筋強直性ジストロフィー1型における脳卒中に関する危険因子の臨床的特徴

Objective: Myotonic dystrophy type 1 (DM1) is a rare autosomal dominant disorder with highly variable phenotypic expression. Some patients have diabetes mellitus, dyslipidemia, and/or arrhythmias, which are risk factors for stroke. However, the mechanism of stroke is poorly understood in patients with DM1. We studied the characteristics of risk-factor profiles for stroke associated with DM1. Patients and methods: We studied 77 patients with DM1 (45 men and 32 women) on the basis of the patients’ clinical histories and laboratory and genetic examination results. Results: The analysis showed that 26 patients (34%) had dyslipidemia, and 16 (21%) had diabetes. Arrhythmias were diagnosed in 46 patients (61%), including 11 (14%) with atrial fibrillation and 9 (12%) with conduction defects. Echocardiographic abnormalities were found in 28 patients (37%). Eight patients (11%) met the criteria for metabolic syndrome. We identified 2 patients (2.6%) with ischemic stroke caused by cardiogenic embolism among 77 patients with DM1. One had paroxysmal atrial fibrillation and sick sinus syndrome, and the other had cardiac dysfunction with an ejection-fraction of 35% and dyslipidemia. Both patients had highly expanded numbers of CTG repeats (1000 and 1500). Conclusion: To our knowledge, this is the first study to report a comprehensive analysis of risk-factor profiles for stroke in patients with DM1. Stroke is a relatively rare, but severe complication of DM1. Our results indicate that it is important to manage risk factors for stroke, especially cardiac involvement and arrhythmias.博士（医学）・乙第1392号・平成29年3月15日Copyright: © 2016 Sugie M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

間欺的低酸素はヒト神経細胞においてGATA転写因子を介してPOMCとCARTのmRNAを増加させる

Sleep apnea syndrome (SAS) is characterized by intermittent hypoxia (IH) during sleep. SAS and obesity are strongly related to each other. Here, we investigated the effect of IH on the expression of major appetite regulatory genes in human neuronal cells. We exposed NB-1, SH-SY5Y, and SK-N-SH human neuronal cells to IH (64 cycles of 5 min hypoxia and 10 min normoxia), normoxia, or sustained hypoxia for 24 h and measured the mRNA levels of proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), galanin, galanin-like peptide, ghrelin, pyroglutamylated RFamide peptide, agouti-related peptide, neuropeptide Y, and melanocortin 4 receptor by real-time RT-PCR. IH significantly increased the mRNA levels of POMC and CART in all the neuronal cells. Deletion analysis revealed that the -705 to -686 promoter region of POMC and the -950 to -929 region of CART were essential for the IH-induced promoter activity. As possible GATA factor binding sequences were found in the two regions, we performed real-time RT-PCR to determine which GATA family members were expressed and found that GATA2 and GATA3 mRNAs were predominantly expressed. Therefore, we introduced siRNAs against GATA2 and GATA3 into NB-1 cells and found that GATA2 and GATA3 siRNAs abolished the IH-induced up-regulation of both POMC and CART mRNAs. These results indicate that IH stress up-regulates the mRNA levels of anorexigenic peptides, POMC and CART, in human neuronal cells via GATA2 and GATA3. IH can have an anorexigenic effect on SAS patients through the transcriptional activation of POMC and CART in the central nervous system.博士（医学）・甲第685号・平成30年6月27日© 2017 Elsevier Ltd. All rights reserved

Increase in Si:N drawdown ratio due to resting spore formation by spring bloom-forming diatoms under Fe- and N-limited conditions in the Oyashio region

