T Matsubara

Rady Children's Hospital, San Diego, California, United States

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Publications (154)442.71 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: It has been claimed that the aneurysm rate for Kawasaki disease (KD) patients in Japan is lower than in the U.S. However it has been difficult to compare coronary artery (CA) outcomes between the two countries because of different definitions for CA abnormalities. Therefore, we compared CA internal diameters between Japanese and U.S. KD patients using standard definitions and methods. We retrospectively reviewed CA outcomes in 1082 KD patients from 2 centers in the U.S. and 3 centers in Japan and compared Z-max scores (maximum internal diameter for the left anterior descending or right coronary artery expressed as standard deviation units from the mean (Z-score) normalized for body surface area) obtained within 12weeks after onset and calculated using two different regression equations from Canada (Dallaire) and Japan (Fuse). We defined a Z-max of <2.5 as normal and a Z-max of ≥10 as giant aneurysm. The median Z-max for the U.S. and Japanese subjects was 1.9 and 2.3 SD units, respectively (p<0.001). There was no significant difference in rates of patients with Z-max≥5.0 between the countries. In a multivariable model adjusting for age, sex, and treatment response, being Japanese was still associated with a higher Z-max score. Previously reported differences in aneurysm rates between Japan and the U.S. likely resulted from use of different definitions and nomenclature. Adoption of Z-scores as a standard for reporting CA internal diameters will allow meaningful comparisons among different countries and will facilitate international, collaborative clinical trials.
    International journal of cardiology 07/2013; · 6.18 Impact Factor
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    ABSTRACT: Kawasaki disease (KD) is a self limited vasculitis in which host genetics plays a prominent role. To further the understanding of the role of host genetics in KD, a three-stage genetic study was conducted that began with a family linkage study and ultimately involved more than 3000 individuals to identify new genetic contributions to KD susceptibility. A 26-family linkage study followed by fine mapping was performed in a cohort of 1284 KD subjects and their family members (total 3248 individuals). Suggestive evidence of disease linkage (logarithm of odds (LOD) ≥3.0, p<1.00×10(-4)) was found for five genomic locations (Chr 3q, 4q, 10p, 13q, 21q). Two of these loci (Chr 4q and Chr 13q) overlapped with validated findings from a recent KD genome-wide association study. Fine mapping analysis revealed three single nucleotide polymorphisms (SNPs) in ATP-binding cassette, subfamily C, member 4 (ABCC4) underlying the Chr 13q linkage peak showing evidence of association to KD (lowest p=8.82×10(-5); combined OR 2.00, 95% CI 1.41 to 2.83). ABCC4 is a multifunctional cyclic nucleotide transporter that stimulates the migratory capacity of dendritic cells. It is also a mediator of prostaglandin efflux from human cells and is inhibited by non-steroidal anti-inflammatory medications such as aspirin. These genetic data suggest that ABCC4 could play a fundamental role in KD pathogenesis with effects on immune activation and vascular response to injury.
    Journal of Medical Genetics 07/2011; 48(7):467-72. · 5.70 Impact Factor
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    ABSTRACT: Aneurysms of the vascular wall represent a final common pathway for a number of inflammatory processes, including atherosclerosis and idiopathic vasculitis syndromes. Kawasaki disease (KD) is an acute, self-limited vasculitis in children and the leading cause of acquired coronary artery aneurysms. We sought to identify shared molecular mechanisms of aneurysm formation by genotyping eight polymorphisms in matrix metalloproteinase (MMP)-1, 3, 7, 12 and 13 in the gene cluster on Chr.11q22, whose gene products have been implicated in aneurysm formation or are known to have elastase activity. We genotyped 482 US-UK KD patients (aneurysm+: n=111, aneurysm-: n=371) and tested our findings in an independent cohort of 200 Japanese KD patients (aneurysm+: n=58, aneurysm-: n=142). Analysis of the five MMP genes identified modest trends in allele and genotype frequencies for MMP-3 rs3025058 (-/T) and haplotypes containing MMP-3 rs3025058 (-/T) and MMP-12 rs2276109 (A/G) (nominal P=2 to 4 × 10(-5)) that conferred increased risk of aneurysm formation in US-UK subjects. This finding was validated in Japanese subjects and suggests the importance of this locus in aneurysm formation in children with KD. The region encompassing these risk haplotypes is a prime candidate for resequencing to look for rare genetic variation that may influence aneurysm formation.
