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Oncogene amplification is uncommon in acute myeloid leukemia (AML). Cytogenetically, it is primarily found as double minute chromosomes (dmin) or homogeneously staining regions (hsr). A 62-year-old woman was admitted to our hospital because of anemia and thrombocytopenia. Her bone marrow was hypercellular with 78.6% myeloperoxidase- positive blasts. Some had micronuclei. The patient was diagnosed with AML M2 and remains in complete remission (CR) after induction therapy. G-banding at diagnosis showed 51,XX,t(11;16)(q13;p11.2),+r1,+mar1×4. Spectral karyotyping confirmed t(11;16) and revealed that the ring and the marker chromosomes were derived from multiple copies of ring chromosome 8. Fluorescence in situ hybridization (FISH) with a MYC probe at 8q24 detected amplified MYC signals on 1 large and 4 small ring chromosomes 8. One MYC signal was deleted from one of the 2 chromosomes 8. FISH with a FUS probe at 16p11.2 showed monoallelic deletion of FUS. Immunohistochemistry demonstrated MYC protein overexpression at diagnosis and almost negative expression in CR. These results indicate that MYC amplification could occur in ring chromosomes without dmin. A cryptic MYC deletion suggests that an episome model could be applicable to MYC amplification in ring chromosomes as observed for dmin and hsr. Furthermore, considering 2 further reported cases, t(11;16)(q13;p11) may be a very rare but recurrent translocation in AML.

Lymph node infarction is very rare, and is frequently associated with neoplasms, such as malignant lymphoma and non-neoplastic disease, or interventions such as fine-needle aspiration (FNA). A 76-year-old-man presented with cervical lymph node swelling. Although FNA was performed, the findings were insufficient for a definitive diagnosis. Consequently, surgical biopsy of the cervical lymph node was performed, which revealed total infarction; a diagnosis of classical Hodgkin lymphoma was made later. Both lymphoma itself and FNA may cause total lymph node infarction, which makes diagnosis confusing. Therefore, it is important to repeat the biopsy rather than repeat FNA to correctly diagnose malignant lymphoma, including Hodgkin lymphoma.

In multiple myeloma (MM), MYC rearrangements that result in increased MYC expression are associated with an aggressive form of MM and adverse outcome. However, the consequences of MYC amplification in MM remain unclear. Here, we describe an unusual case of plasma cell leukemia (PCL) harboring MYC amplification on double minute chromosomes (dmin). A 79-year-old woman was initially diagnosed as having BJP-κ type MM with bone lesions. After seven months, the disease progressed to secondary PCL: leukocytes 49.1 × 109/L with 77% plasma cells showing lymphoplasmacytic appearance. The bone marrow was infiltrated with 76% plasma cells immunophenotypically positive for CD38 and negative for CD45, CD19, CD20, and CD56. The karyotype by G-banding and spectral karyotyping was 48,XX,der(14)t(11;14)(q13;q32),+der(14)t(14;19)(q32;q13.1),+18,6~95dmin[15]/46,XX[5]. Fluorescence in situ hybridization detected multiple MYC signals on dmin and double IGH/CCND1 fusion signals on der(14)t(11;14) and der(14)t(14;19). Most plasma cells were diffusely and strongly positive for MYC and CCND1 by immunohistochemistry. The patient died of progressive disease after one week. MYC amplification led to high expression of MYC and rapid disease progression, indicating its clinical significance in the pathogenesis of MM/PCL. MYC amplification on dmin may be a very rare genetic event closely associated with the progression to PCL and coexistence of IGH/CCND1 fusions.

Kanazawa Sutra (KanS) is a medicinal thread that is used for the treatment of anal fistula. It is used as a substitute for Kshara Sutra (KS) which is used in Ayurvedic medicine. KanS is composed of Ficus carica latex (FCL), Capsicum annuum tincture (CAT), Achyranthes fauriei Kshara (which is processed ash from the whole plant) and powdered Curcuma longa rhizome (CLR). In this study, we evaluated the ingredients of KanS by measuring nitric oxide (NO) production in murine macrophage-like cell line J774.1 as well as examining cytotoxicity to rat skeletal muscle myoblasts (L6) and L6 differentiation, with a view to improving its pharmacological effect. We focused on Mallotus japonicus bark (MJB), which is described in the Japanese Pharmacopeia and belongs to the Euphorbiaceae family. Its biological activities were evaluated in a similar manner to the evaluation of KanS ingredients. We found that MJB extracts showed similar biological activity to Euphorbia neriifolia latex (ENL), an ingredient of KS. We conclude that the NO inhibitory activity of KanS is mainly due to CLR, and its cytotoxicity to L6 and inhibitory activity on L6 differentiation are mainly due to CLR and FCL. As CAT has no characteristic activity, the biological activity and the anal fistula treatment ability of KanS would be improved by substituting MJB for CAT.

