Dynamics of scFv-targeted VAP2 correlating with IL-16, MIF and IL-1Ra in ANCA-associated vasculitis.

Background And Hypothesis: Using a mouse model of MPA with microvascular lesion with a clone (VasSF) of recombinant single chain fragments of the variable region of human IgG, we previously showed that vasculitis-associated apolipoprotein A2 (VAP2) may be a therapeutic target for vasculitis. The present study estimated the target molecules for VasSF and the association between VAP2 and cytokine levels in patient sera in terms of microvascular lesion severity.

Methods: Sera and clinical information were collected from patients with microscopic polyangiitis and granulomatosis with polyangiitis (MPA/GPA) and infectious disease.

Enhanced efficacy of the novel recombinant clone VasSF in a mouse model of antineutrophil cytoplasmic antibody-associated vasculitis.

Based on the efficacy of intravenous immunoglobulin (IVIg) for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), we developed a recombinant single-chain-fragment variable clone, VasSF, therapeutic against AAV in a mouse model (SCG/Kj mice). VasSF is thought to bind to vasculitis-associated apolipoprotein A-II (APOA2) as a target molecule. VasSF is a promising new drug against AAV, but difficulties in the yield and purification of VasSF remain unresolved.

Beneficial effects of anti-apolipoprotein A-2 on an animal model for coronary arteritis in Kawasaki disease.

Background: Kawasaki disease (KD) is usually treated with high-dose intravenous immunoglobulin (IVIg) as severe infectious and other diseases. Due to issues that are associated with immunoglobulin preparation, such as the risk of possible contamination by infectious agents and limited blood banking resources, recombinant immunoglobulins are required. We developed a novel recombinant antibody drug candidate, "VasSF," based on the therapeutic effects it exerted on a mouse spontaneous crescentic glomerulonephritis model (SCG/Kj).

Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis.

Background: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a pauci-immune disease with the inflammation of the small blood vessels. The efficacies of antibody drugs for induction therapies of vasculitis vary among cases. Here, we developed a novel clone of a single chain Fv region (ScFv) with vasculitis-specific therapeutic potential.

The Rare Disease Bank of Japan: establishment, current status and future challenges.

Research on rare diseases cannot be performed without appropriate samples from patients with such diseases. Due to the limited number of such patients, securing biosamples of sufficient quality for extensive research is a challenge and represents an important barrier to the advancement of research on rare diseases. To tackle this problem, the Rare Disease Bank (RDB) was established in 2009 at the National Institute of Biomedical Innovation (NIBIO; currently, the National Institutes of Biomedical Innovation, Health and Nutrition in Japan).

Transcriptional Dynamics of Immortalized Human Mesenchymal Stem Cells during Transformation.

Comprehensive analysis of alterations in gene expression along with neoplastic transformation in human cells provides valuable information about the molecular mechanisms underlying transformation. To further address these questions, we performed whole transcriptome analysis to the human mesenchymal stem cell line, UE6E7T-3, which was immortalized with hTERT and human papillomavirus type 16 E6/E7 genes, in association with progress of transformation in these cells. At early stages of culture, UE6E7T-3 cells preferentially lost one copy of chromosome 13, as previously described; in addition, tumor suppressor genes, DNA repair genes, and apoptosis-activating genes were overexpressed.

Finding the factors of reduced genetic diversity on X chromosomes of Macaca fascicularis: male-driven evolution, demography, and natural selection.

The ratio of genetic diversity on X chromosomes relative to autosomes in organisms with XX/XY sex chromosomes could provide fundamental insight into the process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines. The average X/A diversity ratios in these samples was 0.

Correlation of interleukin-6 and monocyte chemotactic protein-1 concentrations with crescent formation and myeloperoxidase-specific anti-neutrophil cytoplasmic antibody titer in SCG/Kj mice by treatment with anti-interleukin-6 receptor antibody or mizoribine.

Myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) and glomerular crescent formation. Pathogenic factors in RPGN were analyzed by using SCG/Kj mice, which spontaneously develop MPO-ANCA-associated RPGN. The serum concentration of soluble IL-6R was determined by using ELISA and those of another 23 cytokines and chemokines by Bio-Plex analysis.

Whole-genome sequencing and analysis of the Malaysian cynomolgus macaque (Macaca fascicularis) genome.

Background: The genetic background of the cynomolgus macaque (Macaca fascicularis) is made complex by the high genetic diversity, population structure, and gene introgression from the closely related rhesus macaque (Macaca mulatta). Herein we report the whole-genome sequence of a Malaysian cynomolgus macaque male with more than 40-fold coverage, which was determined using a resequencing method based on the Indian rhesus macaque genome.

Results: We identified approximately 9.

Ancient genome-wide admixture extends beyond the current hybrid zone between Macaca fascicularis and M. mulatta.

Macaca fascicularis and Macaca mulatta are two of the most commonly used laboratory macaques, yet their genetic differences at a genome-wide level remain unclear. We analysed the multilocus DNA sequence data of 54 autosomal loci obtained from M. fascicularis samples from three different geographic origins and M.

