Lung infiltration of adult T-cell leukemia cells following the administration of arsenic trioxide. Lung infiltration of ATL by AS(2)O(3).
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Aged↗
Biomedical subjects
Junji Tanaka
Publications and source records attributed to Junji Tanaka.
Enantioselective enol lactone synthesis under double catalytic conditions.
[reaction: see text] The reaction of dimedone with 1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles in THF, catalyzed by catalytic amounts of both DBFOX/Ph-nickel(II) perchlorate trihydrate and 2,2,6,6-tetramethylpiperidine, in the presence of acetic anhydride in THF produces the corresponding enol lactones in high enantioselectivities through enantioselective Michael additions followed by cyclization with removal of the pyrazole auxiliary. Other related nucleophile precursors can be successfully applied in the enantioselective enol lactone synthesis under the double catalytic conditions.
Journal Article↗
Progressive disappearance of anti-hepatitis B surface antigen antibody and reverse seroconversion after allogeneic hematopoietic stem cell transplantation in patients with previous hepatitis B virus infection.
Reactivation of resolved hepatitis B virus (HBV) infection, which is known as reverse seroconversion (RS), has been reported as a rare complication of allogeneic hematopoietic stem cell transplantation. We retrospectively studied HBV serologic markers in 14 recipients with pretransplant anti-hepatitis B surface antigen antibody (anti-HBs). Progressive decreases in anti-HBs titer were observed in all cases. In 12 cases, anti-HBs titer had decreased to under the protective value. RS occurred in seven cases after disappearance of anti-HBs. Although reseroconversion occurred in five cases, two cases remained in an HBV-carrier status after resolution of hepatitis. In the other five cases, RS did not occur even after disappearance of anti-HBs. The actual risks of anti-HBs disappearance and RS were estimated to be 75.0% and 39.8% at 2 years and 100.0% and 70.0% at 5 years, respectively. In conclusion, RS is a late-onset complication with high frequency that can be predicted by careful monitoring of progressive decrease in anti-HBs titer.
Adult↗
Long-term follow-up of a patient with idiopathic myelofibrosis associated with chromosome 11 and 13 abnormalities.
A case of a leukemic transformation following a 27-year history of idiopathic myelofibrosis (IMF) is presented. The patient had two chromosomal abnormalities: a deletion of chromosome 13, del 13(q12q14), and a deletion of chromosome 11, del 11(q14q23). This patient's final diagnosis was acute micromegakaryocytic leukemia, and she died 1 month after leukemic transformation with an additional chromosomal abnormality, trisomy 8. IMF with myeloid metaplasia associated with deletion of the long arms of chromosomes 11 and 13 has not been previously reported. We speculate that the leukemic transformation in this patient was associated with chromosomal abnormalities del 11 and trisomy 8.
Bone Marrow↗
Minimal residual disease (MRD) monitoring using rearrangement of T-cell receptor and immunoglobulin H gene in the treatment of adult acute lymphoblastic leukemia patients.
We evaluate whether molecular monitoring of minimal residual disease (MRD) using TCR delta (TCRD), TCR gamma (TCRG), and immunoglobulin H (IgH) gene rearrangements in the bone marrow (BM) is correlated with clinical events in ALL patients. The 14 patients enrolled in this study included 6 males and 8 females with a median age of 53 years (range, 25-79 years), and the median duration of follow-up was 417 days (range, 57-617 days). The median WBC count was 11.3 x 10(9)/L at diagnosis. All patients had L2 type ALL. Eleven patients had a monoclonal pattern of IgH (7), TCRD (3) and TCRG (1), and 3 patients had two clonal patterns. Eleven of the 14 patients achieved the first complete remission (CR) after the first induction chemotherapy. We analyzed 9 of 11 CR patients who could be examined immediately after induction chemotherapy (including re-induction therapy). Event-free survival (EFS, 0%) and disease-free survival (DFS, 0%) at 1 year in CR patients with MRD level >or=10(-3) (n = 3) were significantly lower than those in CR patients with MRD level <10(-3) (n = 6) (log-rank test, P = 0.013, 0.013). A lower MRD in BM value after induction chemotherapy was associated significantly with longer survival in the log-rank test. Our data provide evidence that molecular MRD status of BM is a strong predictor of outcome in adult ALL.
Adult↗
Acute biphenotypic leukemia and an acquired X chromosome.
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Acute Disease↗
Multicentric contiguous variant of epithelioid angiosarcoma of the bone. A rare variant showing angiotropic spread.
