Harutaka Katano

National Institute of Infectious Diseases, Tokyo, Edo, Tōkyō, Japan

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Publications (130)403.9 Total impact

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    ABSTRACT: Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma that shows malignant effusion most commonly seen in advanced AIDS patients. In this study, we clarified the potential role of VEGF and IL-6 in PEL fluid retention and evaluated the efficacy of humanized anti-VEGF monoclonal antibody (mAb), bevacizumab, and humanized anti-IL-6 receptor mAb, tocilizumab, against PEL.
    Journal of Cancer Research and Clinical Oncology 10/2014; · 2.91 Impact Factor
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    ABSTRACT: We describe a fatal case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with human herpesvirus-6B (HHV-6B)-associated lymphadenitis and virus-associated hemophagocytic syndrome triggered by an over-the-counter medication to treat respiratory and influenza-like symptoms. Histologically, the structure of the lymph node was disrupted with infiltration of large lymphocytes carrying intranuclear acidophilic inclusion bodies. Immunohistochemistry and real-time PCR analysis revealed that these large lymphocytes were positive for HHV-6B. Numerous HHV-6 particles were detected in the inclusion body of the lymphocytes by electron microscopy. Interestingly, immunohistochemistry revealed that HHV-6B-infected cells in the lymph node were CD3(+), CD4(+), CD25(+), and FoxP3(+) T cells, indicating a phenotypic resemblance to regulatory T-cells. This case provides direct evidence of HHV-6 infection in CD25(+)/FoxP3(+) T cells in a case of acute lymphadenitis of DRESS syndrome, suggesting a significant role of HHV-6 infection of regulatory T-cells in the pathogenesis of DRESS syndrome.
    Journal of Clinical Virology. 09/2014;
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    ABSTRACT: Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous amoebic encephalitis. We report herein an autopsy case of B. mandrillaris amoebic encephalitis, which was definitely diagnosed by PCR. An 81-year-old man, who had Sjögren's syndrome, manifested drowsiness 2 months before his death with progressive deterioration. Neuroimaging demonstrated foci of T2- and fluid-attenuated inversion recovery high and T1 low-intensity with irregular post-contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10–60 μm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin-embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature.
    Neuropathology 09/2014; · 1.91 Impact Factor
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    ABSTRACT: It has been unclear whether chromosomally integrated human herpesvirus-6 (ciHHV-6) can be activated with pathogenic effects on the human body. We present molecular and virological evidence of ciHHV-6A activation in a patient with X-linked severe combined immunodeficiency. These findings have significant implications for the management of patients with ciHHV-6.
    Clinical Infectious Diseases 05/2014; · 9.37 Impact Factor
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    ABSTRACT: Opportunistic infections and malignancies such as malignant lymphoma and Kaposi sarcoma are significant complications of human immunodeficiency virus (HIV) infection. However, following the introduction of antiretroviral therapy in Japan in 1997, the incidence of clinical complications has decreased. In the present study, autopsy cases of HIV infection in Japan were retrospectively investigated to reveal the prevalence of opportunistic infections and malignancies. A total of 225 autopsy cases of HIV infection identified at 4 Japanese hospitals from 1985-2012 were retrospectively reviewed. Clinical data were collected from patient medical records. Mean CD4 counts of patients were 77.0 cells/muL in patients who received any antiretroviral therapy during their lives (ART (+) patients) and 39.6 cells/muL in naive patients (ART (-) patients). Cytomegalovirus infection (142 cases, 63.1%) and pneumocystis pneumonia (66 cases, 29.3%) were the most frequent opportunistic infections, and their prevalence was significantly lower in ART (+) patients than ART (-) patients. Non-Hodgkin lymphoma and Kaposi sarcoma were observed in 30.1% and 16.2% of ART (-) patients, and 37.9% and 15.2% of ART (+) patients, respectively. Malignant lymphoma was the most frequent cause of death, followed by cytomegalovirus infection regardless of ART. Non-acquired immunodeficiency syndrome (AIDS)-defining cancers such as liver and lung cancer caused death more frequently in ART (+) patients (9.1%) than in ART (-) patients (1.5%; P = 0.026). The prevalence of infectious diseases and malignancies were revealed in autopsy cases of HIV infection in Japan. The prevalence of cytomegalovirus infection and pneumocystis pneumonia at autopsy were lower in ART (+) patients than ART (-) patients. Higher prevalence of non-AIDS defining malignancies among ART (+) patients than ART (-) patients suggests that onsets of various opportunistic infections and malignancies should be carefully monitored regardless of whether the patient is receiving ART.