    Journal of Human Genetics 12/2010; 55(12):779-84. · 2.53 Impact Factor
  • PLoS ONE 01/2010; 5(7). · 3.53 Impact Factor
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    ABSTRACT: The etiology of Kawasaki Disease (KD) is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5) and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL) and response to intravenous immunoglobulin (IVIG) in Japanese children, who have the highest incidence of KD, is unknown. We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., four copies) was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR)=2.25, p=0.004 and OR=6.26, p=0.089, respectively). Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR=0.21, p=0.026) and CAL development (OR=0.44, p=0.071). The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.
    PLoS ONE 01/2010; 5(7):e11458. · 3.53 Impact Factor
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    ABSTRACT: The purpose of this study was to clarify whether inhaled corticosteroids (ICSs) increased the infectious load of Chlamydophila pneumoniae and/or Mycoplasma pneumoniae in the respiratory tracts of asthmatic children. We studied a total of 310 outpatients with chronic stable asthma. Real-time polymerase chain reaction (PCR)-positive results for C. pneumoniae were obtained in 21 of 310 (6.8%) throat samples and 21 of 293 (7.2%) nasopharyngeal samples. There was no significant difference in the rate of detection or in the quantity of detection for C. pneumoniae between the ICS group and the non-ICS group, nor were there differences among groups classified by Japanese pediatric guidelines (JPGL) severity criteria. Real-time PCR-positive results for M. pneumoniae were obtained in 60 of 310 (19.4%) throat samples and 49 of 293 (16.7%) nasopharyngeal samples. There was no significant difference in the rate of detection or the quantity of detection between the ICS group and the non-ICS group, nor were there differences among age groups. The results of this research do not support the hypothesis that ICSs influence the infectious load of C. pneumoniae and M. pneumoniae. ICSs did not increase C. pneumoniae or M. pneumoniae infection in the upper respiratory tract, in contrast to the effect of ICSs in causing oral candidiasis. Our data exclude the concern that there is an increase in C. pneumoniae and M. pneumoniae infections due to ICS use, the use of ICSs being the gold standard in the long-term anti-inflammatory treatment of persistent asthma in children and adults.
    Journal of Infection and Chemotherapy 05/2009; 15(2):99-103. · 1.55 Impact Factor
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    ABSTRACT: 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). 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. 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. 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.
    Pediatrics International 04/2009; 51(5):657-60. · 0.88 Impact Factor
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    ABSTRACT: 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. 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-kappaB (NF-kappaB) by leukotriene (LT) D(4) and LTC(4) 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-kappaB and pranlukast as a CysLT1 receptor antagonist on induction of MCP-1 production by LTD(4) and LTC(4). LTD(4) and LTC(4) 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-kappaB activation was induced by addition of LTD(4) and LTC(4). Pretreatment with the NF-kappaB inhibitors caffeic acid phenylethyl ester and MG-132 inhibited MCP-1 production by CysLTs. Pranlukast inhibited phosphorylation of ERK1/2 and JNK, NF-kappaB activation, and the MCP-1 production induced by CysLTs. CysLTs induce MCP-1 and this induction is mediated by ERK1/2 and JNK in MAPK, and NF-kappaB pathways via the CysLT1 receptor, for the most part, in human monocytes/macrophages.
    International Archives of Allergy and Immunology 03/2009; 149(3):275-82. · 2.25 Impact Factor
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    ABSTRACT: We describe a case of inflammatory myofibroblastic tumor (IMT) that occurred in the retroperitoneum. The patient manifested systemic symptoms, such as intermittent fever, anemia, thrombocytosis, and hypergammaglobulinemia. In order to elucidate the mechanism of intermittent fever in IMT, we analyzed nuclear factor-kappa B (NF-kappaB) activation in peripheral blood mononuclear cells (PBMCs) using flow cytometry, and serum cytokine levels. NF-kappaB activation was observed in the peripheral blood T cells and monocytes/macrophages. Among the measured cytokines, only interleukin (IL)-6 levels were elevated. IL-6 levels during pyrexia in the afternoon were higher than those during apyrexia in the morning. In contrast to IL-6, NF-kappaB activation in PBMCs was lower during pyrexia than during apyrexia; this is considered to be because the activation is subject to negative feedback. The time lag between the increase of IL-6 in the serum and NF-kappaB activation in the PBMCs at the onset of intermittent fever in IMT may provide further insight into the role of cytokines and NF-kappaB activation in febrile inflammatory diseases.
