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Background: The differential effects of PM2.5 fractions on children’s lung function remain inconclusive. This study aimed to examine whether lung function in asthmatic children was associated with increased PM2.5 fractions in urban areas in Nagasaki prefecture, Japan, where the air pollution level is relatively low but influenced by transboundary air pollution. Methods: We conducted a multiyear panel study of 73 asthmatic children (boys, 60.3%; mean age, 8.2 years) spanning spring 2014–2016 in two cities. We collected self-measured peak expiratory flow (PEF) twice a day and daily time-series data for PM2.5 total mass and its chemical species. We fitted a linear mixed effects model to examine short-term associations between PEF and PM2.5, adjusting for individual and time-varying confounders. A generalized linear mixed effects model was also used to estimate the association for worsening asthma defined by severe PEF decline. Back-trajectory and cluster analyses were used to investigate the long-range transboundary PM2.5 in the study areas. Results: We found that morning PEFs were adversely associated with higher levels of sulfate (− 1.61 L/min; 95% CI: − 3.07, − 0.15) in Nagasaki city and organic carbon (OC) (− 1.02 L/min; 95% CI: − 1.94, − 0.09) in Isahaya city, per interquartile range (IQR) increase at lag1. In addition, we observed consistent findings for worsening asthma, with higher odds of severe PEF decline in the morning for sulfate (odds ratio (OR) = 2.31; 95% CI: 1.12, 4.77) and ammonium (OR = 1.73; 95% CI: 1.06, 2.84) in Nagasaki city and OC (OR = 1.51; 95% CI: 1.06, 2.15) in Isahaya city, per IQR increase at lag1. The significant chemical species were higher on days that could be largely attributed to the path of Northeast China origin (for sulfate and ammonium) or both the same path and local sources (for OC) than by other clusters. Conclusions: This study provides evidence of the differential effects of PM2.5 fractions on lung function among asthmatic children in urban areas, where the Japanese national standards of air quality have been nearly met. Continuous efforts to promote mitigation actions and public awareness of hazardous transboundary air pollution are needed to protect susceptible children with asthma., Environmental Health, 20, art. no. 110; 2021

Objectives Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. Methods Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. Results Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren’s syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren’s syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. Conclusion PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.

Reports of zinc and selenium deficiencies accompanying inflammatory bowel disease (IBD) mostly have originated from Western countries and concerned adult patients. Whether Japanese children with IBD have similar deficiencies remained unclear. We aimed to elucidate differences in serum zinc and selenium concentrations in Japanese children between types of IBD. Children under 17 years old undergoing care at 12 Japanese pediatric centers were retrospectively enrolled between November 2016 and February 2018 to 3 groups representing Crohn’s disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illnesses. Serum zinc and selenium were measured by atomic absorption spectrophotometry. Zinc and selenium deficiencies were defined by serum concentrations

BACKGROUND AND AIM Serologic markers such as myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA) (MPO-ANCA) have been used to screen patients for ulcerative colitis (UC). However, MPO-ANCA shows limited accuracy in Asians. Proteinase 3 ANCA (PR3-ANCA) has performed better at UC diagnosis in Japanese adults than MPO-ANCA. The present study aimed to evaluate usefulness of PR3-ANCA for diagnosis of UC in Japanese pediatric practice. METHODS Patients under 17 years old undergoing assessment at 12 Japanese pediatric centers between November 2016 and February 2018 were prospectively enrolled and divided into groups with UC, Crohn's disease (CD), intestinal disease control (IC), and healthy control (HC). Serum PR3-ANCA and MPO-ANCA were analyzed using chemiluminescence enzyme immunoassay kits. RESULTS Sera from 367 patients (148 with UC at a median age of 12 years; 120 with CD, 13 years; 56 with IC, 10.5 years; and 43 with HC, 10 years) were examined. Median PR3-ANCA values in UC (1.6 U/mL) were greater than in CD (0.2; P