    BMC Infectious Diseases 04/2014; 14(1):229. · 3.03 Impact Factor
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    ABSTRACT: Recently, the critical role of CD47 on the surface of resistant cancer cells has been proposed in their evasion of immunosurveillance. Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion in body cavities, especially in advanced acquired immunodeficiency syndrome (AIDS). PEL is resistant to conventional chemotherapy and has a poor prognosis. In this study, we evaluated the effect of anti-CD47 antibody (Ab) on PEL in vitro and in vivo. Surface CD47 of PEL cell lines was examined by flow cytometry. Efficacy of knocking down CD47 or anti-CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal macrophages and human macrophages in vitro. Primary PEL cells were injected intraperitoneally into NOD/Rag-2/Jak3 double-deficient (NRJ) mice to establish a direct xenograft mouse model. Surface CD47 of PEL cell lines was highly expressed. Knocking down CD47 and anti-CD47 Ab promoted phagocytic activities of macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti-CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared with control IgG-treated mice. CD47 plays the pivotal role in the immune evasion of PEL cells in body cavities. Therapeutic antibody targeting of CD47 could be an effective therapy for PEL.
    European journal of cancer (Oxford, England: 1990) 04/2014; · 4.12 Impact Factor
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    ABSTRACT: Abstract is missing (Short Communication).
    Acta Dermato-Venereologica 04/2014;
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    ABSTRACT: The GP129, GP131 and GP133 genes of guinea pig cytomegalovirus (GPCMV) are homologs of human CMV UL128, UL130 and UL131A, respectively, which are essential for infection of endothelial and epithelial cells and for viral transmission to leukocytes. Our previous study demonstrated that a GPCMV strain lacking the 1.6-kb locus that contains the GP129, GP131, and GP133 genes had a growth defect in animals. Here we demonstrated that the wild-type strain but not the 1.6-kb deleted strain formed capsids in macrophages prepared from the peritoneal fluid. To understand the mechanism, we prepared GPCMV strains defective in each of GP129, GP131 and GP133 and found that they were all essential for the infection of peritoneal, splenic and PBMC-derived macrophages/monocytes and expression of immediate-early antigens in the macrophages/monocytes, although they were dispensable for infection of fibroblasts. Monocyte/macrophage-tropism could be one of the important determinants for viral dissemination in vivo.
    Journal of General Virology 03/2014; · 3.13 Impact Factor
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    ABSTRACT: The introduction of combined antiretroviral therapy (ART) has reduced the mortality of patients with human immunodeficiency virus-1 infection worldwide. However, malignant lymphoma is a severe and frequent complication seen in patients with acquired immunodeficiency syndrome (AIDS). The diagnostic criteria for some categories of AIDS-related lymphoma were revised in the World Health Organization International Classification of Lymphoma, fourth edition. The purpose of this study was to assess the clinicopathological characteristics of Japanese patients with AIDS-related lymphoma according to the revised classification. In this retrospective study, 207 AIDS-related lymphoma cases diagnosed between 1987 and 2012 in Japan were subjected to histological subtyping and clinicopathological analyses. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype throughout the study period (n = 104, 50%). Among the DLBCL cases, 24% were of the germinal center (GC) type and 76% were of the non-GC type. Non-GC-type cases showed a significantly lower 1-year survival rate (43%) than the GC-type cases (82%). Cases of Burkitt lymphoma (n = 57, 28%), plasmablastic lymphoma (n = 16, 8%), primary effusion lymphoma (n = 9, 4%), Hodgkin lymphoma (n = 8, 4%), and large B-cell lymphoma arising in Kaposi sarcoma-associated herpesvirus-associated multicentric Castleman disease (n = 2, 1%) were also observed. Hodgkin lymphoma was more common in patients receiving ART (11.1%) than in ART-naïve patients (1.4%). Statistical analyses identified CD10 negativity, BCL-6 negativity, Epstein-Barr virus positivity, and Kaposi sarcoma-associated herpesvirus positivity as risk factors for poor prognosis. This information will help in the early diagnosis of lymphoma in patients with AIDS.
