ヒトウニョウビョウセイ ジンフゼン デ イジ トウセキチュウ ニ キュウセイ ハッショウ 1ガタ トウニョウビョウ オ ハッショウ シタ コウキ コウレイシャ ノ 1レイ

We herein presented a case of a ７５-year-old man who was referred to our hospital for hyperglycemia in a drowsy state following a convulsive seizure after receiving hemodialysis at another clinic. He had been receiving maintenance hemodialysis for non-diabetic renal failure from the age of ７３ years. He was diagnosed with diabetic ketosis because his blood glucose level was ７０７mg/dl, HbA１c ８．３％, glycoalbumin ４０．５％, serum osmolality ３２３mosm/kg, and ３-hydroxybutyric acid ５．８ mmol/l. Continuous intravenous insulin infusion therapy was immediately initiated and was changed to intensive insulin therapy on the ７th day after his admission. He did not have metabolic acidosis or serious dehydration associated with the acute metabolic derangement observed on arrival because fluid corrections for acid-base and electrolyte imbalances in the blood had been achieved by hemodialysis prior to his referral to our hospital. ΔCPR at six minutes in the glucagon loading test was hardly affected, indicating that his endogenous insulin secretory capacity was markedly reduced. The GAD antibody was negative. He had the haplotype of HLA DR４, which is considered to reflect disease susceptibility for type１diabetes in Japanese individuals. Acuteonset type １ diabetes mellitus was diagnosed based on the diagnostic criteria for acute-onset type１ diabetes mellitus （２０１２） by the Committee of the Japan Diabetes Society. At the time of his discharge, ８ units of insulin lispro were being administered prior to each meal in addition to ２ units of insulin glargine before sleeping. He was transferred to a local clinic on the ２３rd day after his admission. Although glycoalbumin had been measured every six months in the present case, it was not useful for detecting new onset diabetes. Therefore, blood glucose measurements before dialysis need to be regularly performed, even in dialysis patients with non-diabetic renal failure, in order to detect the new onset of diabetes at an early stage

Pulmonary-Renal Syndrome with Negative ANCAs and Anti-GBM Antibody

We report the case of a 76-year-old woman who was referred to our hospital for a gradually worsening cough and renal dysfunction. Although pneumonia was initially suspected, imaging findings of the lungs revealed diffuse alveolar hemorrhage at a later date. Renal failure developed and hemodiafiltration was performed on the 9th day. Rapidly progressive glomerulonephritis with crescent formation was diagnosed by renal biopsy. This case presentation has important clinical implications because uncategorizable pulmonary-renal syndrome (PRS) without the presence of ANCAs and anti-GBM antibody is extremely rare and has high rates of morbidity and mortality. No treatment has been established

Development of a cloud particle sensor for radiosonde sounding

A meteorological balloon-borne cloud sensor called the cloud particle sensor (CPS) has been developed.The CPS is equipped with a diode laser at 790 nm and two photodetectors, with a polarization plate in front of one of the detectors, to count the number of particles per second and to obtain the cloud-phase information (i.e. liquid, ice, or mixed). The lower detection limit for particle size was evaluated in laboratory experiments as 2 μm diameter for water droplets. For the current model the output voltage often saturates for water droplets with diameter equal to or greater than 80 μm. The upper limit of the directly measured particle number concentration is ～2 cm⁻³ (2×10³ L⁻¹/, which is determined by the volume of the detection area of the instrument. In a cloud layer with a number concentration higher than this value, particle signal overlap and multiple scattering of light occur within the detection area, resulting in a counting loss, though a partial correction may be possible using the particle signal width data. The CPS is currently interfaced with either a Meisei RS-06G radiosonde or a Meisei RS-11G radiosonde that measures vertical profiles of temperature, relative humidity, height, pressure, and horizontal winds. Twenty-five test flights have been made between 2012 and 2015 at midlatitude and tropical sites. In this paper, results from four flights are discussed in detail. A simultaneous flight of two CPSs with different instrumental configurations confirmed the robustness of the technique. At a midlatitude site, a profile containing, from low to high altitude, water clouds, mixed-phase clouds, and ice clouds was successfully obtained. In the tropics, vertically thick cloud layers in the middle to upper troposphere and vertically thin cirrus layers in the upper troposphere were successfully detected in two separate flights. The data quality is much better at night, dusk, and dawn than during the daytime because strong sunlight affects the measurements of scattered light

