Naoki Watanabe

Sapporo Medical University, Sapporo, Hokkaidō, Japan

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Publications (201)451.81 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Left ventricular (LV) functions assessed by echocardiography and cardiac biomarkers are strong predictors of mortality in patients with systemic light chain (AL) amyloidosis. However, most previous studies have been conducted in Western countries, and the predictors of mortality in Asian patients with AL amyloidosis have not been characterized. To address this issue, we aimed to determine the predictors of mortality in Asian patients with biopsy-confirmed AL amyloidosis. Methods We retrospectively enrolled 31 patients (59±11 years, 55% men) in whom AL amyloidosis was confirmed by biopsies from cardiac or non-cardiac tissues. Of these patients, 15 (48%) met the international echocardiographic criteria for cardiac amyloidosis (mean LV wall thickness >12 mm without other causes of LV hypertrophy). Results During a mean follow-up period of 21±20 months, 15 patients died. Non-survivors had a higher number of involved organs, lower e', and higher rates of E/e' >15, pericardial effusion (PE), low voltage on an electrocardiogram and a New York Heart Association (NYHA) functional class ≥ III, compared with survivors. In multivariate analysis, a NYHA functional class ≥ III (p=0.024) and cardiac involvement (p=0.032) were independent predictors of PE in patients with AL amyloidosis. Multivariate Cox proportional hazard analysis indicated that PE (hazard ratio: 21.9, p=0.025) and the number of involved organs (hazard ratio: 2.8, p=0.015), but not LV diastolic parameters of tissue Doppler echocardiography, independently predict mortality in patients with AL amyloidosis. Conclusion PE and multiple organ involvement, compared with e' and E/e', are stronger predictors of mortality in patients with AL amyloidosis. The advanced disease stage of AL amyloidosis might underlie the strong association between PE and a poor outcome.
    Internal Medicine 08/2015; 54(15):1833-40. DOI:10.2169/internalmedicine.54.3500 · 0.90 Impact Factor
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    ABSTRACT: Whether an intervendor discordance of myocardial velocities determined by tissue Doppler echocardiography (TDE) can be generalized remains unclear. We compared intervendor variabilities of left ventricular (LV) and right ventricular (RV) myocardial velocities among three TDE systems. Examinations with TDE were performed in 41 healthy subjects and 11 patients with cardiovascular risk factors (CVR) using α-7 (V1, Hitachi Aloka Medical), Artida (V2, Toshiba Medical Systems), and Vivid E9 (V3, GE Healthcare) on the same day. Peak systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities at medial and lateral sites of the mitral annulus and lateral site of the tricuspid annulus were measured using both pulsed-wave TDE and color TDE. Intra-observer and inter-observer variabilities were determined in 10 subjects and test-retest variability in 14 subjects. As for test-retest variability, reproducibilities of LV and RV myocardial velocities determined by pulsed-wave TDE and color TDE were relatively low but comparable between V1, V2, and V3. Myocardial velocities in healthy subjects determined by both pulsed-wave TDE and color TDE were significantly different among the three TDE systems. Myocardial velocities by pulsed-wave TDE in V3 were 2-12% lower (P < 0.05) than those by V2 and 5-14% lower (P < 0.05) than those by V1. Similar differences in myocardial velocities determined by both pulsed-wave TDE and color TDE were found in patients with CVR. LV and RV myocardial velocities determined by both pulsed-wave TDE and color TDE are vendor dependent, and reproducibility of the myocardial velocities determined by both TDE systems is relatively low. © 2015, Wiley Periodicals, Inc.
