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  • 1
    In: Journal of Medical Microbiology, Microbiology Society, Vol. 49, No. 8 ( 2000-08-01), p. 701-707
    Type of Medium: Online Resource
    ISSN: 0022-2615 , 1473-5644
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    Language: English
    Publisher: Microbiology Society
    Publication Date: 2000
    detail.hit.zdb_id: 2083944-3
    SSG: 12
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  • 2
    In: Journal of Medical Microbiology, Microbiology Society, Vol. 61, No. 11 ( 2012-11-01), p. 1556-1562
    Type of Medium: Online Resource
    ISSN: 0022-2615 , 1473-5644
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    Language: English
    Publisher: Microbiology Society
    Publication Date: 2012
    detail.hit.zdb_id: 2083944-3
    SSG: 12
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  • 3
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 5041-5041
    Abstract: The prevalence of Monoclonal Gammopathy of Undetermined Significance (MGUS) in Japanese population and that in radiation-exposed population have not been accurately determined. We performed a M-protein screening to determine the prevalence of MGUS and a cohort study to determine the probability of progression from MGUS to multiple myeloma (MM) in a large Japanese population exposed to radiation. In this study, if we could find any effects of radiation-exposure on outcomes, we may provide etiological clues for MGUS and its progression to MM, or, even if we could not, we may provide the Japanese-specific prevalence of MGUS and its progression. The target population included atomic bomb survivors living in Nagasaki City as of October 1, 1988 (N=71,062; median age 58 years at 1988; range 42 to 97). The screening process consisted of agarose-gel electrophoresis, immuno-electrophoresis and quantitative immunoglobulin. General laboratory test and physical examination were also conducted. Serum samples were obtained from 52,525 subjects (73.9% of population) during October 1, 1988 to March 31, 2004. We identified 1,087 cases of MGUS among screened subjects. The crude prevalence of MGUS was 2.1% (95%CI, 1.9 to 2.2) in all subjects, and was 2.4% when limited subjects 50 years or older at 1988. MGUS prevalence increased by age same as many previous studies had reported. The prevalence was significantly higher in men than in women (2.8% vs. 1.6%, odds ratio 1.7, 95%CI, 1.5–1.9). To investigate the effect of radiation-exposure on occurrence of MGUS, a multiple logistic regression analysis, adjusted for age-at-1988 and sex, were performed including three radiation exposed-states: exposed within 1.5km from the atomic bomb hypocenter, 1.5–3.0km, and beyond 3.0km. There was a significant interaction between age-at-1988 and the exposed distance. We suspected that age at exposed to radiation might influence the occurrence of MGUS. Therefore, we performed multiple logistic regressions separately by dichotomized exposed age at 1945, under 20 years or 20 years or more, including sex, age-at-1988 (every 10 years as continuous data), and exposed distance category as covariates. In both age groups, male sex and the aging were strong risk factors of occurrence of MGUS. The exposed distance was not affected in exposed age 20 years or more at 1945. However, in exposed age under 20 years at 1945, MGUS prevalence was higher in those exposed within 1.5km than those beyond 3.0km (adjusted OR=1.4, 95%CI, 1.7–2.4, p & lt;0.0001). Among MGUS cases, 38 cases developed to MM during the follow-up. Overall cumulative risk of MM from MGUS was 8% during the average follow-up period 4.6 years. The estimated cumulative risk of developing MM was not different in sex, exposed age, and exposed distance, though those exposed proximally tend to develop to MM earlier than those exposed distally. Our results suggest that the higher radiation exposure at the younger age may affect the occurrence of MGUS beyond the effect of aging and sex on it, but the effect was weak for the progression from MGUS to MM. Further population-based studies for people exposed to radiation and external analyses are needed to confirm these findings.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
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  • 4
    In: Blood, American Society of Hematology, Vol. 89, No. 3 ( 1997-02-01), p. 948-956
