ステロイド依存性ネフローゼ症候群患者におけるミゾリビン有効性に関連する因子の検討

藤田医科大

Refined metadynamics through canonical sampling using time-invariant bias potential: A study of polyalcohol dehydration in hot acidic solutions

We propose a canonical sampling method to refine metadynamics simulations a posteriori, where the hills obtained from metadynamics are used as a time‐invariant bias potential. In this way, the statistical error in the computed reaction barriers is reduced by an efficient sampling of the collective variable space at the free energy level of interest. This simple approach could be useful particularly when two or more free energy barriers are to be compared among chemical reactions in different or competing conditions. The method was then applied to study the acid dependence of polyalcohol dehydration reactions in high‐temperature aqueous solutions. It was found that the reaction proceeds consistently via an SN2 mechanism, whereby the free energy of protonation of the hydroxyl group created as an intermediate is affected significantly by the acidic species. Although demonstration is shown for a specific problem, the computational method suggested herein could be generally used for simulations of complex reactions in the condensed phase

Introduction of thickened food for patient with dysphagia after surgical treatment for tumor in oral cavity

口腔腫瘍術後患者は,程度に差はあるが,嚥下･摂食障害をきたしやすい｡その経口摂取開始初期の栄養について,患者が満足して,より快適に摂取でき,経口のみで栄養が満たされるような食事を工夫した｡そのためには,食べやすさを増すためにトロメリンでとろみをつけ, また,食べ残しがないように患者の嗜好を取り入れた｡そして,この嗜好を取り入れたとろみ食を, 口腔腫瘍術後患者一例に提供した｡その結果, とろみ食は,食べやすく,全量摂取でき,良好な栄養状態を維持し,口内の移植皮弁へのトラブルもなく有効であるという結果が得られた｡また,患者が意欲や自信を持つという精神面への効果も見られた｡Following an operation to remove a tumor in the oral cavity, a patient with dysphagia who had received IVH and intubation feeding for 21 days, was given food thickened with proceeded starch and dextrin (Tromelin). The patient acceptance was good and he could chew and swallow safely and easily than if given ordinary food. The psychological and emotional effects of such postoperational care are also discussed

Age-dependent effects on radiation-induced carcinogenesis in the rat thyroid

Childhood radiation exposure is a known thyroid cancer risk factor. This study evaluated the effects of age on radiation-induced thyroid carcinogenesis in rats irradiated with 8 Gy X-rays. We analyzed cell proliferation, cell death, DNA damage response, and autophagy-related markers in 4-week-old (4W) and 7-month-old (7M) rats and the incidence of thyroid tumors in 4W, 4-month-old (4M), and 7M rats 18 months after irradiation. Cell death and DNA damage response were increased in 4W rats compared to those in controls at 1 month post-irradiation. More Ki-67-positive cells were observed in 4W rats at 12 months post-irradiation. Thyroid tumors were confirmed in 61.9% (13/21), 63.6% (7/11), and 33.3% (2/6) of irradiated 4W, 4M, and 7M rats, respectively, compared to 0%, 14.3% (1/7), and 16.7% (1/6) in the respective nonirradiated controls. There were 29, 9, and 2 tumors in irradiated 4W, 4M, and 7M rats, respectively. The expression of several autophagy components was downregulated in the area surrounding radiation-induced thyroid carcinomas in 4W and 7M rats. LC3 and p62 expression levels decreased in radiation-induced follicular carcinoma in 4W rats. Radiosensitive cells causing thyroid tumors may be more prevalent in young rats, and abrogation of autophagy may be associated with radiation-induced thyroid carcinogenesis

Host selection of hematophagous leeches (Haemadipsa japonica): Implications for iDNA studies

The development of an efficient and cost‐effective method for monitoring animal populations or biodiversity is urgently needed, and invertebrate‐derived DNA (iDNA) may offer a promising tool for assessing the diversity and other ecological information of vertebrates. We studied the host species of a hematophagous leech (Haemadipsa japonica) in Yakushima by genetic barcoding and compared the results with those for mammal composition revealed by camera trapping. We analyzed 119 samples using two sets of primers by Sanger sequencing and one set of primer by next generation sequencing. The proportion of the samples that were successfully sequenced and identified to at least one species was 11.8–24.3%, depending on the three different methods. In all of these three methods, most of the samples were identified as sika deer (18/20, 6/15 and 16/29) or human (2/20, 7/15 and 21/29). The nonhuman mammal host species composition was significantly different from that estimated by camera trapping. Sika deer was the main host, which may be related with their high abundance, large body size and terrestriality. Ten samples included DNA derived from multiple species of vertebrates. This may be due to the contamination of human DNA, but we also found DNA from deer, Japanese macaque and a frog in the same samples, suggesting the mixture of the two meals in the gut of the leech. Using H. japonica‐derived iDNA would not be suitable to make an inventory of species, but it may be useful to collect genetic information on the targeted species, due to their high host selectivity