Resting spore formation and Si:N drawdown ratios were investigated under iron (Fe)- and nitrogen (N)-limited conditions using a unialgal culture of Thalassiosira nordenskioeldii and natural phytoplankton assemblages during the spring bloom in the Oyashio region. In the unialgal culture of T nordenskioeldii, 20% and 100% of the cells formed resting spores under Fe- and N-limited conditions, respectively. The Si:N drawdown ratios were 2- and 14-fold higher in Fe- and N-limited conditions, respectively, compared to Fe- and N-sufficient conditions. At the start of the natural phytoplankton incubation, 18 among 47 identified diatom species were known resting spore-forming species. Approximately 15 common diatom species formed resting spores under Fe- and N-limited conditions. During the natural phytoplankton incubation, the percentage of the resting spores increased with time under both Fe- and N-limited conditions, reaching 25% and 40% of total diatom abundance, respectively. The Si: N drawdown ratios significantly increased with an increase in the contribution of resting spores in both the unialgal culture and natural phytoplankton incubations. These results suggest that if the bloom dominated by neritic, resting spore-forming diatom species decline by either Fe- or N-depletion, Si may be utilized preferentially to N in the upper mixed layer due to the formation of heavily silicified resting spores

AUTOPHAGY IN SKELETAL MUSCLE : AUTOPHAGIC VACUOLAR MYOPATHIES

Eukaryotic cells from yeast to human primarily use two distinct major mechanism for intracellular degradation/recycling system: the autophagy and proteasome. Autophagy contributes to the turnover of cellular components by delivering portions of the cytoplasm and organelles to lysosomes, where they are digested. Moreover, autophagy is involved in programmed cell death (PCD) and is called type II PCD, which differs from apoptosis (type I PCD). By mostly morphological studies, autophagy has been linked to disease processes: cancer, liver diseases, neurodegeneration, muscular disorders, and so on. Actually, lysosomes or autophagic vacuoles are morphologically unremarkable in normal muscle. However, in certain muscular disorders, the lysosomal system becomes prominent, indicating that autophagy is essential for muscle fibers. Here, we described current knowledge about the role of autophagy and the autophagy in muscular disorders: autophagic vacuolar myopathies

Temporal variability and bioavailability of iron and other nutrients during the spring phytoplankton bloom in the Oyashio region

Iron [dissolved Fe (D-Fe) and total dissolvable Fe (T-Fe)] and nutrient concentrations in the surface water of the Oyashio region (northwestern North Pacific) were measured before and during spring phytoplankton bloom (March to May in 2007). During the pre-bloom period (middle of March), we observed vertically uniform concentrations of iron (0.3-0.5 nM [D-Fe] and 3-5 nM [T-Fe]), macronutrients (10-15 μM NO3+NO2, 1.0-1.5 μM PO4 and 20-30 μM Si(OH)4) and chlorophyll a (Chl-a, 0.3-0.4 μg ^[-1]) throughout the upper 125 to 150 m due to vertical mixing during winter. Water temperature and salinity before the bloom were also vertically uniform with > 5℃ and S > 33.5, the conditions of a modified Kuroshio warm-water (MKW) ring, higher than those of the Coastal Oyashio Water (COW). The cold COW ( < 2℃, S < 33.2) intruded a few times into the surface during the bloom period with high iron (0.4-0.6 nM [D-Fe] and 10-25 nM [T-Fe]) and Chl-a (10-23 μg l^[-1]) concentrations. The high Chl-a observed in the COW is due to the higher original concentrations of iron and macronutrients in the COW than in the MKW. An incubation experiment conducted during a COW intrusion in early April resulted in robust phytoplankton growth and complete exhaustion of nutrients, indicating an adequate supply of bioavailable iron. This result is also consistent with robust in situ phytoplankton growth and Chl-a production due to the presence of high iron levels in the COW. The most important mechanisms transporting iron to the surface water, which would regulate the primary production during spring bloom in the Oyashio region, are the surface intrusions of iron- and nutrient-rich COW derived from vertical and lateral mixing processes and vertical mixing in MKW during winter and spring

Nutrient and diatom dynamics during late winter and spring in the Oyashio region of the western subarctic Pacific Ocean

