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Objective The current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E). Methods This is a retrospective study on patients with HPeV3 infection, and a two-step questionnaire survey performed on 837 hospitals in Japan between 2014 and 2016. Results We identified 240 infants with HPeV3 infection, of which 34 had been clinically-diagnosed HPeV3E/E (cHPeV3E/E). However, detailed clinical data were provided by 32 of the 34 patients. Among these 32, 23 had undergone MRI and were categorized into two groups, MRI-positive (n = 17) and -negative (n = 6). There were no significant intergroup differences in clinical lab results or symptoms, except for gastrointestinal symptoms that were only present in the MRI-negative patients. The MRI-positive group showed white matter involvement on brain MRI during the acute phase, and 8 patients presented with lesions on follow-up MRI. Furthermore, 4 (50%) of the 8 patients had neurological sequelae. Conclusion Clinical characteristics of cHPeV3E/E patients with and without lesions on brain MRI showed no significant differences. Therefore, considering the difficulty in distinguishing febrile infants with cHPeV3E/E from those with a sepsis-like illness, during an HPeV3 infection epidemic, it is imperative to frequently perform brain MRI in febrile infants presenting with severe disease for the early diagnosis of HPeV3E/E presenting with brain lesions.

The causal effects of vaccines on Kawasaki disease (KD) remain elusive. We aimed to examine the association between vaccines administered during infancy and the development of KD in Japan. We conducted a multicenter prospective case-control study using questionnaires and compared the vaccination status of infants (age: 6 weeks to 9 months) who developed KD (KD group, n = 102) and those who did not develop KD (non-KD group, n = 139). Next, we performed a case-crossover study of 98 cases in the KD group and compared the status of vaccinations between the case and control periods. We also compared the incidence of KD in children for each 5-year period before and after the addition of new vaccines (2012–2013) using data from the Nationwide Survey of KD. In the case-control study, the vaccination status of the KD and control groups did not differ to a statistically significant extent. Multivariable analysis of the vaccination status and patient backgrounds showed no significant association between vaccination and KD development. In the case-crossover study, the status of vaccinations during the case and control periods did not differ to a statistically significant extent. In the analysis of data from the Nationwide Survey of KD, the incidence of KD in children of ages subject to frequent vaccination showed no significant increases in the latter five years, 2014–2018. Based on these prospective analyses, we confirmed that vaccination in early infancy did not affect the risk of KD.

Summary Objectives Patients with primary immunodeficiency diseases (PID) are highly susceptible to various microorganisms. However, no population-based studies have been performed among common viral pathogens, such as respiratory syncytial virus (RSV), rotavirus (RV), varicella-zoster virus (VZV) and influenza virus (IV). The objective of this study was to reveal the clinical burden of these four infections among PID patients in Japan. Methods We conducted a nationwide survey by sending questionnaires to 898 hospitals with pediatric departments throughout Japan. Results Nine hundred ten PID patients from 621 hospitals were registered (response rate: 69.2%). Fifty-four of the patients were hospitalized due to these viral infections. The durations of hospitalization due to RSV and RV infections differed significantly in the PID patients with and without cellular immunodeficiency (12.0 vs 6.5 days, p = 0.041 ; and 14.0 vs 6.0 days, p = 0.031 , respectively). There was no significant difference in the duration of hospitalization in PID patients with and without cellular immunodeficiency who were hospitalized with IV infections (7.3 vs 6.1 days, p = 0.53). Conclusions Special attention should be paid to PID patients with compromised cellular immunity who present with RSV and RV infection due to their high risk for severe disease.