Juvenile primary Sjögren’s syndrome (pSS) is rare. Although recurrent parotitis is reported to be the most common symptom of juvenile pSS, the clinical symptoms and features of the syndrome are not well understood and are poorly defined. Here we report a rare case of juvenile pSS in a patient with plunging ranula. The patient had no symptoms other than swelling of the oral floor and had no symptoms of parotitis. Magnetic resonance imaging (MRI) revealed the diagnosis of plunging ranula. In addition, the findings of the bilateral parotid glands on MRI and subsequent ultrasonography (US) strongly suggested SS. On the basis of these imaging findings and laboratory data, a pediatric rheumatologist confirmed the diagnosis of juvenile pSS. The ranula may be one clinical sign of SS. However, this association remains generally unknown. Hypothesizing that SS might cause ranula development, we retrospectively investigated cases of patients with ranula who underwent MRI at our hospital. We found that many of these patients (> 20%) had characteristic findings strongly suggestive of SS. This result suggests that SS-induced changes in the sublingual glands are one cause of ranula formation. We think that ranula is a sign of early-stage SS. Therefore, patients with ranulae, whether adults or children, should undergo careful assessment of not only the sublingual glands but also the parotid and submandibular glands with MRI and/or US to investigate possible SS. This assessment may lead to early detection of SS.

Objectives This retrospective study compared MRI and US findings among patients with SS over a wide age range. Methods Ninety patients with SS aged 8–84 years who had undergone both MRI and US examinations were divided into four groups according to age, as follows: 69 years, 16 patients. Imaging findings of parotid glands (PGs) and submandibular glands (SMGs) were compared among the four groups. Furthermore, the relationships within and between imaging findings and various clinical findings were examined. Results On MRI, patients with JSS commonly exhibited multiple high-intensity spots in the PGs on MR sialography and fat-suppressed T2-weighted imaging. With increasing SS group age, the frequencies and numbers of the high-intensity spots were lower. Fat areas on MRI and hyperechoic bands on US were rarely observed in the PGs and SMGs of patients with JSS, whereas they were more common in patients with adult SS. In addition, the presence of hyperechoic bands on US, the presence of fat areas on MRI, and decreased salivary flow were associated with one another. Conclusion Salivary gland imaging findings in patients with JSS were characterized by punctate sialectasis, whereas those findings in patients with adult SS were characterized by fatty degeneration. Distinct findings in patients with JSS and adult SS are likely to reflect differences in glandular lesion stage. MRI and US are presumably useful for evaluation of glandular lesion severity during follow-up.

BackgroundA20 haploinsufficiency (HA20) is an early-onset autoinflammatory disease caused by mutations in theTNFAIP3gene, which encodes the protein A20. Numerous truncating mutations in theTNFAIP3gene have been reported in HA20 patients, whereas fewer missense variants have had their pathogenicity confirmed. Here, we evaluated the pathogenic significance of three previously unreported missense variants of theTNFAIP3gene in suspected cases of HA20.MethodsWe obtained the clinical features and immunological data of three patients with missense variants (Glu192Lys, Ile310Thr, and Gln709Arg) of unknown significance ofTNFAIP3. We then performed in vitro functional assays including analysis of nuclear factor (NF)-κB reporter gene activity, detection of A20 expression and phosphorylation of A20 by IκB kinase β (IKKβ), and K63-deubiquitination assay usingTNFAIP3-deficient HEK293 cells. Three known pathogenic missense mutations reported previously were also investigated.ResultsThe inhibitory effect on NF-κB reporter gene activity was significantly disrupted by A20 Glu192Lys and the three known mutations. The variants Ile310Thr and Gln709Arg did not show a difference from the wild type in any of the assays performed in this study.ConclusionsAmong the three variants in theTNFAIP3gene, Glu192Lys was interpreted as being likely pathogenic, but Ile310Thr and Gln709Arg as being not pathogenic (uncertain significance and likely benign, respectively), based on the American College of Medical Genetics and Genomics standards and guidelines. Our study highlights the necessity of performing in vitro functional assays, notably, NF-κB reporter gene assay, to evaluate the pathogenicity ofTNFAIP3missense variants for the accurate diagnosis of HA20.

Background Studies on the adverse effects of Asian dust (AD) on respiratory function in children are scarce. The objective of this study was to examine the association between AD and respiratory function by measuring peak expiratory flow rates (PEFRs) in asthmatic children. Methods The study was carried out from March to May from 2014 through 2016. One hundred ten children with bronchial asthma were recruited from four hospitals in the Goto Islands and south Nagasaki area in Nagasaki prefecture. The parents were asked to record their children’s PEFRs every morning/evening and clinical symptoms in an asthma diary. AD was assessed from light detection and ranging data, and a linear mixed-effects model was used to estimate the effects of AD on daily PEFR. Time-stratified case-crossover analyses were performed to examine the association between AD and asthma attacks defined by reduction levels in PEFR. Results AD was detected on 11 days in the Goto Islands, and on 23 days in the south Nagasaki area. After adjusting for age, sex, temperature, and daily oxidants, we found a consistent association between AD and a 1.1% to 1.7% decrease in PEFR in the mornings and a 0.7% to 1.3% decrease in the evenings at a lag of 0 to 5 days. AD was not associated with the number of asthma attacks, respiratory symptoms, or other symptoms at any lag days examined. Conclusions Exposure to AD was associated with reduced PEFR, although the effects were not large enough to induce clinically apparent symptoms, in clinically well-controlled asthmatic children.

Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS.

A 14-year-old girl developed 4 episodes of anaphylaxis of unknown etiology, which required intramuscular adrenaline administration each time. She had eaten pizza and a cheeseburger immediately before the first 2 episodes, respectively, but had not eaten anything for several hours before the last 2 episodes. It turned out that she had eaten the same ice lolly 4 hours before the first 3 episodes and a Café au lait Swirkle (a half-frozen beverage) 4 hours before the last episode. We detected carboxymethylcellulose sodium as the only common ingredient in all anaphylactic episodes. Skin prick tests were positive for carboxymethylcellulose solution and carboxymethylcellulose-containing food products. We obtained a custom-made carboxymethylcellulose sodium–free ice lolly from the manufacturer and confirmed that it did not induce anaphylactic reactions by a challenge test. Carboxymethylcellulose, an anionic water-soluble polymer derived from native cellulose, is considered to be unabsorbable from the human gut and has been widely and increasingly used in pharmaceutical preparations, cosmetics, and food. This article is the first report of anaphylaxis caused by carboxymethylcellulose-containing foods, whereas anaphylaxis to carboxymethylcellulose has been rarely associated with carboxymethylcellulose-containing pharmaceuticals. Although the exact mechanisms underlying the induction of late-onset anaphylaxis by carboxymethylcellulose remain unclear, a small minority of cellulose-digesting microbial flora in the human colon and contamination of food products with carboxymethylcellulose of low molecular weight might be involved. The induction of recurrent anaphylaxis by various products should be a clue that prompts physicians to suspect food additives as a cause for anaphylaxis.

Background The adverse health effects of Asian dust (AD) on the respiratory system of children are unclear. We hypothesized that AD events may lead to increased visits by children to emergency medical centers due to bronchial asthma and respiratory diseases, including bronchial asthma. Methods We used anonymized data on children receiving primary emergency treatment at Nagasaki Municipal Primary Emergency Medical Center, Japan between March 2010 and September 2013. We used Light Detection and Ranging (LIDAR) data to assess AD exposure and performed time-stratified case-crossover analyses to examine the association between AD exposure and emergency department visits. The main analysis was done with data collected from March through May each year. Results The total number of emergency department visits during the study period was 756 for bronchial asthma and 5421 for respiratory diseases, and the number of "AD days" was 47. In school children, AD events at lag day 3 and lag day 4 were associated with increased emergency department visits due to bronchial asthma, with odds ratios of 1.837 (95% confidence interval [CI], 1.212-2.786) and 1.829 (95% CI, 1.179-2.806), respectively. AD events were significantly associated with respiratory diseases among preschool children at lag day 0, lag day 1, and lag day 2, with odds ratios of 1.244 (95% CI, 1.128-1.373), 1.314 (95% CI, 1.189-1.452), and 1.273 (95% CI, 1.152-1.408), respectively. These associations were also significant when the results were adjusted for meteorological variables and other air pollutants. Conclusions The study findings suggested that AD exposure increases emergency department visits by children.