    Cytokine 11/2008; 44(2):293-7. · 2.52 Impact Factor
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    ABSTRACT: Enterohemorrhagic Escherichia coli (EHEC) induces hemorrhagic colitis and hemolytic uremic syndrome (HUS). Morbidity and mortality are increased in HUS patients with neurologic complications. To determine the pathogenesis of the central nervous system (CNS) involvement in HUS by EHEC, we determined the serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1), IL-10, interferon-gamma (IFN-gamma), IL-2, IL-4, soluble E-selectin (sE-selectin), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) during the acute stage in children with HUS with or without CNS involvement. Serum concentrations of IL-6, IL-10, sTNFR1, sE-selectin, MMP-9, and TIMP-1, but not TNF-alpha, IFN-gamma, IL-2, or IL-4, were significantly higher in patients with HUS with encephalopathy compared with controls. Serum IL-6, sTNFR1 and TIMP-1 concentrations were significantly higher in patients with HUS with encephalopathy compared with those with HUS without encephalopathy (P=0.031, P=0.005, and P=0.007, respectively) and those with acute colitis without HUS (P=0.011, P<0.001, and P=0.005, respectively). There were no significant differences in hemoglobin, platelet counts, leukocyte counts, or serum concentrations of IL-10, sE-selectin, MMP-9, aspartate aminotransferase, lactate dehydrogenase, blood urea nitrogen, creatinine, or C-reactive protein between the HUS patients with and without encephalopathy. Our preliminary study suggests that serum IL-6, sTNFR1 and TIMP-1 levels, particularly sTNFR1 and TIMP-1, are important for predicting neurological complications in patients with HUS.
    Journal of Neuroimmunology 06/2008; 196(1-2):147-52. · 3.03 Impact Factor
  • Susumu Furukawa, Tomoyo Matsubara, Takashi Ichiyama
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    ABSTRACT: Kawasaki disease (KD) is one of the cytokine-associated diseases, which is systemic inflammatory response syndrome. Tumor necrosis factor-alpha(TNF-alpha), as proinflammatory cytokine, plays an important role in the vascular injury of KD. Nuclear factor kappa B (NF-kappaB) is a pivotal transcription factor for genes that encode the proinflammatory cytokines, chemokines and adhesion molecules that mediate inflammation. We have already reported the activation of NF-kappaB in peripheral blood mononuclear cells with the dominant of monocytes/macrophages. There is ample evidence of a central role of peripheral blood monocytes/macrophages during acute KD. The standard therapy of KD is intravenous immunoglobulin (IVIG). According to circumstances, corticosteroid has been used to treat the KD patients. Recently, it has been reported that new biologic therapy, such as anti-TNF agents are useful for the patients who failed to respond to an initial IVIG. We focus on the different mechanism of IVIG, corticosteroid and anti-TNF agents with regard to the anti-inflammatory effects.
    Nippon rinsho. Japanese journal of clinical medicine 03/2008; 66(2):258-64.
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    ABSTRACT: It is known that the use of adjunctive dexamethasone in bacterial meningitis reduces audiologic and neurologic sequelae. The cerebrospinal fluid (CSF) level of soluble tumor necrosis factor 1 (sTNFR1) is an important indicator of neurologic sequelae in bacterial meningitis. We measured the CSF levels of IL-6 and sTNFR1 before administration of antibiotics (CSF1) and 1-3 days after administration of antibiotics (CSF2) in nine patients with bacterial meningitis who received dexamethasone sodium and five without dexamethasone. The CSF2 IL-6 levels of patients with/without dexamethasone were significantly lower than for CSF1 IL-6 levels (p = 0.0077, and p = 0.0431, respectively). There were no significant differences of the ratio of CSF2/CSF1 IL-6 levels between patients with dexamethasone and those without dexamethasone. CSF2 sTNFR1 levels of patients with dexamethasone were significantly lower than for CSF1 sTNFR1 levels (p = 0.0208). However, CSF2 sTNFR1 levels of patients without dexamethasone were significantly higher than for CSF1 sTNFR1 levels (p = 0.0422). The ratio of CSF2/CSF1 sTNFR1 levels of patients with dexamethasone was significantly lower than that without dexamethasone (p = 0.0063). Our present study suggests that dexamethasone inhibits increase of CSF sTNFR1 levels after antibiotics therapy in bacterial meningitis.