The introduction of 4-bromopyridine (4-Brpy) to a self-assembled MII-[NbIV(CN)8] (M = 3d metal ion) coordination system results in the formation of three-dimensional cyanido-bridged networks, {[MII(4-Brpy)4]2[NbIV(CN)8]}·nH2O (M = Zn, n = 1, 1; M = Mn, n = 0.5, 2; M = Ni, n = 2, 3). All these compounds are coordination frameworks composed of octahedral [MII(4-Brpy)4(μ-NC)2] complexes bonded to square antiprismatic [NbIV(CN)8]4– ions bearing four bridging and four terminal cyanides. 1 and 2 crystallize in the chiral I4122 space group as the mixture of two enantiomorphic forms, named 1(+)/1(−) and 2(+)/2(−), respectively. The chirality is here induced by the spatial arrangement of nonchiral but sterically expanded 4-Brpy ligands positioned around MII centers in the distorted square geometry, which gives two distinguishable types of coordination helices, A and B, along a 4-fold screw axis. The (+) forms contain left handed helices A, and right handed helices B, while the opposite helicity is presented in the...

Three-dimensional cyanido-bridged bimetallic assemblies [MnII(4-Xpy)4]2[NbIV(CN)8]·nH2O (4-Xpy: 4-halopyridine; X = I and n = 0, (1); X = Cl and n = 0.5, (2)) are synthesized. 1 and 2 have chiral and achiral structures, respectively. The chiral structure of 1 is composed of achiral building blocks, which lead to an enantiopure compound through a spontaneous resolution process. In the crystal structure of 1, the halogen bonds between 4-Ipy and cyanide distort the structure, lowering the crystal symmetry. Both 1 and 2 show ferrimagnetism with Curie temperatures (TC) of 22 K and 28 K, respectively. Due to the chiral and polar structure in the I41 space group, 1 exhibits SHG phenomena, while such nonlinear optical phenomena are quenched in 2 due to its centrosymmetry.

Background We previously reported that biofilms and innate immunity contribute to the pathogenesis of Kawasaki disease. Therefore, we aimed to assess the efficacy of clarithromycin, an antibiofilm agent, in patients with Kawasaki disease. Methods and Results We conducted an open‐label, multicenter, randomized, phase 2 trial at 8 hospitals in Japan. Eligible patients included children aged between 4 months and 5 years who were enrolled between days 4 and 8 of illness. Participants were randomly allocated to receive either intravenous immunoglobulin (IVIG) or IVIG plus clarithromycin. The primary end point was the duration of fever after the initiation of IVIG treatment. Eighty‐one eligible patients were randomized. The duration of the fever did not differ between the 2 groups (mean±SD, 34.3±32.4 and 31.1±31.1 hours in the IVIG plus clarithromycin group and the IVIG group, respectively [ P =0.66]). The relapse rate of patients in the IVIG plus clarithromycin group was significantly lower than that in the IVIG group (12.5% versus 30.8%, P =0.046). No serious adverse events occurred during the study period. In a post hoc analysis, the patients in the IVIG plus clarithromycin group required significantly shorter mean lengths of hospital stays than those in the IVIG group (8.9 days versus 10.3 days, P =0.049). Conclusions Although IVIG plus clarithromycin therapy failed to shorten the duration of fever, it reduced the relapse rate and shortened the duration of hospitalization in patients with Kawasaki disease. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000015437.

