Prediction of intravenous immunoglobulin resistance in patients with Kawasaki disease according to the duration of illness prior to treatment.

Risk factors predicting intravenous immunoglobulin (IVIG) resistance in patients with Kawasaki disease (KD) were assessed according to the duration of illness prior to treatment. Of 555 KD patients included between 2008 and 2014, 362 were IVIG responders (65.2%) and 193 were IVIG non-responders (34.8%). The risk of IVIG resistance was inversely correlated with the duration of illness prior to treatment. Neutrophil dominance (≥ 80%) was significantly higher in IVIG non-responders regardless of the duration of pre-IVIG illness. While there were no differences between IVIG responders and non-responders who were diagnosed at < 3 days, increasing platelet count and decreasing liver enzyme levels were seen over time in IVIG responders, but not in IVIG non-responders. Multivariable analysis showed that, in addition to neutrophil levels ≥ 80%, risk factors for IVIG resistance were age ≤ 12 months for patients who were diagnosed at ≤ 3 days, and platelet count ≤ 300 × 103/µL and aspartate aminotransferase level ≥ 100 IU/L for patients who were diagnosed at ≥ 6 days.Conclusion: Predictors of IVIG resistance in patients with KD differ according to the duration of pre-treatment illness. Risk assessment according to the duration of illness may improve the prediction of IVIG resistance.What is Known:• Several systems have been developed to predict IVIG resistance in patients with KD but the sensitivity and specificity of these tools are insufficient and ethnic variations have been reported.What is New:• Predictors of IVIG resistance differ depending on the duration of illness prior to treatment.• Risk assessment according to the duration of pre-treatment illness may improve the ability to predict IVIG resistance.

Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte.

BACKGROUND: Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. METHODS: Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. RESULTS: Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. CONCLUSIONS: This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.

Clinical and laboratory profiles of hospitalized children with acute respiratory virus infection.

PURPOSE: Despite the availability of molecular methods, identification of the causative virus in children with acute respiratory infections (ARIs) has proven difficult as the same viruses are often detected in asymptomatic children. METHODS: Multiplex reverse transcription polymerase chain reaction assays were performed to detect 15 common respiratory viruses in children under 15 years of age who were hospitalized with ARI between January 2013 and December 2015. Viral epidemiology and clinical profiles of single virus infections were evaluated. RESULTS: Of 3,505 patients, viruses were identified in 2,424 (69.1%), with the assay revealing a single virus in 1,747 cases (49.8%). While major pathogens in single virus-positive cases differed according to age, human rhinovirus (hRV) was common in patients of all ages. Respiratory syncytial virus (RSV), influenza virus (IF), and human metapneumovirus (hMPV) were found to be seasonal pathogens, appearing from fall through winter and spring, whereas hRV and adenovirus (AdV) were detected in every season. Patients with ARIs caused by RSV and hRV were frequently afebrile and more commonly had wheezing compared with patients with other viral ARIs. Neutrophil-dominant inflammation was observed in ARIs caused by IF, AdV, and hRV, whereas lymphocyte-dominant inflammation was observed with RSV A, parainfluenza virus, and hMPV. Monocytosis was common with RSV and AdV, whereas eosinophilia was observed with hRV. CONCLUSION: In combination with viral identification, recognition of virus-specific clinical and laboratory patterns will expand our understanding of the epidemiology of viral ARIs and help us to establish more efficient therapeutic and preventive strategies.

B7­H1­mediated immunosuppressive properties in human mesenchymal stem cells are mediated by STAT­1 and not PI3K/Akt signaling.