We investigated the nutrient and diatom dynamics during late winter and spring (9-March to 1-May 2007) in the Oyashio region as part of the OECOS-WEST research cruises. Macronutrients, iron, chlorophyll a (Chl-a) and biogenic silica (BSi) concentrations in the upper mixed layer varied remarkably ranges were 1.88-18.8 μmol L^[-1] for NO3+NO2, 0.64-1.85 μmol L^[-1] for PO4, 3.14-35.7 μmol L^[-1] for Si(OH)4, 0.14-0.54 nmol L^[-1] for D-Fe, 0.64-24.6 nmol L^[-1] for T-Fe, 0.30-17.4 μg L^[-1] for Chl-a, and 0.34-14.1 μmol L^[-1] for BSi. Mixed layer depth (MLD) also varied from 8-190 m during the cruises. The growth rate of in situ phytoplankton communities, dominated by centric diatoms, varied in shipboard culture experiments from 0.55 d^[-1] for iron-replete to 0.14 d^[-1] for iron-limited conditions. A relationship between BSi and Chl-a concentrations indicates that the in situ diatom community in the warmer water system (>4℃) was heavily silicified, probably due to iron-limitation. The in situ macronutrient and dissolved iron concentrations below the MLD and estimated macronutrient concentrations during winter were negatively correlated to temperature (1-6℃), that is to the relative proportion of warm modified Kuroshio Water mixed into the colder Oyashio water system. The rate of decrease in Si(OH)4 per ℃ increase was greater than the rates for NO3+NO2 and PO4 for both in situ and estimated winter values. These results suggest that the spring bloom in the cold water system with high macronutrients and iron concentrations would progress rapidly and intensely, and then be terminated by nitrogenous nutrient depletion. However, the diatom bloom in warmer waters with lower macronutrients and iron concentrations would be terminated by Si- and/or iron-limitation of heavily-silicified diatoms. In the OECOS study, variation of macronutrients and iron due to the surface intrusions of several water masses and modification from different chemical conditions during winter were the most important factors regulating the progression, magnitude and probably fate of the spring phytoplankton bloom in the Oyashio region

Acute Autonomic, Sensory and Motor Neuropathy Associated with Meningoencephalitis

We report the first case of acute autonomic, motor and sensory neuropathy (AASMN) associated with meningoencephalitis. A 62-year-old man presented with fever, neck stiffness, and coma. Respiratory failure developed. Magnetic resonance images showed an abnormality in the medial temporal lobe. Cerebrospinal fluid analysis revealed pleocytosis with a high protein level. Intensive care gradually improved the consciousness level, but paralysis of the four extremities persisted. Nerve conduction studies revealed demyelinating sensory and motor polyneuropathy. Severe orthostatic hypotension, urinary retention, and constipation were also present. Clinical autonomic tests suggested both sympathetic and parasympathetic dysfunction. After intravenous immunoglobulin therapy, motor and sensory symptoms resolved rapidly; dysautonomia resolved gradually over the next 2 months. The response to immunological therapy and the presence of antecedent infection suggest that AASMN is a postinfectious, immune-mediated, autonomic, sensory and motor nervous system dysfunction

Importance of intracellular Fe pools on growth of marine diatoms by using unialgal cultures and on the Oyashio region phytoplankton community during spring

We report on the ability for luxury Fe uptake and the potential for growth utilizing intracellular Fe pools for 4 coastal centric diatom isolates and in situ phytoplankton assemblages, mainly composed of diatoms. Iron uptake of the diatom isolates and natural phytoplankton assemblages in the Oyashio region during spring blooms were prevented by adding hydroxamate siderophore desferrioxamine B (DFB). After the addition of DFB, intracellular Fe in the diatom isolates supported 2.4–4.2 cell divisions with 1.2–2.6 Chl a doublings. The intracellular Fe was primarily used for cell generation rather than Chl a production, leading to a reduction in the Chl a cell quota in the Fe-starved cells with time. The metabolic properties of the Fe-starved cells with their cell morphologies were different among species or genera. An on-deck incubation experiment also exhibited 1.9 cell divisions and 0.81 Chl a doublings of phytoplankton after the addition of DFB, also indicating the preference of cell generation over Chl a production. A decrease in the level of cellular Chl a, a main light-harvesting pigment in Fe-starved diatoms, may become a superior survival strategy to protect the cells from high irradiance that can cause photo-oxidative damages through photosynthesis. Such relatively low-Fe with high-light conditions could often occur in surface waters of the Oyashio region from spring to summe