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Biomedical subjects

Akihisa Kanamaru

Publications and source records attributed to Akihisa Kanamaru.

At least 19 recordsLinked to original sources
PubMed2006

Possible molecular target therapy with rapamycin in MDS.

The authors previously reported the mRNA expression of Glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp) in MDS patients. The deletion of 123 bp creates a sequence that is homologues to mammalian target of rapamycin (mTOR). To analyse the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of wild and mutant type GSTT-1 gene of those stable transformants and bone marrow cells from MDS patients by RT-PCR was observed in the presence or absence of rapamycin. In result, exposure of rapamycin led to the disappearance of just the mutant gene band. This phenomenon possibly indicates that rapamycin only attacked the mutant GSTT-1 expressing clone.

Bone Marrow Cells↗
PubMed2005

Prognostic significance of BACH2 expression in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group.

PURPOSE: BACH2, a B-cell-specific transcription repressor, is abundantly expressed in lymphocytes of B-cell lineage as well as B-cell lymphoma cell lines. BACH2 possesses an inhibitory effect on proliferation of Raji cell lines derived from Burkitt's lymphoma. In this study, the prognostic significance of BACH2 expression was examined in diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: BACH2 expression was immunohistochemically examined on the paraffin-embedded sections obtained by biopsy from 108 patients (62 males and 46 females; age range, 23 to 85 years) with DLBCL. Staining intensity in the cytoplasm of the tumor cells was categorized as equal to or stronger (level 1) or weaker (level 2) than that in the endothelial cells in the same specimens. RESULTS: Level 1 and 2 expression of BACH2 was found in 32.4% and 67.6% of patients, respectively. Patients with level 1 expression showed significantly better disease-free and overall survival rate than those with level 2 expression (both P < .05). Multivariate analysis revealed BACH2 expression level together with performance status, elevated serum level of lactate dehydrogenase, and treatment response to be independent factors for prognosis of the patients. CONCLUSION: BACH2 expression level is a useful marker to predict disease-free and overall survival of patients with DLBCL.

Adult↗
PubMed2005

Possible effects of hepatocyte growth factor for the prevention of peritoneal fibrosis.

OBJECTIVE: Some patients who had carried out long-term continuous ambulatory peritoneal dialysis discontinued the treatment because of progressive peritoneal fibrosis. It has been previously reported that transforming growth factor-beta1 (TGF-beta1) is one of the factors that induces peritoneal fibrosis. Also, hepatocyte growth factor (HGF) plays a role in the prevention of fibrosis and in inhibiting TGF-beta1 production. In this study, we examined the effects of HGF on peritoneal fibrosis by TGF-beta1 induced by high concentrations of D-glucose. DESIGN: We transfected a full-length human HGF cDNA in an expression vector into human peritoneal mesothelial cells (HPMCs) using the calcium phosphate method. Transfected HPMCs were cultured with high concentrations of D-glucose solution and co-cultured with fibroblasts using a transwell system. Cell proliferation was determined using the Tetra Color One method. TGF-beta1 and HGF protein were measured by enzyme-linked immunosorbent assay. RESULTS: In addition to recombinant HGF, the growth inhibition of HPMCs by high concentration D-glucose or TGF-beta1 was significant. By transfecting HGF cDNA into HPMCs, growth inhibition by high concentration D-glucose was completely restored. Furthermore, the production of TGF-beta1 was also significantly decreased. CONCLUSION: These results suggested that exogenous HGF could possibly prevent peritoneal fibrosis.

Cell Proliferation↗
PubMed2005

Extramedullary blast crisis derived from 2 different clones in the central nervous system and neck during complete cytogenetic remission of chronic myelogenous leukemia treated with imatinib mesylate.

We describe a patient with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed an extramedullary blast crisis in the central nervous system (CNS) and then a subcutaneous tumor of the neck during treatment with imatinib mesylate. Administered 400 mg of imatinib mesylate after the diagnosis of chronic-phase CML, the patient achieved a complete cytogenetic remission 4 months later. However, he developed a mixed myeloid/B-cell blast crisis with additional karyotype abnormalities only in the CNS during a complete cytogenetic remission in the bone marrow. Several doses of intrathecal chemotherapy and whole-brain irradiation were effective in treating the blast crisis in the CNS. After 7 months of complete cytogenetic remission, the patient experienced a subcutaneous tumor in the right neck. A biopsy of the tumor revealed a mixed myeloid/T-cell blast crisis. The cytogenetic analysis showed that the blast crisis clone in the neck tumor was different from that of the CNS. An increased dose of imatinib mesylate was ineffective in treating the neck tumor. Irradiation to the right neck was therefore undertaken. This case suggests that the development of a clone resistant to imatinib mesylate is not always detected in the bone marrow and that multiple Ph-positive clones have the potential to become transformed into a blast crisis.

