•The decomposition path of acetic acid was experimentally investigated.•A simplified reaction model was built concerning the decomposition path.•The optimum ratio of the H2O2 supply rate to the O3 ...absorption rate was determined.•The main reaction path for each condition was revealed.
Advanced oxidation processes (AOPs) constitute one of the most effective methods to decompose persistent organic pollutants in water using OH radicals. In this study, the parameters of the H2O2/O3 method in the decomposition of acetic acid were investigated through a combination of experiments and numerical simulations. A simplified reaction model was built based on the analysis of the decomposition path. The simulation results showed that effective treatment of acetic acid can be achieved when the H2O2 supply rate is half of the O3 absorption rate as one H2O2 and two O3 molecules are necessary to produce two OH radicals.
BACKGROUND: The Japanese Red Cross (JRC) implemented a fully automated pooling and nucleic acid amplification test (NAT) system for testing seronegative donations. The JRC sample repository and ...repeat blood donations allowed for lookback and follow‐up studies of hepatitis B virus (HBV) DNA–positive donors, who tested negative for hepatitis B surface antigen (HBsAg) and anti–hepatitis B core antigen in the JRC screening system.
STUDY DESIGN AND METHODS: From February 1, 2000, to March 31, 2003, 17,314,486 units were tested in 50‐sample pools with a semiautomated multiplex assay system (AMPLINAT MPX test, Roche). During this period, 328 HBV DNA–positive donations were found. From 26 of these donors, sequential samples were available at short intervals. This enabled us to examine the dynamics of viral markers in acute HBV infection. The length of detectable periods of plasma viremia and antigenemia were estimated by regression analysis from the results obtained in the quantitative polymerase chain reaction assay (JRC) and HBsAg enzyme immunoassay (Auszyme II, AxSYM, Abbott) and chemiluminescence immunoassay (Abbott).
RESULTS: The median length of detectable HBV DNA in individual donation and 20‐sample minipool (MP) NAT format was estimated to be 74 and 50 days, respectively, whereas the median length of detectable HBsAg was estimated to be 42 days. Six of the 26 donors were infected with mutant viruses, and 3 of these 6 donors did not develop detectable HBsAg during the entire observation period, despite a moderately high viral load of 104 to 105 HBV DNA copies per mL.
CONCLUSION: Transmission of mutant virus may cause occult HBV infection in the acute stage. HBV NAT, even in MP configuration, is more effective than HBsAg testing and capable of interdicting infected donors in the pre‐ and post‐HBsAg window periods.
Aim: In Japan, the etiology of 10–20% of cases of acute hepatitis remains unclarified. This study was conducted to verify the agent causing non‐A–E hepatitis.
Methods: Serum samples from 500 blood ...donors with elevated alanine aminotransferase (ALT) levels were screened by polymerase chain reaction using primers constructed from conserved areas of RNA virus helicase. The sequence obtained was investigated for viral properties.
Results: Four blood samples were found to contain a novel DNA sequence of 9496 bp, which was designated KIs‐V. KIs‐V was sensitive to the restriction enzyme SalI and BstXI. Rolling‐circle amplification produced an excessive amount of KIs‐V DNA. In sucrose density gradient ultracentrifugation, KIs‐V banded at a 1.158‐g/cm3 density. Detergent treatment increased the density of KIs‐V. There was no KIs‐V DNA amplification from human leukocyte DNA. Serial filtration suggested that KIs‐V was included in a 30–50‐nm size particle. In silico analysis revealed that KIs‐V contained 13 potential genes, none of which showed homology to any viral proteins reported. One gene showed similarity to a DNA polymerase domain. Strong signals for transcription initiation and a CpG island were identified. The nucleotide composition of KIs‐V showed a characteristic feature of circular DNA genomes that contain a replication origin and a terminus. In a preliminary study, KIs‐V was frequently identified among hepatitis E virus antibody positive individuals with elevated ALT levels.
Conclusion: A new sequence KIs‐V was isolated from blood donors with elevated ALT levels. It was suggested that KIs‐V is a double‐stranded circular DNA genome derived from a novel category of enveloped viruses.