Objective: Extracardiac conduit Fontan procedure (ECFP) using Gore-Tex graft has been performed with increasing frequency for the patients with functional single ventricle. However, lack of growth potential and longevity of the conduit are consistent concerns and main points of criticism of the ECFP. In this study, we investigated the mid-term status of the Gore-Tex graft used in the ECFP by comparingthe internal diameter ofthegraftwiththeinferiorvenacava(IVC)diameter at1monthand5.2yearsaftertheECFP.Methods:Of79 patientswhounderwentECFPusing Gore-TexgraftbetweenNovember 1997andDecember2007,33 patientswhohadcompletedcardiaccatheterization at1 month(21—73days) and 5.2 years (3.3—9.6 years) after the ECFP were included in this study. We measured the internal diameter of the Gore-Tex graft and IVC at both catheterizations retrospectively. Results: The size of the Gore-Tex graft used in the ECFP was 16 mm in 17 patients, 18 mm in 9 patients, and 20 mm in 7 patients. Laminar flow through the conduits was maintained without any stenosis or kinking of the graft in these 33 patients. No intervention or reoperation related to the extracardiac conduit has been required. There were no significant differences in mean cross-sectional area (CSA) of the conduits at 1 month versus 5.2 years after the ECFP for each conduit size, and no significant changes in the conduit-to-IVC CSA ratio (0.98 0.40 vs 0.82 0.21 for 16 mm, 1.09 0.30 vs 0.92 0.33 for 18 mm, and 1.16 0.55 vs 0.94 0.44 for 20 mm conduit). Conclusions:TheconduitCSA andconduit-to-IVCCSA ratioremainedunchangedinsmall calibergrafts downto 16 mm at 5.2yearsafterthe ECFP. However, further investigation is necessary to evaluate the fate of the Gore-Tex graft and late hemodynamics in the patients with small conduits after they achieve full somatic growth. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Kawasaki disease (KD) is an acute febrile disorder characterized by systemic vasculitis primarily occurring in coronary arteries. Matrix metalloproteinases (MMPs) have been considered to play pathophysiologic roles in the development of coronary artery lesions (CALs); therefore, an evaluation of the genetic contributions of the MMP genes to the development of CALs in KD patients would be beneficial for the prediction of CAL formation. We focused on the known functional single nucleotide polymorphisms (SNPs) in the MMP genes (MMP-2-735C>T, MMP-3-1612 5A/6A, MMP-9-1562C>T, MMP-12-82A>G, and MMP-13-77A>G) and performed the association study between these SNPs and CAL formation in KD. The study population consisted of 44 KD patients with CALs and 92 without CALs and 175 healthy controls. As a result, allele and genotype frequencies of MMP-13-77A>G showed significant differences between KD patients with CALs and without CALs (p = 0.00989 and p = 0.00551, respectively). The estimated frequencies of the G-C haplotype in the MMP-13 gene promoter were significantly lower in KD patients with CALs than in those without CALs. There was no association between other MMP genes and CAL formation. In conclusion, the genetic evaluation by association study demonstrated that the MMP-13 gene, at least in part, contributed to the development of CALs in KD.

A 12-year-old girl with aortic valvular stenosis underwent transcatheter balloon aortic valvuloplasty (BAV) using a femoral artery approach. Anticoagulation with heparin during the procedure was used. The patient noted sudden onset of concentric constriction of the visual field in the right eye 40 min after BAV. Brain magnetic resonance imaging and cervical ultrasound revealed no abnormality. Funduscopic examination showed white swelling around the macular region, indicating ischemia, consistent with central retinal artery occlusion (CRAO). CRAO should be recognized as a rare and serious complication associated with BAV even among the pediatric population. This requires careful evaluation of anticoagulation during the left heart procedures.

We evaluated brain lesions in patients with coronary arterial lesions (CAL) as a complication of Kawasaki disease (KD) by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Among 47 patients who underwent coronary angiography for the evaluation of CAL due to KD at Kyushu University Hospital from April 1996 to September 2004, 24 patients were evaluated prospectively by brain MRI and MRA 0.1-21.2 years after the onset of KD. Although most patients had irritability or lethargy, none of them had significant neurological symptoms or signs during the acute phase, except one who showed neck stiffness. In one patient with no apparent neurological symptoms out of the 24 patients, brain MRI and MRA revealed right cerebellar infarction and obliteration of the right posterior inferior cerebellar artery, respectively. These results revealed the presence of cerebrovascular lesion in one of the 24 KD patients with CAL and suggested the need to consider the possibility of brain lesions in severe cases of KD with or without neurological symptoms.