    Cancer Medicine 01/2014;
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    ABSTRACT: Background Recently, the critical role of CD47 on the surface of resistant cancer cells has been proposed in their evasion of immunosurveillance. Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion in body cavities, especially in advanced acquired immunodeficiency syndrome (AIDS). PEL is resistant to conventional chemotherapy and has a poor prognosis. In this study, we evaluated the effect of anti-CD47 antibody (Ab) on PEL in vitro and in vivo. Methods Surface CD47 of PEL cell lines was examined by flow cytometry. Efficacy of knocking down CD47 or anti-CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal macrophages and human macrophages in vitro. Primary PEL cells were injected intraperitoneally into NOD/Rag-2/Jak3 double-deficient (NRJ) mice to establish a direct xenograft mouse model. Results Surface CD47 of PEL cell lines was highly expressed. Knocking down CD47 and anti-CD47 Ab promoted phagocytic activities of macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti-CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared with control IgG-treated mice. Conclusion CD47 plays the pivotal role in the immune evasion of PEL cells in body cavities. Therapeutic antibody targeting of CD47 could be an effective therapy for PEL.
    European Journal of Cancer. 01/2014;
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    ABSTRACT: Trichodysplasia spinulosa-associated polyomavirus (TSV) was identified in a seven-month-old girl with myocarditis. The number of TSV genomes detected was higher in the heart than in the other organs. The full-length TSV genome was cloned from the heart. This suggests a possible role of TSV infection in the pathogenesis of myocarditis in infants.
    International journal of clinical and experimental pathology. 01/2014; 7(8):5308-12.
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    ABSTRACT: Background. Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV) a novel bunyavirus reported to be endemic in central and northeastern China. This paper describes the first identification of a patient with SFTS and a retrospective study on SFTS in Japan.Methods. Virological and pathological examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification, and/or the detection of IgG antibody to SFTSV in sera. Medical doctors were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS.Results. A female patient who died in 2012 was diagnosed with SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged 50 or over, and lived in western Japan. Six cases were fatal. The male to female ratio was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all the Japanese SFTSV isolates formed a genotype independent to in China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis.Conclusions. SFTS has been endemic to Japan and SFTSV has been circulating naturally within the country.
    The Journal of Infectious Diseases 11/2013; · 5.85 Impact Factor
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    ABSTRACT: Primary effusion lymphoma (PEL) is a non-Hodgkin lymphoma that occurs predominantly in patients with advanced AIDS. In this study, we examined the effect of HIV protease inhibitors, Lopinavir (LPV), Ritonavir (RTV) and Darunavir (DRV) on PEL cell lines in vitro and in vivo. LPV and RTV, but not DRV induced caspase-dependent apoptosis and suppressed NF-κB activity by inhibiting IKK phosphorylation in PEL cells. In a PEL xenograft mouse model, LPV significantly inhibited the growth and invasion of PEL cells. These results suggest that LPV may have promise for the treatment and prevention of PEL, which occurs in HIV/AIDS patients.
