Intranuclear topological distribution of HIV-1 trans-activators

AbstractSubcellular localization of human immunodeficiency virus type 1 (HIV-1) Tat and Rev was examined using a confocal laser scanning microscope (CLSM). In transfected COS-7 cells, Tat resided exclusively in the perinocleolar region, while Rev infiltrated fully into the nucleoli. The chimeric Tat in which the nucleolar targeting signal was replaced by that of Rev, which retains trans-acting activity of Tat, remained still in the perinucleolar region as wild-type Tat. Perinucleolar distribution of Tat protein suggests the existence of a novel nucleolar architecture that affects transcription

Study of Genetic Effects of Sulphur Mustard Gas on Former Workers of Ohkunojima Poison Gas Factory and Their Offspring

General health examination and one-dimensional electrophoretic examination to detect mutations at the protein level were conducted in order to elucidate potential genetic effects of sulphur mustard gas on children of the former workers of Ohkunojima Poison Gas Factory. In the general examination, no disease which was definitely considered to be caused by genetic effects was observed, and no examination values obtained for the children proved to be significantly abnormal compared with those for their parents. Blood samples from 456 children were electrophoretically examined for 30 protein systems. A total of 36 protein variants were detected in 10 protein systems, and the frequency of variants was 2.63 per 1,000 tests. Family study was completed for 32 of these variants, all of which were confirmed to be genetic variants. In 29,868 locus tests, mutation occurred in germ cells of parents could not be detected. Among 36 variants, two PGM2 variants and one GPI variant were detected for the first time in this study

CPAPアドヒランスの予測因子としてのCPAP装着下覚醒時の呼吸不規則性

BACKGROUND AND OBJECTIVE: The standard therapy for obstructive sleep apnoea (OSA) is continuous positive airway pressure (CPAP) therapy. However, long-term adherence remains at ~50% despite improvements in behavioural and educational interventions. Based on prior work, we explored whether regularity of breathing during wakefulness might be a physiologic predictor of CPAP adherence. METHODS: Of the 117 consecutive patients who were diagnosed with OSA and prescribed CPAP, 79 CPAP naïve patients were enrolled in this prospective study. During CPAP initiation, respiratory signals were collected using respiratory inductance plethysmography while wearing CPAP during wakefulness in a seated position. Breathing regularity was assessed by the coefficient of variation (CV) for breath-by-breath estimated tidal volume (VT ) and total duration of respiratory cycle (Ttot). In a derivation group (n = 36), we determined the cut-off CV value which predicted poor CPAP adherence at the first month of therapy, and verified the validity of this predetermined cut-off value in the remaining participants (validation group; n = 43). RESULTS: In the derivation group, the CV for estimated VT was significantly higher in patients with poor adherence than with good adherence (median (interquartile range): 44.2 (33.4-57.4) vs 26.0 (20.4-33.2), P 34.0 confirmed to be predicting poor CPAP adherence (sensitivity, 0.78; specificity, 0.83). CONCLUSION: At the initiation of therapy, breathing regularity during wakefulness while wearing CPAP is an objective predictor of short-term CPAP adherence.博士（医学）・乙第1391号・平成29年3月15日© 2016 Asian Pacific Society of RespirologyThis is the peer reviewed version of the following article: Respirology Vol.22 No.2 p.386-393 (2017 Feb), which has been published in final form at http://dx.doi.org/10.1111/resp.12900. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving

慢性閉塞性肺疾患患者における骨塩量の分布と体重および運動能との関連

Background: Although low bone mineral density is highly prevalent in patients with chronic obstructive pulmonary disease (COPD), the distribution of the reduced bone mass has not been fully elucidated. Objectives: To determine regional bone mass loss in patients with COPD and investigate whether the change in distribution may be associated with body weight loss and functional capacity. Methods: Body mass index (BMI) was assessed, and height squared indices were derived for the bone mineral content index (BMCI) of the arms, legs and trunk by dual-energy X-ray absorptiometry in 45 male patients with COPD and 12 age- and sex-matched control subjects. Pulmonary function tests were performed, and maximal oxygen uptake (V·O2max) was measured. Results: The BMCI was lower in the total bone, legs and trunk of patients with COPD than in control subjects, although the BMCI in the arms was similar between the groups. BMI correlated significantly with the BMCI in all 3 segments. Bone mineral content (BMC) in the trunk, expressed as a percentage of total BMC (BMC trunk/total BMC), correlated significantly with BMI. The BMCI in the trunk was closely related with V·O2max but not with airflow limitation. Conclusions: There was a regional difference in BMC reduction, but a predominant reduction of bone mass in the trunk was not associated with the severity of airflow limitation but rather with body weight loss and exercise intolerance. These data suggest that body weight loss and exercise intolerance are important risk factors for vertebral fracture in patients with COPD.博士（医学）・乙第1341号・平成26年7月22日The definitive version is available at " http://dx.doi.org/10.1159/000355095