    Echocardiography 04/2015; DOI:10.1111/echo.12962 · 1.25 Impact Factor
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    ABSTRACT: Autoantibodies against cancer-related antigens may be detected in the sera of patients with various types of cancer, although their clinical utility has not yet been established. In this study, we aimed to demonstrate the diagnostic relevance of autoantibody detection against inhibitor of apoptosis protein (IAP) family members in colon cancer, as compared to anti-p53 antibody, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9. We established an ELISA system using original recombinant proteins of IAP family members (survivin, livin and X-linked IAP) and measured the expression levels in the sera of 62 healthy donors, 250 patients with colon polyps (adenoma) and 176 patients with colon cancer. When the cutoff value was set as the mean value + 2 standard deviations in healthy donors, anti-survivin exhibited the highest positivity rate (24.4%) among IAP autoantibodies in cancer patients. Furthermore, the anti-survivin antibody exhibited a high positivity rate in early-stage carcinoma and adenoma. In the combination assay, reflecting the significantly high positivity rate of CEA in stage IV tumors, the positivity rate was highest when combining the detection of anti-survivin antibody and CEA in cancer patients (50.0%), indicating that this combination may not be useful for the diagnosis of early-stage cancers. By contrast, reflecting the complete independencE of anti-survivin and anti-p53 antibodies, the combination of detecting these two antibodies resulted in the highest positivity rate (35.6%) in early-stage disease (stage 0-I). These results suggest that the combined measurement of anti-survivin and anti-p53 antibodies may be useful for the detection of early-stage colon cancer.
    Molecular and Clinical Oncology 02/2015; 3(3). DOI:10.3892/mco.2015.502
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    ABSTRACT: We examined first evidence for the significance of SALL4, a transcription factor essential for embryonic development and the self‑renewal of embryonic stem (ES) cells, as a natural resistance factor against anticancer drugs in lung cancer. To determine the significance of SALL4 expression in lung cancer cells, small inhibitory RNA (siRNA) against SALL4 was transduced into A549 and SBC‑3 cells, resulting in increased sensitivity towards anticancer drugs [cisplatin (CDDP), carboplatin (CBDCA), and paclitaxel (PTX)]. SALL4 cancer tissues from 31 lung cancer patients were used to assess clinical significance. The analysis showed differences in SALL4 expression corresponding to the therapeutic outcomes. SALL4 expression measured before adjuvant chemotherapy was significantly higher in the patients showing recurrence of cancer than in the disease‑free patients. In addition, the period until recurrence was shorter in the patients showing high SALL4 expression. These results indicate that SALL4 overexpression acts as a natural resistance factor and may be involved in the recurrence of lung cancer after adjuvant chemotherapy.
    International Journal of Oncology 02/2015; 46(4). DOI:10.3892/ijo.2015.2866 · 3.03 Impact Factor
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    ABSTRACT: A 55-year-old woman was admitted for an evaluation of a mediastinal mass, bilateral cervical lymphadenopathy and a left breast tumor. Although pathology revealed a diagnosis of breast cancer, the cervical lymph nodes differed from the breast lesion. An anaplastic lymphoma kinase (ALK) gene analysis revealed ALK rearrangement in the cervical lymph nodes only, which were therefore diagnosed as reflective of metastasis of lung adenocarcinoma. The mediastinal tumor was also diagnosed as an ALK-positive lung adenocarcinoma based on its therapeutic response. ALK gene analyses can be used to identify primary lesions in patients with cancers of unknown primary sites.
    Internal Medicine 12/2014; 53(23):2711-5. DOI:10.2169/internalmedicine.53.2775 · 0.90 Impact Factor
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    ABSTRACT: Background: Increases in tumor marker concentrations usually suggest disease progression. Case report: We here describe on 3 patients with non-small cell lung cancer whose serum concentrations of CYFRA21-1 increased in spite of successful treatment with crizotinib. Discontinuation of crizotinib resulted in a rapid decrease in serum CYFRA21-1 concentrations in all cases. In 1 patient with progressive disease, in spite of increasing the dose of crizotinib, CYFRA21-1 concentrations decreased. Conclusions: Crizotinib can induce increases in CYFRA21-1 concentration without disease progression. Pulmonologists and oncologists should be aware of this novel phenomenon, and focus on interpretation of CYFRA21-1 concentrations in monitoring tumor response to crizotinib treatment.