Epithelioid angiosarcoma of the bone is a rare tumor and is a diagnostic challenge. Here we present an autopsy case of a 62-year-old man with multifocal osteolytic lesions in the extremities and the pelvis. The initial diagnosis of a tibial biopsy was poorly differentiated adenocarcinoma. On the occasion of autopsy, a fungating thrombotic nodule was found at the anterior wall of the right atrium, and small hemorrhagic infarcts with tumor thrombi were found in the lung. Histologically, the above lesions were identical to the former tibial biopsy and they showed large eosinophilic epithelioid cells with irregular ovoid nuclei and prominent eosinophilic nucleoli. Rare intracytoplasmic lumina were identified. Immunohistochemically, the tumor cells were positive for cytokeratins (CAM5.2 and AE1/AE3), CD31, factor VIII-related antigen, and vimentin. This case showed angiotropic spread of the tumor only to the right atrium and the lung, with no solid mass in other organs. Multicentric epithelioid angiosarcoma of the bone is a pitfall in pathological diagnoses, especially if a strong radiological impression of metastatic carcinoma is provided. Therefore, pathologists should be aware of this rare variant.
Adenocarcinoma↗
Influence of antimicrobial treatment for Helicobacter pylori infection on the intestinal microflora in Japanese macaques.
Eradication treatment for Helicobacter pylori is known to cause mild but relatively frequent adverse effects. Some adverse effects such as diarrhoea and soft stools are related to disruption of the composition of the intestinal microflora. This study investigated the microfloral changes resulting from administration of an eradication regimen using proton pump inhibitor (PPI), amoxycillin and clarithromycin. Twenty-eight laboratory-bred Japanese macaques either were administered eradication treatment by this regimen for 7 days or received no medication. Faecal samples were collected for analysis on days 0, 8 and 15, and both aerobic and anaerobic cultures were performed. Among aerobic bacteria, Streptococcus had significantly decreased by day 8, while Enterococcus and Enterobacteriaceae had significantly increased. However, the total number of aerobic bacteria was not significantly decreased from pretreatment levels 1 day after completion of treatment. The number of anaerobic bacteria did not change significantly by day 8. However, the number of Lactobacillus and the detection rate of Bifidobacterium, Peptostreptococcus and Veillonella significantly decreased by day 8, although the number of Bifidobacterium, Peptostreptococcus and Veillonella had almost recovered up to the pretreatment levels 1 week after completion of treatment (day 15). These results suggest that the alterations in the composition of the intestinal microflora caused by the antimicrobial regimen that excludes metronidazole are different from those caused by the regimen including this drug. However, the alterations in bacterial microflora had almost reversed 7 days after completion of treatment in these macaques, which supports clinical findings that diarrhoea or soft stools in humans resolve relatively quickly after a similar treatment.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Ultrastructural features of trafficking defects are pronounced in melanocytic nevus in Hermansky-Pudlak syndrome type 1.
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, a bleeding disorder, and ceroid lipofuscinosis in the lungs and gut. HPS is genetically heterogeneous and the most common variant, HPS type 1, is caused by mutations in HPS1 gene. The protein encoded by HPS1 is considered to facilitate the trafficking of melanocyte-specific gene products into the premelanosome. We report the ultrastructural findings in a melanocytic nevus seen in a 17-y-old Japanese female patient with HPS1 who is a compound heterozygote of HPS1 mutations, including a novel mutation. Electron microscopy of a pinkish papule corresponding to the melanocytic nevus revealed markedly aberrant, immature melanosomes, large membranous structures, and giant melanosomes in the vicinity of trans-Golgi network, the characteristic abnormalities because of protein trafficking defects in HPS1. These ultrastructural features were far more clearly demonstrated in the nevus cells than in the epidermal melanocytes. Thus, ultrastructural analysis of nevus cells may be an additional diagnostic tool for HPS1 and could give us important clues to further understanding of the pathomechanisms of HPS.
Adolescent↗
Geldanamycin, a potent and specific inhibitor of Hsp90, inhibits gene expression and replication of human cytomegalovirus.
