Hitherto-Unnoticed Self-Transmissible Plasmids Widely Distributed among Different Environments in Japan.

Various conjugative plasmids were obtained by exogenous plasmid capture, biparental mating, and/or triparental mating methods from different environmental samples in Japan. Based on phylogenetic analyses of their whole-nucleotide sequences, new IncP/P-1 plasmids that could be classified into novel subgroups were obtained. Mini-replicons of the plasmids were constructed, and each of them was incompatible with at least one of the IncP/P-1 plasmids, although they showed diverse iteron sequences in their oriV regions. There were two large clades of IncP/P-1 plasmids, clade I and II. Plasmids in clade I and II included antibiotic resistance genes. Notably, nucleotide compositions of newly found plasmids exhibited different tendencies compared with those of the previously well-studied IncP/P-1 plasmids. Indeed, the host range of plasmids of clade II was different from that of clade I. Although few PromA plasmids have been reported, the number of plasmids belonging to PromAß, and -γ subgroups detected in this study was close to that of IncP/P-1 plasmids. The host ranges of PromAγ and PromAδ plasmids were broad and transferred to different and distinct classes of Proteobacteria. Interestingly, PromA plasmids and many IncP/P-1 plasmids do not carry any accessory genes. These findings indicate the presence of "hitherto-unnoticed" conjugative plasmids, including IncP/P-1 or PromA derivative ones in nature. These plasmids would have important roles in the exchange of various genes, including antibiotic resistance genes, among different bacteria in nature. IMPORTANCE Plasmids are known to spread among different bacteria. However, which plasmids spread among environmental samples and in which environments they are present is still poorly understood. This study showed that unidentified conjugative plasmids were present in various environments. Different novel IncP/P-1 plasmids were found, whose host ranges were different from those of known plasmids, showing wide diversity of IncP/P-1 plasmids. PromA plasmids, exhibiting a broad host range, were diversified into several subgroups and widely distributed in varied environments. These findings are important for understanding how bacteria naturally exchange their genes, including antibiotic resistance genes, a growing threat to human health worldwide.

[Intravascular large B-cell lymphoma diagnosed by total hysterectomy].

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin B-cell lymphoma which occurs mainly in capillaries and small blood vessels. Successful diagnosis of IVLBCL is challenging since it lacks tumor formation and presents various clinical manifestations. An 82-year-old Asian female patient presented to our emergency department with a history of general fatigue, weight loss, and fever for two weeks. The patient's random skin biopsy was negative, and her bone marrow biopsy revealed hemophagocytic syndrome with no obvious involvement of lymphoma cells. Gallium scintigraphy showed mild uptake in the uterus, pelvis, and spine. The repetitive bone marrow biopsy result and the endometrial cytology/biopsy were negative; however, the pelvic MRI was compatible with lymphoma, revealing lesions in the corpus uteri, pelvis, and vertebral body. After laparoscopic-assisted vaginal total hysterectomy and bilateral salpingo-oophorectomy, the diagnosis of the Asian variant of IVLBCL was made. Although total hysterectomy remains controversial for elderly patients with declining performance status, we could successfully diagnose the condition and initiate the treatment. The patient's general condition improved soon after starting rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen on day 26, and she was discharged on day 45.

Treatment-free remission after first-line dasatinib discontinuation in patients with chronic myeloid leukaemia (first-line DADI trial): a single-arm, multicentre, phase 2 trial.

