Search

Biallelic IGFALS variants lead to acid‒labile subunit (ALS) deficiency characterized by growth hormone resistance with or without delayed puberty. Here, we report a prepubertal boy with a homozygous 2-amino acid deletion within the fourth N-glycosylation motif (c.1103_1108del, p.N368_S370delinsT) associated with parental consanguinity. He showed short stature consistent with ALS deficiency. This case expands the mutation spectrum of IGFALS to include the elimination of only one N-glycosylation motif of ALS., (© 2024. The Author(s).)

Non-tuberculosis mycobacterial (NTM) pulmonary disease (NTM-PD) is quite common, and newly identified species are being reported increasingly frequently thanks to advances in identification technologies. A 56-year-old woman had mild sputum production showed bronchiectasis with multiple small nodules, consistent with NTM-PD, on chest computed tomography. Mycobacterial species were isolated from the specimens; however, conventional methods could not identify the species. We conducted whole-genome sequencing and identified the NTM isolates as Mycobacterium kiyosense, a species newly registered in 2023 from Japan. She was diagnosed with NTM-PD caused by M. kiyosense and received watchful waiting.

Objectives: This study investigated the safety of orthodontic anchor screw (OAS) placement by examining the morphology and degree of depression of the maxillary sinus adjacent to the alveolar bone between the maxillary molars., Methods: We reviewed panoramic and CT imaging data of 25 patients. First, the morphology of the maxillary sinus adjacent to the alveolar bone between the maxillary molars on panoramic images was classified into three types: non-depressed sinus, funnel-like sinus depression, and sawtooth-like sinus depression. Then, the distance from the maxillary buccal bone to the maxillary sinus or to the maxillary lingual bone and the distance between the roots of the maxillary second premolar and first molar at heights of 5, 6.5, and 8 mm from the alveolar crest were measured on CT images and compared between the three sinus morphology groups., Results: The sawtooth-like depression group had significantly smaller bone thickness than the other two groups, with mean thickness of < 4 mm at any height from the alveolar crest. The funnel-like depression and non-depression groups had mean bone thickness of > 8 mm at any height from the alveolar crest., Conclusions: Sawtooth-like sinus depression had increased risk of maxillary sinus perforation, suggesting that OAS placement in this region should be avoided. In contrast, OAS placement between 6.5 and 8 mm from the alveolar crest is advisable in patients with funnel-like sinus depression and at a site > 8 mm from the alveolar crest in those with a non-depressed sinus., (© 2021. The Author(s).)

Knowledge of the factors that determine the distribution ranges of organisms is necessary to understand their evolutionary and ecological significance and contribution to biodiversity. A very effective mean of studying such factors is to compare the distribution characteristics and genetic structures of closely related species with differing habitat preferences. Freshwater aquatic insects are relatively easy to observe and the basis of their corresponding niche differentiation easier to identify. Freshwater habitats are categorized lotic or lentic water according to flow regime. In Japanese Islands, the genus Anisocentropus of the calamoceratid caddisfly, the target group in this study, was morphologically reconfirmed that three species, that is, Anisocentropus kawamurai , A. pallidus, and A. magnificus . Among these, A. kawamurai prefers lotic environments and A. pallidus is adapted to lentic water habitats. The distribution range of these sister species overlaps within the Japanese Islands. We estimated the phylogeny and the evolutionary history of Anisocentropus caddisflies worldwide. We estimated divergence periods by two methods, a single locus with various specimens and multiple loci with reduced numbers of the specimens. As a result, we elucidated the phylogenetic position of Japanese species within the cosmopolitan genus Anisocentropus , and also revealed their dual origin. In addition, we demonstrated that the contrasting genetic structures between the sister species distributed in widely overlapping areas were due to differentiation in their respective adapted environmental preferences. Although, in general, it is known that species adapted to lentic water have greater dispersal potential and so are associated with wider distribution areas by means of examining their comparative genetic structures, we revealed a new pattern of genetic locality existing in the genetic structures of the species adapted to lentic water. We then present evidence that suggests the ecological preferences of a species are an important factor in understanding the evolutionary history of that species., Competing Interests: The authors declare that they have no conflicts of interest., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Acetylcholine (ACh), a quaternary ammonium cation, is known as one of the itch inducer in atopic dermatitis (AD), an inflammatory skin disease with intense itching. Previous research has reported accumulation of ACh in lesional site of AD patients. Generally, ACh is metabolized by cholinesterase (ChE). Therefore, one of the causes of ACh accumulation may be the suppression of ChE activity. Increased levels of the multifunctional bioactive sphingolipid sphingosylphosphorylcholine (SPC) have also been detected in AD. Since SPC possesses a quaternary ammonium cation, like ACh, it is possible that SPC affects the activity of ChE catalyzing ACh metabolization. We investigated whether SPC influences the activity of ChE by performing enzymatic analysis of ChE in the presence of SPC. We found that SPC strongly suppressed acetylcholinesterase (AChE) activity, but the suppression of butyrylcholinesterase by SPC was quite low. The Michaelis constant (K m ) of AChE in the presence of SPC increased, and the maximum velocity (V max ) decreased, indicating that SPC acts as mixed-type inhibitor for AChE. The analysis of SPC analogs clarified the importance of both the quaternary ammonium cation and the carbon chain length of SPC for the AChE inhibitory effect and showed that SPC was unique in AChE inhibition among the sphingolipids in this study. These findings indicate a novel function of SPC on AChE inhibition. Thus, the inhibition activity of SPC may be a factor in the increase of ACh in AD.