    American Journal of Case Reports 11/2014; 15:480-484. DOI:10.12659/AJCR.891194
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    ABSTRACT: Purpose No lung cancer xenograft model using non-obese diabetic (NOD)-scid Il2rg−/− mice has been reported. The purpose of this study is to select a suitable mouse strain as a xenogenic host for testing tumorigenicity of lung cancer. Materials and methods We directly compared the susceptibility of four immunodeficient mouse strains, c-nu, C.B-17 scid, NOD-scid, and NOD/LtSz-scid Il2rg−/− (NSG) mice, for tumor formation from xenotransplanted lung cancer cell lines. Various numbers (101–105 cells/head) of two lung cancer cell lines, A549 and EBC1, were subcutaneously inoculated and tumor sizes were measured every week up to 12 weeks. Results When 104 EBC1 cells were inoculated, no tumor formation was observed in BALB/c-nu or C.B-17 scid mice. Tumors developed in two of the five NOD-scid mice (40%) and in all the five NSG mice (100%). When 103 EBC1 cells were injected, no tumors developed in any strain other than NSG mice, while tumorigenesis was achieved in all the five NSG mice (100%, P=0.0079) within 9 weeks. NSG mice similarly showed higher susceptibility to xenotransplantation of A549 cells. Tumor formation was observed only in NSG mice after inoculation of 103 or fewer A549 cells (40% vs 0% in 15 NSG mice compared with others, respectively, P=0.0169). We confirmed that the engrafted tumors originated from inoculated human lung cancer cells by immunohistochemical staining with human cytokeratin and vimentin. Conclusion NSG mice may be the most suitable strain for testing tumorigenicity of lung cancer, especially if only a few cells are available.
    Cancer Management and Research 10/2014; 6:431-6. DOI:10.2147/CMAR.S71185
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    ABSTRACT: Evidences are accumulating that extract of Acanthopanax senticosus Harms (ASH; syn Eleutherococcus senticosus [Rupr. & Maxim.] Maxim), a shrub native to Northeastern Asia, has antiinflammatory effects. In this study, we examined prophylactic and therapeutic effects of ASH extract (ASHE) on rheumatoid arthritis using collagen-induced arthritis (CIA) mouse model. Acanthopanax senticosus Harms extract was administered before the onset of arthritis in the prophylaxis model. In the therapeutic model, ASHE was administered after the onset of arthritis with or without anti-TNF-α antibody. The ASHE treatment showed efficacy before onset of CIA but there was no effect after CIA was established. The ASHE treatment delayed the onset and decreased severity of CIA. In vitro examinations showed that ASHE is an antioxidant and that ASHE suppresses TNF-α and interleukin-6 production in human peripheral blood mononuclear cells. The combination therapy with ASHE and anti-TNF-α antibody reduced the severity of arthritis compared with anti-TNF-α antibody alone. The present study shows that ASHE has prophylactic effect against CIA and support therapeutic effect of anti-TNF-α antibody. © 2014 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.
    Phytotherapy Research 10/2014; 28(10). DOI:10.1002/ptr.5157 · 2.66 Impact Factor
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    ABSTRACT: Alterations in the mRNA expression or the mutation of previously reported tyrosine kinases have been detected only in a limited number of patients with acute leukemia. In this study, we examined whether the widely expressed serine threonine tyrosine kinase 1 (STYK1)/novel oncogene with kinase domain (NOK) acts as a drug resistance factor in acute leukemia. The transfection of leukemic HL-60 cells with an STYK1 expression vector resulted in the resistance to doxorubicin and etoposide and decreased drug-induced caspase-3/7 activity and sub-G1 population. To investigate the mechanism of STYK1-induced drug resistance, microarray analysis was performed using HL-60 cells transfected with control or STYK1 expression vectors. Three tyrosine kinases (EphA4, FLT4 and STK31), two NF-κB inducers (MAPK4 and TNF-RSF11A), and two genes essential for stem cell replication (SALL4 and NOV) were identified as novel STYK1-induced genes. In addition to the data using cell line, a comparison of the leukemic patients who did and did not respond to therapy revealed that STYK1 expression before therapy was significantly higher in the non-responder group compared with the group that responded completely. These results suggest that STYK1 is a novel drug resistance factor and could be a predictor of the therapeutic response in acute leukemia.
    International Journal of Oncology 09/2014; 45(5). DOI:10.3892/ijo.2014.2633 · 3.03 Impact Factor
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    ABSTRACT: The precise identities of the virulence factors of Pseudomonas aeruginosa after bacteriolysis are still unknown. In the present study, we identified PA0423 protein, which was isolated from the Pseudomonas PAO-1 strain, as the factor responsible for cytotoxicity in lung epithelial cells. Whole bacterial cell lysate of P. aeruginosa PAO-1 caused cytotoxicity in A549 lung epithelial cells. This cytotoxic factor could be partially purified via gel-filtration and anion-exchange column chromatography, and its activity was attenuated by proteinase K treatment. The cytotoxic fraction increased caspase-3/7 activity in A549 cells, suggesting the induction of apoptosis. This fraction was then subjected to amino-acid sequence analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, resulting in the identification of 7 matches, 4 of which were with known proteins (PA0122, PA2687, PA3406, and PA0423). Deletion mutant analysis of these 7 candidates revealed that only the PA0423 mutation led to reduced cytotoxicity, indicating that this protein is the virulence factor. Furthermore, PA0423 recombinant protein was constructed, purified, and refolded. Transduction of recombinant PA0423, but not PA0122, into A549 cells engendered a dose-dependent cytotoxic effect. These results show the first evidence that specific bacteriolysis-induced virulence factor PA0423 from Pseudomonas is toxic to lung epithelial cells.