    Cancer letters 09/2013; · 5.02 Impact Factor
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    ABSTRACT: Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma, causes malignancies frequently in patients with acquired immunodeficiency syndrome. In the United States and Europe, KSHV infection is common among men who have sex with men. However, the seroprevalence of KSHV among men who have sex with men in Japan is unknown. In the present study, the seroprevalence of KSHV was investigated among 230 men who have sex with men and 400 age- and area of residence-matched men (controls) using a mixed-antigen (KSHV-encoded K8.1, open reading frame 59, 65, and 73 proteins) enzyme-linked immunosorbent assay and an immunofluorescence assay. Among the Japanese men who have sex with men, serological assays revealed that 27 (11.7%) were seropositive for KSHV; 20 (5%) of the men in the control group were also KSHV seropositive. The seroprevalence of KSHV among men who have sex with men was significantly higher than in the control group (odds ratio = 2.52, 95% confidence intervals = 1.38-4.62, P = 0.0019, Chi-square test). Infection with the human immunodeficiency virus, Treponema pallidum, or hepatitis B and C virus did not correlate with KSHV infection. Furthermore, the association of KSHV seropositivity with specific sexual activities was not statistically significant. In conclusion, a higher KSHV seroprevalence was found among Japanese men who have sex with men than among the controls, suggesting that the circulation of KSHV infection is more efficient among men who have sex with men in Japan than among men who do not engage in such sexual activities. J. Med. Virol. 85: 1046-1052, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2013; 85(6):1046-52. · 2.37 Impact Factor
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    ABSTRACT: BACKGROUND: Cytomegalovirus (CMV) is the most common cause of congenital virus infection. Infection of guinea pigs with guinea pig CMV (GPCMV) can provide a useful model for the analysis of its pathogenesis as well as for the evaluation of vaccines. Although glycoprotein B (gB) vaccines have been reported to reduce the incidence and mortality of congenital infection in human clinical trials and guinea pig animal models, the mechanisms of protection remain unclear. METHODS: To understand the gB vaccine protection mechanisms, we analyzed the spread of challenged viruses in the placentas and fetuses of guinea pig dams immunized with recombinant adenoviruses expressing GPCMV gB and β-galactosidase, rAd-gB and rAd-LacZ, respectively. RESULTS: Mean body weight of the fetuses in the dams immunized with rAd-LacZ followed by GPCMV challenge 3 weeks after immunization was 78% of that observed for dams immunized with rAd-gB. Under conditions in which congenital infection occurred in 75% of fetuses in rAd-LacZ-immunized dams, only 13% of fetuses in rAd-gB-immunized dams were congenitally infected. The placentas were infected less frequently in the gB-immunized animals. In the placentas of the rAd-LacZ- and rAd-gB-immunized animals, CMV early antigens were detected mainly in the spongiotrophoblast layer. Focal localization of viral antigens in the spongiotrophoblast layer suggests cell-to-cell viral spread in the placenta. In spite of a similar level of antibodies against gB and avidity indices among fetuses in each gB-immunized dam, congenital infection was sometimes observed in a littermate fetus. In such infected fetuses, CMV spread to most organs. CONCLUSIONS: Our results suggest that antibodies against gB protected against infection mainly at the interface of the placenta rather than from the placenta to the fetus. The development of strategies to block cell-to-cell viral spread in the placenta is, therefore, required for effective protection against congenital CMV infection.
