Akihiko Okayama

Miyazaki University, Миядзаки, Miyazaki, Japan

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Publications (156)588.82 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Quantitative PCR (qPCR) analysis of human T-cell leukemia virus type 1 (HTLV-1) was used to assess the amount of HTLV-1 provirus DNA integrated into the genomic DNA of host blood cells. Accumulating evidence indicates that a high proviral load is one of the risk factors for the development of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, inter-laboratory variability in qPCR results makes it difficult to assess the differences in reported proviral loads between laboratories. To remedy this situation, we attempted to minimize discrepancies between laboratories through standardization of HTLV-1 qPCR in a collaborative study. TL-Om1 cells that harbor the HTLV-1 provirus were serially diluted with peripheral blood mononuclear cells to prepare a candidate standard. By statistically evaluating the proviral loads of the standard and those determined using in-house qPCR methods at each laboratory, we determined the relative ratio of the measured values in the laboratories to the theoretical values of the TL-Om1 standard. The relative ratio of the laboratories ranged from 0.84 to 4.45. Next, we corrected the proviral loads of the clinical samples from HTLV-1 carriers using the relative ratio. As expected, the overall differences between the laboratories were reduced by half from 7.4-fold to 3.8-fold on average after applying the correction. HTLV-1 qPCR can be standardized using TL-Om1 cells as a standard and by determining the relative ratio of the measured to the theoretical standard values in each laboratory. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of clinical microbiology 08/2015; DOI:10.1128/JCM.01628-15 · 4.23 Impact Factor
  • K. Umekita · T. Hidaka · S. Miyauchi · K. Kubo · Y. Hashiba · A. Okayama
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):932.1-932. DOI:10.1136/annrheumdis-2015-eular.1629 · 10.38 Impact Factor
  • Kidney International 09/2014; 86(3):655. DOI:10.1038/ki.2014.23 · 8.52 Impact Factor
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    ABSTRACT: Objectives To clarify the mechanism of leukocytapheresis (LCAP) in patients with rheumatoid arthritis (RA). Methods Protein profiles of blood samples from 2 patients with RA obtained via LCAP column inlet and outlet lines were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. Then, the lactoferrin (LTF) levels of peripheral and circulating blood samples from 7 patients obtained via the LCAP column blood circuit were determined by enzyme-linked immune sorbent assay. Peripheral blood samples from 14 patients with RA were exposed to unwoven polyester fiber filter (filter) and LTF level was determined. In addition, morphological change of neutrophils after exposure to filter was examined by optical microscopy, electronic microscopy and LTF immunostaining. Results LTF levels were increased both in the samples from the LCAP column outlet and in peripheral blood at the end of LCAP treatment. Furthermore, peripheral blood samples exposed to filter revealed a decreased number of neutrophils and increased level of LTF. Morphological analysis of the exposed neutrophils showed vacuolization of the cytoplasm and degranulation of LTF positive granules. These data suggested that LTF stored in the granules of neutrophils was released from the neutrophils caught in the LCAP column. Conclusions Because LTF has been reported to have multiple anti-inflammatory properties, increased levels of LTF may contribute to the clinical effect of LCAP in patients with RA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2179
    Rheumatology (Oxford, England) 06/2014; 53(11). DOI:10.1093/rheumatology/keu219 · 4.44 Impact Factor
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    ABSTRACT: Objectives: To investigate the response to and safety of anti-tumor necrosis factor (TNF) therapy in human T-lymphotropic virus type 1 (HTLV-1) positive patients with rheumatoid arthritis (RA). Methods: Therapeutic response was evaluated in 10 HTLV-1 positive and 20 negative patients with RA (sex- and age- matched) at three months after the beginning of anti-TNF therapy using the European League Against Rheumatism improvement criteria. As secondary endpoints, discontinuation rate of anti-TNF therapy and safety, especially the development of adult T-cell leukemia (ATL), were evaluated over a 2-year period. Results: Significantly higher baseline levels of C-reactive protein (CRP) were observed in HTLV-1 positive patients than in HTLV-1 negative patients (P= 0.0003). Response rate to anti-TNF therapy was lower in HTLV-1 positive patients than in HTLV-1 negative patients. The median levels of CRP, erythrocyte sedimentation rate, and DAS28 at 3 months after anti-TNF treatment in HTLV-1 positive patients were significantly higher than those in HTLV-1 negative patients (P= 0.003, P= 0.03 and P= 0.003, respectively). Discontinuation rate due to insufficient response was significantly higher in HTLV-1 positive patients than in HTLV-1negative patients (P= 0.013). During the 2-year observation period, no patients developed ATL. Conclusion: These data suggested that HTLV-1 positive patients with RA had higher inflammation and greater resistance to anti-TNF treatment than HTLV-1 negative patients. Further study is necessary to determine whether HTLV-1 infection should be measured when anti-TNF agents are administrated to patients with RA, especially in endemic areas. © 2013 American College of Rheumatology.
