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Competing Interests: The authors declare no conflict of interest.

Background: Retinoblastoma is an ocular tumor in infants with cancer predisposition. Treatment of the rare tumor needs to be optimized for ocular preserved survival without second primary malignancy (SPM)., Methods: We studied the outcomes of all patients with retinoblastoma at a tertiary center in 1984-2016, when preservation method changed from radiotherapy (1984-2001) to systemic chemotherapy (2002-2016)., Results: One-hundred sixteen infants developed unilateral- (n = 77), bilateral- (n = 38), or trilateral-onset (n = 1) tumor. Ten (8.6%) had a positive family history, despite a few studies on RB1 gene. Contralateral disease occurred in one unilateral-onset case. One-hundred eight of 155 eyes (70%) were enucleated. Nine binocular survivors were from 5 bilateral- and 4 unilateral-onset cases. Two survivors received bilateral enucleation. Six deaths occurred; brain involvement (including 3 trilateral diseases) in 4 bilateral-onset, systemic invasion in a unilateral-onset, and SPM (osteosarcoma) in a bilateral-onset case(s). Two others survived SPM of osteosarcoma or lymphoma. The 10-year overall survival (OS: 98.5% vs. 91.3%, p = 0.068) and binocular survivors (13.2% vs. 5.2%, p = 0.154) between bilateral- and unilateral-onsets did not differ statistically. The 10-year OS and cancer (retinoblastoma/SPM)-free survival (CFS) rates of all patients were 94.9 and 88.5%, respectively. The proportion of preserved eyes did not differ between radiotherapy and chemotherapy eras. The CFS rate of bilateral-onset cases in systemic chemotherapy era was higher than that in radiotherapy era (p = 0.042). The CFS rates of bilateral-onset patients with neoadjuvant chemotherapy (upfront systemic therapy for preservation) was higher than those without it (p = 0.030)., Conclusions: Systemic chemotherapy and local therapy raised OS and binocular survival rates of bilateral-onset patients similarly to those of unilateral-onset patients. All but one death was associated with a probable germline defect of the RB1 gene. Neoadjuvant stratified chemotherapy may support the long-term binocular life with minimized risk of SPM.

Background: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are the leading causes of acute respiratory illness in children. Clinical burden of each infection on the respiratory distress in asthmatic patients remains unclear. The purpose of the study was to clarify the effect of these infections on the severity of asthmatic children in the seasonal outbreaks., Methods: A total of 1,217 pediatric inpatients with hMPV (n = 114) or RSV (n = 1,103) infection in Yamaguchi prefecture, Japan, between 2011 and 2014 were enrolled. Bronchial asthma was defined as having more than 3 episodes of wheezing illness over 1 year of age. Infection was determined by the positive antigen test for each virus in the nasal specimens., Results: The number of patients peaked at age 12-15 months in hMPV infection and at age 0-3 months in RSV infection. The proportion of hypoxic patients (40-50%) did not differ at any age between hMPV-infected and RSV-infected children. In the analysis of date from > 1 year old patients with hypoxia, hMPV-infection group was older (P = 0.036), and more frequently had history of asthma (P = 0.015) or abnormal chest roentgenogram (P < 0.001) than RSV-infection group. Multivariate analysis indicated that the hypoxia-associated factors were history of asthma in both hMPV (odds ratio [OR]: 15.8; P < 0.001) and RSV infections (OR, 2.2; P = 0.005), higher body temperature in hMPV infection (OR, 2.2; P = 0.009), and younger age in RSV infection (OR, 1.4; P = 0.004)., Conclusions: Outbreaks of hMPV, rather than, RSV infection may have a greater impact on the development of hypoxic respiratory illness in asthmatic children.

A 30-year-old primigravid woman without a history of thrombocytopenia was referred to our hospital because of severe thrombocytopenia (<1,000 thrombocytes/µl) at 16 weeks of gestation and diagnosed with idiopathic thrombocytopenic purpura (ITP). There was no improvement in the platelet count after treatment with 0.5-1.0 mg/kg/day prednisolone, and the 400 mg/day intravenous immunoglobulin (IVIg) administered for 5 days gradually became ineffective; therefore, a laparoscopic splenectomy was performed at 25 weeks of gestation. The increase in the platelet count after the splenectomy was temporary, but the effects of IVIg therapy improved, and the patient received IVIg therapy seven times in total during her pregnancy. Her platelet count ranged between 10,000 and 70,000/µl after the splenectomy, compared with <5,000/µl before the surgery. The patient underwent an elective cesarean section at 34 weeks of gestation without any significant bleeding. The baby was diagnosed with thrombocytopenia at birth (34,000 thrombocytes/µl) and was administered only one dose of IVIg, which increased the baby's platelet count to a normal level after 14 days. The patient's platelet count also increased after delivery. Splenectomy and repeated IVIg therapy can be considered for refractory severe ITP during pregnancy.