We analyzed the genetic polymorphisms of vascular endothelial growth factor (VEGF) and its receptors [Fms-related tyrosine kinase-1, kinase insert domain receptor (KDR)] in Japanese patients with Kawasaki disease (KD) and normal control subjects to examine whether these genes would contribute to the KD occurrence and/or the development of coronary artery lesion (CAL) in KD. We found that the frequency of G allele of VEGF g.-634 G>C single-nucleotide polymorphism in the promoter region was significantly higher in KD patients with CAL than in those without CAL (p = 0.012) or control subjects (p = 0.021) because of a significantly higher frequency of the GG genotype in KD patients with CAL. In addition, the frequency of the A1 allele with 11 AC repeats of KDR g.+4422(AC)11-14 dinucleotide repeat polymorphism in intron 2 was significantly higher in KD patients with CAL than in those without CAL (p = 0.013) or control subjects (p = 0.040) as a result of a significantly higher frequency of the A1A1 genotype in KD with CAL patients. The multivariate analysis of clinical features and genotypes of the two polymorphisms showed that the A1A1 genotype of KDR g.+4422(AC)11-14 polymorphism was an independent risk factor for the development of CAL with the highest odds ratio among several clinical parameters (odds ratio 6.76; 95% confidence interval 1.05-43.48). Dual luciferase assay demonstrated that the A1 allele with KDR g.+4422(AC)11 repeats showed a weaker silencer function than the A2 allele with 12 AC repeats. These findings suggested that VEGF and its receptor, KDR, genes contributed to the development of CAL in KD patients.

Background: Nitric oxide (NO) is secreted by immune and vascular endothelial cells, and appears to play important roles in the pathophysiology of Kawasaki disease (KD). Thus, genetic variations in NO synthase (NOS) genes may be involved in the development of coronary artery lesions (CAL) in KD. Methods: The present study investigated the association of endothelial constitutive NOS (ecNOS) and inducible NOS (iNOS) gene polymorphisms with the development of CAL in KD in a Japanese population. Results: The genotype distributions of 27-bp tandem repeat polymorphism within intron 4 of ecNOS gene did not show any significant difference between controls and KD patients with or without CAL. In addition, there was no significant association between whole-allele distribution of iNOS gene promoter (penta-repeat CCTTT) polymorphism and KD with or without CAL. Conclusion: These results did not support any association of ecNOS and iNOS gene polymorphisms to the development of CAL in KD patients in a Japanese population.

A 5-year-old girl with isolated congenital left pulmonary artery agenesis suffered from recurrent attacks of dyspnea and right-sided pneumonia due to the stenosis of the right main bronchus. The division of ligamentum of the ductus arteriosus and suspension of the right pulmonary artery resulted in the disappearance of symptoms. It is notable that the compression of contralateral bronchus by the remaining pulmonary artery can cause respiratory symptoms in patients with isolated unilateral pulmonary artery agenesis.

Neonatal lupus erythematosus, characterized mainly by congenital heart block and transient skin lesions, is usually self-limited. A patient with history of neonatal lupus erythematosus and congenital heart block developed central nervous system vasculopathy resembling moyamoya disease and hypertension at 17 years of age. Careful examination and follow-up of possible central nervous system complications later in life might be important in infants with neonatal lupus erythematosus.

ObjectiveThe objective was to clarify the outcomes of cardiac surgery in trisomy 18 patients.Patients and methodsWe analysed 34 consecutive trisomy 18 patients, of whom 21 were males, with cardiac complications. They were divided into patients who underwent cardiac surgery and those who were conservatively treated. We compared rates of survival and discharge alive between two groups.ResultsThe surgery group included nine patients, with six males, who underwent cardiac surgery – intracardiac repair in three patients, pulmonary arterial banding in five patients, and ligation of the ductus in one patient – at median age of 2.2 months, ranging from 0.5 to 9.8, and with median weight of 2.6 kilograms, ranging from 1.5 to 3.2. Cardiac surgery and pre-operative assisted ventilation were hazardous factors leading to death. In the surgery group, cumulative survival rates at 1 month, 6 months, 12 months, and 24 months were 63%, 38%, 25%, and 22%, respectively, compared with 51%, 26%, 9%, and 9% in the conservative group. There was a significant difference (p = 0.002). The cumulative rates of discharge alive at 1 month, 3 months, and 6 months were 0%, 12%, and 65% in the surgery group, which did not differ from the conservative group (p = 0.80).ConclusionsCardiac surgery contributed to increased survival rate but not the rate of discharge alive in trisomy 18 patients. Cardiac surgery could not prevent all the trisomy 18 patients from death. The indication of cardiac surgery should be carefully individualised to improve the quality of life in trisomy 18 patients and concerned surrounding people.