    Abstract: We examined human T-lymphotropic virus type I (HTLV-I) DNA integration in 68 patients with adult T-cell leukemia/lymphoma (ATL) by Southern blotting using EcoRI, which does not cut within the 9 kb of the genome and probes for pX and gag-pol region of HTLV-I. We detected defective proviral integration as a monoclonal band of various sizes with the pX but not with the gag-pol probe, or a monoclonal band of less than 9 kb with the pX probe, in 20 patients (29.4%). These were designated defective (D) type. With both probes, a single band greater than 9 kb was detected in 34 (50.0%), designated complete (C) type, and two or more bands greater than 9 kb, were designated multiple (M) type, in 14 (20.6%). Advanced age, a high LDH value, and hypercalcemia were more frequent in D type patients. The median survival time (MST) was 6.8, 24.4, and 33.3 months, for D, C, and M types, respectively (log rank P = .006). Among 52 sequentially examined patients, the HTLV-I integration patterns changed in 4 (7.5%). In three of these four, the rearrangements of the T-cell receptor (TCR)b gene concomitantly changed, suggesting the appearance of a new ATL clone. Another patient had the same rearrangement of the TCRb gene, indicating clonal evolution. The HTLV-I integration pattern changed at crisis from indolent to aggressive ATL in three patients. These findings suggested that the HTLV-I integration patterns have clinical implications in ATL pathophysiology. In contrast to the clonal evolution characteristic of the multistep carcinogenesis of most human malignancies, the frequent clonal change of ATL at crisis is a peculiar phenomenon, probably reflecting the emergence of multiple premalignant clones in viral leukemogenesis as suggested in Epstein-Barr virus associated lymphomagenesis in the immunocompromised host.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1997
    detail.hit.zdb_id: 1468538-3
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  • 5
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2911-2911
    Abstract: To evaluate time-trend of HTLV-1 prevalence and the effect of preventative measure against the viral transmission are important in the virus endemic regions. In Nagasaki, Japan, an endemic area of HTLV-1, a routine serological virus screening for blood donors and a prefecture-wide intervention project (the ATL Prevention Program; APP) to prevent milk-borne transmission for the virus carrier mothers have been conducted since 1986 and 1987, respectively. However, the effects of both projects on the virus seroprevalence have not been well evaluated. In this study, we conducted trend analyses of age-specific, birth-year-specific, and period-specific seroprevalence of HTLV-1 for first-time blood donors who donated between January 1999 and December 2006. Among 55668 first-time donors (age at donation; 16–65 years, birth year; 1934–1990), 718 were test positive for HTLV-1, indicating that the overall seroprevalence was1.29% (95%CI, 1.20–1.39). Prevalence was significantly higher in women than men (1.53% vs. 1.13%; OR; 1.36, 95%CI; 1.17–1.57). Seroprevalence increased significantly with increasing age at donation from 0.70% at 16–25 years to 7.34% at over 56 years (Chi-square test, P 〈 0.0001). The annual prevalence was 1.32 in 1999, 1.31 in 2002, and 1.37 in 2006, indicating that there was no significant secular trend during 1999–2006 (P for trend=0.99). In analyses by age at donation, trends of HTLV-1 prevalence significantly declined among age over 56 years (P for trend=0.02) and age 16–25 years (P for trend=0.0007), whereas in birth-year-specific analyses, there was no apparent change of the prevalence over time, except in birth year 1981–90 group in which the prevalence declined from 1.22% in 1999 to 0.44% in 2006 (P for trend 〈 0.0001). In analyses for limited birth year from 1985 to 1990, the seroprevalence declined from 0.75% in birth year 1985–86 group, 0.31% in 1987–88 group, to zero% in 1989–90 group (P for trend =0.0002). HTLV-1 seroprevalence was significantly lower among donors born in 1987–90 (after APP) than 1985–86 (before APP). These results indicate that a birth-year-specific analysis for HTLV-1 prevalence may be appropriate to evaluate secular trend since the virus mostly transmit during infancy, and that a prefecture-wide intervention, the refraining from breast-feeding by the virus carrier mothers, contributes a declining HTLV-1 seroprevalence in our region.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 3575-3575