An automatic pH adjustment instrument was developed for the preparation of analytical samples prior to solid phase extraction, which is widely used as a pretreatment technique for the separation of sample matrixes and preconcentration of elements for analysis. Real-time monitoring of the sample pH condition was performed by observing the light signal intensity of the pH-sensitive wavelength of the pH indicating reagent. A light of pH-insensitive wavelength was selected as the reference light to cancel the signal intensity variation of the pH-sensitive light due to the difference of pH indicating reagent concentration, possible difference in transparency of sample vessels, and minute fluctuation of the light source. The pH condition was elevated by automatic addition of ammonia solution using a nebulizer in the flow line of which an electromagnetic valve was equipped. Open and close operation of the electromagnetic valve was controlled based on the difference between the real-time pH condition and the target pH condition. The effectiveness of the instrument was confirmed by using various pH indicating reagents and by analyzing trace elements in a seawater certified reference material.

Background: Balloon pulmonary angioplasty (BPA) is an alternative therapy for chronic thromboembolic pulmonary hypertension (CTEPH). Right heart catheterization (RHC) is essential to evaluate the efficacy of BPA. Cardiac magnetic resonance imaging (CMR) is also now used to assess the structure and function of the right heart non-invasively. The aim of this study was to correlate improvement in CMR with that on RHC, and compared with improvement in other non-invasive findings after BPA. Methods and Results: Forty-two patients underwent BPA between July 2012 and March 2015, and CMR, electrocardiography (ECG), and echocardiography were performed at the same time before and 6 months after BPA. Median pulmonary vascular resistance (PVR) was improved from 5.7 Wood units (IQR, 3.1-7.9 Wood units) to 2.7 Wood units (IQR, 1.6-3.9 Wood units; P<0.001). Changes in PVR were correlated with the changes in 5 CMR, 9 ECG, and 5 echocardiography parameters. On logistic analysis to identify the indicators of improving PH (i.e., PVR <3 Wood units), 4 CMR parameters were independently correlated with PVR change, one of which was median septal inversion ratio (SIR; 0.59; IQR, 0.54-0.63 to 0.54; IQR, 0.50-0.58, P<0.0001). SIR was the best predictor of PH (OR, 1.27; P<0.05). Conclusions: CMR can be used to estimate hemodynamic changes after BPA, and SIR is useful to predict alleviation of PH., Competing Interests: The authors declare no conflicts of interest. This study was approved by the Faculty of Medicine Research Ethics Committee, Kyorin University (Reference number: H27-157)., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

A new species of the genus Goera, G. rupicola, is described based on adult and immature stages from Amami-Oshima, southwestern Japan. The larvae of this species inhabit wet cliff faces where water trickles over the surface. This is the first madicolous species reported in the genus Goera.

Notes are provided for six microcaddisfly species (Trichoptera, Hydroptilidae) in the Japanese fauna. One is a new species, Hydroptila nago Ito sp. nov., described from southern Japan. The second and third, Hydroptila dorsoprocessuata Botosaneanu 1993, previously known from eastern Russia, and Hydroptila introspinata Zhou and Sun 2009, known from northeastern China and Korea, are recorded from Japan for the first time and redescribed. A fourth, Hydroptila parapiculata Yang and Xue 1994, is known from central and southeastern China and central Japan; the male is redescribed. By synonymizing Ugandatrichia shinshiroensis Ito et al. 2018, described from central Japan, with a Chinese species, Allotrichia rhynchophyllum Zhou et al. 2016, we record the genus Allotrichia McLachlan from Japan for the first time. For a sixth species, Stactobia distinguenda Nozaki and Botosaneanu 1996, previously known in Japan from the male only, the larva and its case are described.

We report on the application of radon inhalation therapy to patients with 4 types of cancer: colon, uterine, lung, and liver cell. The radon treatments were given to improve the efficacy of chemotherapy and were potent in all 4 cases. Marker values decreased and disease symptoms were alleviated. We include a lengthy discussion on the mechanism that may be responsible for the observed results. While employing the radon generator to treat the patient with hepatocellular carcinoma, we discovered that a concentration of 6 MBq/m 3 was very effective, while 1 MBq/m 3 was marginal. This implies different, and rather high, radon concentration thresholds for the treatment of different types of cancer. The evidence from these 4 cases suggests that radon inhalation may be beneficial against various cancer types as an important adjuvant therapy to conventional chemotherapy and for local high-dose radiotherapy, which would address the problem of distant metastasis. A previous case report on 2 patients with advanced breast cancer, who refused chemotherapy or radiotherapy, indicates that radon may be effective as a primary therapy for cancer. Clinical trials should be carried out to determine the best radon concentrations for treatment of other types of cancer, at different stages of progression., Competing Interests: Declaration of Conflicting Interests: The author(s) declare that there are no potential conflicts of interests with respect to the report, the authorship, and/or the publication of this article.

