Necrotic Change of Tunica Media Plays a Key Role in the Development of Coronary Artery Lesions in Kawasaki Disease.

Background: Alarmins resulting from cell death or oxidative stress are involved in the development of Kawasaki disease (KD) vasculitis. In a previous study, we demonstrated the potential role of interleukin (IL)-33 as an alarmin in the development of KD vasculitis. Although edematous dissociation (necrotic change) of the tunica media is thought to be a major source of IL-33 in KD vasculitis, it has not yet been elucidated.

Activation of bystander CD8 T cells in a pediatric patient with acute hepatitis E.

Most children with acute hepatitis A virus (HAV) or hepatitis E virus (HEV) infection are asymptomatic. Bystander CD8 T-cell activation has garnered attention owing to its possible pathophysiological role in adult hepatitis. However, no reports have studied it in pediatric hepatitis.

Nanoparticles of folic acid-methyl-β-cyclodextrin (FA-MβCD)/adamantane-albumin exhibit enhanced antitumor activity compared with FA-MβCD alone.

Supramolecular drug carriers are a promising approach for delivering anticancer drugs with high blood retention after administration. We previously synthesized folic acid-modified methyl-β-cyclodextrin (FA-MβCD) as an anticancer drug. FA-MβCD has a selective autophagy-mediated antitumor effect on folic acid receptor (FR)-expressing cancer cells.

Case Report: Changes in Cytokine Kinetics During the Course of Disease in a Japanese Patient With Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that is reportedly linked to coronavirus disease 2019. Affected patients present with gastrointestinal symptoms and cardiovascular dysfunction, in addition to Kawasaki disease-like features, suggesting the potential for overlapping disease mechanisms. Kawasaki disease has been reported among individuals of East Asian ethnicities, whereas there is minimal clinical literature regarding the occurrence of MIS-C among individuals of Asian ethnicities.

A case of autism spectrum disorder with cleft lip and palate carrying a mutation in exon 8 of .

We report a patient with autism and cleft lip and palate carrying a de novo heterozygous mutation, c.1464_1467del ACTC (p.Tyr488*).

HLA-DQ and RBFOX1 as susceptibility genes for an outbreak of hydrolyzed wheat allergy.

Background: Food allergy is a growing health problem worldwide because of its increasing prevalence, life-threatening potential, and shortage of effective preventive treatments. In an outbreak of wheat allergy in Japan, thousands of patients had allergic reactions to wheat after using soap containing hydrolyzed wheat protein (HWP).

Objectives: The aim of the present study was to investigate genetic variation that can contribute to susceptibility to HWP allergy.

A novel missense mutation identified in a patient with macrocephaly and developmental delay.

Phosphatase and tensin homolog (PTEN) plays an important role in tumor suppression. A germline mutation in the gene induces not only PTEN hamartoma tumor syndrome, including Cowden syndrome, but also macrocephaly/autism syndrome. Here, we describe a boy with macrocephaly/autism syndrome harboring a novel missense heterozygous mutation, c.

Hepatitis B Surface Antibody Titers at One and Two Years after Hepatitis B Virus Vaccination in Healthy Young Japanese Adults.

Objective Since healthcare providers face an increased risk of hepatitis B virus (HBV) infection because of their work, vaccination plays a critical role in preventing HBV transmission. However, the duration for which acquired HBV surface antibodies (anti-HBs) persist remains unknown. To evaluate the primary immunologic response to HBV vaccination and its persistence in healthy Japanese adolescents.

Interinstitutional patient transfers between rapid chemotherapy cycles were feasible to utilize proton beam therapy for pediatric Ewing sarcoma family of tumors.

Aim: To assess the feasibility of transferring to the University of Tsukuba Hospital for proton beam therapy (PBT) during intensive chemotherapy in children with Ewing sarcoma family of tumors (ESFT) who had been diagnosed and started their first-line treatment at prefectural or regional centers for pediatric oncology.

Background: The treatment of ESFT relies on a multidisciplinary approach using intensive neoadjuvant and adjuvant chemotherapies with surgery and radiotherapy. Multi-agent chemotherapy comprising vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide (VDC-IE) is widely used for ESFT, and the interval between each course is very important for maintaining the intensity and effect of chemotherapy.

Key HLA-DRB1-DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine.

Approximately 5-10% of individuals who are vaccinated with a hepatitis B (HB) vaccine designed based on the hepatitis B virus (HBV) genotype C fail to acquire protective levels of antibodies. Here, host genetic factors behind low immune response to this HB vaccine were investigated by a genome-wide association study (GWAS) and Human Leukocyte Antigen (HLA) association tests. The GWAS and HLA association tests were carried out using a total of 1,193 Japanese individuals including 107 low responders, 351 intermediate responders, and 735 high responders.

Compound action potential inhibition produced by various antidepressants in the frog sciatic nerve.