To identify strategies for reducing emesis induced by the CHOP regimen, which includes high-dose steroids, we prospectively evaluated the efficacy of palonosetron in Japanese patients. Palonosetron was administered at a dose of 0.75 mg via intravenous injection over 30 min before chemotherapy on day 1. Patients kept diaries of chemotherapy-induced nausea and vomiting (CINV) incidence from the start of chemotherapy until 168 h afterwards, in which they documented the occurrence and severity of nausea, vomiting, anorexia, and the use of rescue medication. The primary endpoint was the overall occurrence rate of nausea, vomiting, and anorexia; these rates were 56, 12, and 62 %, respectively, including all grades. The rates and severity of symptoms tended to worsen 120-168 h after completing oral prednisolone. We defined complete response (CR) as no vomiting and no use of rescue therapy. The CR rates of post palonosetron 0.75 mg treatment in the acute (0-24 h), delayed (24-168 h), and overall phases (0-168 h) were 86, 66, and 62 %, respectively. Antiemetic strategies of CHOP regimen for day 6 and, thereafter, should be investigated.

Martensitic high-carbon, high-strength bearing steel is used for rolling contact applications when high wear and fatigue resistance are required. Due to its high fatigue strength, SUJ2 is not used for only bearings but for shafts. The objective of this work is a clarification of the relationship between quenching times and retained austenite amount of SUJ2 steel. It was found that repeatedly induction heating increased the retained austenite amount, but did not change the Vickers hardness.

Perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA) and perfluorooctane sulfonate (PFOS) adsorbed onto granular activated carbon (GAC) were thermally treated in N2 gas stream. The purpose was to assess the fate of perfluoroalkyl and polyfluoroalkyl substances (PFASs) during thermal regeneration of GAC, which had been used for water treatment. Mineralized F, residual PFASs including short-chained species, and volatile organic fluorine (VOF) were determined. In a temperature condition of 700 °C, VOF were 13.2, 4.8, and 5.9 % as for PFOA, PFHxA, and PFOS. However, the VOF decreased to 0.1 %, if the GAC and off-gas were kept at 1000 °C. No PFASs remained in GAC at 700–1000 °C; at the same time, short-chained PFASs were slightly detected in the aqueous trapping of off-gas at 800 and 900 °C conditions. The destruction of PFASs on GAC could be perfect if the temperature is higher than 700 °C; however, the process is competitive against volatile escape from GAC. Destruction in gaseous phase needs a temperature as high as 1000 °C. Destruction of PFASs on the surface of GAC, volatile escape from the site, and thermolysis in gas phase should be considered, as to thermal regeneration of GAC.

The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]. Expression of the NUP98/TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2;5) was centromeric to EGR1. In all 10 cases described in the literature, the NUP98 exon 13/TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11;20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML.

The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality. A 74-year-old woman was diagnosed with MPAL, B/myeloid, because bone marrow blasts were positive for myeloperoxidase, CD19, and CD22. Chromosome analysis showed 46,XX, +1,der(1;18)(q10;q10),t(2;16)(q13;q13),t(12;17)(p13;q21). Expression of the TAF15-ZNF384 fusion transcript was confirmed: TAF15 exon 6 was fused in-frame to ZNF384 exon 3. This type of fusion gene has been reported in 1 acute myeloid leukemia case and 3 ALL cases. Thus, at present, it is difficult to find a specific association between the structure of the TAF15-ZNF384 fusion gene and the leukemia phenotype. The TAF15-ZNF384 fusion may occur in early common progenitor cells that could differentiate into both the myeloid and lymphoid lineages. Furthermore, der(1;18)(q10;q10) might play some role in the appearance of an additional myeloid phenotype.

Kleine-Levin syndrome is a rare sleep disorder of unknown etiology characterized by repetitive episodes of hypersomnia between asymptomatic periods. We report the case of a 13-year-old girl who presented with drowsiness triggered by influenza A as the first episode. Magnetic resonance imaging (MRI) on day 6 showed transient reduction of diffusion in the corpus callosum splenium. The patient was diagnosed with encephalopathy with a reversible splenial lesion. The symptoms resolved after 10 days, but additional episodes of hypersomnia lasting 5-10 days occurred 1, 5, 6, 11, 13, and 25 months after the first episode. MRI during hypersomnia indicated no lesions, and sleep duration and cognition were normal between episodes. The patient was diagnosed with Kleine-Levin syndrome. Electroencephalographic and clinical findings during the first episode were similar to those during the other episodes. Encephalopathy with a splenial lesion and Kleine-Levin syndrome may have similar pathological mechanisms causing a disturbance in consciousness.

