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Biomedical subjects

Ken-ichi Sawada

Publications and source records attributed to Ken-ichi Sawada.

At least 19 recordsLinked to original sources
PubMed2006

Adrenal insufficiency complicated with antiphospholipid syndrome (APS).

We describe a 69-year-old woman with bilateral adrenal hemorrhage complicated with antiphospholipid syndrome (APS). She was hospitalized with nausea and vomiting in September 2003. Laboratory data demonstrated hyponatremia, hypoglycemia and prolongation of activated partial thromboplastin time (aPTT). Abdominal computed tomography showed bilateral adrenal enlargement. In October 2003, she demonstrated altered mental status with progressive hyponatremia, a high level of ACTH, and a low level of serum cortisol. She also showed thrombocytopenia, anti-cardiolipin IgG antibody, anti-beta2GPI antibody, and lupus anticoagulants. After four months, anti-cardiolipin IgG antibody was still positive. Based on these findings, she was diagnosed as having APS complicated with adrenal insufficiency due to hemorrhagic infarction. After treatment with corticosteroid, a low dose of aspirin and normal saline infusion, her condition quickly improved. Platelet counts and aPTT were also normalized. To our knowledge, this is the second Japanese case of APS complicated with bilateral adrenal hemorrhage. APS should be considered an important underlying cause of adrenal insufficiency.

Adrenal Gland Diseases↗
PubMed2006

Analysis of mutations in the urate transporter 1 (URAT1) gene of Japanese patients with hypouricemia in northern Japan and review of the literature.

BACKGROUND: Renal hypouricemia is an autosomal recessive disorder resulting from inactivating mutations in the urate transporter 1 (URAT1) encoded by SLC22A12. To date, 10 mutations have been identified and W258X in the URAT1 gene is the predominant cause in middle to southwestern Japan. However, it is still unclear whether there is a regional specific distribution of mutations in northern Japan. In this study, we analyzed mutations in the URAT1 gene of five Japanese patients with renal hypouricemia in northern Japan. METHODS: Peripheral blood mononuclear cells were isolated from patients with hypouricemia and healthy control subjects. A mutation analysis of the URAT1 gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. RESULTS: We identified two mutations. These mutations [c.269G>A (R90H) and c.774G>A (W258X)] have been reported in Japanese patients. Two of five patients were homozygotes (W258X), two carried single heterozygous mutations (W258X), and the remaining one was a compound heterozygote (R90H and W258X). CONCLUSIONS: Our study suggests that there is no regional different distribution of the URAT1 genetic mutations in Japanese with renal hypouricemia.

Adult↗
PubMed2006

Successful reduced-intensity hematopoietic stem cell transplantation in myelodysplastic syndrome with severe coronary artery disease.

A 60-year-old Japanese man with myelodysplastic syndrome (MDS) and effort angina was referred to our clinic for treatment of MDS. The patient was transfusion-dependent and displayed coronary artery disease (CAD) with 99% obstruction of the left anterior descending coronary artery. Treatment comprised reduced-intensity hematopoietic stem cell transplantation with administration of fludarabine phosphate (180 mg/m(2)) and busulfan (8 mg/kg), followed by allogeneic peripheral blood stem cell transplantation from an HLA-matched sister. The regimen was well tolerated, and engraftment occurred rapidly without any therapy-related complications, including cardiovascular attack. Sex chromosome analysis by fluorescence in situ hybridization revealed complete donor chimerism on day 29 for bone marrow cells and on day 59 for peripheral blood leukocytes. The patient became transfusion-independent on posttransplantation day 8. As of 22 months postoperatively, he remains well, with 100% Karnofsky performance status, a limited type of chronic graft-versus-host disease, and no recurrence of disease. The clinical course of the patient suggests that this preparative regimen allows safe allogeneic stem cell transplantation for MDS patients with severe CAD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Late-onset fatal Epstein-Barr virus-associated hemophagocytic syndrome following cord blood cell transplantation for adult acute lymphoblastic leukemia.