Objective: Reflecting excellent mid-term outcomes, extracardiac conduit Fontan procedure (ECFP) using Gore-Tex tube graft has been performedwithincreasingfrequencyinpatientswithfunctionalsingleventricle. Nevertheless,duetothelackofgrowthpotentialoftheartificial conduit, the status of the venous pathway along with somatic growth is a continuing concern. In this study, we evaluated the longitudinal growth of the autologous vessels above and below the Gore-Tex graft used in the ECFP. Methods: This study included 34 patients who had completed cardiac catheterisations at 1 month and 5.1 years after the ECFP. The average age, weight and height at the ECFP were 3.8 2.5 years (1.8—12.7 years), 12.7 4.6 kg (7.4—33.0 kg) and 92.9 16.1 cm (72.5—153.5 cm), respectively. We measured the vertical lengths of three different parts angiographically: thelengthbetweentheconfluence pointoftheinnominateveinandtheanastomoticsiteoftheconduittothepulmonaryartery (SVC-C), the conduit vertical length (C) and the length between the confluence point of the hepatic vein and the conduit’s anastomotic site to the inferior vena cava (IVC-C). Results: We have not observed stenosis or thrombus formation in the conduit or distortion of the conduit or pulmonary artery in any of the cases. No intervention or re-operation related to the extracardiac conduit was required,and laminarflow through the conduit was maintained with efficient Fontan haemodynamics. At 5.1 years after the ECFP, the average weight and height gain were 10.3 4.4 kg and 28.5 1.9 cm, respectively. The length of SVC-C, C and IVC-C were significantly increased as 124 15%, 106 7% and 132 24%, respectively, compared to the lengths at 1 month after the ECFP. The degree of increase in SVC-C and IVC-C was significantly larger than that in C. Conclusions: Along with the patient’s somatic growth, longitudinal growth of the autologous vessels above and below the Gore-Tex graft was demonstrated to compensate for the lack of growth potential of the artificial graft. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

BACKGROUND. Pulmonary arterial hypertension has been reported to be observed in association with acquired portal hypertension. However, the contribution of congenital anomalies occurring in the portal system to the development of pulmonary arterial hypertension remains to be elucidated.METHODS. Nine patients with congenital portosystemic venous shunt were studied from January 1990 through September 2005.RESULTS. Patent ductus venosus was detected in 5 patients, including 3 patients with an absence of the portal vein. The presence of either a gastrorenal or splenorenal shunt was evident in another 4 patients. Six patients had a history of hypergalactosemia with normal enzyme activities, as seen during neonatal screening. Six (66.7%) of the 9 patients were identified to have clinically significant pulmonary arterial hypertension (mean pulmonary artery pressure: 34–79 mm Hg; pulmonary vascular resistances: 5.12–38.07 U). The median age at the onset of pulmonary arterial hypertension was 12 years and 3 months. Histologic studies of lung specimens, which were available in 4 of the 9 patients with congenital portosystemic venous shunt, showed small arterial microthrombotic lesions in 3 patients. This characteristic finding was recognized even in the congenital portosystemic venous shunt patients without PAH.CONCLUSIONS. This study demonstrated thromboembolic pulmonary arterial hypertension to be a crucial complication in congenital portosystemic venous shunt, and this pathologic state may be latently present in patients with pulmonary arterial hypertension of unknown etiology.