    Brain and Development 03/2008; 30(2):95-9. · 1.67 Impact Factor
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    ABSTRACT: To determine the activation of nuclear factor-[kappa]B in peripheral blood CD14+ monocyte/macrophages and CD3+, CD4+, and CD8+ T cells in children with sepsis. Observational study. University hospital. Twenty-six children with sepsis (nine females and 17 males, aged between 10 days and 15 yrs; median, 4.3 yrs) on admission to our hospital between August 1999 and November 2005. None. The percentages of peripheral blood CD14+ monocyte/macrophages and CD3+, CD4+, and CD8+ T cells exhibiting nuclear factor-[kappa]B activity were determined by flow cytometry. In addition, relationships among the degree to which nuclear factor-[kappa]B was activated, serum levels of cytokines (interferon-[gamma], tumor necrosis factor-[alpha], interleukin-2, interleukin-4, interleukin-6, and interleukin-10), and clinical variables were analyzed. The percentage of cells exhibiting nuclear factor-[kappa]B activity was increased among CD14+, CD3+, CD4+, and CD8+ cells in the sepsis group and was significantly higher among CD14+, CD3+, and CD4+ cells of the patients with severe sepsis (n = 9) than those of patients with nonsevere sepsis (n = 17). The percentage of cells exhibiting nuclear factor-[kappa]B activity was significantly higher among CD14+ cells than CD3+ cells in the patients with severe sepsis. In addition, this percentage was significantly higher among CD14+ cells than CD3+, CD4+, and CD8+ cells in septic patients who had positive blood cultures (n = 16). Serum interleukin-6 levels were correlated with the percentages of CD14+, CD3+, CD4+, and CD8+ cells exhibiting nuclear factor-[kappa]B activity, and serum IL-10 levels were correlated with the percentages of CD14+, CD3+, and CD4+ cells exhibiting nuclear factor-[kappa]B activity. Nuclear factor-[kappa]B in peripheral blood mononuclear cells was activated in children with sepsis and was related the severity of sepsis.
    Critical Care Medicine 11/2007; 35(10):2395-401. · 6.12 Impact Factor
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    ABSTRACT: Matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) play important roles in the function of the blood-brain barrier. Serum MMP-9 and TIMP-1 concentrations were determined in influenza virus infection with or without neurologic complications. Our results suggest that an imbalance between MMP-9 and TIMP-1 damages the blood-brain barrier and promotes febrile seizure or encephalopathy in influenza virus infection.
    The Pediatric Infectious Disease Journal 07/2007; 26(6):542-4. · 3.57 Impact Factor
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    ABSTRACT: Matrix metalloproteinase-9 (MMP-9) is an important enzyme responsible for airway remodelling. Monocytes/macrophages have a cysteinyl leukotriene 1 (cysLT1) receptor, but its function is poorly understood. To elucidate the function of the cysLT1 receptor of human monocytes/macrophages in MMP-9 production. We examined the effect of cysLTs (LTC4, -D4 and -E4) on TNF-alpha-induced MMP-9 production in THP-1 cells, a human monocytic leukaemia cell line and peripheral blood CD14+ monocytes/macrophages. In addition, we examined the effect of pranlukast, a cysLT1 receptor antagonist, on the enhancement of TNF-alpha-induced MMP-9 production by cysLTs. ELISA revealed that LTC4 and -D4, but not -E4, enhanced TNF-alpha-induced MMP-9 production in THP-1 cells and peripheral blood CD14+ monocytes/macrophages. Real-time polymerase chain reaction demonstrated that LTC4 and -D4, but not -E4, increased MMP-9 mRNA expression induced by TNF-alpha in THP-1 cells. Moreover, we demonstrated that pranlukast completely inhibited the enhancement of TNF-alpha-induced MMP-9 production by LTC4 and -D4 in THP-1 cells and peripheral blood CD14+ monocytes/macrophages. LTC4 and -D4 enhanced the TNF-alpha-induced MMP-9 production via binding the cysLT1 receptor in human monocytes/macrophages. Pranlukast inhibited the enhancements by LTC4 and D4.