Background: Acute focal bacterial nephritis (AFBN) is a severe form of upper urinary tract infection (UTI) with neurological manifestations and focal renal mass lesions on computed tomography (CT). Prolonged antibiotic therapy may improve the renal outcome, but the early differential diagnosis of AFBN from acute pyelonephritis (APN) is challenging. We searched for effective biomarkers of AFBN based on the pathophysiology of upper UTIs., Methods: Of 52 upper UTI cases treated at Yamaguchi University between 2009 and 2016, 38 pediatric patients with AFBN (n=17) or APN (n=21) who underwent ultrasonography and/or CT were enrolled. The clinical data and serum cytokine concentrations were analyzed to differentiate AFBN from APN., Results: AFBN patients tended to be older, and have a higher body temperature, longer febrile period, more frequent neurological symptoms, higher immature neutrophil count, lower lymphocyte count, higher procalcitonin and urine β 2 -microglobulin levels. AFBN patients showed higher serum levels of IFN-γ, IL-6, IL-10 and soluble TNF-receptor 1 (sTNFR1) (all p<0.05). Although the cytokine levels were variably correlated among each other, multiple logistic regression analysis revealed that combination of IFN-γ and IL-6 levels were most relevant for distinguishing AFBN from APN. The discriminant power of the logistic equation was 0.86 in terms of the area under the curve by the ROC analysis., Conclusions: Circulating 4 out of 7 cytokines in AFBN patients were at higher levels compared with those in APN patients. IFN-γ and IL-6 levels might most effectively distinguish AFBN from APN., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A 38-year-old male with no past history of illnesses visited the out-patient clinic of Nerima Hikarigaoka Hospital complaining of dizziness and persistent anal bleeding. There was a significant anemia on a blood test and colonoscopy showed a thrombus in a markedly swollen internal hemorrhoid. Contrast-enhanced computed tomography (CT) showed a poorly demarcated area with early face enhancement on the right side of the rectum and anal canal. Based on these findings, an arterio-venous malformation (AVM) of the rectum was suspected. Abdominal angiography showed abnormal vessels receiving a blood supply from the bilateral superior rectal arteries. We suspected that the AVM in the rectum was the cause of the hemorrhage from the internal hemorrhoid, and therefore performed embolization of the AVM. Thereafter, the hemorrhage from the internal hemorrhoid stopped completely and the anemia improved to the normal level, without the need for treatment for the internal hemorrhoid. Colonoscopy performed 6 months after embolization showed shrinkage of the internal hemorrhoid. To the best of our knowledge, there are no reports stating a relationship between rectal AVM and internal hemorrhoids. However, we consider that contrast-enhanced CT can be used to detect vessel abnormalities related to severe bleeding of the internal hermorrhoids in patients with internal hemorrhoids and severe anemia.

Background: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease characterized by opsoclonus, myoclonus, ataxia, and behavioral changes. The aim of our study was to investigate the epidemiological characteristics of OMS in Japan and to clarify the association between therapy and prognosis., Methods: We retrospectively collected the data from 626 Japanese medical institutions from 2005 to 2010, and analyzed the clinical features of pediatric patients with OMS based on the data., Results: In this survey, there were 23 patients (10 males and 13 females). The median ages at the disease onset and the time of study were 16.5 months (range: 11-152 months) and 54 months (range: 24-160 months), respectively. The principal symptoms were opsoclonus (23 patients, 100%), myoclonus (21 patients, 91.3%), and ataxia (23 patients, 100%). The related factors were neuroblastoma (10, 43.5%), infection (9, 39.1%), and immunization (2, 8.7%). The treatments for OMS were included intravenous immunoglobulin (17, 73.9%), methylprednisolone pulse (13, 56.5%), oral prednisolone (12 patients, 52.2%), and chemotherapy and/or operation for the underlying tumors (6, 26.1%), and rituximab (2, 8.7%). Complete remissions were obtained in 35.3%, 23.1%, 33.3%, 66.7%, and 100% of these treatments, respectively. At the latest follow-up period, 8 (34.8%) and 17 patients (73.9%) showed neurological sequelae of motor and intellectual functions, respectively. Patients