    05/2014; 66(5). DOI:10.1002/acr.22205
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    ABSTRACT: Objectives To see whether the clinical features and responses to anti-TNF of HTLV-1 positive patients with RA are different from those of HTLV-1 negative patients. Methods The clinical features and response to anti-TNF were compared between 10 female HTLV-1 positive RA patients and 20 age-matched female HTLV-1 negative patients, who were diagnosed based on the 1987 ACR criteria for RA. Therapeutics response was evaluated using the EULAR improvement criteria. Results Significantly higher baseline level of C-reactive protein (CRP) was observed in HTLV-1 positive patients than in HTLV-1 positive patients (P = 0.003). The value of disease activity score in 28 joints (DAS28) and the levels of erythrocyte sedimentation rate (ESR) tended to be higher in HTLV-1 positive patients. The discontinuation rate of anti-TNF was higher in HTLV-1 positive patients 6 months after the beginning of treatment than in HTLV-1 negative patients (30 % v.s 0 %, respectively). Most of reason for discontinuation was inefficacy of anti-TNF. EULAR response rate in 3 months of the treatment was worse in HTLV-1 positive patients than in HTLV-1 positive patients. The levels of CRP, ESR and the value of DAS28 remained to be significantly higher in carrier RA than non-carrier RA. There is no development of lymphoma or myelopathy during 2-years observation period in HTLV-1 positive patients. Conclusions The result of this small study suggested that HTLV-1 positive RA patients have high inflammation and resistance to the treatment with anti-TNF. Further study with larger number of cases is necessary to confirm these data. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A437-A438. DOI:10.1136/annrheumdis-2013-eular.1321 · 10.38 Impact Factor
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    ABSTRACT: Background Leukocytapheresis (LCAP) is a treatment using extracorporial circulation with a filter for the removal of white blood cells (WBCs) from the peripheral blood and has been reported to be an effective treatment for rheumatoid arthritis (RA). The effectiveness of LCAP in inflammatory disease is speculated through the removal of activated WBCs and platelets. However, the precise mechanism of LCAP treatment for the inflammatory diseases is still under investigation. Objectives Because lactoferrin (LTF) and pentraxin 3 (PTX3) are stored in the granulocytes, we analyzed plasma LTF and PTX3 in patients with RA who were treated with LCAP. Methods Plasma levels of LTF and PTX3 before and after LCAP treatment were measured by enzyme linked immunoassays in 7 patients with RA. Four of these patients reached moderate response by LCAP by EULAR criteria. Those levels before and after the LCAP columns in the circuits were also measured. Peripheral blood of 13 patients with RA was exposed to unwoven polyester fiber filters for LCAP in vitro and the changes of LTF and PTX3 were measured. In addition, the morphological changes of granulocytes was also observed. Results Mean plasma levels of LTF and PTX3 after LCAP treatment (942.2ng/ml and 15.4ng/ml, respectively) were significantly higher than those before the treatment (134.2ng/ml and 1.9ng/ml, respectively) (p<0.01). Mean levels of LTF and PTX3 after the LCAP columns in the circuit were also markedly increased (1776.6 ng/ml and 11.2ng/ml, respectively). When the whole blood of 13 patients with RA was incubated with unwoven polyester fiber in vitro, the levels of LTF and PTX3 (2169.7 and 11.2ng/ml) were higher than those without incubation (174.9 and 1.9ng/ml) (p<0.01). Cytoplasmic vacuolation of granulocytes was observed in the incubated samples. Conclusions Release of LTF and PTX3 from the WBCs captured in the LCAP columns was indicated in this study. Because LTF and PTX3 were suggested to have functions to modify the inflammation, the increased levels of these molecules after LCAP can be contributed to the therapeutic effect in RA. Disclosure of Interest None Declared
    Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):673-673. DOI:10.1136/annrheumdis-2012-eular.608 · 10.38 Impact Factor
  • Internal Medicine 01/2014; 53(4):347. DOI:10.2169/internalmedicine.53.1618 · 0.97 Impact Factor
