Search

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. [ABSTRACT FROM AUTHOR]

Background: We have previously demonstrated that cysteinyl leukotriene (CysLT) induced monocyte chemoattractant protein-1 (MCP-1) production in monocytes/macrophages. The intracellular signal transduction pathway of MCP-1 production induced by CysLT in human monocytes/macrophages is unclear. Methods: The activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK by phosphorylation, and nuclear factor-κB (NF-κB) by leukotriene (LT) D4 and LTC4 was determined in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood CD14+ monocytes/macrophages. We examined the inhibitory effects of inhibitors of ERK1/2, JNK, p38 MAPK and NF-κB and pranlukast as a CysLT1 receptor antagonist on induction of MCP-1 production by LTD4 and LTC4. Results: LTD4 and LTC4 induced significant phosphorylations of ERK1/2 and JNK, but not p38 MAPK, in THP-1 cells and peripheral blood CD14+ monocytes/macrophages. Pretreatment with the ERK1/2 inhibitor PD98059 and JNK inhibitor SP600125 attenuated MCP-1 production by CysLTs. NF-κB activation was induced by addition of LTD4 and LTC4. Pretreatment with the NF-κB inhibitors caffeic acid phenylethyl ester and MG-132 inhibited MCP-1 production by CysLTs. Pranlukast inhibited phosphorylation of ERK1/2 and JNK, NF-κB activation, and the MCP-1 production induced by CysLTs. Conclusion: CysLTs induce MCP-1 and this induction is mediated by ERK1/2 and JNK in MAPK, and NF-κB pathways via the CysLT1 receptor, for the most part, in human monocytes/macrophages. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This study aimed to retrospectively investigate the prevalence of Sjögren's syndrome (SS) among patients with ranulas, parotid cysts, or parotid calcifications; identify the characteristic magnetic resonance imaging (MRI) or computed tomography (CT) findings of the lesions associated with SS; and compare the SS disease stages among SS patients with the three lesion types. A total of 228 patients with the lesions were classified into SS, possible SS, and non-SS groups. The prevalence of SS among patients with ranulas, parotid cysts, or parotid calcifications was 16%, 24%, and 40%, and the rates of either SS or possible SS were 25%, 41%, and 64%, respectively. SS was associated with (i) ranulas: ≤17 mm; (ii) parotid cysts: bilateral and multiple; and (iii) parotid calcifications: in females, bilateral, multiple, parenchymal, and no coexisting calcifications in other tissues. SS patients with ranulas were significantly younger and had lower submandibular gland stage scores on MRI/CT than those with other lesions. Additionally, in 58% and 15% of SS patients with ranulas and parotid calcifications, respectively, detection of the lesions led to the diagnosis of primary SS. Therefore, recognizing the prevalence of SS among patients with these lesions and the findings associated with SS can help detect undiagnosed SS. [ABSTRACT FROM AUTHOR]

Background and Aim: Serum leucine‐rich alpha‐2 glycoprotein (LRG) and calprotectin have been studied as disease activity markers in adults with inflammatory bowel disease (IBD). We evaluated them in pediatric IBD patients. Methods: Subjects under 17 years old undergoing care at 11 Japanese pediatric centers were retrospectively assigned to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illness. Serum LRG and calprotectin were measured using commercial enzyme‐linked immunosorbent assay kits. Results: We enrolled 173 subjects, including 74 with CD, 77 with UC, and 22 NC. Serum LRG concentrations in active CD (median, 200 μg/mL) were significantly greater than in remission (81 μg/mL; P < 0.001) or NC (69 μg/mL; P < 0.001). Serum calprotectin concentrations in active CD (2941 ng/mL) also were significantly greater than in remission (962 ng/mL; P < 0.05) or NC (872 ng/mL; P < 0.05). Serum LRG concentrations in active UC (134 μg/mL) were significantly greater than in remission (65 μg/mL; P < 0.01) but not significantly greater than in NC (69 μg/mL); serum calprotectin concentrations in active UC (1058 ng/mL) were not significantly different from those in remission (671 ng/mL) or NC (872 ng/mL). In receiver operating characteristic analyses of LRG, calprotectin, C‐reactive protein, and erythrocyte sedimentation rate for ability to distinguish active IBD from remission, CD and UC showed areas under receiver operating characteristic curves for LRG (0.77 and 0.70, respectively), exceeding those for calprotectin, C‐reactive protein, or erythrocyte sedimentation rate. Conclusions: In pediatric IBD, serum LRG may better reflect disease activity than serum calprotectin, particularly in CD. [ABSTRACT FROM AUTHOR]