Role of BRCA1-associated protein (BRAP) variant in childhood pulmonary arterial hypertension

Although mutations in several genes have been reported in pulmonary arterial hypertension (PAH), most of PAH cases do not carry these mutations. This study aimed to identify a novel cause of PAH. To determine the disease-causing variants, direct sequencing and multiplex ligation-dependent probe amplification were performed to analyze 18 families with multiple affected family members with PAH. In one of the 18 families with PAH, no disease-causing variants were found in any of BMPR2, ACVRL1, ENG, SMAD1/4/8, BMPR1B, NOTCH3, CAV1, or KCNK3. In this family, a female proband and her paternal aunt developed PAH in their childhood. Whole-exome next-generation sequencing was performed in the 2 PAH patients and the proband’s healthy mother, and a BRCA1-associated protein (BRAP) gene variant, p.Arg554Leu, was identified in the 2 family members with PAH, but not in the proband’s mother without PAH. Functional analyses were performed using human pulmonary arterial smooth muscle cells (hPASMCs). Knockdown of BRAP via small interfering RNA in hPASMCs induced p53 signaling pathway activation and decreased cell proliferation. Overexpression of either wild-type BRAP or p.Arg554Leu-BRAP cDNA constructs caused cell death confounding these studies, however we observed higher levels of p53 signaling inactivation and hPASMC proliferation in cells expressing p.Arg554Leu-BRAP compared to wild-type BRAP. In addition, p.Arg554Leu-BRAP induced decreased apoptosis of hPASMCs compared with wild-type BRAP. In conclusion, we have identified a novel variant of BRAP in a Japanese family with PAH and our results suggest it could have a gain-of-function. This study sheds light on new mechanism of PAH pathogenesis.his work was supported by MEXT KAKENHI Grant Number 15K19639 (http://www.mext.go.jp/en/)

Role of BRCA1-associated protein (BRAP) variant in childhood pulmonary arterial hypertension.

Although mutations in several genes have been reported in pulmonary arterial hypertension (PAH), most of PAH cases do not carry these mutations. This study aimed to identify a novel cause of PAH. To determine the disease-causing variants, direct sequencing and multiplex ligation-dependent probe amplification were performed to analyze 18 families with multiple affected family members with PAH. In one of the 18 families with PAH, no disease-causing variants were found in any of BMPR2, ACVRL1, ENG, SMAD1/4/8, BMPR1B, NOTCH3, CAV1, or KCNK3. In this family, a female proband and her paternal aunt developed PAH in their childhood. Whole-exome next-generation sequencing was performed in the 2 PAH patients and the proband's healthy mother, and a BRCA1-associated protein (BRAP) gene variant, p.Arg554Leu, was identified in the 2 family members with PAH, but not in the proband's mother without PAH. Functional analyses were performed using human pulmonary arterial smooth muscle cells (hPASMCs). Knockdown of BRAP via small interfering RNA in hPASMCs induced p53 signaling pathway activation and decreased cell proliferation. Overexpression of either wild-type BRAP or p.Arg554Leu-BRAP cDNA constructs caused cell death confounding these studies, however we observed higher levels of p53 signaling inactivation and hPASMC proliferation in cells expressing p.Arg554Leu-BRAP compared to wild-type BRAP. In addition, p.Arg554Leu-BRAP induced decreased apoptosis of hPASMCs compared with wild-type BRAP. In conclusion, we have identified a novel variant of BRAP in a Japanese family with PAH and our results suggest it could have a gain-of-function. This study sheds light on new mechanism of PAH pathogenesis