Risk Stratification on Pheochromocytoma and Paraganglioma from Laboratory and Clinical Medicine

Pheochromocytoma (PCC) and sympathetic paraganglioma (PGL) are rare neuroendocrine tumors characterized by catecholamine production in the adrenal medulla and extra-adrenal paraganglia. PCC and PGL (PPGL) with metastasis was termed malignant PPGL. However, the distinction between “benign” and “malignant” PPGLs has been debated. Currently, all PPGLs are believed to have some metastatic potential and are assigned malignant tumors (ICD-O/3) by the WHO Classification of Endocrine Organs (2017, 4th edition). Therefore, the previous categories benign and malignant PPGL have been eliminated in favor of risk stratification approach. The Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) is a tool for risk stratification for predicting metastasis and the prognosis of patients. At least 30% of PPGLs are hereditary, with 20 genes identified and genotype-phenotype correlations clarified. Of these genes, VHL, RET and NF1 have been well investigated and are the primary cause of bilateral PCC. In addition, mutation of succinate dehydrogenase gene subunits SDHB and SDHD are strongly correlated with extra-adrenal location, younger age, multiple tumors, metastasis and poor prognosis. Disease stratification by catecholamine phenotype and molecular profiling correlates with histological grading by GAPP. PPGLs should be understood comprehensively based on clinical, biochemical, molecular and pathological data for patient care. A flow chart for pathological diagnosis is included

Research of SDHB as Malignant marker and oncogenesis in malignantpheochromocytomas

科学研究費助成事業(科学研究費補助金)研究成果報告書：基盤研究(C)2009-2011課題番号：2159116

Professional dietary coaching within a group chat using a smartphone application for weight loss: a randomized controlled trial

Purpose: To test the effectiveness of professional dietary coaching via group chat using a smartphone application (app) for weight loss.Methods: This study was a 12-week, assessor-blind, parallel-group, waitlist-controlled randomized trial that included a 4-week follow-up period (trial registration, UMIN000025340). Data were collected between October 2016 and May 2017 and were analyzed between July 2017 and January 2018. Participants were 112 overweight, obese, or abdominally obese Japanese adults, aged 20 to 64 years, with at least one cardiometabolic risk factor. Participants were randomized to the coaching group (n=75) or control group (n=37), with a ratio of 2:1. The coaching group received a commercial weight loss program characterizing dietary coaching by a certified nutrition professional via group chat delivered on a smartphone app. Participants posted photos of every meal into the group chat, and the certified professional gave immediate direct feedback and encouragement. The primary outcome was an 8-week weight change. Secondary outcomes included 8-week changes in cardiometabolic risk factors. The frequency of meal photo uploads was recorded as a measure of adherence.Results: Of the 112 randomized participants, 93 (83.0%) and 81 (72.3%) completed 8-week and 12-week visits, respectively. Intention-to-treat analysis demonstrated significantly larger 8-week weight loss in the coaching group (−1.4 kg; 95% confidence interval [CI]: −2.0, −0.8 kg) than that in the control group (−0.1 kg; 95% CI: −0.6, 0.4 kg). Significantly larger improvements in triglyceride and glycated hemoglobin A1c levels were also obtained in the coaching group. These benefits, except for the triglyceride level, were maintained until week 12. The frequent upload of meal photos was associated with a larger 8-week weight loss in a dose–response fashion (P-value for trend <0.001).Conclusion: This smartphone-delivered commercial weight loss program characterized as dietary coaching via group chat resulted in modest but significant weight loss. Facilitating participants’ active involvement in the program is necessary to achieve greater health benefits

Synchronous bilateral pheochromocytomas and paraganglioma with novel germline mutation in MAX: a case report