Background: Diversity management has gained traction in Japan. The Pediatric Rheumatology Association of Japan (PRAJ) has an Advisory Committee for Diversity Promotion with a broader focus on promoting diversity. The objectives of this study were to better understand the problems faced by PRAJ members regarding the work environment, childcare and nursing care, and work‐life balance. Methods: A web‐based questionnaire was administered to members of the PRAJ and 79 responses were evaluated. Results: Of the respondents, 73% were male and 27% were female. A total of 14% worked for more than 12 h on weekdays, and 22% worked for more than 60 h per week and 38% had fewer than 4 days off per month. Regarding childcare, 54% of the respondents were raising preschool children and 83% had taken parental leave for less than 1 year. A total of 17% of participants had family members in need of care. For both childcare and caregiving, the burden was greater for women. Only 18% of the respondents reported a well‐balanced work‐life balance, and the most common reasons for a lack of balance were not having enough time, heavy workload, and heavy housework load. Conclusions: The working hours of the respondents were long, and female members had a greater burden of childcare and caregiving, which was considered a barrier to the career development of women. In the future, there will be a need to promote a sense of equality in diverse human resources, develop support for family life, and shorten working hours. [ABSTRACT FROM AUTHOR]

Background: 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. Aim: We aimed to elucidate differences in serum zinc and selenium concentrations in Japanese children between types of IBD. Methods: 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 < 70 μg/dL and < 9.5 μg/dL, respectively. Results: Subjects included 98 patients with CD (median age, 13 years), 118 with UC (11 years), and 43 NC (11 years). Serum zinc and selenium were significantly lower in CD (median, 64 and 12.6 μg/dL respectively) than in UC (69 and 14.6; P < 0.05 and P < 0.001) or NC (77 and 15.7; P < 0.01 and P < 0.001). Zinc deficiency was significantly more prevalent in CD (60.2%) than in NC (37.2%; P < 0.05), but not than in UC (51.7%; P = 0.22). Selenium deficiency was significantly more prevalent in CD (15.3%) than in UC (5.9%; P < 0.05) or NC (0%; P < 0.01). Conclusions: In Japanese children under 17 years old, serum zinc and selenium were significantly lower in CD than in UC or NC. Zinc and selenium should be monitored, and supplemented when deficient, in children with IBD, especially CD. [ABSTRACT FROM AUTHOR]

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: <18 years (juvenile SS, JSS), 9 patients; 18–39 years, 12 patients; 40–69 years, 53 patients; >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. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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, CD80, CD11c, and HLA-DR cells, which was consistent with the increased differentiation of myeloid dendritic cells. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Hasegawa S, Hirano R, Hashimoto K, Haneda Y, Shirabe K, Ichiyama T. Characteristics of atopic children with pandemic H1N1 influenza viral infection: Pandemic H1N1 influenza reveals 'occult' asthma of childhood. Pediatr Allergy Immunol 2011; : e119-e123. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS. Methods The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria. Results Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren's syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease. Conclusions Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease. [ABSTRACT FROM AUTHOR]

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 < 0.001), IC (0.15; P < 0.001), and HC (0.1; P < 0.001). In receiver operating characteristic curve analyses, the area under the curve for PR3‐ANCA was 0.79, significantly greater than for MPO‐ANCA (0.58; P < 0.001). Using a cut‐off value of 0.8 U/mL determined from the receiver operating characteristic analyses, PR3‐ANCA showed significantly greater sensitivity (64.9%) than MPO‐ANCA (cut‐off, 0.2 U/mL; sensitivity, 19.6%; P < 0.001) and good specificity (83.6%). Conclusions: In Japanese children and adolescents, PR3‐ANCA performed better as a serologic marker for diagnosis of UC than MPO‐ANCA. To our knowledge, this is the first report of such a comparison. [ABSTRACT FROM AUTHOR]

