Norimasa Arita

Ehime University, Matsuyama-shi, Ehime, Japan

Are you Norimasa Arita?

Claim your profile

Publications (14)48.69 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Environmental context. Contamination by hexabromocyclododecanes (HBCDs), a group of brominated flame retardants, is of great concern due to their bioaccumulative nature and toxic implications. HBCD consumption in Japan is the highest among Asian countries and is still growing. In this regard, human exposure to HBCDs is of great concern in Japan. We present here the results of our investigation on Japanese human adipose tissue using LC-MS/MS. HBCDs were detected in all the samples analysed, and were generally higher in men than in women. Abstract. Residue levels of hexabromocyclododecanes (HBCDs) were measured using LC-MS/MS in the Japanese human adipose tissue samples collected during 2003–2004 from Ehime prefecture (n = 26) and Kanto region (n = 9) of Japan. Concentrations of HBCDs (0.85–39 ng g–1 lipid) in the adipose tissue samples were 1–2 orders of magnitude lower than those of organochlorines (OCs). Regional differences between HBCD levels in Ehime prefecture and Kanto region were not significant. No age-dependent accumulation of HBCDs was observed. HBCD levels in men were significantly higher than those in women. Significant positive correlation between polybrominated diphenyl ethers (PBDEs) and HBCDs implies similar routes of exposure to these contaminants for Japanese citizens. α-HBCD was predominant among the three isomers, which is consistent with the other reports on bioaccumulation of α-HBCD in higher trophic animals.
    Environmental Chemistry. 08/2009; 6(4):328-333.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gene expression profiles in synovial tissues from rheumatoid arthritis (RA) patients have yielded useful information on the pathogenetic process of the synovitis. In one group of them, sphingosine kinase 2 (SPHK2), a nuclear protein regulating cell proliferation, seemed to be highly expressed, undergoing a different pathogenetic process of synovitis. In the present study it was clarified that SPHK2 was expressed in the synovial fibroblasts of the synovial tissues obtained from the knee joints of the RA patients. In the cultured synovial fibroblasts from these patients, SPHK2 was more highly expressed than that in the human macrophage cell line, THP-1 and human dermal fibroblasts. SPHK2 was expressed in and around the nucleus and transferred to the cytoplasm and cell surface by the administration of epidermal growth factor, associated with the increased expression of sphingosine-1-phosphate. A sphingosine analogue, FTY720, which is activated by phosphorylation specifically by SPHK2, mediated apoptotic signaling of the cultured synovial fibroblasts. These findings suggest that SPHK2 may regulate the autonomous proliferation of synovial fibroblasts as one of the predisposing genes to RA and could be a target for a novel therapeutic strategy for RA.
    Pathology International 07/2009; 59(6):382-9. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Innate immunity plays important roles in host defense against pathogens, but may also contribute to the development of autoimmune diseases under certain conditions. Toll-like receptors (TLRs) recognize various pathogens and induce innate immunity. We herein present a mouse model for chronic pancreatitis, which was induced by TLR3 signaling that generated the Fas/Fas ligand (FasL)-mediated cytotoxicity. An analogue of viral double-stranded RNA, polyinosinic:polycytidylic acid (poly I:C), which is recognized by TLR3, was injected into autoimmune-prone strains: MRL/Mp mice (MRL/+), MRL/Mp mice with a deficit of Fas (MRL/lpr) and MRL/Mp mice with a deficit of functional FasL (MRL/gld). The pancreatitis in MRL/+ mice was initiated by the destruction of pancreatic ductules, and its severity was significantly higher than that in MRL/lpr mice or MRL/gld mice. Using a pancreatic duct epithelial cell line MRL/S-1 newly established from the MRL/gld mouse that lacks FasL, we showed that treatment with poly I:C significantly induced the expression of Fas on the cultured cells. MRL/S-1 cells were destructed when co-cultured with splenocytes bearing intact FasL prepared from MRL/+ or MRL/lpr mice, but the magnitude of cytotoxicity was smaller with splenocytes of MRL/gld mice. Likewise, synthetic FasL protein showed cytotoxicity on MRL/S-1 cells. Furthermore, MRL/S-1 cells expressed higher levels of chemokines after the treatment with poly I:C, suggesting that the poly I:C-mediated induction of chemokines may be responsible for recruitment of lymphoid cells to the pancreatic periductular regions. These findings indicate that TLR3 signaling generates the Fas/FasL-mediated cytotoxicity, thereby leading to the development of chronic pancreatitis.
