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Biomedical subjects

Jun Taguchi

Publications and source records attributed to Jun Taguchi.

17 recordsLinked to original sources

Expression of the myeloperoxidase gene in AC133 positive leukemia cells relates to the prognosis of acute myeloid leukemia.

We previously reported that the percentage of myeloperoxidase (MPO) positive blasts had a prognostic impact on survival of patients with acute myeloid leukemia (AML). To extend this observation, we quantitatively measured the level of the MPO gene in AC133 positive leukemia cells that would contain a putative AML stem/progenitor compartment. AML cases were divided into the MPO gene high (MPOg-H) and MPO gene low (MPOg-L) groups. Only patients belonging to the MPOg-H group had a favorable chromosomal translocation, t(8;21), and having no morphological dysplasia that was associated with MPOg-L. The difference in the survival of MPOg-H and MPOg-L was statistically meaningful, demonstrating the possible prognostic impact of the expression of MPO gene in AC133 positive leukemia cells.

AC133 Antigen↗

Non-Hodgkin's lymphoma presenting as multiple bone lesions and hypercalcemia.

We report a rare case of a patient with non-Hodgkin's lymphoma who developed multiple bone lesions and hypercalcemia. A 50-year-old woman complained of drowsiness and multiple bone pain on admission. Radiographic examination revealed multiple bone fractures and osteolytic lesions. She was diagnosed with diffuse large B cell lymphoma by biopsy of an inguinal lymph node. Elevation of parathyroid hormone-related protein (PTHrP) and hypercalcemia were confirmed pretreatment, and those serum levels decreased during chemotherapy for lymphoma. However, the disease was resistant to chemotherapy combined with rituximab. These findings suggest that hypercalcemia is associated with PTHrP and the prognosis of patients with bone lymphoma in advanced stage is poor, although it is thought to be a relatively favorable prognosis in localized primary lymphoma of bone.

Antibodies, Monoclonal↗

Effect of blood cyclosporine concentration on the outcome of hematopoietic stem cell transplantation from an HLA-matched sibling donor.

We retrospectively evaluated the effect of the blood cyclosporine (CsA) concentration on the outcome of allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor in 171 patients who received a continuous infusion of CsA and short-course methotrexate to prevent graft-versus-host disease (GVHD). CsA was started at 3.0 mg/kg/day and the dose was adjusted to maintain the blood CsA concentration between 250 and 350 ng/ml. The actual dose of CsA averaged 1.9 mg/kg/day at the 3rd week after transplantation. The incidence of grade II-IV acute GVHD was 29.9%. Patient age and sex were identified as independent significant risk factors for acute GVHD. The CsA concentration during the 3rd week after transplantation most strongly affected the incidence of grade II-IV acute GVHD (RR 0.995 for an increase in CsA concentration by 1 ng/ml, P = 0.037) adjusted for other risk factors. The incidence of acute GVHD was significantly lower in patients with a 3rd-week CsA concentration higher than 300 ng/ml than in those with values between 200 and 300 ng/ml (20% vs. 35%, P = 0.036). We concluded that the blood CsA concentration at peri-engraftment period may be important in preventing acute GVHD.

Cyclosporine↗

Chemokine expression in human erythroid leukemia cell line AS-E2: macrophage inflammatory protein-3alpha/CCL20 is induced by inflammatory cytokines.

OBJECTIVE: Normal and malignant hematopoietic cells are shown to express and secrete various cytokines and chemokines, some of which are believed to play an important role in normal and abnormal hematopoiesis in an autocrine/paracrine manner. To explore the possibility of a cytokine/chemokine network participating in the pathophysiology of anemic disorders, we evaluated the ability of inflammatory cytokines to induce chemokine expression using erythroid progenitor cells. METHODS: Erythropoietin-dependent human leukemia cell line AS-E2 was used as a model of erythroid colony-forming unit (CFU-E) cells. The expression of mRNA of 8 chemokines was examined using RT-PCR, before and after TNF-alpha, IFN-gamma, and IL-1beta stimulation. For MIP-3alpha, the promoter activity was analyzed by luciferase assay and secretion was confirmed by ELISA. The expression of CCR6, the specific receptor for MIP-3alpha, was analyzed by RT-PCR and flow cytometry. RESULTS: Unstimulated AS-E2 cells constitutively expressed transcripts for MCP-4, IP-10, PF-4, IL-8, and MIP-3alpha. Stimulation with TNF-alpha, IFN-gamma, and IL-1beta upregulated MIP-3alpha mRNA expression and induced its protein secretion. Luciferase assay revealed that these cytokines could upregulate promoter activity of the MIP-3alpha gene, possibly through the NF-kappaB pathway. CCR6 mRNA was detected and its intracellular expression was confirmed. CONCLUSION: These data suggest that inflammatory cytokine-stimulated erythroid progenitors secrete MIP-3alpha, which may function in an autocrine/paracrine manner. Furthermore, the existence of intracellular CCR6 suggests the involvement in cytokine signaling of a MIP-3alpha-dependent internal autocrine mechanism. These mechanisms may play a role in pathophysiology of anemic disorders, such as secondary anemia and bone marrow failure syndromes.