Activated PI3Kδ syndrome (APDS) is a primary immunodeficiency characterized by recurrent respiratory tract infections, lymphoproliferation, and defective IgG production. Heterozygous mutations in PIK3CD, PIK3R1, or PTEN, which are related to the hyperactive phosphoinositide 3-kinase (PI3K) signaling, were recently presented to cause APDS1 or APDS2 (APDSs), or APDS-like (APDS-L) disorder. In this study, we examined the AKT phosphorylation of peripheral blood lymphocytes and monocytes in patients with APDSs and APDS-L by using flow cytometry. CD19+ B cells of peripheral blood in APDS2 patients showed the enhanced phosphorylation of AKT at Ser473 (pAKT) without any specific stimulation. The enhanced pAKT in CD19+ B cells was normalized by the addition of a p110δ inhibitor. In contrast, CD3+ T cells and CD14+ monocytes did not show the enhanced pAKT in the absence of stimulation. These findings were similarly observed in patients with APDS1 and APDS-L. Among CD19+ B cells, enhanced pAKT was prominently detected in CD10+ immature B cells compared with CD10− mature B cells. Enhanced pAKT was not observed in B cells of healthy controls, patients with common variable immunodeficiency, and hyper IgM syndrome due to CD40L deficiency. These results suggest that the enhanced pAKT in circulating B cells may be useful for the discrimination of APDS1, APDS2, and APDS-L from other antibody deficiencies., The Supplementary Material for this article can be found online at https://www.frontiersin.org/articles/10.3389/fimmu.2018.00568/full#supplementary-material., This study was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (16H05355 and 16K15528 to SO, 17H04233 to SN), the Ministry of Health, Labour and Welfare, Japan (17933299 to SN), and Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development, AMED.

We compared the efficacy and safety of infliximab with intravenous immunoglobulin (IVIG), a standard therapy, in a phase 3 trial (NCT01596335) for Japanese patients with Kawasaki disease (KD) showing persistent fever after initial IVIG. Patients with initial IVIG-refractory KD, aged 1–10 years, received a single dose of IV infliximab 5 mg/kg or IV polyethylene glycol-treated human immunoglobulin (VGIH) 2 g/kg on day 0. Primary outcome was defervescence rate within 48 h after the start of treatment. Safety was evaluated through day 56. Overall, 31 patients were randomized (infliximab, n = 16; VGIH, n = 15); 31.3% and 60.0% patients discontinued due to worsening KD. Defervescence rate within 48 h was greater with infliximab (76.7%) than VGIH (37.0%) (p = 0.023), and defervescence was achieved earlier with infliximab (p = 0.0072). Coronary artery lesions occurred in 1 (6.3%) and 3 (20.0%) patients receiving infliximab and VGIH, respectively, up to day 21. Adverse events occurred in 15 (93.8%) and 15 (100.0%) patients in the infliximab and VGIH groups, respectively. No serious adverse events in the infliximab group and one in the VGIH group were observed. Infliximab improved the defervescence rate within 48 h and time to defervescence versus standard therapy, and was well tolerated in patients with IVIG-refractory KD.

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment.

To assess the safety and efficacy of infliximab (IFX) for the treatment of patients with Kawasaki disease (KD).This was a nationwide survey of 274 Japanese institutions exploring how IFX was used to treat patients with KD. The patients' sex, age, treatment course, pre- and post-IFX therapy blood test results, coronary artery lesions (CALs), and adverse events (AEs) were evaluated.We analyzed 434 patients with KD who received IFX between March 2005 and November 2014. The median age at onset was 33 months (range 1-138), and 66 patients (15.2%) were under 1 year old. In all cases, IFX was administered as additional treatment. The median days of illness at the initiation of IFX was 9 days. In 275 patients (63.4%), IFX was administered as third-line treatment, and in 106 patients (24.4%), IFX was administered as fourth-line treatment. Single dose IFX 5 mg/kg was administered to 412 patients (94.9%). After IFX, 363 patients (83.6%) became afebrile within 2 days, and the white blood cell count, percentage of neutrophils, and serum C-reactive protein levels significantly decreased (P .001), although 119 patients (27.4%) received additional treatment. Before IFX, 132 patients (30.4%) had already developed CALs. In patients without CALs before IFX, 31 patients (10.3%) newly developed CAL after IFX, whereas 32 patients (24.2%) with CAL before IFX showed increased CAL severity. Eighty AEs were observed in 69 patients (15.9%); however, serious AEs were few and reversible.IFX might be an effective and tolerable treatment for refractory KD.

Normal peripheral blood leukocytes, such as basophils, eosinophils, B lymphocytes and monocytes/macrophages, have a cysteinyl leukotriene 1 (CysLT1) receptor, while the cysteinyl leukotriene 2 (CysLT2) receptor is expressed in cardiac Purkinje cells, endothelium, brain and leukocytes. However, it is unknown whether or not platelets express the CysLT1 or CysLT2 receptor. In this study we identify and characterize the biological function of the CysLT receptor of human platelets. We determined the CysLT1 or CysLT2 receptor mRNA expression in normal human platelets by RT-PCR and determined protein expression by Western blotting and flow cytometry. Moreover, we examined the effect of cysteinyl leukotrienes (CysLTs) in platelets on the induction of RANTES (Regulated on Activation, Normal T Expressed, and presumably Secreted). We also investigated whether the CysLT1 receptor antagonist pranlukast inhibits CysLT-induced RANTES release. In conclusion, we showed the functional expression of CysLT receptors on human platelets and demonstrated that CysLTs induced the release of significant amounts of RANTES, which suggests a novel role for human platelets in CysLT-mediated allergic inflammation.