BACKGROUND: A previous dasatinib discontinuation (DADI) trial showed that 31 (49%) of 63 patients with chronic-phase chronic myeloid leukaemia who were treated with second-line or subsequent dasatinib could discontinue the drug safely. However, the safety and efficacy of discontinuing first-line dasatinib remains unclear. In this trial (the first-line DADI trial) we aimed to assess molecular relapse-free survival at 6 months after discontinuation of dasatinib in patients with chronic myeloid leukaemia who had been treated with first-line dasatinib and had maintained deep molecular response for at least 1 year. METHODS: The first-line DADI trial was a single-arm, multicentre, phase 2 trial done at 23 hospitals in Japan. Patients with newly diagnosed chronic-phase chronic myeloid leukaemia without hepatosplenomegaly and extramedullary mass, who received at least 24-month dasatinib treatment and had a sustained deep molecular response (defined as BCR-ABL1/ABL1 international scale ≤0·0069% in at least four successive samples spanning a 12 month period) were enrolled. Other eligibility criteria were an age of 15 years or older, an Eastern Cooperative Oncology Group performance status score of 0-2, and no primary organ dysfunction. The primary outcome was molecular relapse-free survival (also known as treatment-free remission) after discontinuation of dasatinib at 6 months and was analysed in all patients who completed the 12-month consolidation phase. Safety was assessed in all patients who received treatment. This study closed early due to accrual and is registered with the UMIN Clinical Trials Registry (UMIN000011099). FINDINGS: Between Sept 20, 2013 and July 12, 2016, 68 patients who had a deep molecular response after receiving first-line dasatinib for at least 24 months were enrolled and assigned to the consolidation phase. Nine patients were excluded during the consolidation phase and one patient was excluded after study completion because of meeting exclusion criteria. 58 patients discontinued dasatinib and were assessed. 32 (55%) of 58 patients had treatment-free remission at 6 months after dasatinib discontinuation, and median follow-up was 23·3 months (IQR 11·7-31·0). Treatment-free remission at 6 months was 55·2% (95% CI 43·7-69·6). No non-haematological adverse events worse than grade 2 occurred before dasatinib discontinuation. The most common haematological adverse event was anaemia (14 [21%] of 68 treated patients); three (4%) of 68 treated patients had grade 3 neutropenia and one (1%) had grade 4 lymphopenia. INTERPRETATION: Our findings suggest that dasatinib could be safely discontinued after first-line treatment in patients with chronic myeloid leukaemia who had received at least 36 months of therapy and sustained deep molecular response; however, further confirmation in larger trials is needed. FUNDING: Epidemiological and Clinical Research Information Network.

Welder's pulmonary hemosiderosis associated with systemic iron overload following exacerbation of acute adult T-cell leukemia/lymphoma.

Herein, we describe a 61-year-old man diagnosed with pulmonary hemosiderosis following chemotherapy for acute adult T-cell leukemia/lymphoma (ATLL). Liver and heart biopsy confirmed hemosiderosis. ATLL progressed, and the patient died from multiorgan damage. Welder's lung may have been involved in hemosiderosis and systemic iron overload. Abnormal iron metabolism or immune reactions may have influenced the clinical course, but these were not validated. Detailed analyses of family medical and lifestyle histories, and genetic examination should be performed in cases of systemic iron overload.

GM-CSF Autoantibody-positive Pulmonary Alveolar Proteinosis with Simultaneous Myeloproliferative Neoplasm.

Pulmonary alveolar proteinosis (PAP) is classified as autoimmune, secondary, or genetic. We herein describe a 69-year-old man with autoimmune PAP, simultaneously diagnosed with myeloproliferative neoplasm (MPN). Two years after the diagnosis, the MPN progressed to acute myeloid leukemia, and the patient died from an alveolar hemorrhage during remission induction chemotherapy. Throughout the clinical course, no progression of PAP was observed, despite the progression to leukemia. There are few reports of autoimmune PAP with hematological malignancy, and this case demonstrated that an evaluation for GM-CSF autoantibodies is important for distinguishing the autoimmune and secondary forms of PAP, even if the patient has hematological malignancy.

Plasmablastic lymphoma of the stomach in an HIV-negative patient.