Adolescent↗
PubMed2005

[Quality of life in patients with systemic lupus erythematosus--preliminary survey using a short questionnaire. ].

Because the prognosis of systemic lupus erythematosus (SLE) has been much improved by recent progress in the treatment of this disease, improvement of quality of life (QOL) will be required more and more. However, QOL in SLE has not been well studied in comparison to that in rheumatoid arthritis. Fifty-four patients with systemic lupus erythematosus were asked about healthy feeling, acceptance of disease and the extent of satisfaction with their life. The percentage of patients who gave affirmative answers to healthy feeling, acceptance, and satisfaction was 64, 87, and 50, respectively. These three parameters were correlated with the following factors; 1. physical activity, especially that for daily living, 2. understanding in the family and workplace, and 3. depression and anxiety, whereas acceptance was not correlated with disease activity. Due to having a chronic disease, there are depression and anxiety derived from loss of existence in the family or workplace in their minds. In order to resolve these issues, education and explanation about the disease is needed for the family and society as well as for the patients. Although compliance of the patients in answering the questionnaire was easily obtained, the reliability and reproducibility, and the relationship between the items and the low-ranking factors should be investigated using a larger number of patients.

Activities of Daily Living↗
PubMed2004

Blockade of IL-18 receptor signaling delays the onset of autoimmune disease in MRL-Faslpr mice.

Autoimmune disease in Fas-deficient MRL-Faslpr mice is dependent on infiltrating autoreactive leukocytes and autoantibodies, and IFN-gamma plays an important role in the pathogenesis. As IL-18 is capable of inducing IFN-gamma production in T cells, we hypothesized that signaling through IL-18R is involved in the pathogenesis. To investigate the impact of IL-18 in this autoimmune disease, we generated an MRL-Faslpr strain deficient in IL-18Ralpha. Compared with the wild-type strain, IL-18Ralpha-deficient MRL-Faslpr mice survived longer and showed a significant reduction in renal pathology, including glomerular IgG deposits, proteinuria, and serum anti-DNA Abs. Intrarenal transcripts encoding IFN-gamma, TNF-alpha, IL-12, and IL-10, which have been linked to nephritis, were all markedly reduced. Skin lesions, lymphadenopathy, and lung pathology characteristic of the MRL-Faslpr mouse disease were diminished in IL-18Ralpha-deficient MRL-Faslpr mice. Thus, we conclude that IL-18Ralpha signaling is critical to the pathogenesis of autoimmune disease in MRL-Faslpr mice.

Animals↗
PubMed2004

CC chemokine ligands 25 and 28 play essential roles in intestinal extravasation of IgA antibody-secreting cells.

CCL25 (also known as thymus-expressed chemokine) and CCL28 (also known as mucosae-associated epithelial chemokine) play important roles in mucosal immunity by recruiting IgA Ab-secreting cells (ASCs) into mucosal lamina propria. However, their exact roles in vivo still remain to be defined. In this study, we first demonstrated in mice that IgA ASCs in small intestine expressed CCR9, CCR10, and CXCR4 on the cell surface and migrated to their respective ligands CCL25, CCL28, and CXCL12 (also known as stromal cell-derived factor 1), whereas IgA ASCs in colon mainly expressed CCR10 and CXCR4 and migrated to CCL28 and CXCL12. Reciprocally, the epithelial cells of small intestine were immunologically positive for CCL25 and CCL28, whereas those of colon were positive for CCL28 and CXCL12. Furthermore, the venular endothelial cells in small intestine were positive for CCL25 and CCL28, whereas those in colon were positive for CCL28, suggesting their direct roles in extravasation of IgA ASCs. Consistently, in mice orally immunized with cholera toxin (CT), anti-CCL25 suppressed homing of CT-specific IgA ASCs into small intestine, whereas anti-CCL28 suppressed homing of CT-specific IgA ASCs into both small intestine and colon. Reciprocally, CT-specific ASCs and IgA titers in the blood were increased in mice treated with anti-CCL25 or anti-CCL28. Anti-CXCL12 had no such effects. Finally, both CCL25 and CCL28 were capable of enhancing alpha4 integrin-dependent adhesion of IgA ASCs to mucosal addressin cell adhesion molecule-1 and VCAM-1. Collectively, CCL25 and CCL28 play essential roles in intestinal homing of IgA ASCs primarily by mediating their extravasation into intestinal lamina propria.