    Microbial Pathogenesis 08/2014; 75. DOI:10.1016/j.micpath.2014.08.002 · 1.79 Impact Factor
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    ABSTRACT: Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau's syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer.
    08/2014; 5(3):197-223. DOI:10.5306/wjco.v5.i3.197
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    ABSTRACT: Stanniocalcin-l (STC-1) is a secreted glycoprotein hormone that regulates calcium and phosphate homeostasis. STC-1 expression is upregulated in several cancers including breast cancer, and has been shown to be prognostic. Although these clinical observations implicate STC-1 as a potential tumor marker, it is still unclear whether STC-1 confers a malignant phenotype. In this study, this question was addressed by overexpressing STC-1 in the human breast cancer cell line MDA-MB-231 and examining the resultant phenotype in vitro and in vivo. Overexpression of STC-1 enhanced invasiveness of MDA-MB-231 cells in vitro and promoted their lung metastasis in vivo, while having no effect on proliferation, adhesion, or proteinase activity. The addition of soluble STC-1 to MDA-MB-231 cultures resulted in the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, suggesting a mechanistic basis for the observed increases in cell motility and metastasis. Taken together, it was indicated that secreted STC-1 promotes metastatic potential of breast cancer cells via activation of PI3K/AKT.
    Clinical and Experimental Metastasis 07/2014; 31(7). DOI:10.1007/s10585-014-9668-z · 3.49 Impact Factor
  • Osamu Imataki · Naoki Watanabe · Akihito Matsuoka · Makiko Uemura
    Internal Medicine 07/2014; 53(14):1585-6. DOI:10.2169/internalmedicine.53.2113 · 0.90 Impact Factor
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    ABSTRACT: The revised version of the guideline JSLM 2012 was published in December 2012 by the Japanese Society of Laboratory Medicine. This version included new sections, such as blood gas analysis, sleep apnea syndrome, interstitial lung disease, liver and pancreas cancer, chronic kidney disease, acute kidney disease, gout and hyperuricemia, bone metabolism abnormality, malignant lymphoma, and rheumatoid arthritis. The guideline committee was composed of specialists in each field of internal medicine, who were responsible for selecting and requesting the authors and also in promoting and proofreading the manuscripts. In special program I at the 60th annual meeting, each specialist gave lectures concerning the points of the revision in their fields. The questionnaire surveys were performed using FAX or the Internet. Analysis of eighty-seven (2.5%) responses from 3,500 individuals/facilities, which were sent the guideline, revealed that this guideline was graded as excellent by 38 readers, fair by 42, and average by in 6. Significant opinions on the guideline were obtained from the readers, and they will be the bases for the next revision. The main subjects of this guideline were confirmed to be the residents and general physicians, by whom it is hoped the routine laboratory tests will be properly utilized. Therefore, based on the section of 'approach of the laboratory test results', which is a representative characteristic of this guideline, the sections of 'symptoms' will be fulfilled for the next version. This guideline needs to be periodically revised with advances in medicine.
    Rinsho byori. The Japanese journal of clinical pathology 07/2014; 62(7):702-9.
