Keiko Nomoto

Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone.

Intravenous immunoglobulin (IVIG) treatment-resistant patients are high risk of developing coronary artery lesions with Kawasaki disease. The IVIG-responsive (Group A; n = 6) and IVIG-resistant patients (Group B) were predicted before starting the initial treatment using the Egami scoring system and randomly allocated as a single-IVIG treatment group (group B1; n = 6) or as a IVIG-plus-methylprednisolone (IVMP) combined therapy group (group B2; n = 5). We investigated the transcript abundance in the leukocytes of those patients using a microarray analysis. Five patients in group A and one patient in group B1 responded to initial IVIG treatment. All group B2 patients responded to IVIG-plus-IVMP combined therapy. Before performing these treatments, those transcripts related to IVIG resistance and to the development of coronary artery lesions, such as IL1R, IL18R, oncostatin M, suppressor of cytokine signaling-3, S100A12 protein, carcinoembryonic antigen-related cell adhesion molecule-1, matrix metallopeptidase-9, and polycythemia rubra vera-1, were more abundant in group B patients in comparison with group A patients. Moreover, those transcripts in group B2 patients were more profoundly and broadly suppressed than group B1 patients after treatment. This study elucidated the molecular mechanism of the effectiveness of IVIG-plus-IVMP combined therapy.

Effect of coenzyme Q10 on superoxide production in rats with reperfusion injuries.

We examined the effect of coenzyme Q10 (Co Q10) on superoxide radical (O2-) production in a model of rat reperfusion injury. The chemiluminescence method using a derivative of luciferin was used to quantify O2- production by erythrocytes in the reperfused limb after a period of ischaemia. A total of 20 limbs from Lewis rats were preserved at 4 degrees C in Euro-Collins solution for 72 hours, and were grafted orthotopically to syngeneic rats by a microsurgical technique. In the treated group (n = 10), Co Q10 (10 mg/kg) was injected intraperitoneally into the recipients one hour before reperfusion. In the control group (n = 10), the same dose of solvent was given. To measure the extent of oxidative stress, heparinised blood from the treated and control recipients was collected before, and at 15, 30, and 60 minutes after reperfusion for the measurement of chemiluminescence. O2- production in the Co Q10-treated group was significantly lower than in the control group (p < 0.05). Although these findings suggest that Co Q10 scavenged O2- that was produced in the replanted limbs as a result of ischaemia-reperfusion injury, we should consider other possible mechanisms by which this agent may protect against ischaemia-induced reperfusion injury.

Transcriptional regulation by infliximab therapy in Kawasaki disease patients with immunoglobulin resistance.

Background:Infliximab (IFX), a known monoclonal antibody against tumor necrosis factor-α (TNF-α), is used to treat Kawasaki disease (KD) patients with intravenous immunoglobulin (IVIG) resistance. The transcriptional modulation of inflammation following IFX therapy has not been reported in KD patients.Methods:We investigated the transcript abundance profiles in whole blood obtained from eight IVIG-resistant KD subjects treated with IFX therapy using microarray platforms and compared them with those in initially IVIG-responsive subjects. A pathway analysis was performed using WikiPathways to search for the biological pathways of the transcript profiles. Four transcripts changed by IFX therapy were subsequently validated using quantitative real-time polymerase chain reaction.Results:The pathway analysis showed the reduced abundance of transcripts in the nucleotide-binding oligomerization domain, matrix metalloproteinase (MMP), and inflammatory cytokine pathways and the increased abundance of transcripts in the T-cell receptor, apoptosis, TGF-β, and interleukin-2 pathways. Additionally, the levels of four transcripts (peptidase inhibitor-3, MMP-8, chemokine receptor-2, and pentraxin-3) related to KD vasculitis and IVIG resistance decreased after IFX therapy.Conclusion:The administration of IFX was associated with both the signaling pathways of KD inflammation and several transcripts related to IVIG resistance factors. These findings provide strong theoretical support for the use of IFX in KD patients with IVIG resistance.Pediatric Research (2014); 76 3, 287–293. doi:10.1038/pr.2014.92

Slowly progressing form of type 1 diabetes mellitus in children: genetic analysis compared with other forms of diabetes mellitus in Japanese children

Abstract:  Aims:  Slowly progressing insulin‐dependent diabetes mellitus (SPIDDM, hereafter referred to as IDDMS in this article) is a unique subtype of type 1 diabetes in Japanese children. To clarify the genetic background of IDDMS, we analyzed HLA‐DRB1, ‐DQB1 and ‐DQA1 alleles, phenotypes, and genotypes and compared them with acute‐onset type 1 diabetes, non‐insulin‐dependent diabetes mellitus (NIDDM), and control subjects.

Nitric oxide metabolite in pregnant women before and after delivery

Background. During pregnancy, systemic vascular resistance as well as vascular sensitivity to vasoconstrictive agents decreases in pregnant women. Methods and materials. The vascular resistance of the fetus is also maintained in the presence of low blood pressure. We believe that the main factors in this phenomenon are nitric oxide (NO), along with prostaglandin. NO is an unstable compound with a short half‐life; it is easily converted to nitrite (NO2) and nitrate (NO3). Since NO cannot be precisely quantified, we measured the NO2 concentration in maternal blood just before and after delivery and compared it with the values of non‐pregnant women. Results. NO2. concentrations in the 13 women who received cesarean deliveries under epidural anesthesia were not significantly changed by the anesthesia. Before anesthesia the NO2 concentration was 216 ± 115 pmol/mg protein, and after the induction of anesthesia, but before surgery, it was 218 ± 112 pmol/mg protein. The NO2 concentration then fell significantly after the surgery to 174 ± 75 pmol/mg protein (P < 0.05). In addition, after vaginal delivery, in 17 other patients we observed marked decreases in NO2 concentration, falling from 160 ± 82 to 125 ± 61 pmol/mg protein (p < 0.05). These values were significantly higher than those of nonpregnant women (3.4 ± 2.1 μM. 33 ± 22 pmol/mg protein) (p < 0.000I) Conclusion. These results suggest that NO contributes to the low vascular resistance observed in the mother and fetus during pregnancy.