α-Lipoic acid is amphipathic with low molecular sulphur-containing fatty acid and has strong antioxidant effects. It has been used at the purposes of anti-ageing, treatment of diabetic neuropathy, and supplement as antioxidant. Though α-lipoic acid is normally administered in oral or injection, it has not been used in a topical use via skin because of its bad penetration. We developed the novel nanocapsule of α-lipoic acid, named α-lipoactive (nLA), to improve skin permeability. The nLA is constructed as micelles of α-lipoic acid mixed with the non-ionic surfactant, and its surface of the micelles was coated with inorganic metal salts. It is water soluble and has a diameter of approximately 8-15 nm. After nLA was applied to the murine skin, epidermal thickening was observed. It was confirmed that this effect is caused by α-lipoic acid molecule, but not by the raw material used for encapsulation. In in vivo experiments, it was found that nLA is very effective for improving UV-induced pigmentation and epidermal thickening. Our findings suggest that nanoencapsulation of α-lipoic acid is considerably effective for topical application., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This study aimed to elucidate the physiological feasibility of aortic valve neocuspidization (AVNeo) by comparing the aortic annulus dimensions between patients after AVNeo and patients with normal aortic valves., Methods: From December 2010 to October 2017, we performed AVNeo for various aortic valve pathologies in 147 patients. Of these patients, the aortic annulus dimensions were measured in 25 patients who underwent AVNeo for aortic valve disease as follow-up examination and compared with those measured in 15 patients who had normal aortic valves. Measurements were recorded using electrocardiography-gated transthoracic echocardiography., Results: No significant differences in the aortic annulus dimensions were observed between the patients who had undergone AVNeo and those who had normal aortic valves. In a cardiac cycle, the annulus area in the systolic phase was consistently larger than that in the diastolic phase, which was a physiological condition., Conclusions: The movement of the aortic annulus after AVNeo is comparable with that of the aortic annulus of a normal aortic valve. Thus, AVNeo can be regarded as a more physiological operation in that it maintains the characteristics of the aortic valve similar to those of a normal aortic valve.

We herein attempted to identify the lowest radiation dose causing molecular changes in the living body. We investigated the effects of radiation in human cells, animals, and humans. DNA double-strand breaks (DSBs) formed in cells at γ- or X-ray irradiation doses between 1 mGy and 0.5 Gy; however, the extent of DSB formation differed depending on the cell species. The formation of micronuclei (MNs) and nucleoplasmic bridges (NPBs) was noted at radiation doses between 0.1 and 0.2 Gy. Stress-responsive genes were upregulated by lower radiation doses than those that induced DNA DSBs or MN and NPBs. These γ- or X-ray radiation doses ranged between approximately 10 and 50 mGy. In animals, chromosomal aberrations were detected between 50 mGy and 0.1 Gy of low linear energy transfer radiation, 0.1 Gy of metal ion beams, and 9 mGy of fast neutrons. In humans, DNA damage has been observed in children who underwent computed tomography scans with an estimated blood radiation dose as low as 0.15 mGy shortly after examination. The frequencies of chromosomal translocations were lower in residents of high background areas than in those of control areas. In humans, systemic adaptive responses may have been prominently expressed at these radiation doses., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Therapy with α-radiation has issues associated with internal exposure; its clinical use has been avoided. However, phase III clinical tests of the α-emitting nuclide 223 Ra on patients with cancer have been conducted, and results were reported in 2011 to 2012. Since then, research has being carried out on targeted internal therapy by introducing α-emitting nuclides directly into the cancers. For many decades, nontargeted radon therapy has been carried out and is controversial because its mechanism of action is stimulation. The low-level radiation sends powerful signals to upregulate many biological protection systems, which protect against the effects of radiogenic and nonradiogenic toxins. These vital systems prevent, repair, and remove DNA and other biomolecular damage being produced endogenously at a very high rate by the very abundant reactive oxygen species associated with aerobic metabolism. Stimulation of protection systems results in beneficial effects, including a lower risk of cancer. This article reports the results of treatments on 4 patients with cancer and reviews the clinical use of α-radiation from 223 Ra and radon. It discusses the prospect of using the novel 225 Ac-prostate-specific membrane antigen ligand-617 ligand as a therapeutic agent for prostate cancer. It presents a new treatment system that we developed, α-Radiorespir o-Rn , which seems to be extremely effective in treating cancer., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children., Methods: We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined., Results: The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075]., Conclusions: The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children., (© 2016 Diabetes UK.)