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    ABSTRACT: A 63-year-old woman presented to our hospital with fever, purpura and pain in both legs and died 4 days after admission. Her blood smear and skin biopsy showed cylinder-like bodies (20×120 μm). She was diagnosed to have monoclonal gammopathy (IgG, lambda type). An autopsy revealed cylinder-like bodies in the vasculature of various organs. We noted a proliferation of atypical plasma cells in her bone marrow, suggesting pre-existing myeloma. Crystalglobulinemia is a rare manifestation of hypergammaglobulinemia that can cause multiple embolisms of the small vessels, and this resulted in the patient's fulminant course. The identification of cylinder-like bodies in the peripheral blood may help in reaching a diagnosis in such cases.
    Internal Medicine 01/2014; 53(16):1847-51. DOI:10.2169/internalmedicine.53.1775 · 0.97 Impact Factor
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    ABSTRACT: Adult T-cell leukemia/lymphoma (ATL) is a fatal malignancy caused by infection with human T-lymphotropic virus type-1 and there is no accepted curative therapy for ATL. We searched for biological active substances for the prevention and treatment of ATL from several species of herbs. The ATL cell growth-inhibitory activity and apoptosis assay showed that carnosol, which is an ingredient contained in rosemary (Rosmarinus officinalis), induced apoptosis in ATL cells. Next, to investigate the apoptosis-inducing mechanism of carnosol, we applied proteomic analysis using fluorescent two-dimensional differential gel electrophoresis and mass spectrometry. The proteomic analysis showed that the expression of reductases, enzymes in glycolytic pathway, and enzymes in pentose phosphate pathway was increased in carnosol-treated cells, compared with untreated cells. These results suggested that carnosol affected the redox status in the cells. Further, the quantitative analysis of glutathione, which plays the central role for the maintenance of intracellular redox status, indicated that carnosol caused the decrease of glutathione in the cells. Further, N-acetyl-L-cystein, which is precursor of glutathione, canceled the efficiency of carnosol. From these results, it was suggested that the apoptosis-inducing activity of carnosol in ATL cells was caused by the depletion of glutathione.
    Human Cell 12/2013; 27(2). DOI:10.1007/s13577-013-0083-6 · 1.74 Impact Factor
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    ABSTRACT: Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.
    Modern Rheumatology 11/2013; DOI:10.3109/14397595.2013.844389 · 2.21 Impact Factor
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    ABSTRACT: Helicobacter cinaedi is now recognized as an increasingly important emerging disease in humans. Although H. cinaedi-like strains have been isolated from a variety of animals, it is difficult to identify particular isolates due to their unusual phenotypic profiles and the limited number of biochemical tests for helicobacters. Moreover, analysis of the 16S rRNA gene sequences is also limited due to the high level of similarity among closely related helicobacters.This study was conducted to evaluate intact cell mass spectrometry (ICMS) profiling using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a tool for identification of H. cinaedi. A total of 68 strains of H. cinaedi isolated from humans, dogs, a cat, and hamsters were examined in addition to other Helicobacter species. The major ICMS profiles of H. cinaedi were identical and differed from H. bilis, which show > 98% sequence similarity at the 16S rRNA sequence level. A phyloproteomic analysis of the H. cinaedi strains examined in this work revealed that human isolates formed a single cluster that was distinct from that of the animal isolates with the exception of two strains from dogs. This phyloproteomic results agreed with those of phylogenetic analysis based on the nucleotide sequences of the hsp60 gene. Because they formed a distinct cluster in both analyses, our data suggest that animal strains may not be a major source of infection in humans. In conclusion, the ICMS profiles obtained using a MALDI-TOF MS approach may be useful for H. cinaedi identification and subtyping.