whose treatment was started more than 30 weeks after the disease onset suffered from the severest neurological sequelae (OMS severity 4) more frequently than those less than 30 weeks (p=0.022)., Conclusion: The annual incidence of OMS was estimated to be 0.27-0.40 cases per million in Japanese children. More than 70% of OMS patients had neurological sequelae, especially intellectual function. Early effective treatments within 30 weeks after the onset may be required to prevent the serious neurological outcome., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Human herpesvirus-6 (HHV-6) is a cause of exanthema subitum and, sometimes, of febrile seizures. However, the pathogenesis of febrile seizures associated with HHV-6 infection remains unclear. We investigated serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in infants with HHV-6 infection. Serum levels of both MMP-9 and TIMP-1 were significantly higher in infants with HHV-6 infection than in controls. Serum TIMP-1 levels were significantly higher in infants with febrile seizures than in infants without febrile seizures. Serum MMP-9/TIMP-1 ratios were significantly lower in infants with febrile seizures than in infants without febrile seizures. In infants with HHV-6 infection, positive correlations were found between serum MMP-9 concentrations and the white blood cells (WBC) count, and between serum TIMP-1 concentrations and the WBC count. Positive correlations were also found between the amounts of HHV-6 DNA and the ratios of MMP-9/TIMP-1 in infants with HHV-6 infection. In conclusion, we suggest that high serum levels of MMP-9 and TIMP-1 in infants with HHV-6 infection may induce dysfunction of the blood-brain barrier, eventually causing febrile seizures., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Several studies support the role of viral infections in the pathogenesis of asthma exacerbation. However, several pediatricians believe that influenza virus infection does not exacerbate bronchial asthma, except for influenza A H1N1 2009 pandemic [A(H1N1)pdm09] virus infection. We previously reported that A(H1N1)pdm09 infection possibly induces severe pulmonary inflammation or severe asthmatic attack in a mouse model of bronchial asthma and in asthmatic children. However, the ability of seasonal H1N1 influenza (H1N1) infection to exacerbate asthmatic attacks in bronchial asthma patients has not been previously reported, and the differences in the pathogenicity profiles, such as cytokine profiles, remains unclear in bronchial asthma patients after A(H1N1)pdm09 and H1N1 infections., Methods: The cytokine levels and viral titers in the bronchoalveolar lavage (BAL) fluid from mice with and without asthma after H1N1 infection (A/Yamagata and A/Puerto Rico strains) were compared., Results: The interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, IL-5, interferon (IFN)-α, IFN-β, and IFN-γ levels were significantly higher in the BAL fluids from the control/H1N1 mice than from the asthmatic/H1N1 mice. The viral titers in the BAL fluid were also significantly higher in the control/H1N1mice than in the asthmatic/H1N1 mice infected with either A/Yamagata or A/Puerto Rico., Conclusions: A(H1N1)pdm09 infection, but not H1N1 infection, can induce severe pulmonary inflammation through elevated cytokine levels in a mouse model of asthma., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Tau protein is a microtubule-associated protein that is present in axons. Elevated tau protein levels in cerebrospinal fluid or serum are associated with several central nervous system diseases and can indicate neuronal injury., Objective: In the present study, we measured and then compared serum tau protein levels between infants with neonatal asphyxia and control subjects. We examined these data to investigate the correlation between serum tau protein levels and neurological outcomes after neonatal asphyxia., Patients and Methods: Serum tau protein levels were determined by an enzyme-linked immunosorbent assay in 19 neonates with neonatal asphyxia. Of these 19 neonates, 3 had severe spastic tetraplegia, and 1 had west syndrome. A group of 19 unaffected neonates was included in the study as a control group., Results: Serum tau protein levels on postnatal day 3 were significantly higher in the poor outcome group than those in the good outcome (p=0.010) and control groups (p=0.006). On postnatal day 7, serum tau protein levels again were significantly higher in the poor outcome group