There is considerable evidence from experimental studies in animals, as well as from clinical reports, that low-dose radiation hormesis is effective for the treatment of cancer and ulcerative colitis. In this study, we present 3 case reports that support the clinical efficacy of low-dose radiation hormesis in patients with these diseases. First, a patient with prostate cancer who had undergone surgical resection showed a subsequent increase in prostate-specific antigen (PSA). His PSA value started decreasing immediately after the start of repeated low-dose X-ray irradiation treatment and remained low thereafter. Second, a patient with prostate cancer with bone metastasis was treated with repeated low-dose X-ray irradiation. His PSA level decreased to nearly normal within 3 months after starting the treatment and remained at the low level after the end of hormesis treatment. His bone metastasis almost completely disappeared. Third, a patient with ulcerative colitis showed a slow initial response to repeated low-dose irradiation treatment using various modalities, including drinking radon-containing water, but within 8 months, his swelling and bleeding had completely disappeared. After 1 year, the number of bowel movements had become normal. Interest in the use of radiation hormesis in clinical practice is increasing, and we hope that these case reports will encourage further clinical investigations., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: The aim of this study was to clarify the significance of previously reported susceptibility variants in the development of autoimmune Type 1 diabetes in non-white children. Tested variants included rs2290400, which has been linked to Type 1 diabetes only in one study on white people. Haplotypes at 17q12-q21 encompassing rs2290400 are known to determine the susceptibility of early-onset asthma by affecting the expression of flanking genes., Methods: We genotyped 63 variants in 428 Japanese people with childhood-onset autoimmune Type 1 diabetes and 457 individuals without diabetes. Possible association between variants and age at diabetes onset was examined using age-specific quantitative trait locus analysis and ordered-subset regression analysis., Results: Ten variants, including rs2290400 in GSDMB, were more frequent among the people with Type 1 diabetes than those without diabetes. Of these, rs689 in INS and rs231775 in CTLA4 yielded particularly high odds ratios of 5.58 (corrected P value 0.001; 95% CI 2.15-14.47) and 1.64 (corrected P value 5.3 × 10 -5 ; 95% CI 1.34-2.01), respectively. Age-specific effects on diabetes susceptibility were suggested for rs2290400; heterozygosity of the risk alleles was associated with relatively early onset of diabetes, and the allele was linked to the phenotype exclusively in the subgroup of age at onset ≤ 5.0 years., Conclusions: The results indicate that rs2290400 in GSDMB and polymorphisms in INS and CTLA4 are associated with the risk of Type 1 diabetes in Japanese children. Importantly, cis-regulatory haplotypes at 17q12-q21 encompassing rs2290400 probably determine the risk of autoimmune Type 1 diabetes predominantly in early childhood., (© 2016 Diabetes UK.)

Introduction: Percutaneous transluminal pulmonary angioplasty (PTPA) was introduced for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) in the late 20(th) century, and first attempts in collective patients were made in 2001 with beneficial effects but a moderate amount of complications. It was refined around 2010, and has been recently established as an effective and safe treatment., Areas Covered: The indication was originally inoperable CTEPH with peripheral lesions, but has now widened to symptomatic or hypoxic patients. The lesion is typically a meshwork-like structure of organized thrombi and is sometimes not seen as a stenosis angiographically, necessitating other means of investigation such as measurement of distal pressure. The technique to treat lesions is the same as for coronary angioplasty except in several ways. Expert commentary: The effects of PTPA are comparable to those of surgical endarterectomy, and the complications of reperfusion pulmonary edema and vascular injury are now controlled by several strategies and based on experience.

Background: Low-density lipoprotein (LDL) is atherogenic and LDL particles are reduced in diameter in the presence of insulin resistance, forming small, dense LDL. This study was conducted to assess the relationship between commonly used lipid indices and LDL particle size and furthermore to clarify the best surrogate lipid markers that could conveniently be used to estimate LDL particle size in children., Methods: We determined LDL particle diameter by gradient gel electrophoresis in 1578 children aged 10-12 years. At the fasting state, the relationships between measured LDL particle size and lipid variables [total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), atherogenic index [(TC-HDL-C)/HDL-C, TG/HDL-C, LDL-C/HDL-C, and LDL-C/apolipoprotein B (Apo B) and non-HDL-C (TC-HDL-C)] were analyzed., Results: The LDL particle diameter was 26.64 (mean) ± 0.48 (SD) nm in boys (n = 820) and 26.66 ± 0.49 nm in girls (n = 758); there was not a statistically significant difference. There were statistically significant correlations between LDL particle size and TG or HDL-C concentrations (r = 0.28∼0.37), but the correlations with LDL-C and ApoB were very weak. The combined lipid measures, such as atherogenic index, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C showed moderate correlations (r = 0.33∼0.38) with LDL particle size; however, the correlation of non-HDL-C with LDL particle size was weak (r = 0.18∼0.19). Simple HDL-C measure appeared to be of comparable value to combined lipid measures., Conclusions: Our data indicate that various lipid indices are not superior to HDL-C levels alone as a clinical tool for estimating LDL particle size. Non-HDL-C was less valuable in this aspect.