Cell Line, Tumor↗

Human herpesvirus 6 meningoencephalitis in allogeneic hematopoietic stem cell transplant recipients.

We retrospectively investigated the clinical characteristics of human herpesvirus 6 (HHV-6) meningoencephalitis within 100 days after allogeneic hematopoietic stem cell transplantation (HSCT). Of 1148 patients who received transplants between January 1999 and December 2003, 11 patients (0.96%) with HHV-6 meningoencephalitis were identified. Ten of 11 recipients received hematopoietic stem cells from donors other than HLA-identical siblings. Confusion was the most frequent central nervous system (CNS) symptom, and a skin rash with high-grade fever preceded the CNS symptoms in 9 patients. Magnetic resonance imaging of the brain showed an abnormal increased T2 signal in the hypothalamus of 5 patients. Eight patients were treated with ganciclovir, and an improvement of CNS symptoms was obtained in 3 patients; 3 patients treated with acyclovir showed no improvement. Improvement in the meningoencephalitis seemed less frequent in patients with abnormal findings in the hypothalamus than in those without such findings. Because the symptoms of HHV-6 meningoencephalitis mimicked those of cyclosporine- or tacrolimus-induced encephalopathy, the drugs were withdrawn at the onset of CNS symptoms in 10 patients, resulting in the development of grade IV graft-versus-host disease (GVHD) in 5 patients. Three patients died of HHV-6 meningoencephalitis, and 6 died of other causes, including GVHD. In conclusion, HHV-6 meningoencephalitis is a rare but potentially life-threatening complication in patients who undergo allogeneic HSCT. Careful assessment of the clinical findings and the brain may allow early and precise diagnosis of HHV-6 meningoencephalitis and contribute to improving its prognosis.

Adolescent↗

[Multiple myeloma presenting as cavernous sinus syndrome].

We report on a 70-year-old male who developed cavernous sinus syndrome as the initial symptom of multiple myeloma. He was admitted with diplopia and ptosis in October 2004. The diagnosis of multiple myeloma and cavernous sinus syndrome due to a gross mass at the sinus base were made. Cerebral computed tomography revealed that the lesion occupied the sphenoid sinus and involved the oculomoter nerve. He underwent local irradiation of the mass followed by systemic chemotherapy. The symptoms caused by the mass disappeared after the treatment. Clinicians need to be aware of the rare manifestation of multiple myeloma.

Aged↗

A possible association between the presence of interleukin-4-secreting cells and a reduction in the risk of acute graft-versus-host disease.

OBJECTIVE: We monitored cytokine-secreting cells using an enzyme-linked immunospot (ELISPOT) assay in a prospective study to assess the cytokine network after transplantation. PATIENTS AND METHODS: Peripheral blood mononuclear cells were collected from 23 patients who received allogeneic stem cell transplantation, from before the preconditioning regimen to 56 days after transplantation. The number of interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha)-secreting cells were measured by ELISPOT assay. For IL-4 and IFN-gamma, in vitro stimulation with phorbol 12-myristate 13-acetate and phytohemagglutinin was performed. RESULTS: The frequency of IL-4-secreting cells was significantly higher in five patients receiving peripheral blood stem cell transplantation (PBSCT) than that in 18 patients who received bone marrow transplantation (BMT). Based on IFN-gamma and TNF-alpha release, there was a trend toward a decrease in the number of cytokine-secreting cells in PBSCT compared with BMT. Furthermore, patients who did not develop acute graft-vs-host disease (GVHD, n=5) showed a significantly higher number of IL-4-secreting cells compared with those who developed acute GVHD (n=18). Both IFN-gamma-secreting cells and TNF-alpha-secreting cells showed a trend to increase in number in patients with acute GVHD. In patients who received reduced-intensity stem cell transplantation (n=7) compared with conventional stem cell transplantation (n=16), there was a large number of cytokine-secreting cells detected by IL-4 and IFN-gamma release. CONCLUSIONS: These results are consistent with the hypothesis that IL-4-producing cells inhibit the development of acute GVHD. In addition, the increased percentage of IL-4-secreting cells may be responsible for the unexpected low incidence of acute GVHD in PBSCT, despite the presence of large numbers of mature T cells in the donor infusion.