Mesenchymal stem cells (MSCs), derived from either bone marrow (BM) or Wharton's jelly (WJ), inhibit the proliferation of activated T cells, and interferon (IFN)­Î³ serves an important role in this process. This process is B7­homolog (H)1­dependent during cell contact inhibition. However, the signaling pathway involved in B7­H1 expression in MSCs remains largely undefined. The present study demonstrated activation of B7­H1 by engaging signal transducer and activator of transcription (STAT)­1 signaling in MSCs. Human BM­ and WJ­MSCs were isolated and cultured. The immunosuppressive effect of BM­ and WJ­MSCs on phytohemagglutinin (PHA)­induced T cell proliferation was compared using direct and indirect co­culture systems. B7­H1 expression on BM­ and WJ­MSCs was detected by flow cytometry. Small interfering (si)RNA was used to knock down the expression of STAT­1. The inhibitory effect of MSCs on T lymphocytes was observed using PHA­induced T cell proliferation assays. IFN­Î³­induced B7­H1 expression on human BM­ and WJ­MSCs increased in a time­dependent manner. Furthermore, the inhibitory effect of MSCs on T cell proliferation was be restored when an anti­B7­H1 monoclonal antibody was used. When STAT­1 signaling was inhibited by siRNA, B7­H1 expression on IFN­Î³­treated MSCs decreased and T cell proliferation was restored; however, the expression of B7­H1 did not alter upon treatment with a phosphatidylinositol­3­kinase (PI3K) inhibitor (LY294002). These results demonstrated that the IFN­Î³­induced immunosuppressive properties of B7­H1 in human BM­ and WJ­MSCs were mediated by STAT­1 signaling, and not by PI3K/RAC­α serine/threonine­protein kinase signaling. Understanding the intracellular mechanisms underlying IFN­Î³­induced expression of B7­H1 in MSCs may ultimately lead to an improved understanding of MSCs and provide insight into their use as cell therapy agents.

Laboratory Markers in Incomplete Kawasaki Disease according to Coronary Artery Outcome.

BACKGROUND AND OBJECTIVES: We defined laboratory marker profiles typical of incomplete Kawasaki disease (iKD) during illness, especially with respect to the presence of a coronary artery abnormality such as coronary artery dilation or aneurysm. METHODS: This retrospective study examined the clinical and laboratory markers of patients with iKD over time, along with those of patients with complete KD (cKD) and febrile controls. RESULTS: Of 795 patients, 178 had iKD, 504 had cKD and 113 were febrile controls. During the transition from the acute to subacute phase, the age-adjusted hemoglobin levels and platelet counts were significantly lower and higher, respectively, in the subacute phase than in the acute phase in both iKD and cKD patients, which differed from those of febrile controls. Lower levels of acute and subacute age-adjusted hemoglobin levels in iKD patients (odds ratio [OR], 0.538 and 0.583; p=0.006 and 0.018, respectively) and higher subacute platelet counts in cKD patients (OR, 1.004; p=0.014) were correlated with the risk of coronary dilation. A higher acute neutrophil-to-lymphocyte ratio was associated with aneurysm only in cKD patients (OR, 1.059; p=0.044). CONCLUSIONS: The iKD patients share KD-specific laboratory marker profiles in terms of complete blood cell counts and acute phase reactant levels with cKD patients. However, the factors predicting coronary dilation differ according to the phenotype; lower acute and subacute age-adjusted hemoglobin levels predict coronary dilation only in iKD patients.

Systemic Juvenile Xanthogranuloma Involving the Bone Marrow, Multiple Bones, and the Skin That Developed During Treatment of Acute Lymphoblastic Leukemia in Remission State.

Juvenile xanthogranuloma (JXG) is a rare benign disorder classified as non-Langerhans cell histiocytosis, with unclear etiology and pathogenesis. JXG is generally characterized by solitary or multiple cutaneous nodules that resolve spontaneously over a few years. JXG rarely presents as extracutaneous lesions that progress to a symptomatic systemic disorder through multiple organ involvement. We encountered a systemic JXG case involving the bone marrow, multiple bones, and the skin during acute lymphoblastic leukemia (ALL) treatment. A 16-year-old boy undergoing ALL treatment experienced unexplained prolonged fever and scalp, hip joint, and right knee joint pain for 2 weeks during interim maintenance chemotherapy. Bone marrow pathologic findings revealed no evidence of leukemia relapse but showed diffuse infiltration of histiocytes with several Touton-type giant cells; the stains were positive for CD68 and negative for CD1a and S100 protein. Bone and skin biopsies confirmed the findings. Symptoms have resolved since maintenance chemotherapy, which included vincristine, dexamethasone, 6-mercaptopurine, and methotrexate. Bone marrow involvement of JXG is very rare, occurring only in patients less than 1 year of age; however, this case was reported in an adolescent during ALL treatment.