    Journal of clinical microbiology 10/2013; 52(1). DOI:10.1128/JCM.01798-13 · 4.23 Impact Factor
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    ABSTRACT: The aim of this study was to establish a broth microdilution method for antimicrobial susceptibility testing of Helicobacter cinaedi and to assess the prevalence and mechanisms of fluoroquinolone resistance in Japanese clinical isolates. A broth microdilution method using modified Levinthal broth was developed and compared with the agar dilution method for testing susceptibility to ampicillin, gentamicin, tetracycline and ciprofloxacin. The minimum inhibitory concentrations obtained by these two methods were almost the same for all the antibiotics tested, demonstrating the broth microdilution method to be a suitable and reliable technique for antimicrobial susceptibility testing. A broth microdilution method for antimicrobial susceptibility test for H. cinaedi was established. This method is expected to help improve treatment.
    Microbiology and Immunology 05/2013; 57(5):353-8. DOI:10.1111/1348-0421.12044 · 1.31 Impact Factor
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    ABSTRACT: We aimed to establish a broth microdilution method for antimicrobial susceptibility testing of H. cinaedi and to assess the prevalence and mechanisms of fluoroquinolone resistance in Japanese clinical isolates. A broth microdilution method using modified levinthal broth was developed and compared with the agar dilution method for testing susceptibility to ampicillin, gentamicin, tetracycline and ciprofloxacin. The MICs obtained by these two methods were almost the same for all the antibiotics tested demonstrating the broth microdilution method to be a suitable and reliable format for antimicrobial susceptibility testing. We established a broth microdilution method for antimicrobial susceptibility test for H. cinaedi. This method is expected to help improvement of the treatment.
    Microbiology and Immunology 03/2013; 57(5). DOI:10.1111/j.1348-0421.12044 · 1.31 Impact Factor
  • 03/2013; 3(1):18-26. DOI:10.3390/plants3010018
  • The Journal of Rheumatology 06/2012; 39(6):1291. DOI:10.3899/jrheum.120183 · 3.17 Impact Factor
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    International Journal of Infectious Diseases 06/2012; 16:e338. DOI:10.1016/j.ijid.2012.05.401 · 2.33 Impact Factor
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    ABSTRACT: High human T-lymphotropic virus Type 1 (HTLV-1) proviral DNA load (PVL) has been reported to be one risk factor for the development of adult T-cell leukemia/lymphoma (ATL). ATL is also believed to develop in HTLV-1 carriers who acquire infection perinatally. ATL cells have been reported to frequently harbor defective provirus. In our study, PVLs for three different regions of HTLV-1 provirus (5'LTR-gag, gag and pX) were measured in 309 asymptomatic carriers with different infection routes. PVLs for the pX region in 21 asymptomatic carriers with maternal infection was significantly higher than in 24 carriers with spousal infection. Among 161 carriers with relatively high pX PVLs (equal to or greater than 1 copy per 100 peripheral blood mononuclear cells), 26 carriers (16%) had low gag PVL/pX PVL (less than 0.5) and four (2%) had low 5'LTR-gag PVL/pX PVL (less than 0.5). Low gag PVL/pX PVL ratio, which reflects deficiency and/or polymorphism of HTLV-1 proviral DNA sequences for the gag region, was also associated with maternal infection. These data suggest that HTLV-1 carriers with maternal infection tend to have high PVLs, which may be related to provirus with deficiency and/or the polymorphism of proviral DNA sequences. In addition, there is a possibility that this ratio may be used as a tool to differentiate the infection routes of asymptomatic HTLV-1 carriers, which supports the need for a large scale study.