A 43-year-old Japanese woman underwent unrelated cord blood transplantation (CBT) during remission for acute lymphoblastic leukemia with t(4; 11)(q21;q23). Tacrolimus was given for prophylaxis of graft-versus-host disease. The posttransplantation clinical course was mostly uneventful, and the leukemia remained in remission. Fourteen months after CBT, the patient developed pancytopenia and hepatic dysfunction with persistent high-grade fever. The bone marrow was hypocellular with increased numbers of macrophages and hemophagocytes. The numbers of Epstein-Barr virus (EBV) copies in peripheral blood samples were remarkably high. Although the patient showed complete donor-type hematopoiesis, the titer of viral capsid antigen immunoglobulin G was low, and the results of a test for EBV nuclear antigen were negative. There was no clinical response to the reduction of immunosuppressive therapy or to the administration of high-dose methylprednisolone, human immunoglobulin, or acyclovir. The patient died 466 days after CBT of massive gastrointestinal hemorrhage due to bone marrow and hepatic failures. This case demonstrates that fatal EBV-associated hemophagocytic syndrome (HPS) can occur more than 1 year after CBT. This report is the first of a case of late-onset EBV-associated HPS following CBT.

Acyclovir↗
PubMed2006

Successful autologous peripheral blood stem cell transplantation using thiotepa in a patient with systemic sclerosis and cardiac involvement.

A 19-year-old man with systemic sclerosis (SSc) was hospitalized for autologous peripheral blood stem cell transplantation (auto-PBSCT) due to progressive scleroderma and cardiac involvement despite conventional treatment. During the administration of cyclophosphamide (60 mg/kg/day for 2 days) for mobilization and collection of CD34+ selected peripheral blood stem cells, he developed congestive heart failure. Echocardiogram showed hypokinetic asynergy from the septum to posterior wall, which might indicate underlying cardiac damage. We were also concerned about the risk of high-dose cyclophosphamide-induced cardiotoxicity. Since the dose-limiting toxicity of thiotepa, an alkylating agent, is myelosuppression, and cardiac toxicity due to thiotepa is less common, we used a conditioning regimen consisting of thiotepa (10 mg/kg/day, day -5) and low-dose cyclophosphamide (50 mg/kg/day, days -3 and -2), instead of the conventional high-dose cyclophosphamide (50 mg/kg/day x 4 days/course). The post-transplant course was uneventful, and the modified Rodnan skin thickness score improved from 32 to 15. The present case report demonstrates that thiotepa can be employed as a conditioning regimen for auto-PBSCT in SSc patients with cardiac involvement in order to reduce cyclophosphamide-induced cardiotoxicity.

Adult↗
PubMed2006

Oligoclonal T cell expansion in blood but not in the thymus from a patient with thymoma-associated pure red cell aplasia.

Despite the well-known association between thymoma and PRCA, the role of thymoma remains uncertain. There is accumulating evidence that clonal T cells are involved in acquired PRCA. We examined T cell receptor repertoires in blood and thymus from a patient with PRCA associated with thymoma and myasthenia gravis. Oligoclonal expansions of Vdelta1- and Vbeta1-expressing T cells were found in peripheral blood, whereas the repertoires of Vdelta1+ and Vbeta1+ T cells in thymoma were not skewed. Oligoclonal expansion of Vdelta1-expressing T cells remained unchanged after thymectomy. Thymus may not be the site of clonal T cell expansion in thymoma-associated PRCA.

Clone Cells↗
PubMed2005

TCRalphabeta repertoire diversity of human naturally occurring CD4+CD25+ regulatory T cells.

We examined the alphabeta T cell receptor (TCR) repertoire of naturally occurring CD4+CD25+ regulatory T (Treg) cells isolated from healthy human blood. Three-color FACS analysis demonstrated that the usage of variable region segments of TCRbeta chains by CD4+CD25+ cells did not differ from those of CD4+CD25- cells. Complementarity-determining region 3 (CDR3) size distribution analyses demonstrated that the repertoire diversity of CDR3beta was almost identical between CD4+CD25+ and CD4+CD25- T cell subsets, and that there was no skewing of the CDR3beta repertoire of CD4+CD25+ T cells. In contrast, in vitro activated CD4+CD25+ T cells by cytomegalovirus-derived antigens showed a skewed CDR3 size distribution pattern. These findings support the hypothesis that naturally occurring CD4+CD25+ T cell subset in humans is 1argely composed of a T cell lineage positively selected in the thymus as a consequence of the interaction between self-peptides and TCRs and not derived from recent activation by a limited array of antigens.