Familial Mediterranean fever presenting as fever of unknown origin in Korea.

Familial Mediterranean fever (FMF) is the most common Mendelian autoinflammatory disease, characterized by uncontrolled activation of the innate immune system that manifests as recurrent brief fever and polyserositis (e.g., peritonitis, pleuritic, and arthritis). FMF is caused by autosomal recessive mutations of the Mediterranean fever gene, MEFV which encodes the pyrin protein. Although FMF predominantly affects people from Mediterranean and Middle Eastern ethnic origins, 3 cases of FMF have been reported in Korea since 2012. We report another case of FMF in Korea in which the patient presented with a month-long fever without serositis. After treatment with colchicine was initiated, the patient's symptoms quickly subsided. The response to colchicine was helpful for diagnosis. We compare the FMF genotypes in Korea with in other countries. Studying FMF cases in Korea will help establish the best MEFV exons to use for screening and diagnosis of Korean FMF.

Characteristics and Outcomes of Second Malignant Neoplasms after Childhood Cancer Treatment: Multi-Center Retrospective Survey.

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.

Value of neutrophil-lymphocyte ratio in predicting outcomes in Kawasaki disease.

Total and differential leukocyte counts are useful inflammatory biomarkers. The ability of the neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in patients with Kawasaki disease (KD) was assessed in this study. All patients with KD who underwent consecutive complete blood count analyses during the acute febrile phase before intravenous immunoglobulin (IVIG), 2 days after IVIG regardless of defervescence, and 3 to 4 weeks after defervescence were enrolled. NLR was calculated by dividing the neutrophil count by the lymphocyte count. NLR values that best predicted IVIG resistance and the development of coronary artery abnormalities were determined by receiver-operating characteristic curve and multivariate analyses. Of the 587 patients with KD, 222 were IVIG resistant. IVIG-resistant patients had higher NLRs than IVIG-responsive patients. The best NLR cut-off values during the acute febrile phase and 2 days after IVIG for predicting IVIG resistance were 5.49 (p <0.001) and 1.26 (p <0.001), respectively. Sixty-two patients developed coronary artery abnormalities; 47 had coronary dilatation, and 15 had aneurysms. Patients with aneurysms, but not patients with dilatation, had higher NLRs than patients without coronary artery abnormalities. The best NLR cut-off value 2 days after IVIG for predicting aneurysm development was 1.01 (p <0.001). Multivariate analysis revealed that the NLR 2 days after IVIG independently predicted coronary aneurysm development (p = 0.03) and IVIG resistance (p <0.001). In conclusion, the NLR can be used for risk stratification in patients with KD. An NLR 2 days after IVIG that exceeded 1 was predictive of coronary aneurysm development and IVIG resistance.

The association between influenza treatment and hospitalization-associated outcomes among Korean children with laboratory-confirmed influenza.

There are limited data evaluating the relationship between influenza treatment and hospitalization duration. Our purpose assessed the association between different treatments and hospital stay among Korean pediatric influenza patients. Total 770 children ≤ 15 yr-of-age hospitalized with community-acquired laboratory-confirmed influenza at three large urban tertiary care hospitals were identified through a retrospective medical chart review. Demographic, clinical, and cost data were extracted and a multivariable linear regression model was used to assess the associations between influenza treatment types and hospital stay. Overall, there were 81% of the patients hospitalized with laboratory-confirmed influenza who received antibiotic monotherapy whereas only 4% of the patients received oseltamivir monotherapy. The mean treatment-related charges for hospitalizations treated with antibiotics, alone or with oseltamivir, were significantly higher than those treated with oseltamivir-only (P < 0.001). Influenza patients treated with antibiotics-only and antibiotics/oseltamivir combination therapy showed 44.9% and 28.2%, respectively, longer duration of hospitalization compared to those treated with oseltamivir-only. Patients treated with antibiotics, alone or combined with oseltamivir, were associated with longer hospitalization and significantly higher medical charges, compared to patients treated with oseltamivir alone. In Korea, there is a need for more judicious use of antibiotics, appropriate use of influenza rapid testing.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.