Animals↗
PubMed2004

Microbiological data for patients with febrile neutropenia.

The pattern of bacterial infections and antimicrobial susceptibility has changed significantly during the past 20-30 years. The causative organisms for bacteremia or fungemia identified at Kinki University Hospital in 1985-1996 were compared with the isolates identified during 1997-2002. The prevalence of gram-negative organisms decreased, whereas the prevalence of gram-positive organisms increased. Staphylococcal species predominated in the second period, accounting for 22% of isolates, and methicillin-resistant Staphylococcus aureus (MRSA) increased from 5% to 14% of isolates. Pseudomonas aeruginosa ranked second, although the prevalence decreased in the second period compared with the first. Candida species were also relatively frequent (11%). Enterococcal species had an 8% prevalence. A comparison of all culture isolates showed that gram-negative isolates still predominated among the general patient population, whereas almost equal prevalence was observed in patients with hematological diseases. MRSA was the organism most frequently isolated in the general patient population, followed by P. aeruginosa. Among staphylococcal species, MRSA accounted for as much as 90% of isolates.

Adolescent↗
PubMed2004

NK-cell related neoplasms in Osaka, Japan.

The frequency of NK-cell related neoplasms was estimated among lymphoproliferative diseases diagnosed and treated in Osaka, Japan, from 1999 to 2003. The total number of registered cases was 1,400, among which 1,092 patients were diagnosed as having malignant lymphomas. There were 987 cases of non-Hodgkin's lymphoma (NHL) and 105 (9.6%) of Hodgkin's lymphoma. Immunophenotypic analysis revealed that 743 patients had B-cell lymphomas and 209 T/NK-cell lymphomas. Among the T/NK-cell lymphomas, 40 showed positive immunoreactivity for CD56, and thus they were judged to be NK/T-cell lymphomas. They included one blastic NK-cell lymphoma and 39 NK/T-cell lymphomas. NK/T-cell lymphomas were further divided into three categories based on the main site of lesions: nasal type (23 cases), non-nasal extranodal type (11 cases), and nodal type (5 cases). The positive rate of infection with the Epstein-Barr virus determined by in situ hybridization was 83%, 36%, and 25% in the nasal, non-nasal, and nodal type, respectively. A mosquito allergy was found in one patient with EBV-positive non-nasal NK/T-cell lymphoma. The present study showed that the frequency of NK-cell related neoplasms among all NHLs was 4% in an ATL-non-endemic area of Japan.

Antineoplastic Agents↗
PubMed2004

A perforin/granzyme-positive MDS-derived T cell line, K2-MDS, induces apoptosis in CD34+ cells through the fractalkine-CX3CR1 system.

Fractalkine (CX3CL1) and its receptor CX3CR1 play an important role in natural killer (NK) cell- and cytotoxic T cell-mediated endothelium damage. Here we describe the cytotoxicity of myelodysplastic syndrome (MDS)-derived T cell line, K2-MDS, through the fractalkine-CX3CR1 system. K2-MDS cells induced apoptosis against CD34(+) cells from normal bone marrow (BM) in a direct cell contact manner. K2-MDS cells expressed perforin and granzyme B, but they lacked Fas ligand expression. A specific inhibitor for perforin, concanamycin A, blocked K2-MDS-dependent cytotoxicity. Furthermore, a CX3C-chemokine, fractalkine, was expressed in CD34(+) cells, and its receptor, CX3CR1, was expressed on K2-MDS cells. The neutralizing monoclonal antibody (MoAb) for fractalkine and soluble fractalkine significantly inhibited K2-MDS-dependent cytotoxicity. K2-MDS cells also induced the cytotoxicity against human umbilical cord endothelial cells (HUVECs) expressing fractalkine. These data indicate that K2-MDS may be a perforin-granzyme-positive T cell line that exerts a cytotoxic effect on CD34(+) cells mediated through the fractalkine-CX3CR1 system.

Antigens, CD34↗
PubMed2004

Expression of CCL28 by Reed-Sternberg cells defines a major subtype of classical Hodgkin's disease with frequent infiltration of eosinophils and/or plasma cells.