Background: There have been no reports on the evaluation of the usefulness of long-term asthma management based on the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2005 (JPGL 2005). Methods: The purpose of the present study was to retrospectively investigate the records of 350 patients admitted to Yamaguchi University Hospital who had asthma attacks from January 2006 to June 2008. There were 149 patients who were treated for more than 3 months in accordance with the guideline (long-term management group) and 201 who were not (non-long-term management group). The patients were divided into three age groups: 100 infants, 159 toddlers, and 91 schoolchildren. Results: The onset age of asthma in the long-term management group was earlier than that in the non-long-term management group in toddlers and schoolchildren. The white blood cell counts and C-reactive protein levels were higher in the non-long-term management group in schoolchildren, suggesting the complication of some infections. The severity of asthma in the long-term management group was greater than that in the non-long-term management group among all three age groups. There were no significant differences, however, in the severity of asthma attack at admission between the long-term and non-long-term management groups in the three age groups. Conclusion: Patients who had severe asthma tended to be treated with long-term management, which suggests that long-term asthma management according to JPGL 2005 may reduce the severity of asthma attack at that admission, because the severity of asthma in patients undergoing long-term management correlates with the severity of asthma attack.

We have developed a mechanically controllable break junction (MCBJ) system in ultra high vacuum (UHV). The Au atomic contact in a hydrogen environment was investigated using this newly developed system. The conductance of the Au atomic contact decreased with the introduction of hydrogen gas. The vibration spectra showed symmetric peaks around ±50 meV, which could be assigned to the vibration mode between Au and hydrogen. The conductance and vibration spectroscopy measurement suggested that the hydrogen atom or molecule would adsorb on or incorporate into the Au atomic contact. [DOI: 10.1380/ejssnt.2009.53]

Background: Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β are known for their chemotactic and proinflammatory effects on monocytes/macrophages which have a cysteinyl leukotriene 1 (CysLT1) receptor. Methods: We examined MIP-1α and MIP-1β production stimulated by CysLTs (LTC4, LTD4, and LTE4) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs). Moreover, we examined the inhibitory effect of pranlukast, a CysLT1 receptor antagonist, and inhibitors of three major mitogen-activated protein kinases (MAPK) on the induction of MIP-1α and MIP-1β production by CysLTs. Results: ELISA demonstrated that CysLTs induced MIP-1α and MIP-1β production in THP-1 cells and PBMCs. PCR demonstrated that LTD4 increased MIP-1α and MIP-1β mRNA expressions in THP-1 cells. Pranlukast blocked MIP-1α and MIP-1β production promoted by LTD4 in THP-1 cells and PBMCs. Moreover, an inhibitor of extracellular signal-regulated kinase (ERK) attenuated the induction of MIP-1α and MIP-1β production by LTD4 in THP-1 cells whereas the inhibitors of c-Jun NH2-terminal kinase or p38 MAPK did not. Conclusion: CysLTs induce MIP-1α and MIP-1β production mediated by ERK via binding to the CysLT1 receptor in human monocytes/macrophages.

Airway immunopathogenesis is unclear in patients with profound multiple disabilities (PMD) who undergo tracheostomy.The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10, and IL-12p70 cytokines were determined in sputum of 28 patients with PMD who underwent tracheostomy and in 14 healthy subjects, using a cytometric bead array.The concentrations of IL-1beta, IL-6 and IL-8 in the patients were significantly higher than those in controls (p0.001). IL-6, and IL-8 levels in eight PMD patients in the febrile period were significantly higher than those in the afebrile period (p0.01 and p0.05, respectively). Serum CRP levels were slightly elevated in 12 of the 28 patients (43%) in the afebrile period, but there were no significant differences in the level of any cytokine between patients with normal and elevated serum CRP.PMD patients with tracheostomy have chronic airway inflammation.