    The Tohoku Journal of Experimental Medicine 04/2009; 217(3):175-84. · 1.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This is the first report of segmental arterial mediolysis (SAM) accompanied with polyarteritis nodosa (PN), and manifesting aneurysms of the renal arteries. A 73-year-old woman was admitted to hospital because of a high fever. Laboratory tests showed leukocytosis with increased CRP level in the serum. Myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) and proteinase 3 (PR3)-ANCA were negative. There were no signs indicating infection or malignancy. After admission renal function rapidly deteriorated. Treatment was then started with daily oral prednisolone and hemodialysis. On the 40th day of hospitalization the patient suddenly became comatose. Cranial CT showed a subarachnoid hemorrhage. The patient died and an autopsy was performed. The pathological findings showed necrotizing vasculitis of the small arteries in various organs, but not associated with that of arterioles or renal glomerular lesions, indicating PN. Unexpectedly, the segmental arteries of the bilateral kidneys showed vascular lesions of dissecting aneurysms, indicating SAM. This case indicates that SAM is one of the causes of aneurysms in PN and is clinically important when the clinical course of PN patients rapidly advances.
    Pathology International 04/2009; 59(3):197-200. · 1.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The present study determined concentrations of polybrominated diphenyl ethers (PBDEs) and persistent organochlorines (OCs) in Japanese human adipose tissues collected during 2003-2004. Concentrations of PBDEs in adipose tissues were 1-2 orders of magnitude lower than those of OCs. However, observed PBDE congener levels in this study were relatively higher than those in Japanese human adipose tissues collected during 2000 reported previously, while OC levels were comparable to those in specimens collected during 1999 reported by our group. In addition, no age-dependent accumulation of PBDEs was observed, while OC levels except chlordane compounds increased with age. These results indicate recent human exposure to PBDEs in Japan. Among PBDE congeners accumulated in Japanese adipose tissues, BDE-153 was dominant, but this trend was different from those in human milk (BDE-47) and blood (BDE-209) reported previously in Japan, implying the congener-specific kinetics in human bodies. The significant positive correlations between PBDEs and OCs were observed in Japanese adipose tissues, indicating the similar exposure route of these contaminants for Japanese citizens, probably via fish intake.
    Environment International 12/2007; 33(8):1048-56. · 6.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Crescent formation in the renal glomerulus is a typical manifestation of progressive glomerulopathy associated with fatal renal failure; therefore, its prevention is of clinical importance. Little is known about the pathogenic mechanism for crescent formation. This study was undertaken in an attempt to identify the events that are critical for crescent formation in immune complex crescentic glomerulonephritis (CGN) by analyzing a novel mutant strain of mice. A spontaneous mutant strain of mice was isolated from the autoimmune-prone strain EOD, which stably develops fatal CGN. The mutant phenotypes were assessed histopathologically, hematologically, and immunologically. The mutation was searched for with positional cloning using microsatellite markers. Compared with wild-type EOD (WT-EOD) mice, mutant EOD (mut-EOD) mice showed marked improvement in CGN in conjunction with an improvement in spontaneous mortality. In WT-EOD mice, an inverse correlation between blood urea nitrogen concentration and blood platelet count and massive accumulation of platelets in the glomerulus were evident, suggesting that an accumulation of platelets in the glomerulus contributes to the progression of CGN. The mutant platelets showed an abnormal aggregation in response to collagen and thrombin, associated with a bleeding tendency in mut-EOD mice. Genetic analysis revealed a deleterious mutation in the cappuccino gene (cno), which encodes a protein that belongs to a complex called the biogenesis of lysosome-related organelle complex 1 and is profoundly involved in platelet function. Morphologic examination revealed a partial defect in dense body formation in the delta-granule of platelets. The present findings suggest that platelet functions have a critical role in crescent formation in autoimmune GN.