    Vaccine 05/2013; · 3.77 Impact Factor
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    ABSTRACT: BACKGROUND: Merkel cell polyomavirus (MCPyV), human polyomavirus-6 (HPyV6), and human polyomavirus-7 (HPyV7) were identified as viruses shed from the skin. Serological analysis revealed that these viruses are common among the general population. However, there is little information about the presence of MCPyV, HPyV6, and HPyV7 in the sera and tissues of immunocompromised individuals. The aims of this study are to know if immune status affects the presence of MCPyV, HPyV6, and HPyV7 in the serum, and to reveal the presence of these viruses in diseased tissues of unknown etiology. METHODS: Sera from HIV-1-positive and -negative patients were examined by real-time PCR and nested PCR detecting MCPyV, HPyV6 and HPyV7. In addition, diseased tissue samples of unknown etiology were examined. RESULTS: Nine out of 23 serum samples (39.1%) from HIV-1-positive patients who had not received anti-retroviral therapy were positive for MCPyV, which is significantly higher than HIV-1-negative patients (6/110, 5.5%, P < 0.01, Chi-square test). MCPyV DNA was detected in tissue samples of Merkel cell carcinoma (22/30 [73%]), encephalitis (4/19 [21%]), pneumonia (3/17 [18%]), and myocarditis (8/14 [57%]). With the exception of Merkel cell carcinoma samples, MCPyV-positive tissues showed low copy numbers of MCPyV DNA by real-time PCR and no expression of the MCPyV large T antigen by immunohistochemistry. HPyV6 and HPyV7 were rarely detected in serum and tissue samples. CONCLUSIONS: These results suggest that MCPyV viremia is associated with host immunity, and that circulation of HPyV6 and HPyV7 in the serum is rare.
    Virology Journal 03/2013; 10(1):84. · 2.09 Impact Factor
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    ABSTRACT: Primary effusion lymphoma (PEL) is a subtype of aggressive and resistant non-Hodgkin lymphoma that occurs predominantly in patients with advanced AIDS. In this study, we examined the antitumor activity of zoledronic acid (Zol) -induced Vγ9Vδ2 T cells against PEL cells in vitro and in vivo. Vγ9Vδ2 T cells recognized endogenous mevalonate metabolites and MICA/B of PEL cell lines, inducing cytotoxicity via granule exocytosis and TRAIL-mediated pathway. Vγ9Vδ2 T cells suppressed the development of PEL cells and existed in a PEL xenograft mouse model. These results show that immunotherapy with Zol-induced Vγ9Vδ2 T cells could demonstrate an efficient strategy for PEL.
    Cancer letters 01/2013; · 5.02 Impact Factor
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    ABSTRACT: Primary effusion lymphoma (PEL) caused by Kaposi's sarcoma-associated herpesvirus (also known as human herpesvirus-8) shows serious lymphomatous effusion in body cavities. PEL is difficult to treat and there is no standard treatment strategy. Hippuristanol is extracted from Okinawan coral Isis hippuris, and inhibits translational initiation by blocking eukaryotic initiation factor 4A, an ATP-dependent RNA helicase, binding to mRNA. Recently, there has been much interest in targeting translation initiation as an anticancer therapy. Here, we show that treatment of PEL cell lines with hippuristanol resulted in cell cycle arrest at G1 phase, and induced caspases activation and apoptosis. Hippuristanol also reduced the expression of cyclin D2, CDK2, CDK4, CDK6 and prosurvival XIAP and Mcl-1 proteins. Activation of activator protein-1, signal transducers and activators of transcription protein 3 and Akt pathways plays a critical role in the survival and growth of PEL cells. Hippuristanol suppressed the activities of these three pathways by inhibiting the expression of JunB, JunD, c-Fos, signal transducers and activators of transcription protein 3 and Akt proteins. In a xenograft mouse model that showed ascites and diffused organ invasion of PEL cells, treatment with hippuristanol significantly inhibited the growth and invasion of PEL cells compared with untreated mice. The results of the in vitro and in vivo experiments underline the potential usefulness of hippuristanol in the treatment of PEL.