Objective: The purpose of the present study was to examine the effects of 3 days isoenergetic high-fat/low-carbohydrate diet (HF-LC) relative to low-fat/high-carbohydrate diet (LF-HC) on the exercise-induced growth hormone (GH) response in healthy male subjects., Design: Ten healthy young males participated in this study. Each subject consumed the HF-LC (18±1% protein, 61±2% fat, 21±1% carbohydrate, 2720 kcal per day) for 3 consecutive days after consuming the LF-HC (18±1% protein, 20±1% fat, 62±1% carbohydrate, 2755 kcal per day) for 3 consecutive days. After each dietary intervention period, the hormonal and metabolic responses to an acute exercise (30 min of continuous pedaling at 60% of V˙O2max) were compared. The intramyocellular lipid (IMCL) contents in the vastus lateralis, soleus, and tibialis anterior were evaluated by proton magnetic resonance spectroscopy., Results: Serum GH concentrations increased significantly during the exercise after both the HF-LC and LF-HC periods (P<0.05). However, the exercise-induced GH response was not significantly different between the two periods. Fat utilization and lipolytic responses during the exercise were enhanced significantly after the HF-LC period compared with the LF-HC period. IMCL content did not differ significantly in any portion of muscle after the dietary interventions., Conclusions: We could not show that short-term HF-LC consumption changed significantly exercise-induced GH response or IMCL content in healthy young males., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The terminal deletion of the long arm of chromosome 18 is relatively common among cytogenetic abnormalities, which occur incidentally in approximately 1 in 40,000 live births. Proximal interstitial deletions of the long arm of chromosome 18 are less frequent. The critical region on chromosome 18 of this syndrome is del(18)(q12.2q21.1) and has recently been recognized as a new clinical entity. We describe a 8-year-old boy with developmental delay, obesity, and epilepsy, with characteristic facial anomalies in whom G-banding chromosome analysis revealed a unique karyotype of 46, XY, del(18)(q12.2q21.1). The patient was diagnosed with interstitial deletion chromosome 18q-syndrome. He received weight control therapy from a medical dietitian. For his epilepsy, he was administered oral carbamazepine at 4 mg/kg/day. At age six, he entered a special needs elementary school. After entering school, he often showed hyperkinesis, and was diagnosed with attention deficit hyperactivity disorder with mild mental retardation. Because patients with only del(18)(q12.2q21.1) have no serious associated malformations, physicians should be aware that even adult patients may have 18q-syndrome. Therefore, if epilepsy occurs in patients with minor facial anomalies, psychomotor retardation, obesity, and the possibility of 18q-syndrome with del(18)(q12.2q21.1) should be kept in mind, and chromosome testing should be performed.

Si-Si atomic columns separated by 45 pm were successfully resolved with a 300-kV aberration-corrected scanning transmission electron microscope (STEM) equipped with a cold-field emission gun. Using a sufficiently small Gaussian effective source size and a 0.4-eV energy spread at 300 kV, the focused electron probe on the specimen was simulated to be sub-50 pm. Image simulation showed that the present probe condition was sufficient to resolve 45 pm Si-Si dumbbells. A silicon crystalline specimen was observed from the [114] direction with a high-angle annular dark field STEM and the intensity profile showed 45 pm separation. A spot corresponding to (45 pm)(-1) was confirmed in the power spectrum of the Fourier transform., (© The Author 2015. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pulmonary endarterectomy (PEA) has been the most effective therapy for chronic thromboembolic pulmonary hypertension (CTEPH). However, residual or recurrent pulmonary hypertension often persists after PEA. Recently, catheter-based angioplasty, called percutaneous transluminal pulmonary angioplasty (PTPA) or balloon pulmonary angioplasty, has been developed as a promising strategy for CTEPH. Therefore, the usefulness of PTPA for residual or recurrent pulmonary hypertension after PEA was investigated., Methods: Thirty-nine patients underwent PEA from January 2000, and a total of 423 consecutive PTPA sessions in 110 patients were performed from January 2009 to May 2014. Of them, 9 patients (23.0% of 39 patients undergoing PEA and 8.2% of 110 patients undergoing PTPA) had undergone previous PEA and additional PTPA., Results: In these 9 patients, pulmonary vascular resistance (PVR) was 15.6 (7.8-18.9) wood units at baseline, and significantly improved after PEA [5.6 (3.5-6.5) wood units] (p<0.05). However, PVR gradually deteriorated before PTPA [8.1 (6.1-12.3) wood units] compared to after PEA, suggesting that these 9 patients had residual or recurrent pulmonary hypertension after PEA. PTPA was performed at 4.1 (2.7-7.9) years after PEA. Follow-up catheterization at 1.9 (1.3-3.3) years after PTPA revealed significant improvement of PVR [4.2 (2.8-4.8) wood units] (p<0.05)., Conclusions: A hybrid approach combining PEA and additional PTPA may be reasonable for patients with both proximal and very distal lesions not easily approachable by PEA. PTPA could be a promising alternative therapeutic strategy for residual or recurrent pulmonary hypertension after PEA., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate whether increments of weight gain in early infancy are related to the timing of adiposity rebound (AR)., Study Design: A total of 271 children (147 boys and 124 girls) in 1 community were enrolled in the study. Serial measurements of body mass index were carried out at the ages of 4, 8, and 12 months and 1.5, 2, 3, 4, 5, 6, 7, 8, 9, and 10 years, based on which the age of AR was determined. We also calculated body weight increments in 3 separate periods: birth to 4 months, 4-8 months, and 8-12 months., Results: There was no significant relationship between weight gain in any period of infancy and the age of AR. Weight gain between birth and 4 months was positively correlated only with body mass index at 7 years of age., Conclusions: We could not find an association between body weight gain during infancy and the timing of AR. This suggests that infantile weight gain is not related to childhood obesity through AR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Oxidation of the facial-type trichloridoruthenium(III) complex bearing ethylbis(2-pyridyl-methyl)amine (ebpma), fac-[Ru(III)Cl3(ebpma)], with an equimolecular amount of (NH4)2[Ce(IV)(NO3)6] in acetonitrile afforded a ligand-based oxidation product of an acetonitriledichloridoruthenium(III) complex having bis(2-pyridylcarbonyl)aminato (bpca), [Ru(III)Cl2(NCCH3)(bpca)]. The complex changed into a trichloridoruthenium(III) complex by a reaction with hydrochloric acid and the triacetonitrileruthenium(II) complex by reduction with Zn in ethanol-acetonitrile. The bpca moiety showed interactions with cations such as protons.