    Arthritis & Rheumatology 10/2006; 54(9):2934-43. · 7.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a case with pleomorphic carcinoma of the lung in a 70-year-old man. Pleomorphic carcinoma is characterized by a heterogenous composition that includes epithelial and mesechymal malignancies. In the present case, the tumor was composed of a mixture of unequivocal squamous cell carcinoma and spindle cell components resembling sarcomatous overgrowth. The spindle component did not include a heterologous mesenchymal element characterized by overt differentiation for bone, cartilage, neuron or muscle tissue. To evaluate a state of differentiation of the spindle cell component, we immunohistochemically examined expression of the antigens including vimentin, cytokeratin, sarcomeric actin, alpha-smooth muscle actin, S-100 protein, CD34, Factor VIII, and CD68. The results showed sole expression of vimentin in the spindle cell component, suggesting an immature state of the mesenchymal lineage. Furthermore, the spindle cell component of this case was genetically characterized by loss of heterozygosity (LOH) at a codon 234 of exon 7 of the p53 gene. This mutation causes an amino-acid replacement (Tyr to Cys), which was previously proven to attenuate p53 function. The present case may suggest a relation between somatic alteration of the p53 gene and histogenesis of pleomorphic carcinoma.
    The Tohoku Journal of Experimental Medicine 07/2005; 206(2):181-5. · 1.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To analyze the influence of the genetic background of an arthritis-prone strain of mice, MRL, on the spontaneous development of arthropathy in DBA/1 mice, which histopathologically resembles enthesopathy in humans, and to clarify the strain-specific gene loci and their interactions that confer susceptibility to arthropathy. MRL, DBA/1, (MRL x DBA/1)F(1), and (MRL x DBA/1)F(2) intercross mice were prepared, and the severity and onset of arthropathy of the ankle joints in individual mice were quantified (0-3 and 0-5 scale, respectively). A genome-wide scan of 271 male F(2) intercross mice with polymorphic microsatellite markers was performed. Only male DBA/1, (MRL x DBA/1)F(1), and (MRL x DBA/1)F(2) mice developed arthropathy. The macroscopic and histopathologic findings of arthropathy in the F(2) mice were similar to those in the parental DBA/1 mice, but the onset was significantly earlier. In the quantitative trait locus analysis of male F(2) mice, 1 susceptibility locus for both the severity and early onset of the disease in the region of an MRL allele, Amd1, was located at marker D10Mit259 (map position 40.0 cM), which was common to 1 of the sialadenitis susceptibility loci in MRL mice, Asm1. Another susceptibility locus for the severity and early onset of arthropathy in the region of a DBA allele, Amd2, was located at D3Mit46 (29.5 cM). These loci manifested an additive effect on the development of arthropathy. Arthropathy in DBA/1 mice is under the control of an allelic combination of gene loci, one of which is common to the locus for sialadenitis in MRL/MpJ-lpr/lpr mice.