    Clinical & Experimental Allergy 05/2007; 37(4):608-14. · 4.79 Impact Factor
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    ABSTRACT: The hygiene hypothesis proposes an association between the change in exposure to microbes and the increased incidence of atopic disease. The purpose of the present study was to perform a prospective epidemiological study of the effect of perinatal infection on the development of allergy. Eight hundred and ten children were born at Umeda Gynecological Hospital in Yamaguchi prefecture in Japan between April 1997 and March 1998. A questionnaire survey on the development of allergic diseases was sent by mail in 2002. The presence or absence of neonatal infectious disease (clinical sepsis) and maternal complications during the gestational period and delivery, and the incidence of bacterial infection during the perinatal period, were investigated by examining hospital records. Data were obtained for 410 children (51%). One hundred and forty-eight children (36.1%) developed allergic diseases. Among children whose mothers had allergies, the percentage of children who developed allergic disease(s) was significantly lower in children who had had clinical sepsis in the neonatal period than in those without clinical sepsis (26.1% vs 49.7%, P < 0.03). Clinical sepsis in neonates might reduce the risk of developing allergic diseases in early childhood in children whose mothers have allergies.
    Pediatrics International 03/2007; 49(1):15-8. · 0.88 Impact Factor
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    ABSTRACT: High-dose intravenous immunoglobulin (IVIG) is a well-established standard therapy for Kawasaki disease (KD) that reduces the risk of developing coronary artery aneurysms. On the other hand, some reports have recommended an alternative therapy with steroids for KD patients. In this study we investigated the anti-inflammatory effect of IVIG in comparison with dexamethasone at clinical doses in vitro. High-dose IVIG inhibited tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappaB (NF-kappaB) to a greater degree than dexamethasone in human monocytic U937 cells and human coronary arterial endothelial cells (HCAEC), but not in human T lymphocytic Jurkat cells. IVIG was more potent than dexamethasone in reducing the expression of CD16 (FcgammaRIII) in human monocytic THP-1 cells stimulated with lipopolysaccharide and in Jurkat cells stimulated with dimethyl sulfoxide. In HCAEC exposed to TNF-alpha, IVIG and dexamethasone inhibited interleukin-6 production to a similar degree, whereas the expression of E-selectin was inhibited more strongly by IVIG. Our results show that high-dose IVIG inhibits the activation of monocytes/macrophages and coronary arterial endothelial cells more strongly than that of T cells, whereas dexamethasone inhibits the activation of all three cell types. These findings suggest that IVIG or dexamethasone therapy should be chosen to match the types of cells that are activated during acute KD.
    Archiv für Experimentelle Pathologie und Pharmakologie 09/2006; 373(5):325-32. · 2.15 Impact Factor
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    ABSTRACT: In this report we describe a case of severe chronic infantile neurologic, cutaneous, articular (CINCA) syndrome with a novel G307V cryopyrin mutation and all of the characteristic clinical and laboratory features of this autoinflammatory disease. There was no clear response to standard therapies, including human interleukin-1 (IL-1) receptor antagonist (anakinra) and soluble tumor necrosis factor receptor (etanercept). The patient finally had a partial clinical response (reduction in fever and irritability) and complete laboratory response (improved C-reactive protein and serum amyloid A levels) to humanized anti-IL-6 receptor antibody (MRA), but died from congestive heart failure and interstitial pneumonia 2 months after initiation of therapy. We serially measured the serum cytokine levels and expression of NF-kappaB activation in the patient's peripheral blood mononuclear cells before and during consecutive therapies. Pathologic examination of autopsy specimens was also performed. This case illustrates the continued difficulty in management of patients with CINCA syndrome and the complexity of the inflammatory pathways in this disorder.