Noncompaction of the ventricular myocardium (NCVM) is a rare form of cardiomyopathy with a poor prognosis, and it is characterized by prominent trabeculations and deep intertrabecular recesses. This disease is speculated to occur because of arrest of the normal myocardial development process during early embryogenesis. In symptomatic infants, cardiac transplantation may be the only current curative option. Although NCVM is a congenital disorder, there are only a few previous reports on its status during fetal life. Here we report a case of nonimmune hydrops fetalis caused by this rare disease; in this case, digoxin administration to the mother could improve the fetal hemodynamics, and evaluation of the circulatory state of the fetus by using the preload index of the inferior vena cava (PLI) was proven to be sensitive and useful.

Congenital absence of the portal vein (CAPV) is a rare malformation of the mesenteric vasculature in which visceral venous blood bypasses the liver, completely draining into the systemic circulation through a congenital porto-systemic shunt. Liver transplantation has rarely been indicated for patients with this disease. We present a child with CAPV who was managed successfully by living donor auxiliary partial orthotopic liver transplantation (APOLT), while preserving the right lobe of the native liver. In conclusion, APOLT for patients with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is not necessary. Liver Transpl 12:845-849, 2006. © 2006 AASLD.

SummaryChromosome 22q11.2 deletion syndrome is a common disorder characterized by thymic hypoplasia, conotruncal cardiac defect and hypoparathyroidism. Patients have a risk of infections and autoimmunity associated with T lymphocytopenia. To assess the immunological constitution of patients, the numerical changes and cytokine profile of circulating T cells were analysed by flow cytometry and real-time polymerase chain reaction (PCR). CD3+, CD4+, T cell receptor (TCR)αβ+ or CD8αα+ cell counts were lower, and CD56+ cell counts were higher in patients than in controls during the period from birth to adulthood. The ageing decline of CD3+ or CD4+ cell counts was slower in patients than in controls. The proportion of CD8αα+ cells increased in controls, and the slope index was larger than in patients. On the other hand, both the number and proportion of Vα24+ cells increased in patients, and the slope indexes tended to be larger than in controls. The positive correlation of the number of T cells with CD8αα+ cells was observed only in patients, and that with Vα24+ cells was seen only in controls. No gene expression levels of interferon (IFN)-γ, interleukin (IL)-10, transforming growth factor (TGF)-β, cytotoxic T lymphocyte antigen 4 (CTLA4) or forkhead box p3 (Foxp3) in T cells differed between patients and controls. There was no significant association between the lymphocyte subsets or gene expression levels and clinical phenotype including the types of cardiac disease, hypocalcaemia and frequency of infection. These results indicated that T-lymphocytopenia in 22q11.2 deletion patients became less severe with age under the altered composition of minor subsets. The balanced cytokine profile in the limited T cell pool may represent a T cell homeostasis in thymic deficiency syndrome.

Objective To investigate whether the CD25 + CD4 + regulatory T-cell population, which plays important roles not only in maintaining immunologic self-tolerance but also in controlling the magnitude and character of antimicrobial immune responses, is related to the pathophysiology of Kawasaki disease (KD). Study design The patient group consisted of 54 patients (median age, 30 months; 27 female and 27 male patients) fulfilling the criteria for KD. Age-matched control subjects included 17 patients with active infections and 24 healthy children. We analyzed CD25 + CD4 + cells and the mRNA expression of Foxp3, cytotoxic T lymphocyte–associated antigen 4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and transforming growth factor β in peripheral blood mononuclear cells and purified CD4 + T cells. Results The proportions of CD25 + CD4 + cells in patients with acute-phase KD (median, 2.35% of total lymphocytes) were significantly lower than those in healthy control subjects (median, 3.14%) and control subjects with disease (median, 3.15%). The proportions returned to the normal level after intravenous gammaglobulin treatment (median, 3.86%). The mRNA expression of Foxp3, CTLA4, and GITR showed similar tendencies. Conclusions The decrease of CD25 + CD4 + regulatory T cells in the acute phase might have a role in the development of KD.