    Arthritis & Rheumatology 04/2005; 52(3):959-66. · 7.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The disease category of early rheumatoid arthritis (RA) has been limited with respect to clinical criteria. Pathological manifestations of synovitis in patients whose disease is clinically classified as early RA seem to be heterogeneous, with regular variations. To clarify the relation between the molecular and histopathological features of the synovitis, we analyzed gene-expression profiles in the synovial lining tissues to correlate them with histopathological features. Synovial tissues were obtained from knee joints of 12 patients with early RA by targeted biopsy under arthroscopy. Surgical specimens of long-standing RA (from four patients) were examined as positive controls. Each histopathological parameter characteristic of rheumatoid synovitis in synovial tissues was scored under light microscopy. Total RNAs from synovial lining tissues were obtained from the specimens selected by laser capture microdissection and the mRNAs were amplified by bacteriophage T7 RNA polymerase. Their cDNAs were analyzed in a cDNA microarray with 23,040 cDNAs, and the levels of gene expression in multilayered lining tissues, compared with those of normal-like lining tissues in specimens from the same person, were determined to estimate gene-expression profiles characteristic of the synovial proliferative lesions in each case. Based on cluster analysis of all cases, gene-expression profiles in the lesions in early RA fell into two groups. The groups had different expression levels of genes critical for proliferative inflammation, including those encoding cytokines, adhesion molecules, and extracellular matrices. One group resembled synovitis in long-standing RA and had high scores for some histopathological features - involving accumulations of lymphocytes and plasma cells - but not for other features. Possible differences in the histopathogenesis and prognosis of synovitis between the two groups are discussed in relation to the candidate genes and histopathology.
    Arthritis research & therapy 02/2005; 7(4):R825-36. · 4.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To clarify whether vascular endothelial adhesion molecules in glomeruli might contribute to the severity and diversity of glomerular lesions in lupus nephritis, their expression in lupus models was analyzed. The expression levels of E- and P-selectin and vascular cell adhesion molecule-1 (VCAM-1) in glomeruli of different histopathologic grades of MRL/MpJ-lpr/lpr (MRL/lpr) lupus mice was studied using laser-capture microdissection of the glomeruli, followed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The glomerular lesions in SCID mice injected with the 2B11.3 and 7B6.8 clones, which are derived from an MRL/lpr mouse and induce endocapillary proliferative and wire loop type of glomerular lesions, respectively, were analyzed. To investigate the effect of a soluble form of E-selectin (sE-selectin) on the development of glomerular lesions, sE-selectin-producing L cells were prepared by transfection of the cDNA encoding sE-selectin and injected into SCID mice. The glomeruli in MRL/lpr mice showed increased expression of these adhesion molecules, corresponding to the severity of the glomerular lesions. The endocapillary proliferative type lesions in SCID mice induced by the 2B11.3 clone showed significantly increased expression of the adhesion molecules, especially E-selectin and P-selectin, but the wire loop type lesion induced by the 7B6.8 clone expressed only VCAM-1. Formation of the endocapillary proliferative type lesions induced by the 2B11.3 clone was markedly prevented in association with elevation of the serum level of sE-selectin produced by the tansfected L cells. The severity and diversity of the histopathology of lupus nephritis are partially associated with the expression of vascular endothelial adhesion molecules in glomeruli.
    Kidney International 05/2004; 65(4):1290-300. · 8.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: One of the crucial events in lupus nephritis is the glomerular deposition of immunoglobulins (Igs), of which pathogenic properties have been proposed mostly to be either type IIor type III allergic reactions. Some of IgG3-producing hybridoma clones established from an MRL/MpTn-gld/gld (MRL/gld) lupus mouse generate wire loop-like lesions in glomeruli resembling lupus nephritis when injected into SCID mice. These clones are useful for analyzing the mechanisms of glomerular deposition of antibodies in lupus nephritis at the monoclonal level. Glomerular lesions of SCID mice injected with the hybridoma clones, 17H8a or 1G3 as control were analyzed by light and electron microscopy. Interaction of the antibodies with human glomerular endothelial cells (HGECs) and human umbilical vein endothelial cells (HUVECs) in vitro was studied by fluorescence microscopy, electron microscopy, and flow cytometry. Both antibodies did not show any antigen specificity for mouse glomeruli. The glomerular lesions generated by 17H8a, but not by 1G3, contained electron-dense deposits not only in subendothelial regions but also in the cytoplasm of endothelial cells, suggesting internalization of the 17H8a antibodies by endothelial cells. In cell culture studies, internalization of only 17H8a antibodies by HGECs and HUVECs was observed, but the antibodies did not have antigen specificity for both types of endothelial cells. The internalization by HUVECs was mediated by actin polymerization, and it was inhibited by RGDS (Arg-Gly-Asp-Ser) tetrapeptide, antihuman fibronectin and antihuman integrin beta1 monoclonal antibodies. The interaction between particular antibodies and endothelial cell surface integrins via fibronectin may be involved in their subsequent internalization by endothelial cells leading to antibody deposition in glomeruli. This may be one of the mechanisms of glomerular injury in lupus nephritis.