Objectives: This study sought to prove the safety and effectiveness of pressure-wire-guided percutaneous transluminal pulmonary angioplasty (PTPA)., Background: PTPA has been demonstrated to be effective for treatment of chronic thromboembolic pulmonary hypertension. However, a major and occasionally fatal complication after PTPA is reperfusion pulmonary edema. To avoid this, we developed the PEPSI (Pulmonary Edema Predictive Scoring Index). The pressure wire has been used to detect insufficiency of flow in a vessel., Methods: We included 350 consecutive PTPA sessions in 103 patients with chronic thromboembolic pulmonary hypertension from January 1, 2009 to December 31, 2013. During these 5 years, 140 PTPA sessions were performed without guidance, 65 with guidance of PEPSI alone, and 145 with both PEPSI and pressure-wire guidance. Each PTPA session was finished after achieving PEPSI scores of <35.4 with PEPSI guidance and each target lesion achieving distal mean pulmonary arterial pressure <35 mm Hg with pressure-wire guidance., Results: The occurrence of clinically critical reperfusion pulmonary edema and vessel injuries were lowest in the group using the guidance of both pressure wire and PEPSI (0% and 6.9%, respectively). Furthermore, the group guided by pressure wire and PEPSI accomplished the same hemodynamic improvements with fewer numbers of target lesions treated and sessions performed., Conclusions: The combined approach using pressure wire and PEPSI produced more efficient clinical results and greatly reduced reperfusion pulmonary edema and vessel complications. This is further evidence that PTPA is an alternative strategy for treating chronic thromboembolic pulmonary hypertension., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous transluminal pulmonary angioplasty (PTPA) is a recently developed catheter-based therapy for chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the present study was to investigate the safety and efficacy of PTPA in elderly patients with CTEPH., Methods: In all, 257 PTPA sessions in 70 patients (median age 63 years) were analyzed. Patients were divided into two groups according to age: (i) a younger group (<65 years; n=39); and (ii) an elderly group (≥65 years; n=31)., Results: Hemodynamic improvements were comparable between the younger and elderly groups (63.1% vs. 68.2% decrease in pulmonary vascular resistance, respectively; P>0.05). The median length of stay in the intensive care unit after each session (1.0 vs. 1.0 days) and in hospital per session (9.2 vs. 9.4 days) was similar between the two groups (P>0.05 for all). The prevalence of reperfusion pulmonary edema (23.4% vs. 26.3% across all sessions) and other complications, such as contrast dye-induced nephropathy (0% vs. 2.0%), infection (0% vs. 0%), and neurological complications (0% vs. 1.0%), was comparable in the younger vs. elderly groups (P>0.05 for all). One-year all-cause mortality was similar in the younger and elderly groups (0% vs. 3.2%, respectively; P>0.05)., Conclusions: PTPA can be performed safely and effectively, even in elderly patients, and could be considered as an alternative therapeutic strategy for elderly patients who are too fragile for pulmonary endarterectomy (PEA) or who are treated in institutions without highly experienced PEA surgeons., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The present study examined the impact of the supplementation of glutathione (GSH), γ-L-glutamyl-L-cysteinyl-glycine, on human blood GSH levels. Healthy human volunteers were orally supplemented with GSH (50 mg/kg body weight). Venous blood was collected from the cubital vein before and after ingestion. Plasma was mixed with 3 volumes of ethanol. The supernatant and precipitate were used for the deproteinized and protein fractions of plasma, respectively. Blood cell and plasma fractions were pretreated with 5% trichloroacetic acid-2% 2-mercaptoethanol to reduce the oxidized form of GSH and liberate protein-bound GSH. The 2-mercaptoethanol-pretreated GSH was determined by precolumn derivatization with 6-aminoquinolyl-N-hydroxy succinimidyl carbamate and liquid chromatography-tandem mass spectrometry. There was no significant difference in GSH contents in the deproteinized fraction of plasma and blood cell fraction after GSH ingestion. However, the GSH contents in the protein-bound fraction of plasma significantly (P<0.01) increased from 60 to 120 min after GSH supplementation.