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    ABSTRACT: Extramedullary involvement (EMI) is a factor that defines prognosis of acute lymphoblastic leukemia; however, the molecular mechanism(s) remain elusive. Here, we show that CD7 promotes EMI of the human B-cell acute lymphoblastic leukemia cell line Tanoue. The Tanoue cell line expressing firefly luciferase, Luc-Tanoue, was transplanted into non-obese diabetic/severe combined immunodeficient mice, and cells infiltrated into the brain were cultured ex vivo. This process was repeated 4 times to obtain the highly invasive line Luc-Tanoue-F4. Comparison of the global gene expression signatures of Luc-Tanoue-F4 and Luc-Tanoue indicated that the CD7 gene showed the largest increase in expression among EMI-related genes in Luc-Tanoue-F4 cells. Overexpression of CD7 in Tanoue enhanced cell invasiveness. Among cell migration, proliferation, adhesion and protease activity, only cell adhesiveness showed enhancement in Luc-Tanoue-F4. Expression of the intracellular domain, but not the extracellular domain, of CD7 enhanced cell adhesiveness. Luc-Tanoue-F4 showed a higher level of integrin β2 expression; overexpression of CD7 induced the expression of integrin β2 in Luc-Tanoue. These results show that CD7 induces integrin β2 and enhances cell adhesiveness and invasiveness in Tanoue cells. This study highlights the role of the CD7/integrin β2 axis as a critical pathway in the process of EMI of human B-cell acute lymphoblastic leukemia.
    International Journal of Oncology 06/2014; 45(3). DOI:10.3892/ijo.2014.2492 · 3.03 Impact Factor
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    ABSTRACT: The phosphatidylinositol 3-kinase pathway transduces cell survival signals in different malignancies. Protein kinase C ζ (PKCζ) is one of the molecules involved in this pathway. In this study, we investigated the role of PKCζ in apoptosis. Short interfering RNA against PKCζ (siPKCζ) sensitized HCT116 and SW480 colon cancer cells to TRAIL‑induced apoptosis. Among anti-apoptotic proteins, survivin protein and mRNA expression levels decreased after siPKCζ transfection while protein half-life did not change. The expression levels of survivin and PKCζ were correlated in 18 colon cancer specimens (r=0.72, P=3.01x10‑4). Chemosensitivity to 5-FU was enhanced by siPKCζ in HCT116 and SW480 cells. These results indicate that PKCζ regulates survivin expression levels and inhibits apoptosis in colon cancer cells. This study provides a rationale for targeting PKCζ in combination with chemotherapy for colon cancer treatment.
    International Journal of Oncology 06/2014; 45(3). DOI:10.3892/ijo.2014.2489 · 3.03 Impact Factor
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    ABSTRACT: Background Inter-vendor discordance in three-dimensional speckle-tracking echocardiography (3DS) remains uncharacterized. We aimed to examine inter-vendor discordance of left ventricular (LV) volumes, and functional parameters and their reproducibilities between two commercially available 3DS systems.Methods Echocardiographic examinations with 3DS were performed in 26 healthy subjects (age 34 ± 13 years, 85% men) using a Vivid E9 system (V1) with 4V probe (GE Health Care) and Artida (V2) with PST-25SX probe (Toshiba Medical Systems) on the same day. LV variables and global LV longitudinal, circumferential, radial, and area strains were measured by vendor-specific softwares, 4D strain EchoPAC BT11 (for V1) and 3D WMT (for V2), respectively. Reproducibility of data was assessed by an intra-class correlation coefficient (ICC).ResultsThe mean time required for 3DS analysis was 5.4 ± 1.5 min for V1, being 21% less than that for V2 (6.8 ± 1.9 min, P < 0.01). Reproducibilities of all LV strains were comparable between V1 (ICC 0.50–0.82) and V2 (ICC 0.51–0.76), except for intra-observer and inter-observer reproducibilities of radial strain being lower in V2 (ICC for V1 0.82 and 0.82 and ICC for V2 0.44 and 0.40, respectively). LV strains in all directions and area were significantly different between V1 and V2, though LV volumes and ejection fraction were comparable.Conclusions Global longitudinal, circumferential, and area LV strains are reproducible in both 3DS vendors. However, values of three-dimensional LV strains by 3DS are highly vendor-dependent.
    Echocardiography 05/2014; 31(5). DOI:10.1111/echo.12432 · 1.25 Impact Factor
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    ABSTRACT: Key Clinical Message Monocytosis is often profoundly implicated in chronic myelomonocytic leukemia (CMML). We diagnosed a 63-year-old woman with CMML involving heterochronological systemic polyserositis with infiltrating benign monocytes. The patient's pleural effusion was eliminated completely with corticosteroid therapy. We speculate that our case represents an immunological reaction with activated monocytes triggered by infection.