The effect of geldanamycin (GA), a specific inhibitor of heat shock protein 90 (Hsp90), on gene expression and replication of human cytomegalovirus (HCMV) was studied in human embryonic lung (HEL) fibroblasts. Kinetic analysis indicated that GA delayed synthesis of major immediate early (MIE), early and late viral proteins, and blocked a second tier of the synthesis of these proteins that occurred in untreated cells after 48 h post-infection (pi). Moreover, when HCMV-infected HEL cells were maintained with medium containing 40 nM GA for 6 days, with medium changes at 2-day intervals, the virus yield was reduced to an undetectable level. On a molecular level, the cellular kinase Akt and the transcription factor NFkappaB were activated in HCMV-infected cells within 30 min pi. NFkappaB was shown to be essential for MIE gene expression. However, in GA-treated cells, activation of both Akt and NFkappaB was greatly inhibited. Because LY294002, an inhibitor of cellular phosphatidylinositol 3-kinase (PI3-K), also prohibited HCMV-mediated activation of Akt and NFkappaB and synthesis of the MIE proteins, PI3-K signalling was necessary for expressing the MIE genes. These results suggest that the inhibitory effect of GA on HCMV replication is primarily caused by the disruption of the PI3-K signalling pathway, leading to the activation of NFkappaB, which plays a crucial role in expression of the critical MIE genes.
Antiviral Agents↗
Reactivation of hepatitis B virus with rituximab.
Rituximab has become a useful drug for the treatment of non-Hodgkin's lymphoma (NHL) and such autoimmune diseases as idiopathic thrombocytopenic purpura and rheumatoid arthritis. When combined with cytotoxic agents, rituximab showed synergistic effects for the treatment of NHL. In such treatment, hepatitis B virus (HBV) reactivation is a crucial complication when patients are treated with immunosuppressive or chemotherapeutic agents. Despite its treatment efficacy, several studies have pointed out unusual viral infections after its administration that resulted in fatal hepatitis due to HBV reactivation. In the cases at the authors' institute, the authors analysed the kinetics of HBV antibodies, HBV-reactivation timing, and the prophylactic efficacy of lamivudine. The authors reviewed their cases and the previous literature to clarify the characteristics of HBV-reactivated patients who were administered rituximab.
Antibodies, Monoclonal↗
Potential role of natural killer cell receptor-expressing cells in immunotherapy for leukemia.
Natural killer cell receptor (NKR)-expressing cells have cytolytic activity against leukemic cells, and solid tumor cells escape from T-cell recognition because of the low expression levels of class I HLA molecules in both allogeneic and autologous settings. This characteristic feature of NK cell recognition of target cells in contrast with that of T-cells provides a strategy to overcome tolerance in the tumor-bearing host. Furthermore, inhibitory NKR-expressing cells may have cytolytic activity and immunoregulatory functions. Several methods can be used to expand NKR-expressing cells for adoptive immunotherapy for leukemia and other malignant diseases. We review recent developments in the biology and clinical application of NKR-expressing cells, such as NK cells, lymphokine-activated killer cells, cytokine-induced killer cells, NKT cells, and other NKR-expressing cells.
Humans↗
Successful reduced-intensity stem cell transplantation (RIST) for a patient with malignant lymphoma and an ileostomy.
A 56-year-old man was admitted for treatment of non-Hodgkin's lymphoma (NHL). He had undergone a partial small bowel and colon resection and had ileostomy due to bowel perforation induced by chemotherapy. After the operation, his disease status was in partial remission (PR), and reduced-intensity allogeneic stem cell transplantation (RIST) was therefore performed for further improvement of disease status. The conditioning regimen consisted of fludarabine and busulfan. Graft-versus-host disease (GVHD) prophylaxis was performed using cyclosporin and short-term methotrexate. The occurrence of serious infection during the period of neutropenia was prevented by the administration of amphotericin B, fluconazole and acyclovir. This case report provides important information on the appropriate strategy for treating patients who have ileostomy.
Antineoplastic Agents↗
[Itraconazole capsules as antifungal prophylaxis for neutropenic patients with hematological malignancies from a single institution].
We have previously reported that itraconazole (ITCZ) at a dose of 200 mg/day is more effective than ITCZ at a dose of 100 mg/day and is safe for prophylaxis of mycosis. In this prospective study, 37 patients with hematological malignancies were administered 200 mg/day of ITCZ for prophylaxis of mycosis during neutropenia. Although none of the patients developed mycosis, 31 patients (83.8%) of the ITCZ administered patients developed neutropenia (neutrophil < 1000/microL), and 12 patients of them showed the possibility of fugitive fungal infection. The prolonged neutropenia and low neutrophil level were observed in the patients with malignant lymphoma at stage III-IV, which suggested the necessity of prophylactic antifungal drugs. Four patients showed the adverse events which might be caused by drug interactions between ITCZ and vinca alkaloid. However adequately modified administration of ITCZ prevented these effect. There were no other obvious side effects which were supposed to be caused by prophylactic ITCZ administration. Twenty-eight patients were measured plasma concentration of ITCZ about 10 days after the beginning of administration and mean trough ITCZ level was expected to be above the effective level (250 ng/ml). These results suggested that ITCZ is effective and safe for prophylaxis of mycosis during neutropenia in patients with hematological malignancies.