Background: Various serologic markers such as anti-glycoprotein 2 antibodies and anti-Saccharomyces cerevisiae antibodies have been reported to be diagnostically useful in Crohn's disease. Mitsuyama et al. reported that antibodies to Crohn's disease peptide 353, a newly proposed serologic marker, were more useful in Japanese adults than anti-Saccharomyces. We addressed the same issue in Japanese children and adolescents.Methods: Prospectively enrolled subjects under 17 years old assessed and treated at 12 pediatric centers in Japan included groups with Crohn's disease, ulcerative colitis, other intestinal diseases, or good health. The 3 serum markers were analyzed by enzyme-linked immunosorbent assays.Results: Enrolled subjects, numbering 367, included 120 with Crohn's disease, 148 with ulcerative colitis, 56 with other intestinal diseases, and 43 healthy subjects. In Crohn's disease, anti-Crohn's disease peptide 353, anti-glycoprotein 2, and anti-Saccharomyces concentrations (median, 2.25, 3.0, and 8.9 U/mL) were significantly greater than in ulcerative colitis (1.1, 1.9, and 3.4; all P < 0.001), other intestinal diseases (1.1, 1.85, and 2.95; all P < 0.001), and healthy controls (1.1, 1.7, and 2.8; all P < 0.001), respectively. At 95% specificity, sensitivity of anti-Crohn's disease peptide (45.0%) was significantly higher than for anti-glycoprotein 2 (30.8%; P < 0.05) or anti-Saccharomyces (26.7%; P < 0.01).Conclusions: Anti-Crohn's disease peptide 353 proved more useful for diagnosis of Crohn's disease in Japanese children than the other 2 markers. To our knowledge, this is the first pediatric report to that effect. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic mitogens specific for vascular endothelial cells. It also induces vascular hyperpermeability and protein leakage into the extracellular space. Leukotriene D4 (LTD4), one of the cysteinyl leukotrienes (CysLTs), is known to be one of the key molecules of allergic inflammation. The interaction between LTD4 and VEGF production in human monocytes/macrophages is not well characterized. Methods: We examined VEGF production by THP-1 cells, a human monocytic leukemia cell line, and human peripheral blood CD14+monocytes/macrophages stimulated with LTD4 and/or tumor necrosis factor-α (TNF-α). We also determined the inhibitory effects of pranlukast, a CysLT1 receptor antagonist, on VEGF production by LTD4 stimulation. Results: LTD4 significantly induced VEGF production and enhanced TNF-α-induced VEGF release in THP-1 cells and human peripheral blood CD14+monocytes/macrophages. VEGF mRNA expression was also induced by stimulation of THP-1 cells with LTD4 and TNF-α. In addition, 10−7–10−10 M pranlukast completely inhibited VEGF production enhanced by LTD4. The 50% inhibitory concentration (IC50) for VEGF production in THP-1 cells was 10−10–10−11 M. Conclusions: LTD4 induced VEGF production and enhanced VEGF release induced by TNF-α via CysLT1 receptors in human monocytes/macrophages. These effects were completely inhibited by pranlukast. [Copyright &y& Elsevier]

Abstract: Background. Airway immunopathogenesis is unclear in patients with profound multiple disabilities (PMD) who undergo tracheostomy. Methods. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), 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. Results. The concentrations of IL-1β, IL-6 and IL-8 in the patients were significantly higher than those in controls (p < 0.001). IL-6, and IL-8 levels in eight PMD patients in the febrile period were significantly higher than those in the afebrile period (p < 0.01 and p < 0.05, 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. Conclusion. PMD patients with tracheostomy have chronic airway inflammation. [Copyright &y& Elsevier]