BackgroundRecent advance of genetic testing has contributed to the diagnosis of hereditary pheochromocytoma and paraganglioma (PPGL). The clinical characteristics of hereditary PPGL are varying among the types of mutational genes. It is still difficult to specify the pathognomonic symptoms in the case of rare genetic mutations. Here, we report the case of synchronous bilateral pheochromocytomas and paraganglioma with novel MYC associated factor X (MAX) gene mutation.Case presentationA 24-year-old female had hyperhidrosis and hypertension. Her urine test showed high normetanephrine and vanillylmandelic acid. Enhanced computed tomography revealed three enhanced masses in right adrenal gland, left adrenal gland, and left renal hilus. She was diagnosed with PPGL. Because 123I-metaiodobenzylguanidine scintigraphy indicated the accumulations in the left adrenal gland mass and the left renal hilus mass and not in the right adrenal gland mass, we performed laparoscopic left adrenalectomy and extirpation of the left renal hilus mass to preserve the right adrenocortical function. However, her symptoms recurred shortly after the operation presumably due to unveiling of the activity of the right pheochromocytoma. Following right adrenalectomy as the second operation, the catecholamine levels declined to normal range. Her genetic testing indicated the novel germline mutation in MAX gene (c.70_73 del AAAC/p.Lys24fs*40).ConclusionsMAX germline mutation is recently identified as a rare cause of hereditary PPGL. The deletion mutation in MAX gene in this patient has never reported before. In the case of bilateral pheochromocytomas, the surgical indication should be decided considering each patient’s genetic background. Due to the possibility for other types of malignant tumors, close follow-up is essential for MAX mutation carriers

Detection of Transgenes in Gene Delivery Model Mice by Adenoviral Vector Using ddPCR

With the rapid progress of genetic engineering and gene therapy, the World Anti-Doping Agency has been alerted to gene doping and prohibited its use in sports. However, there is no standard method available yet for the detection of transgenes delivered by recombinant adenoviral (rAdV) vectors. Here, we aim to develop a detection method for transgenes delivered by rAdV vectors in a mouse model that mimics gene doping. These rAdV vectors containing the mCherry gene was delivered in mice through intravenous injection or local muscular injection. After five days, stool and whole blood samples were collected, and total DNA was extracted. As additional experiments, whole blood was also collected from the mouse tail tip until 15 days from injection of the rAdv vector. Transgene fragments from different DNA samples were analyzed using semi-quantitative PCR (sqPCR), quantitative PCR (qPCR), and droplet digital PCR (ddPCR). In the results, transgene fragments could be directly detected from blood cell fraction DNA, plasma cell-free DNA, and stool DNA by qPCR and ddPCR, depending on specimen type and injection methods. We observed that a combination of blood cell fraction DNA and ddPCR was more sensitive than other combinations used in this model. These results could accelerate the development of detection methods for gene doping

Risk Stratification on Pheochromocytoma and Paraganglioma from Laboratory and Clinical Medicine

Pheochromocytoma (PCC) and sympathetic paraganglioma (PGL) are rare neuroendocrine tumors characterized by catecholamine production in the adrenal medulla and extra-adrenal paraganglia. PCC and PGL (PPGL) with metastasis was termed malignant PPGL. However, the distinction between &ldquo;benign&rdquo; and &ldquo;malignant&rdquo; PPGLs has been debated. Currently, all PPGLs are believed to have some metastatic potential and are assigned malignant tumors (ICD-O/3) by the WHO Classification of Endocrine Organs (2017, 4th edition). Therefore, the previous categories benign and malignant PPGL have been eliminated in favor of risk stratification approach. The Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) is a tool for risk stratification for predicting metastasis and the prognosis of patients. At least 30% of PPGLs are hereditary, with 20 genes identified and genotype-phenotype correlations clarified. Of these genes, VHL, RET and NF1 have been well investigated and are the primary cause of bilateral PCC. In addition, mutation of succinate dehydrogenase gene subunits SDHB and SDHD are strongly correlated with extra-adrenal location, younger age, multiple tumors, metastasis and poor prognosis. Disease stratification by catecholamine phenotype and molecular profiling correlates with histological grading by GAPP. PPGLs should be understood comprehensively based on clinical, biochemical, molecular and pathological data for patient care. A flow chart for pathological diagnosis is included

カテスタチンの多型を指標としたメタボリック症候群の分子診断法と新規治療法開発

科学研究費助成事業 研究成果報告書：基盤研究(C)2014-2016課題番号 : 2635088

Data from: A simple micropump based on a freeze-dried superabsorbent polymer for multiplex solution processing in disposable devices

The data present mainly the performances and characterization of the superabsorbent polymer-based micropump. Specifically, the data include the comparison of the absorbing rate and capacity using SAP, comparison of SAP with other absorbent materials,comparison of the SAP pump with tissue paper pump, influence of the SAP-CA ratio on rate of absorption, influence of NaCl on the rate of absorption of SAP, solution displacement by the SAP pump, the influence of the size of SP disc, dimension of the flow channel on the pumping rate and current response on different concentration of glucose. Supporting movie 1, 2, 3 and 4 show the operation principle of the SAP pump, continuous flow of solutions for long time, multiple pumping realized with SAP pump and multiplex processing of solution with SAP pump and switchable valve respectively