Adolescent↗
Successful treatment of lymphoma with fludarabine combined with rituximab after immune thrombocytopenia induced by fludarabine.
A 47-year-old man was diagnosed with non-Hodgkin's lymphoma (NHL) follicular B-cell type (stage IVB). Although partial remission was observed after the administration of several combination chemotherapeutic agents, no more improvement was observed. After we finished the FND (fludarabine, mitoxantrone, dexamethasone) regimen, the patient's status improved. After the administration of the FND regimen, thrombocytopenia developed, and the platelet count did not recover to previous levels. After rituximab was administered for the treatment of thrombocytopenia, the platelet count recovered. Then we combined fludarabine and rituximab for the treatment of NHL. Although fludarabine was administered, the platelet count did not decrease when combined with rituximab. In the discussion, we analyze the characteristics and the treatment outcome of the thrombocytopenia induced by fludarabine reviewed in the literature.
Antibodies, Monoclonal↗
Usefulness of magnifying endoscopic evaluation of the terminal ileum for a patient with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
The gastrointestinal tract is one of the common targets of acute graft-versus-host disease (GVHD), but accurate diagnosis is difficult because of the nonspecific nature of complicated diseases and the lack of diagnostic findings by conventional endoscopy. Recently, a magnifying endoscope has been developed and used for examining microstructures of the mucosa. Herein, we report the first use of a magnifying endoscope for a patient with gastrointestinal (GI) GVHD. Magnified endoscopic findings of atrophic and coalescent villi of the terminal ileum reflect histological findings of GVHD. Magnifying endoscopy of the terminal ileum may be useful for early detection and follow-up of GI GVHD.
Adolescent↗
Generation of leukemia-specific T-helper type 1 cells applicable to human leukemia cell-therapy.
Leukemic dendritic cells (DC) were induced from the peripheral blood (PB) or bone marrow (BM) of leukemia patients by culture with (i) GM-CSF + IL-3 (neutral condition); (ii) GM-CSF + IL-3 + IL-12 + IFN-gamma (type 1-condition); or (iii) GM-CSF + IL-3 + IL-4 (type 2-condition). Although leukemic cells rapidly differentiated into adhesive leukemic DC in all culture conditions, type1-conditions were the most suitable for inducing leukemic DC expressing high levels of HLA and costimulatory molecules. Addition of IL-2 after 2 days of culture induced a preferential growth of minor T cell populations interacting with leukemic DC. In particular, IFN-gamma-producing CD4+ Th1 cells were efficiently expanded in type 1 culture conditions but nor in neutral or type 2-conditions. However, CD4+ T cells expanded in neutral conditions showed Th1-like functions if they were pulsed with IFN-gamma for 2 days before harvest. Such Th1 cells produced IFN-gamma and exhibited cytotoxicity in response to autologous leukemia cells. We further demonstrated that IFN-gamma production of leukemia-specific Th1 cells was blocked by anti-HLA-DR mAb. Thus, we established a novel culture system for inducing leukemia-specific Th1 cells.
Adult↗
Cytolytic activity and regulatory functions of inhibitory NK cell receptor-expressing T cells expanded from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells.
Inhibitory natural killer cell receptor (NKR)-expressing cells may induce a graft-versus-leukemia/tumor (GVL/T) effect against leukemic cells and tumor cells that have mismatched or decreased expression of HLA class I molecules and may not cause graft-versus-host disease (GVHD) against host cells that have normal expression of HLA class I molecules. In our study, we were able to expand inhibitory NKR (CD94/NKG2A)-expressing CD8+ T cells from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMCs) by more than 500-fold using stimulation by an anti-CD3 monoclonal antibody with interleukin 15 (IL-15). These expanded and purified CD94-expressing cells attacked various malignant cell lines, including solid cancer cell lines, as well as the patients' leukemic cells but not autologous and allogeneic phytohemagglutinin (PHA) blasts in vitro. Also, these CD94-expressing cells prevented the growth of K562 leukemic cells and CW2 colon cancer cells in NOD/SCID mice in vivo. On the other hand, the CD94-expressing cells have low responsiveness to alloantigen in mixed lymphocyte culture (MLC) and have high transforming growth factor (TGF)-beta1- but low IL-2- producing capacity. Therefore, CD94-expressing cells with cytolytic activity against the recipient's leukemic and tumor cells without enhancement of alloresponse might be able to be expanded from donor G-PBMCs.
Antigens, CD↗