No abstract

Severe systemic Geotrichum capitatum (G. capitatum) infection is rare, especially in Japan. G. capitatum infection has been reported mainly in immunocompromised patients and the prognosis is poor with a mortality rate of approximately 50-75%. Here, we report a Japanese case of systemic G. capitatum infection in a severe neutropenic patient who was receiving chemotherapy for acute myelogeneous leukemia with multilineage dysplasia. G. capitatum was isolated from blood cultures, and also formed multiple nodular lesions in lung fields. The infection was successfully cured with a combination of amphotericin B, itraconazole, and voriconazole.

Cancer immunotherapy using heat shock protein (HSP) derived from autologous tumor requires cluster of differentiation (CD)4+ as well as CD8+ T-cells for the prolongation of patient survival, suggesting that a humoral immune response through CD4 + T-cells is important in addition to cellular immunity. However, the role of humoral responses in HSP-based autologous tumor immunotherapy remains unclear. In the present study, we investigated whether leukemia-specific antibodies and antibodymediated cytotoxicity against autologous leukemia cells have a crucial role in a mouse A20 leukemia model by immunizing A20-derived HSP70. Immunization with A20-derived HSP70 induced the production of anti-A20-antibodies and the antibodies recognized HSP70-binding peptides derived from A20. One of those was a major histocompatibility complex ( (1) HSP70 is one of the HSP localized in the cytoplasm and carries peptides to the endoplasmic reticulum, in which glycoprotein (gp)96, another class of HSP, transports the peptides onto the major histocompatibility complex (MHC) class-I molecules.(2-4) In addition, it is known that HSPpeptide complexes are taken up by the antigen-presenting cells (APC) though the cluster of differentiation (CD)91 receptors expressed on APC, and the peptides bound to these HSP are then presented on the MHC class-I or II molecules.(5,6) Because the tumor-derived HSP bind the tumor-specific antigenic peptides, (5)(6)(7) tumor-derived HSP-antigenic peptide complexes are used for vaccination against cancer. As individual HSP are homogeneous, HSP-based cancer vaccine has the advantage of inducing specific immunity against tumor cells of each different haplotype without the need to identify any tumor-specific antigenic peptides. (5,8) In recent years, clinical efficacies of HSP derived from autologous tumor cells have been reported in several cancer patients, including patients suffering renal cell carcinoma, melanoma or chronic myelogenous leukemia, especially in subgroups of patients with relatively few tumors. (9)(10)(11)(12) Although chemotherapies and autologous stem cell transplantations (SCT) have been performed on many patients with leukemia or lymphoma, clinical results have not been satisfactory because of a relapse owing to the presence of minimal residual disease (MRD) and the lack of a graft-versus-leukemia (GVL) effect, both of which can be overcome by allogeneic transplantation. (13)(14)(15) We have established a mouse model with a minimum amount of leukemia cells after syngeneic bone marrow transplantation, and have reported that the immunization of mice with leukemia-cell-derived HSP70 or gp96 induces leukemia-specific immunities by CD8 positive (+) cytotoxic T-cells (CTL) and prolongs the survival of the mice. (16,17) These findings showed the possibility of a clinical application of HSP-based immunotherapy for patients with leukemia, especially for those with minimal residual leukemia cells after SCT.In HSP-based immunotherapy for cancer, cell-mediated immune response by tumor-specific CD8+ CTL is...

Hepcidin, a key regulator of iron homeostasis, is known to have three isoforms: hepcidin-20, -22, and -25. Hepcidin-25 is thought to be the major isoform and the only one known to be involved in iron metabolism; the physiological roles of other isoforms are poorly understood. Because of its involvement in the pathophysiology of hereditary hemochromatosis and the anemia of chronic disease, the regulatory mechanisms of hepcidin expression have been extensively investigated, but most studies have been performed only at the transcriptional level. Difficulty in detecting hepcidin has impeded in vitro research. In the present study, we developed a novel method for simultaneous quantification of hepcidin-20, -22, and -25 in the media from hepatoma-derived cell lines. Using this method, we determined the expression patterns of hepcidin isoforms and the patterns of responses to various stimuli in human hepatoma-derived cultured cells. We found substantial differences among cell lines. In conclusion, a novel method for simultaneous quantification of hepcidin isoforms is presented. Heterogeneous expressions of hepcidin isoforms in human hepatoma-derived cells were revealed by this method. We believe our method will facilitate quantitative investigation of the role hepcidin plays in iron homeostasis.

An isodicentric (X)(q13) (idicXq13) is a rare, acquired chromosomal abnormality originated by deletion of the long arm from Xq13 (Xq13-qter), and is found in female patients with hematological disorders involving increased ringed sideroblasts (RSs), which are characterized by mitochondrial iron accumulation around the erythroblast nucleus. The cause of increased RSs in idicXq13 patients is not fully understood. Here, we report the case of a 66-year-old female presenting with refractory anemia with ringed sideroblasts (RARS), and idicXq13 on G-banded analysis. We identify the loss of the ABCB7 (ATP-binding cassette subfamily B member-7) gene, which is located on Xq13 and is involved in mitochondrial iron transport to the cytosol, by fluorescent in situ hybridization (FISH) analysis and the decreased expression level of ABCB7 mRNA in the patient's bone marrow cells. Further FISH analyses showed that the ABCB7 gene is lost only on the active X-chromosome, not on the inactive one. We suggest that loss of ABCB7 due to deletion of Xq13-qter at idicXq13 formation may have contributed to the increased RSs in this patient. These findings suggest that loss of the ABCB7 gene may be a pathogenetic factor underlying mitochondrial iron accumulation in RARS patients with idicXq13.