Collection of Macaca fascicularis cDNAs derived from bone marrow, kidney, liver, pancreas, spleen, and thymus.

Background: Consolidating transcriptome data of non-human primates is essential to annotate primate genome sequences, and will facilitate research using non-human primates in the genomic era. Macaca fascicularis is a macaque monkey that is commonly used for biomedical and ecological research.

Findings: We constructed cDNA libraries of Macaca fascicularis, derived from tissues obtained from bone marrow, liver, pancreas, spleen, and thymus of a young male, and kidney of a young female.

IL-10 is a negative regulatory factor of CAWS-vasculitis in CBA/J mice as assessed by comparison with Bruton's tyrosine kinase-deficient CBA/N mice.

Candida albicans water-soluble fraction (CAWS), a mannoprotein-beta-glucan complex obtained from the culture supernatant of C. albicans NBRC1385, exhibits vasculitis-inducing activity (CAWS-vasculitis) in mice. The sensitivity to CAWS-vasculitis varies greatly among mouse strains.

Development of an integrative database with 499 novel microsatellite markers for Macaca fascicularis.

Background: Cynomolgus macaques (Macaca fascicularis) are a valuable resource for linkage studies of genetic disorders, but their microsatellite markers are not sufficient. In genetic studies, a prerequisite for mapping genes is development of a genome-wide set of microsatellite markers in target organisms. A whole genome sequence and its annotation also facilitate identification of markers for causative mutations.

Large-scale analysis of Macaca fascicularis transcripts and inference of genetic divergence between M. fascicularis and M. mulatta.

Background: Cynomolgus macaques (Macaca fascicularis) are widely used as experimental animals in biomedical research and are closely related to other laboratory macaques, such as rhesus macaques (M. mulatta). We isolated 85,721 clones and determined 9407 full-insert sequences from cynomolgus monkey brain, testis, and liver.

Impact of two novel mutations on the structure and function of human myeloperoxidase.

The heme protein myeloperoxidase (MPO) contributes critically to O(2)-dependent neutrophil antimicrobial activity. Two Japanese adults were identified with inherited MPO deficiency because of mutations at Arg-499 or Gly-501, conserved residues near the proximal histidine in the heme pocket. Because of the proximity of these residues to a critical histidine in the heme pocket, we examined the biosynthesis, function, and spectral properties of the peroxidase stably expressed in human embryonic kidney cells.

A new record of Paragonimus other than P. westermani in southern Thailand.

Field surveys of Paragonimus in Surat Thani Province, southern Thailand, revealed a new record of a lung fluke species other than P. westermani. The metacercariae were obtained from the crab, Ranguna smalleyi.

Arginine to cysteine mutation (R499C) found in a Japanese patient with complete myeloperoxidase deficiency.

Animal models suggest that a deficiency in myeloperoxidase (MPO; EC 1.11.1.

Molecular discrimination between individual metacercariae of Paragonimus heterotremus and P. westermani occurring in Thailand.

To accurately discriminate between individual metacercariae of Paragonimus heterotremus and P. westermani occurring in Thailand, polymerase chain reaction (PCR)-based molecular methods were established and subjected to an evaluation. We first amplified and sequenced the second internal transcribed spacer (ITS2) region of the nuclear ribosomal DNA of the two species.

Elevated levels of soluble fractalkine in active systemic lupus erythematosus: potential involvement in neuropsychiatric manifestations.

Objective: To determine levels of the soluble form of the chemokine fractalkine (sFkn) and its receptor, CX(3)CR1, in patients with systemic lupus erythematosus (SLE) with neuropsychiatric involvement (NPSLE) and in SLE patients without neuropsychiatric involvement, and to assess their relationship with disease activity and organ damage.

Methods: Levels of sFkn in serum and cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified using real-time polymerase chain reaction.

Susceptibility loci to coronary arteritis in animal model of Kawasaki disease induced with Candida albicans -derived substances.

We have established an animal model of coronary arteritis which is histopathologically similar to that observed in cases of Kawasaki disease (KD), is a well-known childhood vasculitis syndrome. Coronary arteritis in this mouse model has been induced by intraperitoneal injection of Candida albicans -derived substances (CADS). Arteritis varied by mouse strain with the highest incidence by 71.

Genomic variations in myeloperoxidase gene in the Japanese population.

Myeloperoxidase (MPO; EC 1.11.1.

Paragonimus ohirai metacercariae in crabs collected along the Arakawa River in Tokyo, Japan.

Brackish water crabs infected with Paragonimus ohirai metacercariae have been reported in various regions in Japan. However, infected crabs have not been identified in Tokyo. We therefore collected the crab, Chiromantes dehaani, between August 2002 and July 2003 from 12 locations along the Arakawa River that flows through Tokyo.

Novel missense mutation found in a Japanese patient with myeloperoxidase deficiency.

Myeloperoxidase (MPO; EC 1.11.1.