We reviewed the beneficial or harmful effects of low-dose ionizing radiation on several diseases based on a search of the literature. The attenuation of autoimmune manifestations in animal disease models irradiated with low-dose γ-rays was previously reported by several research groups, whereas the exacerbation of allergic manifestations was described by others. Based on a detailed examination of the literature, we divided animal disease models into two groups: one group consisting of collagen-induced arthritis (CIA), experimental encephalomyelitis (EAE), and systemic lupus erythematosus, the pathologies of which were attenuated by low-dose irradiation, and another group consisting of atopic dermatitis, asthma, and Hashimoto's thyroiditis, the pathologies of which were exacerbated by low-dose irradiation. The same biological indicators, such as cytokine levels and T-cell subpopulations, were examined in these studies. Low-dose irradiation reduced inter-feron (IFN)-gamma (γ) and interleukin (IL)-6 levels and increased IL-5 levels and the percentage of CD4(+)CD25(+)Foxp3(+)Treg cells in almost all immunological disease cases examined. Variations in these biological indicators were attributed to the attenuation or exacerbation of the disease's manifestation. We concluded that autoimmune diseases caused by autoantibodies were attenuated by low-dose irradiation, whereas diseases caused by antibodies against external antigens, such as atopic dermatitis, were exacerbated.

Objective: The age of adiposity rebound (AR) is defined as the time at which BMI starts to rise after infancy and is thought to be a marker of later obesity. To determine whether this age is related to future occurrence of metabolic syndrome, we investigated the relationship of the timing of AR with metabolic consequences at 12 years of age., Methods: A total of 271 children (147 boys and 124 girls) born in 1995 and 1996 were enrolled in the study. Serial measurements of BMI were conducted at the ages of 4 and 8 months and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 years, based on which age of AR was calculated. Plasma lipids and blood pressure were measured at 12 years of age., Results: An earlier AR (<4 years of age) was associated with a higher BMI (≥ 20) and a lipoprotein phenotype representative of insulin resistance. This phenotype consists of elevated triglycerides, apolipoprotein B, and atherogenic index and decreased high-density lipoprotein cholesterol in boys and elevated apolipoprotein B in girls at 12 years of age. The earlier AR was also related to elevated blood pressure in boys., Conclusions: This longitudinal population-based study indicates that children who exhibit AR at a younger age are predisposed to future development of metabolic syndrome. Therefore, monitoring of AR may be an effective method for the early identification of children at risk for metabolic syndrome.

An automatic polymerase chain reaction (PCR) product detection system for food safety monitoring using zinc finger (ZF) protein fused to luciferase was developed. ZF protein fused to luciferase specifically binds to target double stranded DNA sequence and has luciferase enzymatic activity. Therefore, PCR products that comprise ZF protein recognition sequence can be detected by measuring the luciferase activity of the fusion protein. We previously reported that PCR products from Legionella pneumophila and Escherichia coli (E. coli) O157 genomic DNA were detected by Zif268, a natural ZF protein, fused to luciferase. In this study, Zif268-luciferase was applied to detect the presence of Salmonella and coliforms. Moreover, an artificial zinc finger protein (B2) fused to luciferase was constructed for a Norovirus detection system. In the luciferase activity detection assay, several bound/free separation process is required. Therefore, an analyzer that automatically performed the bound/free separation process was developed to detect PCR products using the ZF-luciferase fusion protein. By means of the automatic analyzer with ZF-luciferase fusion protein, target pathogenic genomes were specifically detected in the presence of other pathogenic genomes. Moreover, we succeeded in the detection of 10 copies of E. coli BL21 without extraction of genomic DNA by the automatic analyzer and E. coli was detected with a logarithmic dependency in the range of 1.0×10 to 1.0×10(6) copies., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objectives: This study sought to identify useful predictors for hemodynamic improvement and risk of reperfusion pulmonary edema (RPE), a major complication of this procedure., Background: Percutaneous transluminal pulmonary angioplasty (PTPA) has been reported to be effective for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). PTPA has not been widespread because RPE has not been well predicted., Methods: We included 140 consecutive procedures in 54 patients with CTEPH. The flow appearance of the target vessels was graded into 4 groups (Pulmonary Flow Grade), and we proposed PEPSI (Pulmonary Edema Predictive Scoring Index) = (sum total change of Pulmonary Flow Grade scores) × (baseline pulmonary vascular resistance). Correlations between occurrence of RPE and 11 variables, including hemodynamic parameters, number of target vessels, and PEPSI, were analyzed., Results: Hemodynamic parameters significantly improved after median observation period of 6.4 months, and the sum total changes in Pulmonary Flow Grade scores were significantly correlated with the improvement in hemodynamics. Multivariate analysis revealed that PEPSI was the strongest factor correlated with the occurrence of RPE (p < 0.0001). Receiver-operating characteristic curve analysis demonstrated PEPSI to be a useful marker of the risk of RPE (cutoff value 35.4, negative predictive value 92.3%)., Conclusions: Pulmonary Flow Grade score is useful in determining therapeutic efficacy, and PEPSI is highly supportive to reduce the risk of RPE after PTPA. Using these 2 indexes, PTPA could become a safe and common therapeutic strategy for CTEPH., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