SUMMARYTo clarify the functional state of T cells in Kawasaki disease, we analysed mRNA expression levels of Th1/Th2 cytokines (IFN-γ and IL-4) along with Th1/Th2-inducing transcription factors, T-bet and GATA-3, which play pivotal roles in the development of Th1 and Th2 cells, respectively. By real-time PCR, IFN-γ mRNA levels in peripheral blood mononuclear cells (PBMNC) were significantly decreased in Kawasaki disease patients compared with those with measles, and tended to be lower than those in healthy controls. T-bet mRNA levels were significantly decreased in patients with Kawasaki disease compared with healthy controls. In addition, IL-4 and GATA-3 mRNA levels were significantly decreased in Kawasaki disease compared with healthy controls. Regulatory cytokine mRNA levels (TGF-β and IL-10) were also decreased in Kawasaki disease. The mRNA levels of IFN-γ showed a significant positive correlation with those of T-bet in Kawasaki disease. These results suggest that the suppressed function of Th1 and Th2, associated with the suppression of both T-bet and GATA-3 gene expression, may be one of the immunological characteristics of Kawasaki disease.

We investigated the possible use of serum hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels as a predictive indicator for the occurrence of coronary artery lesions (CAL) in Kawasaki disease (KD). Serum HGF and VEGF levels were measured by enzyme-linked immunosorbent assay in 41 patients with KD and 25 afebrile controls. Serum HGF levels of patients in the acute phase of KD were significantly higher than those of afebrile controls (Pc

We investigated serum vascular endothelial growth factor (SVEGF) levels in Kawasaki disease and determined whether these levels had any association with the development of coronary artery lesions. We measured SVEGF levels in 66 patients with Kawasaki disease, 18 patients with active infections and 18 afebrile controls. SVEGF levels of patients in the acute phase of Kawasaki disease (0.0-2003.6 pg/ml, median 59.87 pg/ml) were significantly higher than those of patients with active infections (0.0-45.2 pg/ml, median 8.10 pg/ml; P0.05) or afebrile controls (0.0-49.8 pg/ml, median 7.75 pg/ml; P0.05) and decreased to undetectable or low levels in the recovery phase (n = 31, acute phase: 0.0-2003.6 pg/ml, median 62.50 pg/ml versus recovery phase: 0.0-146.5 pg/ml, median 26.90 pg/ml; P = 0.0007) of the disease. There existed a positive correlation between SVEGF levels and serum C-reactive protein concentrations in the acute phase of Kawasaki disease (rs = 0.347, P = 0.0051). In addition, SVEGF level and duration of fever were found to be major risk factors for the occurrence of coronary artery lesions by univariate (P = 0.012 and P = 0.003, respectively) and multivariate (P = 0.037, OR 6.16 and P = 0.0059, OR 7.59, respectively) analyses.Serum vascular endothelial growth factor level, in combination with persistence of fever, could be a powerful predictor for the development of coronary aneurysms.

To identify cytokine genes uniquely expressed in peripheral blood mononuclear cells (PBMNCs) in the acute phase of Kawasaki disease (KD) with coronary artery lesions (CALs).We screened the mRNA expression levels of PBMNCs from 4 pairs of KD patients with and without CAL using DNA microarray. The result was confirmed by real-time polymerase chain reaction (RT-PCR). The genetic association study was performed to analyze the significance of single nucleotide polymorphisms in the identified gene for the development of CAL in KD patients (184 controls, 144 KD patients with CAL, 64 KD patients without CAL).The microarray analysis showed that tissue inhibitor of metalloproteinases 2 (TIMP2) was expressed at higher levels in PBMNCs of KD patients with CAL than in KD patients without CAL. Quantitative RT-PCR confirmed that the expression levels were significantly higher in the KD patients with CAL than in those without CAL (P.05). Among KD patients, TIMP2 promoter polymorphisms were significantly associated with a risk of CAL (P.01). There was a significant difference in the transcriptional activities between the haplotypes of the TIMP2 promoter polymorphisms by reporter assay using U-937.TIMP2 overexpression and the promoter polymorphisms might play a role in the development of CALs.