Classical Hodgkin's disease (HD) is characterized by rare neoplastic Hodgkin and Reed-Sternberg (H-RS) cells within abundant reactive cellular backgrounds. In most cases, H-RS cells originate from the B-cell lineage, but their immunophenotypes are unusual. Here we newly found frequent expression of chemokine receptors CXCR6 and CCR10 and their respective ligands CXCL16 and CCL28 in HD-derived cell lines. CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3. Therefore, we examined their expression in HD tissues by immunohistochemistry. We found that H-RS cells in 15 of 19 cases were positive for CCL28. Among them, seven cases were also positive for CCR10, suggesting a potential autocrine effect. In situ hybridization confirmed the expression of CCL28 mRNA in H-RS cells. The CCL28 positivity in H-RS cells did not significantly correlate with that of LMP-1, CCL17, CCL22, or CCL11. However, it significantly correlated with the background accumulation of eosinophils, plasma cells, and CCR10+ cells. Thus, the production of CCL28 by H-RS cells may play a major role in tissue accumulation of eosinophils and/or plasma cells in classical HD. The frequent expression of CCR10 in H-RS cells themselves also supports their close relationship to plasma cells.

Adolescent↗
PubMed2004

Mu-heavy chain disease associated with systemic amyloidosis.

mu-heavy chain disease (HCD) is very rare, with only 30 cases reported in the literature. We report a patient with mu-HCD associated with systemic amyloidosis. The diagnosis of mu-HCD was based on findings of mu-heavy chain fragments in the serum, Bence Jones proteinuria and vacuolated plasma cells in the bone marrow. To our knowledge, this is the third case in which systemic amyloidosis led to the patient's death.

Adult↗
PubMed2004

Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan.

: To determine and directly compare the clinical course of white and Asian patients with paroxysmal nocturnal hemoglobinuria (PNH), data were collected for epidemiologic analysis on 176 patients from Duke University and 209 patients from Japan. White patients were younger with significantly more classical symptoms of PNH including thrombosis, hemoglobinuria, and infection, while Asian patients were older with more marrow aplasia. The mean fraction of CD59-negative polymorphonuclear cells (PMN) at initial analysis was higher among Duke patients than Japanese patients. In both cohorts, however, a larger PNH clone was associated with classical PNH symptoms, while a smaller PNH clone was associated with marrow aplasia. Thrombosis was significantly more prevalent in white patients than Asian patients, and was associated with a significantly higher proportion of CD59-negative PMN. For individual patients, CD59-negative populations varied considerably over time, but a decreasing PNH clone portended hematopoietic failure. Survival analysis revealed a similar death rate in each group, although causes of death were different and significantly more Duke patients died from thrombosis. Japanese patients had a longer mean survival time (32.1 yr vs. 19.4 yr), although Kaplan-Meier survival curves were not significantly different. Poor survival in both groups was associated with age over 50 years, severe leukopenia/neutropenia at diagnosis, and severe infection as a complication; additionally, thrombosis at diagnosis or follow-up for Duke patients and renal failure for Japanese patients were poor prognostic factors. These data identify important differences between white and Asian patients with PNH. Identification of prognostic factors will help the design of prospective clinical trials for PNH.

Adolescent↗
PubMed2003

Retinoic acid reduces autoimmune renal injury and increases survival in NZB/W F1 mice.

Retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent antiproliferative and anti-inflammatory properties. Recently, retinoic acids were reported to inhibit Th1 cytokine production. We investigated the effects of retinoic acid on lupus nephritis in a model of NZB/NZW F(1) (NZB/W F(1)) mice. Three-month-old NZB/W F(1) mice were separated into two groups: one treated with all-trans-retinoic acid (ATRA; 0.5 mg i.p., three times weekly for 7 mo) and one with saline as a control. Compared with controls, ATRA-treated mice survived longer and exhibited a significant reduction of proteinuria, renal pathological findings including glomerular IgG deposits, and serum anti-DNA Abs. Splenomegaly was less marked in the treated mice than in controls. Transcripts encoding IFN-gamma, IL-2, and IL-10 in splenic CD4(+) T cells were significantly reduced in treated mice compared with controls. We conclude that treatment with ATRA in SLE-prone NZB/W F(1) mice significantly alleviates autoimmune renal disorder and prolongs survival; this may thus represent a novel approach to the treatment of patients with lupus nephritis.

Animals↗