Adult↗

[Triple secondary malignancy of gingiva, palate and esophagus after an allogeneic bone marrow transplantation for cutaneous T-cell lymphoma].

A 31-year-old man was diagnosed as having cutaneous T-cell lymphoma in January 1994. He received an allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor in May 1995, because of refractoriness to chemotherapy. The patient had been treated with immunosuppressants including prednisolone and cyclosporin A for chronic graft-versus-host disease (GVHD) of the extensive type following acute GVHD. Five years after the BMT, he developed moderately differentiated squamous cell carcinoma (SCC) on the mandibular gingival mucosa and underwent surgical resection. Furthermore, 6 years after the BMT well differentiated SCC developed on his palate and was resected. Concurrently, he was diagnosed as having esophageal cancer (poorly differentiated SCC) and underwent a subtotal esophagotomy. One year later he had a recurrence of the esophageal cancer with dysphagia and was treated with radiation and chemotherapy. He remains free of triple cancer and lymphoma. It is suggested that total body irradiation, immunosuppressants, and chronic GVHD are associated with a risk of secondary malignancies following allogeneic BMT. These factors might have contributed to the onset of triple cancer in our patient.

Adult↗

[Hematopoietic stem cell transplantation in the second or later complete remission in acute promyelocytic leukemia initially treated with all-trans retinoic acid].

Despite the use of all-trans retinoic acid (ATRA) as the first-line treatment for acute promyelocytic leukemia (APL), relapse occurs in about 20% of cases. Most relapsing APL patients can achieve second remission (CR2) following ATRA combined with chemotherapy or arsenic trioxide. Stem cell transplantation (SCT) has been widely adopted in CR2, but optimal SCT (auto- or allo-SCT) remains controversial. We analyzed the outcomes for 8 APL patients initially treated using ATRA, who relapsed, achieved CR2 and underwent auto-SCT (n = 4) or allo-SCT (n = 4). The mean age of patients who underwent allo-SCT was 39 years. Minimal residual disease (MRD) just prior to SCT was positive in 1 patient and negative in 3. Engraftment was achieved in all patients, but 2 patients died of transplantation-related complications within 6 months. Complete molecular remission has been maintained in the remaining 2 patients. The mean age of patients who underwent auto-SCT was 48 years. MRD just prior to SCT was negative in all 4 patients. Complete molecular remission has been maintained in all 4 patients (mean follow-up, 3 years 9 months). The results for auto-SCT are favorable in patients with MRD-negative APL.

Adult↗

Long-term cytogenetic remission with ubenimex monotherapy in a case of chronic myeloid leukemia.

A 65-year-old man was diagnosed with chronic myeloid leukemia (CML) in February 1990, and was treated with busulfan and ubenimex. Cytogenetic analysis of the bone marrow revealed the Philadelphia (Ph) chromosome in 100% of cells of analyzed at diagnosis. Treatment with busulfan was stopped in March 1993 due to bone marrow suppression. The Ph chromosome was seen in 80% of cells in June 1993. He received ubenimex monotherapy after cessation of busulfan. Complete disappearance of the Ph chromosome was confirmed in May 1995 and has continued to date. This suggests that ubenimex might specifically affect the Ph chromosome and be useful as maintenance therapy for CML.

Aged↗

Membranous nephropathy after allogeneic stem cell transplantation: report of 2 cases.

Nephrotic syndrome (NS) is a rare complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cases of 2 patients who developed NS after receiving allo-HSCT for chronic myelogenous leukemia and acute lymphoblastic leukemia are described. In both cases, renal biopsy revealed membranous nephropathy (MN), and the patients achieved remission after treatment with prednisolone. Previously reported cases and our experience suggest that most NS patients show MN in histologic tests after allo-HSCT and that its development is related to graft-versus-host disease. Early treatment with steroids seems effective for resolving symptoms of NS and improving renal function.

Adolescent↗

[Allogeneic peripheral blood stem cell transplantation for a hepatitis B virus carrier with Epstein-Barr virus associated with hemophagocytic syndrome].