A 14-year-old girl with aortitis syndrome in the early pre-pulseless phase was admitted to our hospital because of slight fever, neck bruit, asymmetrical blood pressure, stenosis or dilatation of the main branch arteries in aorta on chest computed tomography. Laboratory examination revealed a high level of C-reactive protein and an elevated erythrocyte sedimentation rate, as well as hypergammaglobulinemia, and 18F-FDG-PET revealed an accumulation of 18 fluorodeoxyglucose in the great vessels. She was first given pulse therapy with a combination of methylprednisolone and intravenous cyclophosphamide, and then maintenance therapy with oral prednisolone and azathioprine. All the abnormal laboratory parameters improved to normal levels within a month. We suggest that early diagnosis of aortitis syndrome may permit early treatment in the early pre-pulseless phase and could possibly prevent progression to the occlusive phase.

Background: Echocardiography remains the cornerstone of diagnosis of cardiac complications in patients with Kawasaki disease (KD), and is also useful for the diagnosis of incomplete KD (i-KD). Since echocardiographic evaluation is based on somewhat subjective assessment by pediatric cardiologists, objective diagnostic measures by which general pediatricians can screen high-risk patients or make diagnosis of i-KD are desired. Objective: To assess D-dimer and fibrinogen degradation products (FDP) as possible markers of coronary vascular damage in KD patients. Design/Methods: Between June 2008 and March 2014, we recruited 121 KD patients: 86 with complete KD (c-KD) treated with intravenous immunoglobulin (IVIG), 10 with c-KD treated only with aspirin (a-KD), 16 with i-KD fulfilling four major criteria, and seven with severe refractory KD (s-KD). Control patients included five with Henoch-Schonlein purpura (HSP), 15 with fibrile convulsion (FC), and 39 with pneumonia. We retrospectively checked their medical records, echocardiography, and blood test results on admission and after IVIG therapy. Results: Peak D-dimer values (normal range < 1.0 μg/ml) were significantly higher in c-KD (2.9±2.4) than in a-KD (1.1±0.7), FC (0.8±0.4) and pneumonia (1.3±1.1) groups (p < 0.05). Peak FDP value in the c-KD group was 6.8±4.7 μg/ml (< 5.0). Peak D-dimer and FDP values were the highest in the HSP group, followed by the s-KD group, and were comparable between the i-KD and c-KD groups. D-dimer values (2.9±1.4) at post IVIG were higher than those on admission (1.8±1.1) (p < 0.0001), while there was no significant change in FDP values. There was no significant difference in D-dimer or FDP values between KD with cardiac finding(s) and without. WBC and CRP values had no correlation with those of FDP or D-dimer. Receiver operating characteristic analysis determined a cut-off value of 1.1 μg/ml for D-dimer for c-KD, with the area under the curve (AUC) 0.85, sensitivity 0.95, specificity 0.59 and probability 0.44. Similarly, a cut-off value for FDP was determined as 2.5 μg/ml with AUC 0.90, sensitivity 0.89, specificity 0.70 and probability 0.40. Conclusions: Elevated D-dimer and FDP values help assist diagnosis of i-KD, but cannot predict cardiac complications in KD patients.

Background: Amelioration of systemic inflammatory changes during the acute phase of Kawasaki Disease (KD) is critical for preventing coronary artery lesions (CALs). Plasma exchange (PE) therapy has been applied to patients with severe KD in several medical facilities in Japan and been covered by health insurance since 2012. Methods: We reviewed medical records of five KD patients, aged 3 to 44 months, who were treated with PE in Nagasaki University Hospital from December 2012 to August 2015. Results: All patient were treated with two courses of intravenous immunoglobulin (IVIG). After IVIG that had offered little or no improvement, two of the five patients used infliximab and another used cyclosporine A before PE. PE was performed for the consecutive 3 or 5 days until defervescence and clinical improvement were obtained. Acute inflammatory changes were successfully ameliorated upon PE therapy in all five patients, although two patients who had already developed CALs before PE on days 20 and 21, respectively, residual CALs were confirmed one year after the treatment. No CALs had developed in the remaining three patients who started PE therapy within nine days after onset (days 8, 8 and 9, respectively). PE therapy was carefully performed in the intensive care unit, and no severe adverse events occurred. Discussion: PE therapy is able to ameliorate acute inflammation in most cases of severe KD refractory to standard IVIG therapy; however, it is critical to start PE therapy earlier than day-10 in order to prevent CALs. Thus, pediatricians have to make prompt decision on referral of their KD patient who did not respond IVIG to the institutions where PE is applicable in Japan.