This review highlights the current status on the synthesis and applications of mesoporous silica spherical particles. Mesoporous silica spherical particles are expected to be applied in various fields and the properties depend on the size and size distribution. Many researchers have been working on the synthesis of mesoporous silica spherical particles by means of several approaches and a variety of synthetic parameters have been correlated to the nature of the products. The synthetic approaches are categorized into following four; emulsion based approach, formation from a homogeneous solution, aerosol and morphology template. In this review, the preparation and the potential applications of mesoporous silica spherical particles are summarized.

Studies on plant metabolites have attracted significant attention in recent years. Over the past 8 years, we have constructed a unique metabolite database, called KNApSAcK, that contains information on the relationships between metabolites and their expressing organism(s). In the present paper, we introduce KNApSAcK-3D, which contains the three-dimensional (3D) structures of all of the metabolic compounds included in the original KNApSAcK database. The 3D structure for each compound was optimized using the Merck Molecular Force Field (MMFF94), and a multiobjective genetic algorithm was used to search extensively for possible conformations and locate the global minimum. The resulting set of structures may be used for docking studies to identify new and potentially unexpected binding sites for target proteins. The 3D structures may also be utilized for more qualitative studies, such as the estimation of biological activities using 3D-QSAR. The database can be accessed via a link from the KNApSAcK Family website (http://kanaya.naist.jp/KNApSAcK&#95;Family/) or directory at http://kanaya.naist.jp/knapsack3d/.

The immune system is a very complex and dynamic cellular system, and its intricacies are considered akin to those of human society. Disturbance of homeostasis of the immune system results in various types of diseases; therefore, the homeostatic mechanism of the immune system has long been a subject of great interest in biology, and a lot of information has been accumulated at the cellular and the molecular levels. However, the sociological aspects of the immune system remain too abstract to address because of its high complexity, which mainly originates from a large number and variety of cell-cell interactions. As long-range interactions mediated by cytokines play a key role in the homeostasis of the immune system, cytokine secretion analyses, ranging from analyses of the micro level of individual cells to the macro level of a bulk of cell ensembles, provide us with a solid basis of a sociological viewpoint of the immune system. In this review, as the first step toward a comprehensive understanding of immune cell sociology, cytokine secretion of immune cells is surveyed with a special emphasis on the single-cell level, which has been overlooked but should serve as a basis of immune cell sociology. Now that it has become evident that large cell-to-cell variations in cytokine secretion exist at the single-cell level, we face a tricky yet interesting question: How is homeostasis maintained when the system is composed of intrinsically noisy agents? In this context, we discuss how the heterogeneity of cytokine secretion at the single-cell level affects our view of immune cell sociology. While the apparent inconsistency between homeostasis and cell-to-cell heterogeneity is difficult to address by a conventional reductive approach, comparison and integration of single-cell data with macroscopic data will offer us a new direction for the comprehensive understanding of immune cell sociology., (Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.)

Background: Chronic thromboembolic pulmonary hypertension leads to pulmonary hypertension and right-sided heart failure. The purpose of this study was to investigate the efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) for the treatment of chronic thromboembolic pulmonary hypertension., Methods and Results: Twenty-nine patients with chronic thromboembolic pulmonary hypertension underwent PTPA. One patient had a wiring perforation as a complication of PTPA and died 2 days after the procedure. In the remaining 28 patients, PTPA did not produce immediate hemodynamic improvement at the time of the procedure. However, after follow-up (6.0 ± 6.9 months), New York Heart Association functional classifications and levels of plasma B-type natriuretic peptide significantly improved (both P<0.01). Hemodynamic parameters also significantly improved (mean pulmonary arterial pressure, 45.3 ± 9.8 versus 31.8 ± 10.0 mm Hg; cardiac output, 3.6 ± 1.2 versus 4.6 ± 1.7 L/min, baseline versus follow-up, respectively; both P<0.01). Twenty-seven of 51 procedures in total (53%), and 19 of 28 first procedures (68%), had reperfusion pulmonary edema as the chief complication. Patients with severe clinical signs and/or severe hemodynamics at baseline had a high risk of reperfusion pulmonary edema., Conclusions: PTPA improved subjective symptoms and objective variables, including pulmonary hemodynamics. PTPA may be a promising therapeutic strategy for the treatment of chronic thromboembolic pulmonary hypertension., Clinical Trial Registration: URL: http://www.umin.ac.jp. Unique identifier: UMIN000001572.