human skin measurement

Abstract: Metal meshes work as band-pass filters in the terahertz (THz) region with their transmission spectra acutely being affected by the refractive index of the material inside and above the metal mesh openings. We used a metal mesh for high-sensitivity observations by focusing on the "dip", i. e. a sudden change in transmittance that only appeared when the THz wave was obliquely incident onto the metal mesh. Here we report a measurement of stratum corneum to inspect the feasibility of applying the metal mesh sensor to observations of human skin

Clinical Characteristics of Coronary-to-Pulmonary Artery Fistula in Patients with Pulmonary Atresia and Ventricular Septal Defect

The existence of a coronary-to-pulmonary artery fistula (CPF) in pulmonary atresia with ventricular septal defect (PAVSD) potentially affects treatment; however, its clinical features have not been comprehensively described due to the disease’s rarity. We reviewed 69 cases from 42 studies to reveal the clinical overview of patients with CPF and PAVSD. Among the included patients, the male-to-female ratio was exactly 1:1, and only two patients (3%) exhibited the 22q11.2 microdeletion syndrome. Regarding anatomical features, CPFs originated from the left coronary artery in 65% of patients, and 62% had other major aortopulmonary collateral arteries. Thirty-nine percent of patients had a definitive CPF diagnosis at 0 years of age, whereas 10% were diagnosed in adulthood. Seventy percent underwent catheter angiography to obtain a definitive CPF diagnosis. Ninety-five percent of patients underwent cardiac surgery, and among them, 43% underwent palliative surgery, whereas 52% underwent one-stage repair. Four patients including three adult patients developed cardiac dysfunction due to myocardial ischemia, and three of them exhibited improved cardiac function after the intervention for CPF. Of all the patients, 88% survived and 12% died. The surgical strategy and prognosis were similar to those in PAVSD patients without CPF. This review provides detailed clinical phenotypes that are potentially useful in enhancing the management of patients with this rare disease