    Abstract: Background: Previous report on the subclassification and the clinical course of ATLL with maximum follow-up duration of 7 years revealed that the prognosis of indolent (smouldering or chronic) type was much better than that of aggressive (lymphoma or acute) types. (Shimoyama M, et al. Brit J Haematol, 1991). The median survival time (MST) was 6.2, 10.2 and 24.3 months for acute, lymphoma and chronic types, respectively. A MST has not been established for the smouldering type. However, long-term prognosis of the indolent types has not been elucidated. Method: The diagnosis of ATLL was made based on seropositivity for HTLV-1 and histologically- and/or cytogically-proven peripheral T-cell malignancy. Subclassification of ATLL was based on the Shimoyama’s criteria. A total of 90 patients with indolent ATLL (65 chronic type and 25 smouldering type) with a median age of 61 years, newly diagnosed from 1974 to 2003 at Nagasaki University, were analyzed for the clinical course and prognostic factors. Results: MST for the patients was 4.5 years with 12 patients alive for more than 10 years. Projected 5-, 10- and 15-yr survival rates were 47%, 23% and 13%, respectively, with first steep slope and sequential slow slope without plateau phase of the survival curve. Sixty-three of the patients died; 46 died of ATLL, 11 of other disease, 2 of transplantation related death and 4 of unknown. Unfavorable prognostic factor for survival included advanced performance status (PS) (p=0.005), high LDH value (p=0.004), more than 4 total involved lesions (p=0.03), more than 3 extranodal lesions (p=0.004), the presence of neutrophilia (p=0.02) by univariate analyses. In multivariate analysis, advanced PS was significant. There was no significant survival-difference in relation to age, subtypes of ATLL or lymphocyte count. Thirty-five patients with complications at diagnosis tended to be poor prognostic, especially those with active multiple cancers (n=7) or opportunistic infections (n=9). Most patients were treated as a subtype of chronic lymphoid leukemia (CLL) with watchful waiting until disease progression to acute ATLL. Twelve patients, who were treated with chemotherapy immediately after diagnosis of indolent ATLL, showed poorer prognosis as compared to the others. Five patients with at least one of the following 4 factors: alteration in tumor suppressor genes, p14ARF, p16 INK4a or p53, or aneuploidy & gt;1 chromosomal locus by Comparative Genomic Hybridization analysis in ATLL cells, showed extremely poor prognosis. Conclusions: The long-term prognosis of indolent ATLL was not good without plateau phase in the survival curve, similar to the findings in B-CLL. Advanced PS and genetic alterations in ATLL cells were poor prognostic factors.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 2515-2515
    Abstract: Adult T cell Leukemia/Lymphoma (ATLL) is a neoplasm of T-lymphocyte origin etiologically associated with HTLV-I and is known to be resistant to standard anti-cancer therapies. Recently, a small-molecule antagonist of MDM2, Nutlin-3a, has been developed, which inhibits the p53-MDM2 interaction and activates p53 signaling. The p53 tumor suppressor retains its wild-type conformation and transcriptional activity in half of all human tumors. Since anti-proliferative effects are imparted through a variety of mechanisms that include cell cycle arrest, apoptosis, and cellular senescence, and hence its activation may offer a therapeutic benefit in malignancies. Considering the future clinical use of Nutlin-3a, we characterized the sensitivity of leukemia cell lines to Nutlin-3a in the present study. Nutlin-3a requires not only wild-type p53 but also functional signaling in the p53 pathway. Thus, we first performed p53 mutation-analysis in all cell lines used, then evaluated the efficacy of Nutlin-3a. Here, we report for the first time that Nutlin-3a induces cellular senescence in hematological cell lines. Material and methods : We used 19 hematological cell lines including 8 HTLV-I related cell lines: 5 ATLL cell lines and 3 HTLV-I infected T-cell lines. The p53 mutations were examined using cDNA of each cell line, amplified by PCR targeting ORF, and sequenced using an ABI-PRISM model 310 Genetic Analyzer. Cell proliferation was assessed by MTS assay after 5 days incubation with 10μM Nutlin-3a. Apoptosis was evaluated by Annexin V binding and propidium iodide (PI) staining. Sodium butyrate (SB), known to induce cellular senescence in many types of cells, was used and senescence was assessed by SA-β-galactosidase (SA-β-gal) staining. We also analyzed expressions of p53, MDM2, p21, caspases, and pro- or anti-apoptotic proteins by Western blot. Results and Discussion : In mutation-analysis, 10 cell lines had the wild-type and 9 cell lines had mutated p53. Nine of 10 cell lines with wild-type p53 showed more than 60% inhibition of cells growth following Nutlin-3a treatment. In contrast, 8 of 9 cell lines with mutated p53 were not affected by Nutlin-3a. In ATLL cell lines with wild-type p53, Western blot analysis after 12-48h exposure to Nutlin-3a showed an increased level of p53, the p53 targets MDM2 and p21 especially in wild type cells. Of note, some of these cell lines were stained by SA-β-gal, but showed faint signals of apoptotic cell death on Annexin V and PI staining. Although it has been reported that p53 dependent proteins puma, noxa, and Bax play key roles in p53 dependent apoptosis, we did not find any change in these factors. Although 7 days of incubation with 1mM SB led senescence even in p53-mutated cell lines and these cells were stained by SA-β-gal, these cells were not stained by SA-β-gal when treated with Nutlin-3a. Moreover, mutated cell lines did not show any apoptotic change following Nutilin-3a treatment. These findings suggest that cellular senescence is more important than p53 dependent apoptosis in Nutlin-3a treatment in ATLL cells.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2385-2385