Rapid growing superficial cutaneous leiomyosarcoma of the face.

Leiomyosarcomas are uncommon malignant smooth muscle tumors, mainly derived from vessels or viscera. Superficial leiomyosarcomas are a rare soft tissue sarcoma arising from the dermis or subcutaneous tissue in the skin. According to tumor origin and location, they are divided into cutaneous and subcutaneous leiomyosarcoma. They have distinctly different histologic and prognostic features from each other. Superficial leiomyosarcomas show a predilection for the proximal extremities and tend to be slow growing. We report one rare case of superficial cutaneous leiomyosarcoma on the right temporal area of face, which showed an extremely rapid growing mass within 3 months.

Quantitative comparison of CDKN2B methylation in pediatric and adult myelodysplastic syndromes.

BACKGROUND/AIMS: Transcriptional repression of tumor suppressor genes is determined by the quantity of promoter hypermethylation. We analyzed the methylation quantity of CDKN2B in pediatric myelodysplastic syndromes (MDS). METHODS: Quantitative measurement of CDKN2B methylation was performed in 25 pediatric MDS patients and 12 controls using pyrosequencing, and the result was compared with those from 74 adult MDS cases and 31 adult controls. The association between CDKN2B methylation quantity and factors related to prognosis including bone marrow blast percentage and karyotype was analyzed. RESULTS: Pediatric MDS patients showed a higher methylation level (MtL) of CDKN2B than pediatric controls (2.94 vs. 1.62; p = 0.031) but a lower level than adult MDS patients (8.76; p < 0.001). MtL was higher in pediatric MDS cases with >5% blasts than in pediatric controls (3.78 vs. 1.62; p = 0.052). Pediatric MDS cases with abnormal karyotype showed a higher MtL than pediatric controls (5.95 vs. 1.62; p = 0.045). CONCLUSIONS: We confirmed that methylation of CDKN2B is associated with the pathogenesis and prognosis in pediatric MDS. The difference in MtLs between pediatric and adult MDS might be related to the physiological hypermethylation of tumor suppressor genes in aging.

Idiopathic acute eosinophilic pneumonia in a 14-month-old girl.

Idiopathic acute eosinophilic pneumonia (IAEP), characterized by acute febrile respiratory failure associated with diffuse radiographic infiltrates and pulmonary eosinophilia, is rarely reported in children. Diagnosis is based on an association of characteristic features including acute respiratory failure with fever, bilateral infiltrates on the chest X-ray, severe hypoxemia and bronchoalveolar lavage fluid >25% eosinophils or a predominant eosinophilic infiltrate in lung biopsies in the absence of any identifiable etiology. We present a 14-month-old girl who was admitted to our pediatric intensive care unit because of acute respiratory distress. She had a fever, dry cough, and progressive dyspnea for 1 day. Chest X-ray showed multifocal consolidations, increased interstitial markings, parenchymal emphysema and pneumothorax. IAEP was confirmed by marked pulmonary infiltrates of eosinophils in the lung biopsy specimen. Most known causes of acute eosinophilic pneumonia, such as exposure to causative drugs, toxins, second-hand smoking and infections were excluded. Her symptoms were resolved quickly after corticosteroid therapy.

Clinical and hematologic manifestations in patients with Diamond Blackfan anemia in Korea.

BACKGROUND: Diamond Blackfan anemia (DBA), characterized by impaired red cell production, is a rare condition that is usually symptomatic in early infancy. The purpose of this study was to assess nationwide experiences of DBA encountered over a period of 20 years. METHODS: The medical records of 56 patients diagnosed with DBA were retrospectively reviewed from November 1984 to July 2010. Fifteen institutions, including 13 university hospitals, participated in this study. RESULTS: The male-to-female ratio of patients with DBA was 1.67:1. The median age of diagnosis was 4 months, and 74.1% were diagnosed before 1 year of age. From 2000 to 2009, annual incidence was 6.6 cases per million. Excluding growth retardation, 38.2% showed congenital defects: thumb deformities, ptosis, coarctation of aorta, ventricular septal defect, strabismus, etc. The mean hemoglobin concentration was 5.1±1.9 g/dL, mean corpuscular volume was 93.4±11.6 fL, and mean number of reticulocytes was 19,700/mm(3). The mean cellularity of bone marrow was 75%, with myeloid:erythroid ratio of 20.4:1. After remission, 48.9% of patients did not need further steroids. Five patients with DBA who received hematopoietic transplantation have survived. Cancer developed in 2 cases (3.6%). CONCLUSION: The incidence of DBA is similar to data already published, but our study had a male predilection. Although all patients responded to initial treatment with steroids, about half needed further steroids after remission. It is necessary to collect further data, including information regarding management pathways, from nationwide DBA registries, along with data on molecular analyses.