    International Journal of Cancer 05/2012; 130(10):2318-26. DOI:10.1002/ijc.26289 · 5.01 Impact Factor
  • Ichiro Takajo · Ikuo Yamamoto · Kazumi Umeki · Akihiko Okayama
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    ABSTRACT: Procalcitonin (PCT), a precursor for calcitonin, has been reported to be elevated in bacterial infection. However, its significance in the diagnosis of bacterial infection in patients with systemic autoimmune diseases, who have treatment with corticosteroid and immunosuppressive drug, is limited. To investigate the usefulness of serum procalcitonin measurement in the diagnosis of bacterial infection in patients with systemic autoimmune diseases, we analyzed 28 patients with systemic autoimmune diseases hospitalized because of fever and/or C-reactive protein (CRP) elevation. PCT was measured by the immunochromatography assay. Fourteen patients were considered having bacterial infections and the other 14 patients were considered having disease flare of their systemic autoimmune diseases. Serum CRP levels in the bacterial infection group was higher than that in the systemic autoimmune disease flare group; however, the difference did not reach statistical significance. The positive rate of serum PCT was significantly higher in the bacterial infection group (10/14, 71%) than that in the systemic autoimmune disease flare group (1/14, 7%), although there were 2 cases showing false positive PCT probably due to rheumatoid factor. This study suggested that PCT is useful in the diagnosis of bacterial infection in patients with systemic autoimmune diseases who are treated with corticosteroid and immunosuppressive drug.
    Rinsho byori. The Japanese journal of clinical pathology 04/2012; 60(4):294-9.
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    ABSTRACT: Cell adhesion molecule 1 (CADM1/TSLC1) was recently identified as a novel cell surface marker for adult T-cell leukemia/lymphoma (ATLL). In this study, we developed various antibodies as diagnostic tools to identify CADM1-positive ATLL leukemia cells. In flow cytometric analysis, the percentages of CD4(+)CADM1(+) double-positive cells correlated well with both the percentages of CD4(+)CD25(+) cells and with abnormal lymphocytes in the peripheral blood of patients with various types of ATLL. Moreover, the degree of CD4(+)CADM1(+) cells over 1% significantly correlated with the copy number of the human T-lymphotropic virus type 1 (HTLV-1) provirus in the peripheral blood of HTLV-1 carriers and ATLL patients. We also identified a soluble form of CADM1 in the peripheral blood of ATLL patients, and the expression levels of this form were correlated with the levels of soluble interleukin 2 receptor alpha. Moreover, lymphomas derived from ATLL were strongly and specifically stained with a CADM1 antibody. Thus, detection of CD4(+)CADM1(+) cells in the peripheral blood, measurement of serum levels of soluble CADM1 and immunohistochemical detection of CADM1 in lymphomas would be a useful set of markers for disease progression in ATLL and may aid in both the early diagnosis and measurement of treatment efficacy for ATLL.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 01/2012; 26(6):1238-46. DOI:10.1038/leu.2011.379 · 9.38 Impact Factor

Publication Stats

2k Citations
588.82 Total Impact Points

Institutions

  • 1997–2014
    • Miyazaki University
      • • Faculty of Medicine
      • • Department of Laboratory Medicine
      • • Department of Internal Medicine 3
      Миядзаки, Miyazaki, Japan
  • 2007
    • The University of Tokyo
      • Research Center for Asian Infectious Diseases
      Tokyo, Tokyo-to, Japan
  • 2005
    • Boston University
      Boston, Massachusetts, United States
  • 2003
    • Miyazaki Prefectural Nursing University
      Миядзаки, Miyazaki, Japan
  • 2002–2003
    • Kumamoto University
      • Department of Oral and Maxillofacial Surgery
      Kumamoto, Kumamoto, Japan
  • 1999–2002
    • Harvard University
      • Department of Epidemiology
      Cambridge, Massachusetts, United States
  • 1995
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 1989–1990
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States