We report herein a 21-year-old hepatitis B virus (HBV) female carrier who developed persistent fever, lymphadenopathy and pancytopenia in September of 2000. Hemophagocytes were found in the bone marrow smears. Epstein-Barr virus (EBV) serology showed positive for VCA-IgG, IgM and EB-ER and negative for EBNA. The EBV genome was detected in the peripheral blood. The patient was diagnosed as having EBV-associated hemophagocytic syndrome (EBV-AHS) and received chemotherapy. Although she was treated with lamivudine three months after the initiation of chemotherapy, she developed severe hepatitis. She recovered from the hepatitis through a combination of plasma exchange, immunosuppressive and antiviral therapies. Because of the refractoriness of her EBV-AHS to chemotherapy, she received allogeneic peripheral blood stem cell transplantation (PBSCT) from her HLA-identical brother. Hepatitis B did not recur after the PBSCT under administration of lamivudine. The EBV genome in the peripheral blood disappeared soon after the PBSCT but it was revealed again after the initiation of prednisolone for the treatment of acute GVHD. A donor lymphocyte infusion (DLI) was given on day 169 and the EBV genome copy number in the peripheral blood gradually decreased and disappeared. Although the origin of the EBV-infected cells could not be determined as being from the host or donor, DLI was a useful treatment for the recurrence of EBV infection after allogeneic stem cell transplantation for EBV-AHS.

Adult↗

[Fatal acute visceral disseminated varicella-zoster virus infection in a patient with chronic graft-versus-host disease].

A 34-year-old woman was admitted for chronic graft-versus-host disease ten months after an unrelated bone marrow transplantation. Cytomegalovirus (CMV) antigenemia on day 5 of hospitalization was negative. Thrombocytopenia occurred on day 9. Laboratory findings revealed severe liver dysfunction on day 13. On day 14, the patient developed interstitial pneumonia and disseminated intravascular coagulation, and died from progressive respiratory failure. Multinucleated giant cells were found in the lung, liver, spleen, esophagus, pancreas and intestine obtained at autopsy. Varicella-zoster virus (VZV) was detected in the blood using the polymerase chain reaction (PCR) technique. CMV, herpes virus type 6 and Epstein-Barr virus were detected in the liver and lung with the PCR technique. We concluded visceral VZV infection was the main cause of her death because of her aggressive clinical course and the histology at autopsy. In this case, chronic GVHD and its immunosuppressive treatment resulted in her fatal VZV reactivation.

Adult↗

The level of MEF but not ELF-1 correlates with FAB subtype of acute myeloid leukemia and is low in good prognosis cases.

ETS proteins (such as PU.1, Fli-1 and ETS-1) have been shown to play important roles in normal and abnormal hematopoiesis. We examined the expression of the ELF subfamily of ETS genes (ELF-1, MEF and NERF) in acute myeloid leukemia (AML) cells using Northern blot analysis. ELF-1 and MEF were expressed in all samples, whereas NERF was not. The relative expression (RE) of MEF, but not ELF-1, was significantly lower (P<0.0001) in AML with t(8;21) and t(15;17) compared with AML with normal karyotype. The pattern of MEF expression was not uniform among cells with CD34(+)/CD33(+). It is suggested that the low RE of MEF might be part of a gene expression profile characterizing AML with a good prognosis.

Acute Disease↗

[Effectiveness of oral vitamin B12 therapy for pernicious anemia and vitamin B12 deficiency anemia].

We investigated the efficacy of oral vitamin B12 (B12) therapy in patients with B12-deficiency anemia. Between June 1994 and June 2000, 17 patients, who were diagnosed as having B12-deficiency anemia and gave their informed consent, were enrolled in this study. Of these patients, 7 were further treated with a maintenance dose of methylcobalamin (1,500 micrograms daily for 7 days every 1-3 months). Correction of hematological and neurological abnormalities was prompt. The hemoglobin level and serum concentration of B12 were normalized within two months after starting the treatment. Recovery from neurological disturbance was observed within one month. To maintain a normal serum concentration of B12, a 7-day regime of administration was needed every month in 3 patients, every 2 months in 3 patients, and every 3 months in 1 patient. These results demonstrate the effectiveness of oral cobalamin therapy, and also that oral intermittent therapy is useful for maintaining a normal serum B12 concentration. Oral cobalamin therapy might be as effective as conventional injection therapy, and useful for long-term treatment.

Administration, Oral↗