Factual survey of the clinical use of deformable image registration software for radiotherapy in Japan

Deformable image registration (DIR) has recently become commercially available in the field of radiotherapy. However, there was no detailed information regarding the use of DIR software at each medical institution. Thus, in this study, we surveyed the status of the clinical use of DIR software for radiotherapy in Japan. The Japan Society of Medical Physics and the Japanese Society for Radiation Oncology mailing lists were used to announce this survey. The questionnaire was created by investigators working under the research grant of the Japanese Society for Radiation Oncology (2017–2018) and intended for the collection of information regarding the use of DIR in radiotherapy. The survey was completed by 161 institutions in Japan. The survey results showed that dose accumulation was the most frequent purpose for which DIR was used in clinical practice (73%). Various commissioning methods were performed, although they were not standardized. Qualitative evaluation with actual patient images was the most commonly used method (28%), although 30% of the total number of responses (42% of institutions) reported that they do not perform commissioning. We surveyed the current status of clinical use of DIR software for radiotherapy in Japan for the first time. Our results indicated that a certain number of institutions used DIR software for clinical practice, and various commissioning methods were performed, although they were not standardized. Taken together, these findings highlight the need for a technically unified approach for commissioning and quality assurance for the use of DIR software in Japan

IL-17F Induces CCL20 in Bronchial Epithelial Cells

IL-17F plays a crucial role in airway inflammatory diseases including asthma, but its function has not been fully elucidated. CCL20 is also involved in allergic airway inflammation, while its regulatory mechanisms remain to be defined. To further identify a novel role of IL-17F, the expression of CCL20 by IL-17F in bronchial epithelial cells and the signaling mechanisms involved were investigated. Bronchial epithelial cells were stimulated with IL-17F, and the levels of CCL20 gene and protein measured, with the effects of the addition of various kinase inhibitors and siRNAs also investigated. IL-17F significantly induced the expression of CCL20 gene and protein. Pretreatment with inhibitors for MEK1/2, Raf1 and MSK1, and overexpression of a Raf1 dominant-negative mutant significantly diminished IL-17F-induced CCL20 production. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked CCL20 expression. These findings suggest that IL-17F is able to induce CCL20 via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. The IL-17F/CCL20 axis may be a novel pharmacological target for asthma

局所型前立腺癌に対する3次元原体照射後の晩期消化管障害に関連する臨床因子

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miR-200b Precursor Can Ameliorate Renal Tubulointerstitial Fibrosis

Members of the miR-200 family of micro RNAs (miRNAs) have been shown to inhibit epithelial-mesenchymal transition (EMT). EMT of tubular epithelial cells is the mechanism by which renal fibroblasts are generated. Here we show that miR-200 family members inhibit transforming growth factor-beta (TGF-beta)-induced EMT of tubular cells. Unilateral ureter obstruction (UUO) is a common model of EMT of tubular cells and subsequent tubulointerstitial fibrosis. In order to examine the role of miR-200 family members in tubulointerstitial fibrosis, their expression was investigated in the kidneys of UUO mice. The expression of miR-200 family miRNAs was increased in a time-dependent manner, with induction of miR-200b most pronounced. To clarify the effect of miR-200b on tubulointerstitial fibrosis, we injected miR-200b precursor intravenously. A single injection of 0.5 nM miR-200b precursor was sufficient to inhibit the increase of collagen types I, III and fibronectin in obstructed kidneys, and amelioration of fibrosis was confirmed by observation of the kidneys with Azan staining. miR-200 family members have been previously shown to inhibit EMT by reducing the expression of ZEB-1 and ZEB-2 which are known repressors of E-cadherin. We demonstrated that expression of ZEB-1 and ZEB-2 was increased after ureter obstruction and that administration of the miR-200b precursor reversed this effect. In summary, these results indicate that miR-200 family is up-regulated after ureter obstruction, miR-200b being strongly induced, and that miR-200b ameliorates tubulointerstitial fibrosis in obstructed kidneys. We suggest that members of the miR-200 family, and miR-200b specifically, might constitute novel therapeutic targets in kidney disease