Characterization of the novel mutant A78T-HERG from a long QT syndrome type 2 patient: Instability of the mutant protein and stabilization by heat shock factor 1

Background:The human ether-a-go-go-related gene (HERG) encodes the α-subunit of rapidly activating delayed-rectifier potassium channels. Mutations in this gene cause long QT syndrome type 2 (LQT2). In most cases, mutations reduce the stability of the channel protein, which can be restored by heat shock (HS). Methods: We identified the novel mutant A78T-HERG in a patient with LQT2. The purpose of the current study was to characterize this mutant protein and test whether HS and heat shock factors (HSFs) could stabilize the mutant protein. A78T-HERG and wild-type HERG (WT-HERG) were expressed in HEK293 cells and analyzed by immunoblotting, immunoprecipitation, immunofluorescence, and whole-cell patch clamping. Results: When expressed in HEK293 cells, WT-HERG gave rise to immature and mature forms of the protein at 135 and 155 kDa, respectively. A78T-HERG gave rise only to the immature form, which was heavily ubiquitinated. The proteasome inhibitor MG132 increased the expression of immature A78T-HERG and increased both the immature and mature forms of WT-HERG. WT-HERG, but not A78T-HERG, was expressed on the plasma membrane. In whole-cell patch clamping experiments, depolarizing pulses evoked E4031-sensitive HERG channel currents in cells transfected with WT-HERG, but not in cells transfected with A78T-HERG. The A78V mutant, but not A78G mutant, remained in the immature form similarly to A78T. Maturation of the A78T-HERG protein was facilitated by HS, expression of HSF-1, or exposure to geranyl geranyl acetone. Conclusions: A78T-HERG was characterized by protein instability and reduced expression on the plasma membrane. The stability of the mutant was partially restored by HSF-1, indicating that HSF-1 is a target for the treatment for LQT2 caused by the A78T mutation in HERG

Insulin-producing cells derived from ‘induced pluripotent stem cells’ of patients with fulminant type 1 diabetes: vulnerability to cytokine insults and increased expression of apoptosis-related genes

Aims/Introduction: The present study was carried out to generate induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes, and evaluate the cytokine‐induced apoptotic reactions of β‐like insulin‐producing cells differentiated from the iPSCs.Materials and Methods: iPSCs were generated from fibroblasts of patients with fulminant type 1 diabetes by inducing six reprogramming factors. Insulin‐producing cells were differentiated from the iPSCs in vitro. The proportion of cleaved caspase‐3‐positive or terminal deoxynucleotidyl transferase 2′‐deoxyuridine, 5′‐triphosphate nick end labeling‐positive cells among insulin (INS)‐positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines was evaluated under treatment with tumor necrosis factor‐α, interleukin‐1β and interferon‐γ. Ribonucleic acid sequencing was carried out to compare gene expressions in INS‐positive cells derived from fulminant type 1 diabetes iPSC and control human iPSC lines.Results: Two iPSC clones were established from each of three patients with fulminant type 1 diabetes. The differentiation of insulin‐producing cells from fulminant type 1 diabetes iPSC was confirmed by immunofluorescence analysis and KCl‐induced C‐peptide secretion. After treatment with pro‐inflammatory cytokines, these INS‐positive cells showed higher expression of cleaved caspase‐3 than those derived from control human iPSCs. Altered expression levels of several apoptosis‐related genes were observed in INS‐positive cells derived from the fulminant type 1 diabetes iPSCs by ribonucleic acid sequencing.Conclusions: We generated iPSCs from patients with fulminant type 1 diabetes and differentiated them into insulin‐producing cells. This in vitro disease model can be used to elucidate the disease mechanisms of fulminant type 1 diabetes

Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004

We analyze the data of TAMA300 detector to search for gravitational waves from inspiraling compact star binaries with masses of the component stars in the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the years 2000-2004, are used for the event search. We combine the results of different observation runs, and obtained a single upper limit on the rate of the coalescence of compact binaries in our Galaxy of 20 per year at a 90% confidence level. In this upper limit, the effect of various systematic errors such like the uncertainty of the background estimation and the calibration of the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was correcte