Alteration of CD4CD25Foxp3 T cell level in Kawasaki disease.

PURPOSE: Exaggerated pro-inflammatory reactions during the acute phase of Kawasaki disease (KD) suggest the role of immune dysregulation in the pathogenesis of KD. We investigated the profiles of T regulatory cells and their correlation with the clinical course of KD. METHODS: Peripheral blood mononuclear cells were collected from 17 KD patients during acute febrile and subacute afebrile phases. T cells expressing CD4, CD25, and Foxp3 were analyzed using flow cytometry, and the results were correlated with the clinical course of KD. RESULTS: The percentage of circulating CD4(+)CD25(high)Foxp3(+) T cells among CD4(+) T cells was significantly higher during the subacute afebrile phase than during the acute febrile phase (1.10%±1.22% vs. 0.55%±0.53%, P=0.049). Although levels of CD4(+)CD25(low)Foxp3(+) T cells and CD4(+)CD25(-)Foxp3(+) T cells were only slightly altered, the percentage of CD4(+)CD25(+)Foxp3(-) T cells among CD4(+) T cells was significantly lower during the subacute afebrile phase than during the acute febrile phase (2.96%±1.95% vs. 5.64%±5.69%, P=0.036). Consequently, the ratio of CD25(high)Foxp3(+) T cells to CD25(+)Foxp3(-) T cells was higher during the subacute afebrile phase than during the acute febrile phase (0.45%±0.57% vs. 0.13%±0.13%, P=0.038). CONCLUSION: Decreased CD4(+)CD25(high)Foxp3(+) T cells and/or an imbalanced ratio of CD4(+)CD25(high)Foxp3(+) T cells to CD4(+)CD25(+)Foxp3(-) T cells might play a role in KD development. Considering that all KD patients were treated with intravenous immunoglobulin (IVIG), recovery of CD4(+)CD25(high)Foxp3(+) T cells during the subacute afebrile phase could be a mechanism of IVIG.

Epidemiology and clinical long-term outcome of childhood aplastic anemia in Korea for 15 years: retrospective study of the Korean Society of Pediatric Hematology Oncology (KSPHO).

PURPOSE: Aplastic anemia (AA) is a rare hematologic disease characterized by pancytopenia and hypocellular marrow. The Korean Society of Pediatric Hematology Oncology investigated retrospectively the incidence, survival, and transfusion independency according to treatment strategies in AA. METHODS: All the questionnaires were sent to members for medical records. We collected and analyzed 702 available data. RESULTS: The male and female ratio was 1.2, and the median age at diagnosis was 9.3 years. The annual incidence of Korean children with AA was 5.16 per million per year. Constitutional anemia was diagnosed in 44 children. In acquired AA, causes were identified in 39 children. Severe AA (SAA) at initial diagnosis was more common than nonsevere AA. The overall survival was 47.8% with supportive care, 68.1% with immunosuppressive therapy (IST), and 81.8% with hematopoietic stem cell transplantation. In IST, response rate was 65.7%, and relapse rate after response was 54.4% within a median of 23.0 months. The factors with overall survival were severity of disease in supportive care, severity and response in IST, donor type, graft failure, and posttransplant events in hematopoietic stem cell transplantation. CONCLUSIONS: Long-term outcome in AA was dependent on treatment strategies. These Korean results may help research and prospective international clinical trials for childhood AA.

Increased serum interleukin-5 and vascular endothelial growth factor in children with acute mycoplasma pneumonia and wheeze.