We investigated the capability of microorganisms isolated from environments polluted with perfluoroalkyl adds (PFAAs) to conduct biotransformation of these emerging pollutants. Two different microbial consortia (chemoorganoheterotrophic bacteria and total yeast and molds) were isolated from two river sediments in Saitama and Osaka, Japan, known for long term pollution with perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). The microbial consortia were incubated in the presence of added PFOS and PFOA, and decreases in concentrations of these compounds were between 46-69% and 16-36%, respectively. Decreases in concentrations were, in part, due to sorption on biomass, but defluorinated PFOS and PFOA products were not detected. However, untargeted analysis suggested the presence of several metabolites found only in samples from consortia with PFOS and PFOA but not in the control samples. Molecular formula candidates were narrowed down to two options, C18H28O5F and C21H27O4. It was assumed that these formulas were associated with unsaturated monofluorinated fatty acids and hydrocarbons with multiple unsaturated bonds or ring structures. (C) 2018 Elsevier B.V. All rights reserved. Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3114]

The interior noise of a passenger cabin mainly comprises the transmitted noise and structure-borne noise. To reduce the level of the interior noise, new countermeasures against the structure-borne noise from the floor panel are required. In this study, we verified the vibration characteristics of a car body and clarified that the vertical vibration of the side structure is less than that of the floor structure, which supports the floor panel. On the basis of this result, we devised a new floor structure, wherein the floor panels are suspended from the side panel. Moreover, we evaluated the effectiveness of the design by numerical analysis and excitation tests using a test vehicle. Here we outline the suspended floor structure, predict the noise reduction effect by numerical analysis, test the vibration reduction effect, and compare the results with those for a conventional fixed floor structure in a Shinkansen-type test vehicle.

Civil service employee pension reform began by removing non-clerical work from the main body of the Mutual Aid Association (MAA) pension system. Further changes were based on administrative reform and pension jealousy. In particular, the Nakasone cabinet's administrative reform privatized the non-clerical sector. Before the 1979 reform, the pensionable age was 55 for the MAA and 60 for the Employee Pension Insurance (EPI) scheme. The MAA pension benefit formula adopted the final salary system, which was larger than the average lifetime salary calculation used for EPI benefits. The final salary system was abolished during the 1986 reform. Public employee criticism over “Amakudari” led to further civil service employee remuneration reform in 2005. In 2007, the Social Insurance Agency pension record scandal led to a change of government by 2009. The biggest reform of the MAA pension system was the abolishment of the occupational portion of the pension, a compromise between the government and unions. We project that this compromise will cost 22 trillion yen over 90 years old. After 2055, the newly established MAA pension scheme will be abolished; thus the public pension may finally be sustainable.

Waste disposal site is one of the important sinks of chemicals. A significant amount of perfluoroalkyl and polyfluoroalkyl substances (PFASs) such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexanoic acid (PFHxA) have been brought into it. Because of their aqueous solubility, PFASs are released to landfill effluent waters, from which PFASs are efficiently collected by adsorption technique using granular activated carbon (GAC). The exhausted GAC is reactivated by heating processes. The mineralization of PFASs during the reactivation process was studied. Being thermally treated in N2 atmosphere, the recovery rate of mineralized fluorine and PFC homologues including short-chained perfluorocarboxylic acids was determined. If the reagent form of PFOA, PFHxA, and PFOS were treated at 700 °C, the recovery of mineralized fluorine was less than 30, 46, and 72 %, respectively. The rate increased to 51, 74, and 70 %, if PFASs were adsorbed onto GAC in advance; moreover, addition of excess sodium hydroxide (NaOH) improved the recovery to 74, 91, and 90 %. Residual PFAS homologue was less than 1 % of the original amount. Steamed condition did not affect destruction. The significant role of GAC was to suppress volatile release of PFASs from thermal ambient, whereas NaOH enhanced destruction and retained mineralized fluorine on the GAC surface. Comparing the recovery of mineralized fluorine, the degradability of PFOS was considered to be higher than PFOA and PFHxA. Whole mass balance missing 9~26 % of initial amount suggested formation of some volatile organofluoro compounds beyond analytical coverage.