    04/2014; 2(2). DOI:10.1002/ccr3.55
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    ABSTRACT: Patient: Male, 83 Final Diagnosis: Membranous glomerulonephritis Symptoms: Producting cough Medication: - Clinical Procedure: - Specialty: Nephrology. Rare disease. Membranous glomerulonephritis can occur secondarily from infectious diseases. There are no reports describing membranous glomerulonephritis caused by non-tuberculous mycobacterium infection. However, several cases with membranous glomerulonephritis due to Mycobacterium tuberculosis have been reported. Mycobacterium shimoidei is an uncommon pathogen, and less than 20 cases with this species have been reported. A therapeutic regimen for this infection has not been established yet. An 83-year-old Japanese man presented with productive cough for 6 months. Computed tomography scan showed multiple cavities in the bilateral pulmonary fields. Acid-fast bacilli were evident in his sputum by Ziehl-Neelsen staining (Gaffky 3). PCR amplifications for Mycobacterium tuberculosis, Mycobacterium avium, and Mycobacterium intracellulare were all negative. Finally, Mycobacterium shimoidei was identified by rpoB sequencing and 16S rRNA sequencing. Urine examination showed a sub-nephrotic range of proteinuria and histology of the kidney showed membranous glomerulonephritis. Antimycobacterial treatment with clarithromycin, rifampicin, and ethambutol dramatically improved not only the pulmonary disease, but also the proteinuria. To the best of our knowledge, the presented case is the first report showing non-tuberculous mycobacterium-induced secondary membranous glomerulonephritis. A combination with clarithromycin, ethambutol, and rifampicin might be effective for treatment of Mycobacterium shimoidei infection.
    American Journal of Case Reports 12/2013; 14:543-7. DOI:10.12659/AJCR.889684
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    ABSTRACT: Arginine catabolic mobile element (ACME), a genomic island consisting of the arc and/or opp3 gene clusters found in staphylococcal species, is related to increased bacterial adaptability to hosts. Staphylococcus epidermidis is considered a major ACME reservoir; however, prevalence and genetic diversity of ACME in coagulase-negative staphylococci (CNS) have not yet been well characterized for clinical isolates in Japan. A total of 271 clinical isolates of CNS in a Japanese hospital were investigated for the presence and genotype of ACME and SCCmec. The prevalence of ACME-arcA was significantly higher (p<0.001) in S. epidermidis (45.8%) than in other CNS species (3.7%). ACME in S. epidermidis isolates (n=87) were differentiated into type I (n=33), variant forms of type I (ΔI, n=26) newly identified in this study, type II (n=6), and type ΔII (n=19). ACME-type ΔI, which were further classified into three subtypes, lacked some genetic components between the arc and opp3 clusters in archetypal type I, whereas the arc and opp3 clusters were intact. The arc cluster exhibited high sequence identity (95.8-100 %) to that of type I ACME; in contrast, the opp3 cluster was highly diverse, and showed relatively lower identities (94.8- 98.7%) to the identical regions in type I ACME. Twenty-one isolates of ΔI ACME-carrying S. epidermidis possessed SCCmec IVa and belonged to ST5 (clonal complex 2). Phylogenetic analysis revealed that isolaets harbouring ACME ΔI in this study clustered with previously reported S. epidermidis strains with other lineges, suggesting that S. epidermidis originally had some genetic variations in the opp3 cluster. In summary, ACME type ΔI, a truncated variant of ACME-I, was first identified in S. epidermidis, and revealed to be prevalent in ST5 MRSE clinical isolates with SCCmec IVa.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 10/2013; 20. DOI:10.1016/j.meegid.2013.09.018 · 3.02 Impact Factor

Publication Stats

3k Citations
451.81 Total Impact Points


  • 1986–2015
    • Sapporo Medical University
      • • Department of Clinical Laboratory Medicine
      • • Division of Surgery II
      • • Division of Laboratory Diagnosis
      • • School of Medicine
      • • Division of Internal Medicine II
      Sapporo, Hokkaidō, Japan
  • 2012–2014
    • Kagawa University
      • Department of Internal Medicine I (Endocrinology and Metabolism, Hematology, Rheumatology and Respiratory Medicine)
      Takamatu, Kagawa, Japan
  • 2010
    • Health Sciences University of Hokkaido
      • Department of Pediatric Dentistry
      Tōbetsu, Hokkaido, Japan