Although an inhibition of action potential conduction in nerve fibers possibly contributes to at least a part of antinociception produced by analgesics and the adjuvants, it has not been fully examined yet how the conduction inhibition differs in extent among their drugs. We investigated the effects of various antidepressants used as analgesic adjuvants on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. The results were compared with those of the other adjuvants that were reported previously.

Anti-allergic effects of novel sulfated polysaccharide sacran on mouse model of 2,4-Dinitro-1-fluorobenzene-induced atopic dermatitis.

In this study, in order to investigate the potential of the novel polysaccharide sacran from Aphanothece Sacrum for development of atopic dermatitis (AD), we evaluated the potential of pretreatment with topical sacran to prevent the development of hapten (dinitrofluorobenzene: DNFB)-induced AD-like disease in mice. In the AD model mice, sacran markedly ameliorated AD symptoms such as scratching behavior and edema in ear. In addition, sacran significantly increased water content of the stratum corneum which regulates the skin barrier function.

Preaxial polydactyly in an individual with Wiedemann-Steiner syndrome caused by a novel nonsense mutation in KMT2A.

Wiedemann-Steiner syndrome (WDSTS) is an autosomal dominant disorder characterized by hypertrichosis, intellectual disability, and dysmorphic facial appearances (down-slanted vertically narrow palpebral fissures, wide nasal bridge, broad nasal tip, and thick eyebrows). In 2012, Jones and co-workers identified heterozygous mutations in KMT2A (lysine methyltransferase 2A) as the molecular cause of WDSTS. Although the phenotype of this syndrome continues to expand, the associated features are not fully understood.

A novel mutation identified in a patient with Bardet-Biedl syndrome with a violent emotional outbreak.

We report a 10-year-old girl with Bardet-Biedl syndrome caused by a novel mutation in the () gene. She had multiple malformations, including a dysmorphic face, postaxial polydactyly, polycystic kidney and amblyopia. She presented with typical BBS features, including intellectual disability with emotional outbursts and mild obesity.

Association of Japanese cedar pollinosis and sensitization with HLA-DPB1 in the Japanese adolescent.

Background: Allergic rhinitis (AR) is a heterogeneous disorder that significantly affects daily activity, work productivity, sleep, learning, and quality of life in all generations. Japanese cedar (JC) pollen is the most common allergen responsible for the development of AR in Japan. AR caused by JC pollen is considered to be a multifactorial inheritance disease that is caused by both environmental and genetic factors.

Effects of vaccine-acquired polyclonal anti-HBs antibodies on the prevention of HBV infection of non-vaccine genotypes.

Background: In universal hepatitis B (HB) vaccination, single vaccine-derived polyclonal anti-HBs antibodies (anti-HBs) need to inhibit infection of HB viruses (HBV) of non-vaccine genotypes. We experimentally addressed this issue.

Methods: Anti-HBs-positive sera were obtained by vaccination with genotype A- or C-derived HBs antigen (HBsAg, gtA-sera or gtC-sera).

Identification of amino acids in antigen-binding site of class II HLA proteins independently associated with hepatitis B vaccine response.

Background & Aims: Genetic factors in class II human leukocyte antigen (HLA) have been reported to be associated with inter-individual variation in hepatitis B virus (HBV) vaccine response. However, the mechanism underlying the associations remains elusive. In particular, the broad linkage disequilibrium in HLA region complicates the localization of the independent effects of genetic variants.

Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age.

The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth.

Tailor-made treatment combined with proton beam therapy for children with genitourinary/pelvic rhabdomyosarcoma.

Background: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas among children. Patients who developed genitourinary/pelvic rhabdomyosarcoma (GU/P-RMS) have a higher complication ratio and relatively poorer event free survival, with local therapy being very important. While proton beam therapy (PBT) is expected to reduce co-morbidity, especially for children, this lacks firm evidence and analysis.

Influence of SLCO1B1 polymorphism on maintenance therapy for childhood leukemia.

Background: Management of the adverse effects of chemotherapy is essential to improve outcome of children with leukemia. Some genetic polymorphisms can predict treatment-related toxicity, and be used individually in dose modification of 6-mercaptopurine (6-MP) and methotrexate (MTX) in maintenance therapy for childhood acute lymphoblastic leukemia (ALL). We investigated associations between clinical course and candidate gene polymorphisms less evaluated in Japanese patients.

Imatinib-induced Severe Hepatitis in a 9-Year-old Girl With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia.

Imatinib mesylate has dramatically improved the outcome of children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph* ALL) and is now included as first-line therapy. Uncommon adverse effects of this drug for pediatric use, however, are largely unknown. We report the first case of a 9-year-old child who developed severe acute hepatitis with grade 4 transaminases and bilirubin elevation during imatinib treatment for Ph* ALL.

Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies.

Backgrounds. Outcome of childhood malignancy has been improved mostly due to the advances in diagnostic techniques and treatment strategies. While methotrexate (MTX) related polymorphisms have been under investigation in childhood malignancies, many controversial results have been offered.