No optimum treatment of iatrogenic immunodeficiency-associated lymphoproliferative disorders due to methotrexate in patients with rheumatoid arthritis (MTX-LPD) has yet been established, although MTX withdrawal is known to have a substantial effect on tumor regression. Here, we retrospectively analyzed 20 cases of MTX-LPD. Tumor shrinkage occurred in 18 of 20 cases, but only following MTX withdrawal. This tumor regression ratio was considerably better than in previous reports, and appeared due to longer "watchful waiting." Lymphocyte recovery at 2 weeks after MTX withdrawal was significantly higher in cases with tumor regression in 1 month than in those without tumor regression (p = 0.001). Median time to maximal efficacy after MTX cessation in cases without chemotherapy was 12 weeks (range 2-76). In conclusion, watchful waiting for a longer period after MTX cessation with observation of early lymphocyte recovery and uninterrupted continuation of other anti-rheumatoid drugs may be an acceptable management plan for MTX-LPD.

We examined serum levels of various cytokines, chemokines, growth factors, and adhesion molecules in patients with uncomplicated influenza (n = 20) and influenza virus-associated encephalopathy (IE) (n = 18) to understand the underlying mechanism of IE. We found that IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, G-CSF, GM-CSF, TNF-α, TIMP-1, MMP-9, sE-selectin, and neutrophil elastase were elevated significantly in sera from patients with uncomplicated influenza and those with IE, compared with normal controls (n = 20). Of note, neutrophil elastase, sE-selectin, IL-8, and IL-13 were elevated significantly in IE as compared with uncomplicated influenza. In the present study, for the first time, we found that serum levels of neutrophil elastase were increased in patients with IE compared with uncomplicated influenza, which suggested that cerebral endothelial damage in the development of IE was mediated by neutrophil elastase. The present study implied that anti-elastase agents are possibly an effective therapeutic protocol for IE, but this needs further elucidation.

The t(8;21)(q22;q22) translocation is specifically observed in acute myeloid leukemia (AML) M2 subtype, whereas del(5q) is one of the most common cytogenetic aberrations in myelodysplastic syndromes (MDS). Thus, t(8;21)(q22;q22) and del(5q) appear to be mutually exclusive, and the association between them has not been characterized yet. Here, we report an 81-year-old woman with coexistent t(8;21)(q22;q22) and del(5q) at initial diagnosis. The bone marrow was infiltrated with 18.4% myeloblasts, and showed marked myeloid and erythroid dysplasia. Myeloblasts were positive for CD19 and CD56 as well as CD13, CD33, CD34 and HLA-DR. G-banding and spectral karyotyping showed 46,XX,del(5)(q?),t(8;21)(q22;q22)[18]/46,XX[2]. Both del(5)(q?) and t(8;21)(q22;q22) were present in a single clone. Fluorescence in situ hybridization (FISH) on metaphase spreads detected a RUNX1/RUNX1T1 fusion signal on the der(8)t(8;21)(q22;q22), and confirmed deletion of CSF1R signaling at 5q33-q34 on the del(5)(q?). Furthermore, FISH on interphase nuclei revealed that the RUNX1/RUNX1T1 fusion signal and deletion of CSF1R signaling were found in 66.0% and 58.0% of interphase cells, respectively, suggesting that del(5)(q?) occurred in cells with RUNX1/RUNX1T1. These results indicated a diagnosis of AML with t(8;21)(q22;q22)/RUNX1/RUNX1T1 rather than MDS, even though the percentage of bone marrow myeloblasts was less than 20%. Based on these findings, together with those of other reported cases, del(5q) seems to be an extremely rare but recurrent secondary aberration in AML with t(8;21)(q22;q22).

Rhabdomyolysis is characterized by a marked elevation of the creatine kinase (CK) levels and myoglobinuria, thus leading to renal dysfunction. Various viruses or bacteria can be etiologic agents, but mycosis has only rarely been reported to be a cause of rhabdomyolysis. In this report, we describe an adolescent male with acute myeloid leukemia who underwent allogeneic bone marrow transplantation and thereafter developed rhabdomyolysis and Candida parapsilosis fungemia almost at the same time. Following treatment for C. parapsilosis, the transaminase and CK levels both satisfactorily decreased. This case illustrates that C. parapsilosis infection may be a causative agent of rhabdomyolysis in immunocompromised patients.