症例は59歳,男性.特に症状はなかったが,胃潰瘍の経過観察中に施行された上部消化管内視鏡検査で中部食道に粘膜下腫瘍を発見された.食道造影検査では中部食道の右前壁に長径5cmでなだらかな立ち上がりを有する陰影欠損像を認めた.超音波内視鏡検査で腫瘍は固有筋層に連続する低エコー像として描出された.以上より,食道平滑筋腫の診断で手術適応と判断し,全身麻酔下で5本のトロッカーを使用し,胸腔鏡下に腫瘍を核出した.切除標本では腫瘍は大きさ5×4cm,割面は黄白色充実性で,壊死,変性の所見は認めなかった.病理学的に良性の食道平滑筋腫と診断された.術後経過は良好で, 6日目より食事を開始し, 14日目に軽快退院した.今回われわれは,無症状の食道平滑筋腫に対し胸腔鏡下手術を施行し,低侵襲に切除できたので,文献的考察を加えて報告する.

To quantitatively elucidate the effects of the benzo group on the extraction-selectively and -ability of benzo-15-crown-5 (B15C5)for alkali metal ions, the constants of the overall extraction (Kex), thedistribution for various diluents having low dielectric constants (KD,MLA), and the aqueousion-pair formation (KMLA) of B15C5-alkali metal (Li, Na, K) picrate 1:1:1 complexes (MLA) weredetermined at 25 °C. The partition constants of B15C5were also measured at 25 °C. The log KMLA values for Li+, Na+, and K+ are -0.32 ± 0.22, 2.66 ± 0.19, and 0.71 ± 0.47, respectively. In going from 15-crown-5 (15C5) to B15C5, the benzo group considerably decreasesthe KMLA value for the same alkali metal ion. The distributionbehavior of B15C5 and its 1:1:1 complexes with the alkali metal picrates closely obeys regularsolution theory, omitting chloroform. Molar volumes and solubility parameters of B15C5and the 1:1:1 complexes were determined. For every diluent, the Kex valuefor B15C5 increases in the order Li+ < K+ < Na+. KD,MLA makes anunfavorable contribution to the Na+ extraction-selectivity of B15C5 because of the smallest molar volume of the Na(B15C5)A complex. The Na+ extraction-selectivity of B15C5 is determined completely by much the highest KNa(B15C5)A value.The extraction-ability and -selectivity of B15C5 for the alkali metal picrates are compared with those of 15C5on the basis of the underlying equilibrium constants.

Background Intrauterine inflammation has been associated with preterm birth and neonatal complications. Few reports have comprehensively investigated multiple cytokine profiles in cord blood and precisely identified surrogate markers for intrauterine inflammation. Aim To identify the cytokines and surrogate markers associated with intrauterine inflammation and subsequent neonatal complications. Patients and methods We analyzed cord blood samples from 135 patients admitted to the neonatal intensive care unit at Sasebo City General Hospital. We retrospectively determined the associations between the presence of neonatal complications and cord blood cytokines, prenatal factors, and laboratory data at birth. A total of 27 cytokines in the cord blood were measured using a bead-based array sandwich immunoassay. Results Both Th1 and Th2 cytokine levels were low, whereas the levels of growth factors and chemokines were high. In particular, chemokines IL-8, MCP-1, and MIP-1α were significantly higher in very premature neonates when compared with more mature neonates. In addition, some have been shown to be associated with multiple neonatal complications, including patent ductus arteriosus (PDA), respiratory distress syndrome (RDS), and chronic lung disease (CLD). Similarly, the levels of N-Terminal pro-brain natriuretic peptide, nucleated RBC, and urinary β2-microglobulin were associated with these complications and chemokine levels. Conclusions Our results suggest the association of inflammatory chemokines IL-8, MCP-1, and MIP-1α with intrauterine inflammation, premature birth, and neonatal complications in these perinatal subjects. Furthermore, the association of the aforementioned biomarkers with PDA, RDS, and CLD may help establish early diagnostic measures to predict such neonatal complications following intrauterine inflammation., PLOS ONE, 12(5), e0175082; 2017