Plasmablastic lymphoma (PBL) is a rare B-cell neoplasm with an aggressive clinical behavior that predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients. However, it has recently been recognized that PBLs can also affect individuals without HIV infection, and suggested that these neoplasms show different clinicopathological characteristics between HIV-positive and -negative patients. Herein we describe a case of gastric PBL in a female HIV-negative patient. The tumor was composed of a diffuse and cohesive proliferation of large neoplastic cells, which resembled immunoblasts or plasmablasts with a starry sky appearance. Immunophenotypically, the neoplastic cells were diffusely positive for CD138, MUM1, IgM, and BOB-1, and negative for CK, LCA, CD3, CD20, CD79a, Pax5, kappa, lambda, CD30, ALK, S-100, HMB-45, MPO, and HHV-8. The MIB-1 index was nearly 100%. Epstein-Barr virus-encoded RNA in situ hybridization was negative. A monoclonal immunoglobulin heavy chain gene rearrangement was detected in polymerase chain reaction (PCR) and heteroduplex analyses. A combination of PCR-based analysis of immunoglobulin gene rearrangement and immunohistochemistry can be useful to substantiate the diagnosis by utilizing routine paraffin-embedded tissue sections, because PBL in the setting of extra-oral localization and immunocompetence is a diagnostic challenge, given its rarity, morphology, and absence of CD20 expression.

How repeated 15-minute assertiveness training sessions reduce wrist cutting in patients with borderline personality disorder.

OBJECTIVE: The aim of this work was to examine a possible treatment for patients with borderline personality disorder who have wrist-cutting syndrome, a condition characterized by repeated, superficial wrist cutting in a non-suicidal fashion. Within the current healthcare system in Japan, the average amount of time a doctor can spend with a psychiatric outpatient is about 8 to 15 minutes. We, therefore, examined whether repeated 15-minute psychotherapy sessions to improve patient assertiveness would be effective for reducing wrist cutting and possibly other forms of self-mutilation. METHODS: We treated 13 patients diagnosed with borderline personality disorder and wrist-cutting syndrome with assertiveness training during 15-minute, biweekly therapy sessions over a course of one to four years. RESULTS AND CONCLUSIONS: At the conclusion of psychotherapeutic treatment, 69% of outpatients showed a statistically significant reduction in wrist-cutting behavior.

Clinical significance of minimal residual disease in patients with t(8;21) acute myeloid leukemia in Japan.

To examine the prognostic significance of minimal residual disease (MRD) in t(8;21) acute myeloid leukemia (AML), 96 bone marrow samples from 26 Japanese patients in complete remission (CR) were analyzed regarding the RUNX1/MTG8 transcript using real-time reverse transcriptase polymerase chain reaction assay. All patients were treated with intensive chemotherapy. The median copy number of the RUNX1/MTG8 transcript, measured after each treatment course decreased over time. However, an increase in the MRD level was documented in three patients after the second consolidation, and all of them subsequently relapsed. The relapse-free survival (RFS) did not differ between the patients whose MRD levels were below or above 1,000 copies/microg after the first consolidation, with respective 2-year rates of 62 and 86% (P = 0.21). With respect to the MRD level after induction therapy, our data also failed to show any favorable effect of a lower MRD on RFS. Although these findings need to be confirmed with a larger number of patients, our data indicate that the MRD level at a given time during the early course in CR does not predict the outcome in Japanese patients.

[Mantle cell lymphoma mimicking chronic lymphocytic leukemia].

A 62-year-old male was admitted to our hospital complaining of dyspnea in March, 2002. He had remarkable bone marrow invasion with a significant number of leukemic cells, anemia and thrombocytopenia. In addition he had generalized lymphadenopathy including a bulky mass in the left cervix. Surface marker analysis of abnormal cells showed CD 5+, 10-, 19+, 20+, 23+, and kappa+, and immunohistochemistry revealed cyclin D1-positive cells. Chromosome analysis showed del(11q). The patient was diagnosed as having mantle cell lymphoma, stage IVB, and received combination chemotherapy. He could not obtain complete remission and died after 29 months. We found it very difficult in this case to make a differential diagnosis between mantle cell lymphoma and chronic lymphocytic leukemia. We report on this case and summarize the problem of the differential diagnosis.