Oncogene amplification is uncommon in acute myeloid leukemia (AML). Cytogenetically, it is primarily found as double minute chromosomes (dmin) or homogeneously staining regions (hsr). A 62-year-old woman was admitted to our hospital because of anemia and thrombocytopenia. Her bone marrow was hypercellular with 78.6% myeloperoxidase- positive blasts. Some had micronuclei. The patient was diagnosed with AML M2 and remains in complete remission (CR) after induction therapy. G-banding at diagnosis showed 51,XX,t(11;16)(q13;p11.2),+r1,+mar1×4. Spectral karyotyping confirmed t(11;16) and revealed that the ring and the marker chromosomes were derived from multiple copies of ring chromosome 8. Fluorescence in situ hybridization (FISH) with a MYC probe at 8q24 detected amplified MYC signals on 1 large and 4 small ring chromosomes 8. One MYC signal was deleted from one of the 2 chromosomes 8. FISH with a FUS probe at 16p11.2 showed monoallelic deletion of FUS. Immunohistochemistry demonstrated MYC protein overexpression at diagnosis and almost negative expression in CR. These results indicate that MYC amplification could occur in ring chromosomes without dmin. A cryptic MYC deletion suggests that an episome model could be applicable to MYC amplification in ring chromosomes as observed for dmin and hsr. Furthermore, considering 2 further reported cases, t(11;16)(q13;p11) may be a very rare but recurrent translocation in AML.

A 49-year-old female was initially diagnosed with acute myeloid leukemia (AML) M4 with a CD45＋CD13＋CD33＋CD34-HLA-DR＋ immunophenotype. She underwent allogeneic bone marrow transplantation, but the disease recurred. The bone marrow was infiltrated with 87.0% blasts negative for myeloperoxidase (MPO) staining. Immunophenotyping by flow cytometry identified the presence of a CD45-negative blast population. These blasts exhibited a CD13＋CD33＋CD19-CD10-CD34-HLA-DR- immunophenotype. The lack of CD45 expression is often observed in B-cell acute lymphoblastic leukemia, whereas CD45-negative AML is extremely rare; only one older male with AML-M0 has been reported. In the present case, the CD45-negative blasts had an MPO-CD13＋CD33＋ phenotype, which is similar to AML-M0.

This paper presents a controller tuning method for nonlinear systems by using the so-called virtual reference feedback tuning method and nonlinear compensation based on multilayer neural networks. To demonstrate the effectiveness of the presented method, simulation is carried out for systems with nonlinearities such as hysteresis, cubic functions, and dead zones. Moreover, architectures and computational efficiency of neural networks are investigated through a widely-used deep learning framework.

The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]. Expression of the NUP98/TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2;5) was centromeric to EGR1. In all 10 cases described in the literature, the NUP98 exon 13/TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11;20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML.

The t(8;21)(q22;q22) translocation involving RUNX1 at 21q22 and RUNX1T1 at 8q22 is found in 10% of cases of acute myeloid leukemia (AML) M2 subtype. This translocation results in the formation of a RUNX1/RUNX1T1 fusion gene, which contributes to leukemic transformation by transcriptional repression of normal RUNX1 target genes, on der (8)t(8;21)(q22;q22). AML with t(8;21) is usually associated with a good response to chemotherapy and long-term diseasefree survival. It has been reported that variant translocations, the majority of which are complex three-way translocations, occur in approximately 3 to 4% of cases of AML with t(8; 21). However, clinical and hematological features of AML with variant t(8;21) remain to be completely characterized. Here, we describe a new complex translocation t(8;11;21) (q22;q24;q22) in a case of AML with RUNX1/RUNX1T1. A 62-year-old man was admitted because of anemia and thrombocytopenia. He had no history of chemotherapy or radiotherapy. Peripheral blood analysis showed hemoglobin 7.8 g/dL, platelets 33 × 10/L, and leukocytes 4.6 × 10/L with 14% myeloblasts. Bone marrow was hypercellular with 18.2% myeloblasts, 60.0% mature myeloid cells, 5.6% eosinophils, 4.4% monocytes, 6.6% lymphocytes, and 2.6% erythroblasts. Myeloblasts had Auer rods and a few azurophilic granules in the basophilic cytoplasm. Myeloid dysplasia including the pseudo-Pelger-Huet anomaly was also found (Fig. 1A). Myeloblasts were positive for myeloperoxidase staining and immunophenotypically positive for CD13, CD19, CD33, CD34, CD56, and HLA-DR. In light of the cytogenetic and genetic abnormalities described below, we made a diagnosis of AML with RUNX1/RUNX1T1 according to the World Health Organization classification. Initial induction therapy with cytarabine and idarubicin failed, but the patient achieved hematological and cytogenetic complete remission (CR) after re-induction therapy with cytarabine and daunorubicin. The residual myeloblasts were negative for CD19 and CD56 after the attainment of CR. He received a further three courses of consolidation therapy with high-dose cytarabine, and remained in molecular CR for more than 10 months. G-banding analysis of bone marrow cells at diagnosis showed 46, XY, t (8;11;21) (q22; q24; q22) [20] (Fig. 1B). Spectral karyotyping confirmed three derivative chromosomes: der(8)t(8;21)(q22;q22), der(11)t(8;11)(q22;q24), and der(21)t(11;21)(q24;q22) (Fig. 1C). Fluorescence in situ hybridization (FISH) on metaphase spreads detected the RUNX1/RUNX1T1 fusion signal on the der (8) t (8;21) (q22; q22) (Fig. 1D). Reverse-transcription polymerase chain reaction also confirmed the RUNX1/RUNX1T1 fusion transcript. We have presented a complex three-way translocation t(8; 11;21)(q22;q24;q22) and detected the RUNX1/RUNX1T1 fusion gene in a patient with AML. In the Mitelman database, four AML M2 cases with t (8;11; 21) involving 8q22 and 21q22 have been described (Table 1). Their breakpoints in chromosome 11 were clustered to 11p15 (two cases) and 11q13 (two cases). Thus, to our knowledge, this is the first case with a complex t(8;21) translocation involving the breakpoint 11q24. With regard to breakpoints in other chromosomes, Kim et al. summarized 24 adult cases of AML with variant t(8;21), and demonstrated that there was no overlap of breakpoints in the involved chromosomes, except for 20p13 (two cases). Thus, there seem to be few recurrent breakpoints involved in variant t(8;21). The t(8;11;21)(q22;q24;q22) translocation generated only the RUNX1/RUNX1T1 fusion gene on the der(8)t(8;21)(q22