AIDSに合併した小腸悪性リンパ腫の穿孔性腹膜炎を緊急手術により救命しえたので報告する. 症例は32歳の男性. 平成8年9月カンジダ性食道炎, 食道潰瘍を契機にAIDSと診断され. 当院の感染症科で治療を開始された. 平成10年12月から右上顎洞悪性リンパ腫に対し放射線療法を施行した. 平成11年9月, 悪性リンパ腫の肺, 骨, 腹腔転移を認め, 腹部CTで小腸に6.5×6cmの腫瘤を認めた.平成12年3月2日, 腹痛が出現し, 消化管穿孔の診断で手術を行った. トライツ靱帯から250cmの空腸から回腸にかけて計7カ所の腫瘤を認め, 口側から2番目の腫瘤が穿孔しており, 空腸・回腸部分切除, 腹腔ドレナージ, 空腸瘻造設術を施行した. 病理組織学的に腫瘤は非ホジキンリンパ腫, B細胞型であった.術後は合併症なく. 14病日から経口摂取可能となり2回外泊可能となったが悪性リンパ腫の進行により143病日に死亡した.

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory, non-infectious disorder of skeletal system mainly seen in children. We report a case of CRMO presenting with fever and leg pain. The patient was an 11-year-old boy complaining of a fever, swelling and pain on his right foot, and pain on both legs. Although serum levels of CK and aldolase were not increased, MRI imaging suggested polymyositis. Muscle biopsy showed interstitial infiltration of inflammatory cells without any evidences of dermatomyositis or polymyositis. One month later, he complained of a swelling, pain and redness of his left clavicle as recurrently experienced during the recent 6 months, and MRI investigation indicated the diagnosis of osteomyelitis. Bone biopsy was performed and showed chronic inflammatory changes with negative bacterial culture. Multiple bone lesions and muscle uptake of FDG in his legs were revealed by whole body FDG-PET/CT, and he was diagnosed as having CRMO with interstitial myositis. The combinatorial administration of non-steroidal anti-inflammatory drugs and bisphosphonate successfully improved his clinical symptoms and laboratory abnormalities. To our knowledge, there is no report of a patient of CRMO associated with interstitial myositis.

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment.

Human thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine, promotes inflammatory T helper type 2 cell (Th2) differentiation of naive CD4(+) T cells. TSLP is highly produced in keratinocytes of patients with atopic dermatitis and bronchial epithelia of patients with asthma and was thought to be a master switch for allergic inflammation. We sought to examine the effect of TSLP in human monocytes/macrophages.The effect of TSLP on the expression of cell surface antigens (CD11c, CD16, CD54, CD80, CD86, and HLA-DR) in peripheral blood CD14(+) monocytes/macrophages was examined.TSLP enhanced the expression of CD80 in peripheral blood CD14(+) monocytes/macrophages but not that of other cell surface antigens. It was associated with an increased percentage of CD14(dim/-), CD80(+), CD11c(+), and HLA-DR(+) cells, which was consistent with the increased differentiation of myeloid dendritic cells.TSLP induces CD80 expression in human peripheral blood CD14(+) monocytes/macrophages; this indicates monocyte/macrophage activation. This may be associated with their differentiation into myeloid dendritic cells.

The formation of a Pd atomic chain in a hydrogen atmosphere was investigated by measurements of conductance and vibrational spectroscopy of a single molecular junction and the theoretical calculation. While atomic chains were not formed for clean $3d$ and $4d$ metals, in the case of Pd (a $4d$ metal) atomic chains could be formed in the presence of hydrogen. Stable atomic chains with two different atomic configurations were formed when the Pd atomic contact was stretched in a ${\text{H}}_{2}$ atmosphere: highly conductive short hydrogen-adsorbed atomic chain and low conductive long hydrogen incorporated atomic chain.

We have investigated Au atomic contacts in ${\text{H}}_{2}$ and ${\text{D}}_{2}$ environment by conductance measurement and $dI/dV$ spectroscopy. A single ${\text{H}}_{2}$ or ${\text{D}}_{2}$ molecule was found to bridge Au electrodes. In the case of the $\text{Au}/{\text{H}}_{2}/\text{Au}$ junction, symmetric peaks were observed in $dI/dV$ spectra while they were not observed for the $\text{Au}/{\text{D}}_{2}/\text{Au}$ junction. The shape of the peaks in $dI/dV$ spectra originated from the structural change in the single-molecule junction induced by the phonon excitation. The structural change could occur only for the $\text{Au}/{\text{H}}_{2}/\text{Au}$ junction. The difference in the two single-molecule junctions could be explained by larger zero-point energy of ${\text{Au-H}}_{2}$ vibration mode than that in the $\text{Au}/{\text{H}}_{2}/\text{Au}$ junction.