Idiopathic thrombocytopenic purpura (ITP) occurs more commonly in young women during the reproductive years. To obtain information for management of ITP in pregnancy, we performed a nationwide ...retrospective survey. Findings from a total of 284 pregnant women with ITP and their 286 newborn infants were available for analysis. The bleeding tendency at delivery was managed chiefly with corticosteroid, intravenous high-dose gamma-globulin, and platelet transfusion. Maternal complications occurred in 77 cases (27.1%) and were frequently seen in cases with poor control of ITP. Neonatal abnormalities, which were not influenced by the clinical state of the mother, occurred at a frequency of 17.8%. Thrombocytopenia in neonates occurred in 48 cases (22.4%), and bleeding tendency was found in 16 cases (6.3%) without severe bleeding. Prediction of thrombocytopenia in neonates was difficult. However, infants from splenectomized mothers with well-controlled ITP showed thrombocytopenia more frequently than those from nonsplenectomized mothers. Mothers treated with steroids at doses greater than 15 mg/day showed a high frequency of maternal complications and fetal abnormal body weight. These observations will be useful in the management of pregnant women with ITP and their infants.
We retrospectively analyzed 336 patients with primary chronic myelofibrosis from 203 medical institutes in Japan. Notwithstanding their heterogeneous treatments, the median survival in 298 patients ...that could be evaluated was 10.0 years. Average age at onset was 60.7 years. Men were affected 1.4 times more frequently than women. The factors associated with shorter survival included anemia, leukocytosis/leukocytopenia, thrombocytopenia, and increased blasts in the peripheral blood, and sex (male), age (>60), and the presence of symptoms. A new scoring system based on the peripheral blood findings (hemoglobin Hb level, platelet count, and rate of blast formation) at initial diagnosis clearly correlated with survival rate. Accordingly, patients could be categorized into 3 groups by severity grading. Through stepwise multivariate survival analysis, the significant prognostic factors were identified as the severity grading based on the new scoring system (P = .0002), age (P = .0024), sex (P = .0153), and Hb (P = .0198). Chromosomal abnormalities were found in 58 of 154 patients (38%), although these did not influence survival.
A 69-year-old man with blastic natural killer cell lymphoma (BNKL) was treated mainly with methotrexate (MTX). He presented with skin and bone marrow involvement at onset. Neoplastic cells were ...blastic in appearance with CD3−, CD4−, CD8−, CD7−, CD16−, CD56+ and HLA-DR+ phenotype. Molecular studies showed germline configuration of both immunoglobulin H and T cell receptor genes, and negative results for Epstein–Barr virus-encoded small RNA (EBER). He was treated with standard acute lymphoblastic leukemia (ALL) induction therapy, followed by 1 cycle of high-dose MTX (HD-MTX) as consolidation therapy. However, BNKL relapsed during standard ALL maintenance therapy. Three cycles of HD-MTX were effective in achieving a second complete remission and then he received low dose MTX as maintenance therapy. BNKL remained well controlled for 4 years. Chemotherapeutic toxicity was mild and manageable. Since BNKL reportedly has a poor prognosis, this encouraging result warrants further investigation of MTX as either a single agent or in a combination regimen as a first-line treatment for patients with BNKL.
Cytogenetic abnormalities were often observed in primary myelofibrosis patients. The presence of specific cytogenetic abnormalities, such as sole abnormalities of chromosome 13q−, 20q−, or −7/7q−, is ...reported to have the influence on the prognosis of primary myelofibrosis. We analyzed the data from the prospective survey of Japanese primary myelofibrosis patients which was conducted from 1999 to clarify the impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis. A total of 202 primary myelofibrosis patients had the cytogenetic and the prognostic data. Eighty (40%) out of 202 cases had cytogenetic abnormalities, and an association was evident for platelet counts. Although the presence of an abnormal karyotype did not affect the prognosis, primary myelofibrosis patients with cytogenetic abnormalities other than 13q− and 20q− showed an inferior prognosis compared to patients with a normal karyotype or sole 13q− or 20q− abnormalities. Patients with an unfavorable cytogenetic profile (abnormal cytogenetics other than 13q− or 20q−) also had a greater tendency to transform to leukemia than patients with a favorable cytogenetic profile (normal cytogenetics, sole abnormalities of either chromosome 13q−, or 20q−). Abnormal cytogenetics other than 13q− or 20q− in primary myelofibrosis patients has the poor prognostic effect for both survival and the risk of leukemic transformation.