The aim of this study was to investigate 12 perfluorinated compounds (PFCs) including perfluorinated carboxylates (C4-C12) and perfluorinated alkyl sulfonates (C4, C6, and C8) in river and seawater samples to determine contamination levels in the aquatic environment of Hyogo prefecture, Japan. High levels of perfluorohexanoic acid (PFHxA; 2300-16,000 ng/L) were detected in the Samondogawa River at Tatsumi Bridge downstream of a PFC production facility; this location also had the highest mass flow rate of PFCs (3900-29,000 kg/y). Widespread contamination of coastal waters was confirmed with PFHxA as the dominant compound. Perfluorooctanoic acid was also prevalent in coastal waters. The concentration of PFHxA in coastal seawater and the distance from the mouth of the Samondogawa River were inversely related. This discharge of high concentrations of PFHxA from the Samondogawa River may have affected concentrations of PFCs in Osaka Bay.

Background Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. Methods and results We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. Conclusions Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.

chromosomes, and revised the karyotype as follows (Fig. 2ab): 44,XY,-2,inv(3)(p25q21),der(5)del(5)(p?) del(5)(q?),der(7)(11?::7p13→7q22::7?::1?),add(9) (p13),-11,der(17)t(2;17)(q11.2;p11.2),der(20)t(2;20) (? ;q11 .2 ) ,2dmin[2] /42 , s l ,de l (1 ) (q? ) , r (6 ) ,de r (7 ) (7? : :p13→qter ) , -12 , -16 , -der (17) t (2 ;17) ,der (17) (2?::?::2?::17p11.2→17q23::12?),-2dmin[1]. Furthermore, dmin were shown to be derived from chromosomes 8. We next performed fluorescence in situ hybridization (FISH) with a probe for MYC located at 8q24 (Vysis LSI IGH/ MYC/CEP 8 Tri-Color Dual Fusion Probes), and detected multiple MYC signals on dmin (Fig. 1c). The patient underwent non-myeloablative cord blood transplantation (CBT) after conditioning with total body irradiation (TBI), fludarabine, and melphalan. However, the disease relapsed due to graft failure. G-banding at relapse after CBT showed 41~42,XY,2,inv(3)(p25q21),-4,der(5)del(5)(p?)del(5)(q?),der(7) (11?::7p13→7q22::7?::1?),add(9)(p13),-11,-12,-16,der(17) (2?::?::2?::17p11.2→17q23::12?),der(20)t(2;20)(?;q11.2) [cp5]/46,XY[15]. Thus, dmin disappeared, although other structural abnormalities remained. The patient next received an unrelated bone marrow transplant (u-BMT) after conditioning with TBI, fludarabine, and busulfan, but the disease progressed again. Unexpectedly, some of the myeloblasts had micronuclei (Fig. 1d). The similar karyotype did not include dmin (Fig. 1e): 40~43,XY,2,inv(3)(p25q21),-4,der(5)del(5)(p?)del(5)(q?),der(7) (11?::7p13→7q22::7?::1?),add(9)(p13),-11,-12,-16,der(17) (2?::?::2?::17p11.2→17q23::12?),der(20)t(2;20)(?;q11.2) [cp14]/41,sl,add(2)(q11.2),add(8)(q24),-add(9),+add(9) (p13)[5]/46,XY[1]. FISH also showed only three or four MYC signals (Fig. 1f). The patient succumbed to pneumonia 19 months after initial diagnosis. Double minute chromosomes (dmin) are small, acentric, extrachromosomal fragments that frequently mediate oncogene amplification and reflect rapid disease progression in human tumors. It has been shown that elimination of dmin can be induced by treating cancer cells with low concentrations of hydroxyurea or gemcitabine in vitro, resulting in reduced tumorigenicity and reversion of phenotype [1, 2]. Morphologically, the loss of dmin is facilitated by incorporation of dmin into micronuclei. However, this phenomenon has been reported only infrequently in primary tumor cells from patients [3]. A 58-year-old man was initially diagnosed with myelodysplastic syndrome, refractory cytopenia with multilineage dysplasia (MDS-RCMD). G-banding showed 44~45,XY,der(2;17)(q10;q10),inv(3)(p25q21),-5,-7,add(9) (p13),-11,-20,+mar1,+mar2,+mar3[cp8]/45,sl,+8[3]/46 ,XY[9]. After 11 months, the disease progressed to acute myeloid leukemia (AML). Peripheral blood values were as follows: hemoglobin 105 g/L, platelets 80 × 10/L and leukocytes 3.9 × 10/L with 22 % myeloblasts. Bone marrow was hypercellular with 46.6 % myeloblasts, which had many granules with vacuoles but no micronuclei (Fig. 1a). G-banding revealed the appearance of dmin (Fig. 1b): 42~45,XY,der(2;17)(q10;q10),inv(3)(p25q21),-5,-7,add(9) (p13),-11,-20,+mar1,+mar2,+mar3,0~85dmin[cp13]/42,sl ,add(1)(q21),add(1)(q32),+der(2)add(2)(p21)add(2)(q21),der(2;17),-inv(3),add(7)(p22),-12,-16,+mar4[2]/46,XY[5]. Spectral karyotyping (SKY) clarified the origin of marker