    Abstract: Adult T cell leukemia/lymphoma (ATL) is a mature T-cell neoplasm in adult that is caused by human T-cell leukemia virus type 1 (HTLV-1) and highly intractable to conventional therapeutics. Since there are 1.2 million HTLV-1 carriers in Japan and more than 50,000 carriers are expected to develop ATL from now on, it is of particular importance to understand the pathogenesis of ATL. The malignant processes of T-cell transformation in ATL are initiated by HTLV-1 infection in early childhood, and the HTLV-1 infected and immortalized T-cells are thought to accumulate a series of genetic hits during the later life, ultimately giving rise to malignant ATL clones after decades of latency periods. However, little is known about the nature of these genetic hits that take place after the early immortalization processes of T-cells mediated by HTLV-1 Tax protein. So in order to clarify the genetic alterations involved in the later processes of T-cell transformation in ATL, we analyzed a total of 130 ATL samples using Affymetrix® GeneChip® 250K Nsp arrays. Combined with CNAG/AsCNAR software, these arrays allow for accurate determination of allele-specific copy numbers in extremely high-resolution (less than 12kb) to detect copy number alterations as well as allelic imbalances in ATL genomes without depending on the availability of constitutive DNA of tumor specimens (molecular allelo-karyotyping). ATL genomes show characteristic copy number profiles and unique patterns of allelic imbalances, which are distinct from acute lymphoblastic ALL and non-Hodgikin’s lymphomas and include gains of 1q arm, 2q33, 3p and 3q arms, 9p12, 17q12, and 19p13, and losses of 1p13.1, 2q end, 3q22, 4q31, 6p22, 7q31, 9p21, 10p14, 12q13, 14q24, and 19q13. Moreover, allele-specific determination of copy numbers disclosed a number of regions showing copy number neutral LOH. Numerous homozygous deletions and gene amplifications were also identified and commonly mapped to less than 500Kb regions, which facilitated identification of candidate gene targets. Interestingly, these genetic lesions involved many T-cell related genes, indicating that the de-regulation of normal T cell functions may contribute the pathogenesis of ATL. In conclusion, molecular allelo-karyotyping of ATL genomes using SNP arrays provides valuable information about the molecular targets in ATL pathogenesis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: British Journal of Haematology, Wiley, Vol. 88, No. 2 ( 1994-10), p. 234-241
    Abstract: Summary. We established IL‐2‐dependent T cells from an adult T‐cell leukaemia (ATL) patient whose leukaemic cells changed from CD4 single‐p‐positive in the initial phase to double‐negative (CD4 ‐ CD8 ‐ ) at the time of exacerbation. The cells termed SO‐4 were of ATL cell origin and showed the double‐negative TCRαβ/CD3 + T‐cell phenotype. SO‐4 cells acquired CD4 antigen expression following stimulation with concanavlin A (ConA) or immobilized anti‐CD3 antibody. The induction was inhibited by herbimycin A, an inhibitor of protein tyrosine kinase (PTK) activity. No CD4 mRNA was detectable in unstimulated SO‐4 cells but a 3.0 kb signal specific for CD4 mRNA was detected after stimulation. These findings indicate that SO‐4 cells return to their original phenotype (CD4 single‐positive) by stimulation involving PTK. The results indicate that there is a pathway of phenotypic cycling between CD4 single‐positive and double‐negative T cells.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 1994
    detail.hit.zdb_id: 1475751-5
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  • 10
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 36, No. 6 ( 1998-06), p. 1790-1792
    Abstract: MICs of antibiotics against Bilophila wadsworthia isolates were measured by agar and broth microdilution with pyruvic acid and by Etest. The inoculum size influenced greatly agar dilution. Despite discrepancies in MICs depending on the measurement method used, clindamycin consistently showed potent activity. Broth microdilution and Etest appear to be candidates for laboratory susceptibility testing.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1998
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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