    Arthritis & Rheumatology 08/2006; 54(7):2314-20. · 7.48 Impact Factor
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    ABSTRACT: In multiple sclerosis, there have been many reports on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). However, MMPs and TIMPs have not been reported in acute disseminated encephalomyelitis (ADEM). We determined the relationship between the serum concentrations of MMP-9 and TIMP-1 and activity of lesions on MRI in 14 patients with ADEM to investigate the roles of MMP-9 and TIMP-1 in the pathogenesis of ADEM. Serum MMP-9 and TIMP-1 levels, measured by ELISA and gadolinium-enhanced (Gd+) brain MRI, were analyzed. Serum MMP-9 and TIMP-1 levels at the acute stage were higher than controls, and the serum MMP-9 levels at the acute stage were higher than those at the convalescent stage in ADEM. In seven patients with Gd+ lesions on brain MRI, serum MMP-9 levels and the MMP-9/TIMP-1 ratio at the acute stage were higher than those at the convalescent stage, and serum TIMP1 levels at the acute stage were lower than those at the convalescent stage. In seven patients without Gd+ lesions on brain MRI, serum TIMP-1 levels at the acute stage were higher than those at the convalescent stage. We speculated that MMP-9 is related to lesion formation at the early stage in ADEM and that TIMP-1 is induced to modulate MMP-9 activity. These findings suggest that MMP-9 and TIMP-1 secondarily play some roles in the inflammatory cascade of ADEM.
    Journal of Neuroimmunology 04/2006; 172(1-2):182-6. · 3.03 Impact Factor
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    ABSTRACT: CD40 ligand (CD40L) is mainly expressed on activated platelets and CD4+T cells, and it can be cleaved from the cell surface, releasing a soluble CD40L (sCD40L). Most sCD40L is derived from activated platelets. A previous paper revealed that the platelet number of patients with influenza virus-associated encephalopathy (IE) was correlated with the outcome. We determined the utility of sCD40L as a predictor for the prognosis of IE. We measured the serum concentration of sCD40L and the platelet number on the day of hospitalization in 34 patients with IE, 16 with influenza virus-associated febrile seizures (IFS), 19 with influenza virus infection without complications (Flu), and 7 with Epstein-Barr virus (EBV) infection. The serum sCD40L concentrations in IE and IFS were significantly lower than those in controls, Flu, and EBV infections. Serum sCD40L concentrations in the IE group were 0.70+/-0.43 ng/ml for deceased patients, 1.73+/-1.36 ng/ml for those with sequelae, and 3.85+/-2.91 ng/ml for those without sequelae. There was no significant difference in platelet number between IE patients with and without sequelae, while the platelet number of deceased patients with IE was significantly lower than in controls, Flu, and IFS. Serum sCD40L concentration on the day of hospitalization was more correlated with the outcome of IE than platelet number. Our findings suggest that the serum sCD40L concentration during acute IE is important for predicting the prognosis at an early stage.
    Journal of the Neurological Sciences 01/2006; 239(1):53-7. · 2.24 Impact Factor

Publication Stats

2k Citations
442.71 Total Impact Points


  • 2013
    • Rady Children's Hospital
      San Diego, California, United States
  • 2011
    • Genome Institute of Singapore
      Tumasik, Singapore
  • 2010
    • University of Texas Health Science Center at San Antonio
      San Antonio, Texas, United States
  • 1996–2010
    • University of California, San Diego
      • Department of Medicine
      San Diego, California, United States
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 1998–2008
    • Yamaguchi University
      • Division of Pediatrics
      Yamaguti, Yamaguchi, Japan
  • 2004
    • National Hospital Organization Sagamihara Hospital
      Sagamihara, Kanagawa, Japan
  • 2001
    • University of Tennessee
      • Department of Pediatrics
      Knoxville, TN, United States
  • 1981–2001
    • Nagoya University
      • Division of of Internal Medicine
      Nagoya-shi, Aichi-ken, Japan
  • 2000
    • University of Texas Southwestern Medical Center
      • Department of Physiology
      Dallas, TX, United States
  • 1988–1997
    • Juntendo University
      • Department of Paediatrics
      Tokyo, Tokyo-to, Japan