myeloperoxidase and α -naphthyl butyrate esterase staining. Surface marker analyses with three-color fl ow cytometry by CD45/side scatter gating revealed that immature cells (76.9% of all bone marrow cells) were positive ( 20%) for CD4 (25.3%), CD13 (86.7%), CD33 (100.0%) and CD34 (99.2%). Considering cytogenetic abnormalities and MLL rearrangements described below, we made a diagnosis of AML with a variant MLL translocation in the World Health Organization classification, or AML M4 in the French – American – British classification. Induction therapy with idarubicin and cytosine arabinoside was started, and the patient achieved a hematological complete remission (CR). However, she suffered from severe pneumonia and heart failure, and died of multiple organ failure 2 months after the initial diagnosis. Chromosome analysis of the bone marrow cells at the initial diagnosis showed 50,XX, 4, 6, 8,?t(10;11)(p12;q14)

Chromosomal abnormalities of intravascular large B-cell lymphoma (IVLBCL), a rare form of extranodal diffuse large B-cell lymphoma, have been described in only a small number of cases. A 59-year-old female presented with pancytopenia and splenomegaly. Bone marrow was normocellular with 30.4% abnormal large lymphoid cells that were positive for CD5, CD19, CD20, HLA-DR and λ chain. Bone marrow biopsy showed intrasinusoidal infiltration of large lymphoid cells. G-banding and spectral karyotyping of the bone marrow cells demonstrated a complex karyotype as follows : 48,XX,-8,+r(11),+12,del(12)(p?) ×2,+18,der(19)(19?::p13 → qter),der(21)t(8;21)(q11.2;p11.2). Fluorescence in situ hybridization on interphase nuclei revealed three signals of CCND1 at 11q13, but two signals of BIRC3 at 11q22 and MLL at 11q23, indicating that r(11) contained CCND1. Together with other reported cases, our results indicate that the gain of 11q as well as trisomy 18 may be among the recurrent chromosomal aberrations in IVLBCL. Furthermore, an additional ring chromosome 11 could be a novel mechanism leading to the gain of 11q.

The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality. A 74-year-old woman was diagnosed with MPAL, B/myeloid, because bone marrow blasts were positive for myeloperoxidase, CD19, and CD22. Chromosome analysis showed 46,XX, +1,der(1;18)(q10;q10),t(2;16)(q13;q13),t(12;17)(p13;q21). Expression of the TAF15-ZNF384 fusion transcript was confirmed: TAF15 exon 6 was fused in-frame to ZNF384 exon 3. This type of fusion gene has been reported in 1 acute myeloid leukemia case and 3 ALL cases. Thus, at present, it is difficult to find a specific association between the structure of the TAF15-ZNF384 fusion gene and the leukemia phenotype. The TAF15-ZNF384 fusion may occur in early common progenitor cells that could differentiate into both the myeloid and lymphoid lineages. Furthermore, der(1;18)(q10;q10) might play some role in the appearance of an additional myeloid phenotype.