In treating elderly non-Hodgkin's lymphoma (NHL) patients, it is particularly important to use drugs that have a low incidence of adverse events and high efficacy. In this multicenter study, THP ...(pirarubicin)-COP (cyclophosphamide, vincristine, and prednisolone) was compared to two thirds dosage of full CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen with regard to both adverse events and efficacy. For a third group, etoposide (E) was added to the THP-COP regimen (THP-COPE) in order to achieve high dose-intensity. Subjects were 486 previously untreated patients, aged 65 or older (range, 65-92 years; median, 74 years), with NHL. Subjects were randomly assigned to receive THP-COP, two thirds CHOP, or THP-COPE. Four hundred and forty-three patients were assessed for response and followed for 8 years after the last subject registered. The complete remission rates for the THP-COP, CHOP, and THP-COPE groups were 42.5%, 41.4%, and 48.0%, respectively. There was no difference in overall survival or progression-free survival among these 3 groups. In aggressive lymphoma, there was also no difference in complete response (CR) rate (45.3% in THP-COP, 44.9% in CHOP, 48.0% in THP-COPE), overall survival, and progression-free survival among these groups. The 5- and 8-year survival rates for all patients were 29.4% and 18.7%, respectively. The 5- and 8-year survival rates for patients with aggressive lymphoma were 27.4% and 17.4%, respectively. Although long-term survival for patients with aggressive lymphoma on our regimens was not worse compared to previous reports, the CR rate was lower. Because severe adverse events were not observed, higher dose chemotherapy may be directed to achieve better CR rates. In patients with T-cell-type lymphoma, the CR rate was greater after treatment with THP-COP (51.4%) or THP-COPE (57.7%) compared to treatment with CHOP (19.4%). Pirarubicin may be more useful for T-cell lymphoma than doxorubicin. Because adverse cardiac events were reported only in CHOP, adverse cardiac events might be low in the THP group.
To understand molecular pathways underlying 9p21 deletions, which lead to inactivation of the p16/CDKN2A, p14/ARF , and/or p15/CDKN2B genes, in lymphoid leukemia, 30 breakpoints were cloned from 15 ...lymphoid leukemia cell lines. Seventeen (57%) breakpoints
were mapped at five breakpoint cluster sites, BCS-LL1 to LL5, each of <15 bp. Two breakpoint cluster sites were located within
the ARF and CDKN2B loci, respectively, whereas the remaining three were located >100 kb distal to the CDKN2A , ARF , and CDKN2B loci. The sequences of breakpoint junctions indicated that deletions in the 11 (73%) cell lines were mediated by illegitimate
V(D)J recombination targeted at the five BCS-LL and six other sites, which contain sequences similar to recombination signal
sequences for V(D)J recombination. An extrachromosomal V(D)J recombination assay indicated that BCS-LL3, at which the largest
number of breakpoints ( i.e. five breakpoints) was clustered, has a V(D)J recombination potential 150-fold less than the consensus recombination signal
sequence. Three other BCS-LLs tested also showed V(D)J recombination potential, although it was lower than that of BCS-LL3.
These results indicated that illegitimate V(D)J recombination, which was targeted at several ectopic recombination signal
sequences widely distributed in 9p21, caused a large fraction of 9p21 deletions in lymphoid leukemia.
Myelodysplastic syndrome (MDS) is a common neoplasm of haematopoietic pluripotent stem cells. Although one third of MDS patients evolve to acute myeloid leukaemia (AML), little is understood about ...the mechanisms responsible for this progression. We have previously detected the frequent loss of heterozygosity (LOH) on the short arm of chromosome 1 in blast crisis of chronic myelocytic leukaemia. In this study, we examined the chromosomal arm 1p for allelic loss in the progression of MDS to AML, using 17 microsatellite markers spanning chromosome 1 in 20 patients who progressed from MDS to AML. DNA was extracted from slides of bone marrow smears. In each patient, DNA from MDS was analysed alongside DNA from AML. Allelic loss on 1p was observed in six of the 20 individuals (30%). Serial cytogenetic information was available in five of the six patients with LOH on 1p; no deletions in this region were detected. Three samples showed LOH at all informative loci on 1p. The other three samples showed LOH on at least one but not all loci on 1p with consensus regions of LOH located distal to D1S253 (1p36.3) and probably proximal to D1S496 (1p32−). Our results suggest that tumour suppressor genes that play an important role in the progression of MDS to AML may reside in at least two different regions on 1p.