Acute mycoplasma pneumonia may be accompanied by wheeze in some children considered not to have asthma. The aim of the present study was to evaluate cytokine secretion in children with acute mycoplasma pneumonia and wheeze. We studied 58 patients with mycoplasma pneumonia (12 with wheeze, Group 1; 46 without wheeze, Group 2) and 36 patients of non-mycoplasma pneumonia (Group 3). Serum levels of interleukin (IL)-4, IL-5, interferon (IFN)-gamma, and vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay kits. The mean +/- SD IL-5 level of Group 1 was 97.1 +/- 73.0 pg/ml, which was significantly higher than that of Group 2 (28.2 +/- 32.2 pg/ml) and that of Group 3 (35.7 +/- 42.0 pg/ml). The mean +/- SD VEGF level of Group 1 was 687.5 +/- 385.8 pg/ml, which was significantly higher than that of Group 2 (310.0 +/- 251.9 pg/ml) and that of Group 3 (402.3 +/- 279.5 pg/ml). No significant differences in serum levels of IL-4, IFN-gamma, and IgE were observed between the groups. Our results show that children with mycoplasma pneumonia and wheeze have significantly higher serum levels of IL-5 and VEGF. These increased immune responses may be associated with the pathophysiological mechanisms by which the Mycoplasma pneumoniae contribute to the development of wheeze during acute mycoplasma pneumonia.

Use of RNA interference to elucidate the effect of MYCN on cell cycle in neuroblastoma.

BACKGROUND: MYCN amplification marks poor prognosis in neuroblastoma (NB) tumors. In evaluating the mechanisms by which retinoic acid (RA) or nerve growth factor (NGF) decrease cell number in MYCN amplified NB cells, we have identified a number of proteins whose expression either decreases (E2F, CDC2, CDK6, cyclin dependent kinase activity) or increases (p27) in association with a decrease in MYCN expression. However, it was still unclear which were MYCN dependent effects or not. PROCEDURE: This study aimed to determine which changes in cell cycle gene expression are modulated as a consequence of the decrease in MYCN. We silenced MYCN expression using siRNA targeted to the coding region of MYCN. Then, by using siRNA transient transfections, we analyzed the change of cell cycle related genes and cell cycle in MYCN amplified NB cell lines. RESULTS: We demonstrate that expression of MYCN can be suppressed by almost 60% in MYCN amplified NB cell using siRNAs targeted to MYCN. Functionally, the decrease in MYCN leads to a decrease in cells in the S-phase of the cell cycle. Decreases in MYCN are associated with decreases in E2F1-2 and ID2 along with increases in p27 protein levels by post-transcriptional modification. Moreover, we find that a decrease in MYCN is accompanied by a decrease in cdk6 mRNA and protein expression. CONCLUSIONS: These results show that E2F and ID2 expression is associated with MYCN regulation and that cdk6 is a possible new transcriptional target of MYCN.

Immunogenicity and safety of Vi capsular polysaccharide typhoid vaccine in healthy persons in Korea.

The purpose of this study was to evaluate the immunogenicity and safety of Salmonella Typhi Vi capsular polysaccharide vaccine (Vi vaccine) in Korea. The immunogenicity of a single dose of Vi vaccine was evaluated in 157 subjects (75 children and 82 adults) before and at 1, 6, and 12 months after vaccination. Immunogenicity was measured with a passive hemagglutination assay (PHA), quantified as geometric mean titers (GMTs) and seroconversion rates. The safety of the vaccine was investigated by determining adverse reactions occurring within 4 h, 3 days, and 1 month after injection. The seroconversion rate for children and adults 1 month after vaccination was 96.92% and 89.02%, respectively. In the case of children, the GMTs of Vi antibodies before vaccination were 5.87 +/- 1.34 and 142.59 +/- 2.39 at one month after vaccination. For adults, the GMTs before and one month after vaccination were 5.58 +/- 1.28 and 58.56 +/- 3.67, respectively. Vi antibodies persisted for as long as 6 and 12 months after vaccination. All adverse reactions in adults and children were minor and did not require treatment. The Vi CPS vaccine was safe and immunogenic in adults and children older than 5 years.