Background In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation. Patient A 41-year-old male with a large mediastinal mass, pleural effusion, and lymphadenopathy was diagnosed as having T-LBL. Lymphoma cells were positive for CD4, CD8, CD2, CD3, CD5, CD7, CD10, and TdT. Results G-banding and spectral karyotyping of pleural effusion cells showed 47,XY,dup(1)(q21q32),t(7;9)(q34;q34),+20. Genomic polymerase chain reaction (PCR) revealed that the 5' end of TRB@ J1-5 was connected with the middle of NOTCH1 exon 25 (434 bp downstream from its 5' end) in a 'head-to-head' configuration on the der(9)t(7;9), although nine extra bases were inserted between the two genes. Reverse transcription-PCR confirmed expression of the TRB@/NOTCH1 fusion transcripts. Similarly, the 5' end of J1-5 was fused to the shortened exon 25 with nine extra bases. The NOTCH1 breakpoint in exon 25 was very close to transcription start sites of deleted Notch1 in murine T-ALL. Conclusions The TRB@/NOTCH1 fusion gene with a NOTCH1 breakpoint in exon 25, which has not previously been detected in four other reported cases with t(7;9), could lead to aberrant expression of the truncated NOTCH1 by TRB@ enhancer elements. The resultant NOTCH1 receptor deleting most of the extracellular domain may be implicated in the pathogenesis of T-LBL by ligand-independent, constitutive activation of the NOTCH1 pathway, suggesting avenues for future therapy with γ-secretase inhibitors.

Objectives: The t(9;11)(p22;p15) is a very rare but recurrent translocation in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) blast crisis. The translocation results in a fusion gene between NUP98 at 11p15 and PSIP1 encoding two transcriptional coactivators, p52 and p75, at 9p22. Here, we describe the first case of myelodysplastic syndrome (MDS) with t(9;11)(p22;p15). Patient: A 64-yr-old woman presented pancytopenia, trilineage dysplasia, and 9.2% blasts in the bone marrow, indicating the diagnosis of MDS. Results: G-banding and spectral karyotyping showed 46,XX,t(9;11)(p22;p15)[20]. Reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing detected four types of NUP98/PSIP1-p52 and two types of NUP98/PSIP1-p75 fusion transcripts. Essentially, the NUP98 exon 12 or exon 11 by alternative splicing was fused in-frame with the PSIP1 exon 8. Real-time quantitative (RQ) PCR for NUP98/PSIP1/GAPDH demonstrated a 4-log decrease after cord blood transplantation and a 2-log increase at relapse. Conclusions: The fusion genes combining NUP98 exon 11/12 with PSIP1 exon 8, which have never been detected in other AML/CML cases, may be implicated in the pathogenesis of MDS. Furthermore, RQ-PCR for NUP98/PSIP1 could be useful to monitor minimal residual disease.

Myelodysplastic syndromes (MDS) with pure red cell aplasia (PRCA) have been shown to be a rare form of MDS. A 35-year-old man presented with pancytopenia: hemoglobin 59 g/L, reticulocytes 2 × 10(9)/L, platelets 33 × 10(9)/L, and leukocytes 1.8 × 10(9)/L with 1% blasts. Bone marrow was hypercellular with 50.4% myeloid cells, 0.0% erythroblasts, 25.4% basophils, and 5.6% myeloblasts. Dysplastic changes including pseudo-Pelger-Huët anomaly of neutrophils and mononuclear micromegakaryocytes were found. Immunohistochemistry with glycophorin C confirmed erythroid aplasia. Cytogenetic analysis showed 46,XY,i(17)(q10)[18]/47,XY,+8[2]. Considering two reported cases, these findings indicate that isolated i(17q) may be implicated in the pathogenesis of MDS with PRCA as a recurrent cytogenetic aberration.

研究(Article)

研究

Pure erythroid leukemia (PEL) is an extremely rare disorder characterized by neoplastic proliferation of immature erythroblasts. A 66-year-old man, who had received chemoradiotherapy for hypopharyngeal cancer, was admitted because of pancytopenia. Bone marrow was infiltrated with 81% proerythroblasts positive for CD71 and CD235a. An increased number of macrophages with active hemophagocytosis was also present. Chromosome analysis showed hypodiploid complex abnormalities. The patient died of progressive disease despite induction chemotherapy. Erythroblastic infiltration into the liver and hemophagocytosis in the spleen were found at autopsy. Therapy-related PEL with hemophagocytic syndrome and hepatic infiltration of PEL has never been reported.