Identification of nonsynonymous polymorphisms in the superantigen-coding region of IDDMK1,222 and a pilot study on the association between IDDMK1,222 and type 1 diabetes

AbstractTo investigate the possible involvement of IDDMK1,222/HERV-K18 in childhood type 1 diabetes mellitus, we identified two nonsynonymous A/G polymorphisms in the superantigen-coding region of IDDMK1,222 at the 290- and 461-nucleotide (nt) positions from the initial methionine codon and compared their frequencies in 74 Japanese patients with type 1 diabetes and in 54 nondiabetic controls. Although the G substitution was observed more frequently at either site in the patients than it was in the controls (7% vs. 4% at 290 nt, and 29% vs. 20% at 461 nt), the differences were not statistically significant. A weak significance of difference in the frequency of 461G was obtained only in an early-onset group of patients manifesting the disease at 5 years of age or less (n = 24) when compared with controls (38% vs. 20%; P = 0.03). However, in addition to the common absence of a particular allele among the expected four alleles, remarkable differences in allele frequencies were present between Japanese and European populations. This first trial investigating the association of IDDMK1,222 with type 1 diabetes presents intriguing suggestions for the role of this region in the etiology of autoimmune and infectious diseases.

Autogenous production of hydroxyl radicals from thiopental

It is generally believed that barbiturates can protect neural tissues from the damage induced by cerebral hypoxia. One of the mechanisms for protecting neurons is through the inhibition of lipid peroxidation (LPO). We therefore examined LPO in rat brain, liver and kidney by measuring the accumulation of thiobarbituric acid‐reactive substances (TBAR) after thiopental administration under 21% O2. We also designed an in vitro study to gain insight into free radical generation leading to the formation of LPO from thiopental by electron spin resonance (ESR). An accumulation of TBAR in the rat liver was observed after the administration of a large dose of thiopental (70 mg/kg intraperitoneally). However, no change in LPO in the brain and kidney was observed. In the in vitro study, thiopental could scavenge superoxide (O2‐) radicals, while it spontaneously generated hydroxyl radicals (·OH) in solution. We conclude that thiopental can scavenge O2‐, while producing ·OH, subsequently resulting in membrane lipid peroxidation under physiologic O2 conditions. This formation of ·OH may damage cell membrane lipids.

Changes in Neonatal Microbiota Distribution Influenced by the Environment of the Neonatal Intensive Care Unit in the First Month of Life

Commensal bacterial colonization is crucial for human health, and the early neonatal period is important for the establishment of microbial populations. However, studies on the developmental patterns of microbiota in early life, particularly in those exposed to the environment of the neonatal intensive care unit (NICU), are limited. Using a 16S ribosomal RNA polymerase chain reaction assay, this study aimed to evaluate the changes in the levels of representative microbiota in healthy term infants and infants who were admitted to the NICU during the first month of life. Compared with term infants, the NICU group showed lower levels of Bifidobacterium in the early days after birth but achieved the same levels as those of term infants after day 30 of probiotics use. In addition, we found that the presence of Staphylococcus aureus, including methicillin-resistant S. aureus, from fecal samples was not associated with disturbances in Bifidobacterium during the neonatal period. Clinical factors such as the mode of delivery, antibiotic therapy, and intubation for mechanical ventilation could change the neonatal distribution of microbiota, but the most important factor was insufficient enteral nutrition. This group, which had experienced poor general conditions and/or underwent surgery early in the neonatal period, showed are markable decrease in Bifidobacterium level at day 30. In conclusion, infants in the NICU developed similar microbiota composition as in the healthy term infants group in 1 month afterbirth; however, insufficient enteral nutrition could lead to disintegration of the microbiota distribution.

Timing of Haemophilus influenzae type b vaccination after cardiac surgery

The best time for vaccination in infants with congenital heart disease (CHD) after cardiopulmonary bypass (CPB) surgery is unclear, but it is important to prevent Haemophilus influenzae type b (Hib) infection in infants with CHD after CPB surgery. To identify the best time for Hib vaccination in infants with CHD after CPB surgery, we investigated the immunological status, and the efficacy and safety of Hib vaccination after CPB surgery.

Hemophagocytic lymphohistiocytosis with high serum levels of IL-18 and predominant lymphocyte activation in a neonate born to a mother with adult-onset Still's disease

Please cite this article as: Megumi Hashimoto, Shohei Ogata, Ayano Yamaguchi, Kota Kawada, Manabu Kenmochi, Takasuke Ebato, Keiko Nomoto, Yuki Bando, Saeko Shimodera, Hirofumi Shibata, Shintaro Ono, Manabu Nakayama, Takahiro Yasumi, Masahiro Ishii , Hemophagocytic lymphohistiocytosis with high serum levels of IL-18 and predominant lymphocyte activation in a neonate born to a mother with adult-onset Stills disease. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Yclim(2017), doi: 10.1016/j.clim.2017.04.007