than those in the good outcome (p=0.007) and control groups (p=0.006)., Conclusions: The present findings indicate serum tau protein levels measured on postnatal days 3 and 7 can predict neurological prognosis following neonatal asphyxia., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has recently been recognized as an encephalopathy subtype. Typical clinical symptoms of AESD are biphasic seizures, and MRI findings show reduced subcortical diffusion during clustering seizures with unconsciousness after the acute phase. Visinin-like protein-1 (VILIP-1) is a recently discovered protein that is abundant in the central nervous system, and some reports have shown that VILIP-1 may be a prognostic biomarker of conditions such as Alzheimer's disease, stroke, and brain injury., Methods: However, there have been no reports regarding serum and cerebrospinal fluid (CSF) levels of VILIP-1 in patients with AESD. We measured the serum and CSF levels of VILIP-1 in patients with AESD, and compared the levels to those in patients with prolonged febrile seizures (FS)., Results: Both serum and CSF levels of VILIP-1 were significantly higher in patients with AESD than in patients with prolonged FS. Serum and CSF VILIP-1 levels were normal on day 1 of AESD., Conclusions: Our results suggest that both serum and CSF levels of VILIP-1 may be one of predictive markers of AESD., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Patients with 2009 pandemic H1N1 influenza-associated encephalopathy (pIE) have been reported in Japan. The most common clinical symptoms of this condition are seizures and progressive coma with high-grade fever. We previously highlighted the cytokine profile of pIE; our results suggest that proinflammatory cytokines play an important role in the pathogenesis. High mobility group box 1 (HMGB1) protein is a late mediator of inflammation or sepsis. However, there are few reports regarding the serum and cerebrospinal fluid (CSF) levels of HMGB1 in pIE patients., Methods: We measured serum and CSF levels of HMGB1 in the following: pIE patients with poor outcomes, pIE patients without neurological sequelae, influenza patients without pIE, and control subjects., Results: Serum HMGB1 levels were significantly higher in pIE patients with poor outcomes compared to those without neurological sequelae. In contrast, there was no difference in CSF HMGB1 levels among all groups. Regarding pIE patients, we found a significant positive correlation between HMGB1 levels and IL-6 in the serum but not in the CSF., Conclusions: Our results suggest that HMGB1 protein may be involved in the pathogenesis of pIE and that a high serum, but not CSF, level of inflammatory cytokines plays an important role in the severity of pIE., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

It has been suggested that cytokines are associated with refractory Mycoplasma pneumoniae pneumonia, and steroid administration is reported to be effective in this situation. In order to elucidate the characteristics of refractory M. pneumoniae pneumonia, we analyzed five pediatric patients with refractory M. pneumoniae pneumonia, which was defined as showing prolonged fever and deterioration of clinical and radiological findings despite administration of appropriate antibiotics, compared with 15 pediatric patients with M. pneumoniae pneumonia who responded to treatment promptly (control group). Serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin (IL)-18 levels were significantly higher in the refractory group than in the control group at the initiation of corticosteroid use (LDH: 571 vs 292 IU/L, p = 0.0129; ALT: 25 vs 11 IU/L, p = 0.0143; AST: 41 vs 26 IU/L, p = 0.0404; IL-18: 579 vs 365 pg/mL, p = 0.0402). Significant correlation was found between serum values of IL-18 and LDH (r(2) = 0.504, p = 0.0433). The administration of corticosteroids to patients in the refractory group resulted in the rapid improvement of symptoms and decrease in serum LDH levels in all patients. A serum LDH level of ≥410 IU/L, which was calculated from receiver operating characteristic curve analysis, seemed to be an appropriate criterion for the initiation of steroid therapy. In conclusion, serum IL-18 and LDH levels can be used as parameters to determine which patients are candidates for corticosteroid therapy. In addition, serum LDH levels seem to be a useful marker for the evaluation of therapeutic efficacy in refractory M. pneumoniae pneumonia., (Copyright © 2014. Published by Elsevier Ltd.)