    Marine Drugs 01/2013; 11(9):3410-24. · 3.98 Impact Factor
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    ABSTRACT: Highly pathogenic avian H5N1 influenza virus (H5N1) infection in humans causes acute respiratory distress syndrome, leading to multiple organ failure. Five fatal cases of H5N1 infection in Vietnam were analyzed pathologically to reveal virus distribution, and local proinflammatory cytokine and chemokine expression profiles in formalin-fixed, paraffin-embedded lung tissues. Our main histopathological findings showed diffuse alveolar damage in the lungs. The infiltration of myeloperoxidase-positive and/or CD68 (clone KP-1)-positive neutrophils and monocytes/macrophages was remarkable in the alveolar septa and alveolar spaces. Immunohistochemistry revealed that H5N1 mainly infected alveolar epithelial cells and monocytes/macrophages in lungs. H5N1 replication was confirmed by detecting H5N1 mRNA in epithelial cells using in situ hybridization. Quantitation of H5N1 RNA using quantitative reverse transcription PCR assays revealed that the level of H5N1 RNA was increased in cases during early phases of the disease. We quantified the expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, regulated on activation normal T-cell expressed and secreted (commonly known as RANTES), and interferon-gamma-inducible protein of 10 kDa (IP-10) in formalin-fixed, paraffin-embedded lung sections. Their expression levels correlated with H5N1 RNA copy numbers detected in the same lung region. Double immunofluorescence staining revealed that TNF-α, IL-6, IL-8 and IP-10 were expressed in epithelial cells and/or monocytes/macrophages. In particular, IL-6 was also expressed in endothelial cells. The dissemination of H5N1 beyond respiratory organs was not confirmed in two cases examined in this study.Modern Pathology advance online publication, 23 November 2012; doi:10.1038/modpathol.2012.193.
    Modern Pathology 11/2012; · 5.25 Impact Factor
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    ABSTRACT: BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our envelopment. METHODS: Microarray assays with ontology and pathway analyses were performed with the lungs of mice. A comparison was made of the expression patterns of biological pathways between our model and those published for IPAH. RESULTS: Some pathways in our model showed the same expression patterns in IPAH, which included bone morphogenetic protein (BMP) signaling with down-regulation of BMP receptor type 2, activin-like kinase type 1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP) signaling and its downstream Rho/ROCK signaling were found alone to be activated in IPAH and not in our model. CONCLUSIONS: Activation of Wnt/PCP signaling, in upstream positions of the pathway, found alone in lungs from end stage IPAH may play essential roles in the pathogenesis of the disease.
    Respiratory research 11/2012; 13(1):103. · 3.64 Impact Factor

Publication Stats

2k Citations
403.90 Total Impact Points

Institutions

  • 1999–2014
    • National Institute of Infectious Diseases, Tokyo
      Edo, Tōkyō, Japan
    • Tottori University
      TTJ, Tottori, Japan
  • 2009–2013
    • Kumamoto University
      • Center for AIDS Research
      Kumamoto-shi, Kumamoto Prefecture, Japan
    • Osaka Red Cross Hospital
      Ōsaka, Ōsaka, Japan
  • 2012
    • Nippi Inc.
      Edo, Tōkyō, Japan
    • Noguchi Memorial Institute for Medical Research
      • Department of Bacteriology
      Accra, Greater Accra Region, Ghana
  • 2004–2009
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      Maryland, United States
  • 2006
    • Tokyo Metropolitan Komagome Hospital
      Edo, Tōkyō, Japan
    • Kagoshima University
      • Graduate School of Medical and Dental Sciences
      Kagosima, Kagoshima, Japan
    • Tokyo Medical and Dental University
      Edo, Tōkyō, Japan
  • 2001–2006
    • Saitama Medical University
      • • Department of Immunology
      • • Department of Medical Oncology
      Saitama, Saitama-ken, Japan
    • Nippon Medical School
      • Nippon Medical School Hospital
      Edo, Tōkyō, Japan
  • 1995–2002
    • The University of Tokyo
      • • Department of Pathology
      • • Institute of Medical Science
      Tokyo, Tokyo-to, Japan
  • 2000
    • Nerima General Hospital
      Edo, Tōkyō, Japan