    Kidney International 12/2003; 64(5):1662-70. · 8.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A 49-year-old female was admitted to our hospital because of worsening of congestive heart failure on November 2000 in a state after insertion of permanent pacemaker for complete atrioventricular block in 1986, followed by a clinical history of chronic heart failure due to dilated cardiomyopathy. After admission, her general condition had been improved, but, she had massive hemoptysis suddenly and died on February 2001. At autopsy, noncaseating granulomas were observed scattering in lungs, liver and spleen, not associated with any infectious lesions, therefore indicating systemic sarcoidosis. In lungs, granulomatous arteritis in small- and medium-sized muscular arteries associated with disputation of the media and elastic laminae were observed, suggesting the direct cause of hemoptysis. This is the extremely rare case of pulmonary arteritis with systemic sarcoidosis resulting the death from massive hemoptysis.
    Ryūmachi. [Rheumatism] 11/2002; 42(5):807-14.
  • [Show abstract] [Hide abstract]
    ABSTRACT: We describe a case of a 61-year-old woman with amyopathic dermatomyositis (ADM), who developed rapidly progressive interstitial pneumonia and died of respiratory failure. An autopsy revealed interstitial pneumonia with diffuse alveolar damage, associated with infiltration of T cells, mostly positive for CD 8. The alveolar lining epithelial cells manifested the remarkable expression of immediate early/early antigen of human cytomegalovirus (HCMV). Moreover, the extract of the lung was transmittable of HCMV infection to cultured human embryo-fibroblasts in vitro. On the other hand, in the semi-quantitative analysis of HCMV genome, using laser-assisted microdissection, followed by PCR method, the genomic DNA in the alveolar lining epithelial cells was little detected in this case, although it was remarkable in the case of immunodeficiency with cytomegalovirus pneumonia. This case may be important to know the role of the immune response of host to HCMV infection on the development of rapidly progressive interstitial pneumonia.
    Ryūmachi. [Rheumatism] 07/2002; 42(3):597-604.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Residue levels of brominated flame retardants (BFRs), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) were measured in the Japanese human adipose tissues collected during 2003–2004 from Ehime prefecture and Kanto region of Japan. Concentrations of PBDEs (1.5–27 ng/g lipid wt) and HBCDs (0.85–39 ng/g lipid wt) in adipose tissues were 1–2 orders of magnitude lower than those of organochlorines (OCs). However, observed PBDE levels in this study were relatively higher than those in Japanese human adipose tissues reported previously in the samples collected during the year 2000, while OC levels were comparable to those in specimens reported by our group in the samples collected during 1999. No age-dependent accumulation of PBDEs and HBCDs was observed, while OC levels except chlordane compounds increased with age. These results indicate recent human exposure to PBDEs and HBCDs in Japan. This is the first report on HBCDs in Japanese human tissue. Among PBDE congeners accumulated in Japanese adipose tissues, BDE-153 was dominant, but this trend was different from those in human milk (BDE-47) and blood (BDE-209) reported previously in Japan. α-HBCD was predominant among the three isomers, which is consistent with the other reports on high trophic animals. These results imply some inferences and explain the congener-specific kinetics in human bodies. The significant positive correlations between PBDEs and HBCDs observed in Japanese adipose tissues indicate similar exposure routes of these contaminants for Japanese citizens.