Background: Acute disseminated encephalomyelitis (ADEM) is clinically characterized by the acute onset of neurological symptoms after a viral infection or immunization, and is thought to represent an autoimmune disease directed against myelin. Tau protein is a phosphorylated microtubule-associated protein, primarily located in neuronal axons. Increased levels of tau protein in cerebrospinal fluid (CSF) are found in various pathological conditions., Methods: We used tau protein as a marker of axonal damage and examined its concentration in the CSF of 27 children with ADEM., Results: CSF tau protein concentration in children with ADEM was significantly higher than that in the CSF of control subjects (P=0.008). There were no significant differences in CSF tau protein concentrations in the ADEM patients with and without encephalopathy. The CSF tau protein concentration in patients with partial lesion resolution in follow-up brain MRI was significantly higher than in patients with complete lesion resolution (P=0.014)., Conclusions: In conclusion, we demonstrated that CSF tau protein concentration was significantly increased in ADEM patients. Our findings suggest that axonal damage may occur in addition to demyelination in children with ADEM., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Bronchial asthma is known as a risk factor of admission to the intensive care unit. However, the mechanism by which pandemic 2009 H1N1 (A(H1N1)pdm09) infection increases the severity of symptoms in patients with bronchial asthma is unknown; therefore, we aimed at determining this mechanism., Methods: Inflammatory cell levels in the bronchoalveolar lavage (BAL) fluid from the non-asthma/mock, non-asthma/A(H1N1)pdm09, asthma/mock, and asthma/A(H1N1)pdm09 groups were determined using BALB/c mice. Cell infiltration levels, cytokine levels, and viral titers were compared among the groups., Results: Neutrophil, monocyte, interleukin (IL)-5, IL-6, IL-10, IL-13, and tumor necrosis factor (TNF)-α levels were significantly higher in the BAL fluid from the non-asthma/A(H1N1)pdm09 and asthma/A(H1N1)pdm09 groups than in the mock groups (p<0.05 for neutrophils and monocytes; p<0.01 for the rest). The number of eosinophils and CD8(+) lymphocytes and the level of transforming growth factor beta 1 (TGF-β1) in BAL fluid in the asthma/A(H1N1)pdm09 group were significantly higher among all groups (p<0.05 for eosinophils and CD8(+) lymphocytes; p<0.01 for TGF-β1). The levels of IL-6, IL-10, IL-13, and TNF-α were significantly higher in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group (p<0.05 for IL-6 and IL-10; p<0.01 for IL-13 and TNF-α). The level of IFN-γ in the asthma/A(H1N1)pdm09 group was significantly lower than that in the non-asthma/A(H1N1)pdm09 group (p<0.05). The viral titers in the BAL fluids were higher in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group (p<0.05). Histopathological examination showed more severe infiltration of inflammatory cells and destruction of lung tissue in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group., Conclusions: Severe pulmonary inflammation induced by elevated levels of cytokines, combined with increased viral replication due to decreased IFN-γ levels, may contribute to worsening respiratory symptoms in patients with bronchial asthma and A(H1N1)pdm09 infection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients., Methods: We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects., Results: Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases., Conclusions: Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE., (Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurodegenerative encephalitis caused by some variants of measles virus (MV). The structure of SSPE virus in the brains of SSPE patients is different from that of MV. The difference in interferon (IFN) production between cells infected with SSPE virus and those infected with MV remains unclear., Methods: We measured the concentrations of IFN-α, β, γ, and λ1 (interleukin (IL)-29) from MV- or SSPE virus-infected B95a cells (a marmoset B-lymphoblastoid cell line)., Results: SSPE virus-infected B95a cells produced significantly higher levels of IFN-α and λ1 than did MV-infected or mock-infected cells., Conclusion: Our results suggest that SSPE virus and MV induce different IFN production profiles., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: Since April 2009, the number of patients with 2009 pandemic H1N1 influenza virus infection has been increasing in Japan just as in the rest of the world. Patients with 2009 pandemic H1N1 influenza-associated encephalopathy (pIE) have also been reported. The common clinical symptoms of this condition are seizures and progressive coma with high-grade fever. We previously reported the possible association between seasonal influenza-associated encephalopathy (sIE) and proinflammatory cytokines. However, the pathogenesis of pIE remains to be elucidated., Results: In pIE patients with a poor outcome, the serum levels of interleukin (IL)-6, IL-10, and soluble tumor necrosis factor (TNF) receptor (sTNFR1) were significantly higher than those in pIE patients without neurological sequelae. Similarly, the cerebrospinal fluid (CSF) IL-6 levels in pIE patients with a poor outcome were significantly higher than those in pIE patients without neurological sequelae., Conclusion: Our results suggest that IL-6, TNF-α, and IL-10 play important roles in pIE, and that the serum levels of IL-6, IL-10, and sTNFR1 and the CSF levels of IL-6 are related to neurological complications., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Beta1-integrins mediate cell attachment to different extracellular matrix proteins, intracellular proteins, and intercellular adhesions. Recently, it has been reported that prostaglandin E2 (PGE2) has anti-inflammatory properties such as inhibition of the expression of adhesion molecules or production of chemokines. However, the effect of PGE2 on the expression of beta1-integrin remains unknown. In this study, we investigated the effects of PGE2 on the expression of beta1-integrin in the human monocytic cell line THP-1 and in CD14+ monocytes/macrophages in human peripheral blood. For this, we examined the role of four subtypes of PGE2 receptors and E-prostanoid (EP) receptors on PGE2-mediated inhibition. We found that PGE2 significantly inhibited the expression of beta1-integrin, mainly through EP4 receptors in THP-1 cells and CD14+ monocytes/macrophages in human peripheral blood. We suggest that PGE2 has anti-inflammatory effects, leading to the inhibited expression of beta1-integrin in human monocytes/macrophages, and that the EP4 receptor may play an important role in PGE2-mediated inhibition., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)