CD4 Antigens↗
PubMed2005

Up-regulation of TRAIL mRNA expression in peripheral blood mononuclear cells from patients with minimal-change nephrotic syndrome.

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) is considered to be associated with T-cell dysfunction and with the abnormal secretion of putative glomerular permeability factors; however, the nature of such factors remains elusive. METHODS: To identify up-regulated genes during the nephrosis phase, we undertook serial analyses of gene expression (SAGE) in peripheral blood mononuclear cells (PBMC) from a patient with MCNS sampled during the nephrosis and remission phases. To confirm the SAGE results, we performed quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. We also measured the serum levels of the identified gene product in nephrosis and remission samples from 29 MCNS patients, 57 patients with nephrotic syndrome due to other types of glomerular diseases and 30 healthy individuals. RESULTS: Using more than 20,000 SAGE tags, we identified 15 functionally known genes that were up-regulated (>or=4-fold) in PBMC from the MCNS patient during the nephrosis phase. For further examination, we selected two genes encoding secretory proteins, namely tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and tissue inhibitor of metalloprotease 1. Real-time RT-PCR analysis confirmed a higher expression of TRAIL mRNA in PBMC during nephrosis than during remission in eight MCNS patients. The expression pattern of TRAIL mRNA, however, was variable among four patients with membranous nephropathy. There was no significant increase of serum levels of a soluble form of TRAIL in MCNS patients during the nephrosis phase. CONCLUSIONS: These results suggest that the intracellular TRAIL mRNA expression in PBMC is up-regulated in MCNS patients during the nephrosis phase. This change may represent either an epiphenomenon or it may provide a potential explanation for the altered T-cell function in MCNS.

Adolescent↗
PubMed2004

Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.

Adult↗
PubMed2004

Effective high-dose chemotherapy combined with CD34+-selected peripheral blood stem cell transplantation in a patient with cutaneous involvement of nasal NK/T-cell lymphoma.

The prognosis of nasal natural killer (NK)/T-cell lymphoma with cutaneous involvement especially is morbid despite intensive chemotherapy and radiotherapy. We treated a 52-yr-old Japanese woman with cutaneous dissemination of nasal NK/T-cell lymphoma. Six cycles of chemotherapy, irradiation to skin lesion were administered and complete remission (CR) was attained. High-dose chemotherapy (HDC; etoposide 750 mg/m(2) x 2 d, cyclophosphamide 60 mg/kg x 2 d, total body irradiation 12 Gy two daily fractions x 3 d) followed by CD34(+)-selected autologous peripheral blood stem cell transplantation (CD34(+)-APBSCT) was then prescribed. Complete remission (CR) was obtained and she has been free of disease for 34 months since CD34(+)-APBSCT. We suggest that marrow-ablative chemotherapy facilitated by autologous stem cell transplantation should be considered part of the primary therapy for subjects with a poor prognosis for nasal NK/T-cell lymphoma with cutaneous involvement.

Antigens, CD34↗
PubMed2004

Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy.

BACKGROUND: Several studies have shown a predominant glomerular deposition of IgG4 in patients with idiopathic membranous nephropathy (MN), whereas significant depositions of other IgG subclasses have been shown in patients with lupus-associated MN and bucillamine-induced MN. METHODS: We examined the distribution patterns of glomerular IgG subclass deposits in 10 patients with malignancy-associated MN (M-MN) and in 15 patients with idiopathic MN by immunofluorescence (IF) microscopy. RESULTS: The glomerular IF intensities of IgG1 and IgG2 were significantly stronger in the malignancy group than in the idiopathic group (P<0.05). In contrast, there were no differences in glomerular IF intensities of IgG3 and IgG4 between the two groups. CONCLUSION: Our findings suggest that the distribution patterns of glomerular IgG subclass deposits are different in idiopathic MN and M-MN. The strong IF intensity of glomerular IgG1 and IgG2 in M-MN may provide a possible predictor for this condition.

Adult↗
PubMed2004

Monitoring the expression profiles of doxorubicin-resistant K562 human leukemia cells by serial analysis of gene expression.

We examined the expression profiles of doxorubicin-resistant K562 cells by serial analysis of gene expression (SAGE) to identify novel and/or partially characterized genes that might be related to drug resistance in human leukemia. SAGE complementary DNA (cDNA) libraries were constructed from K562 and doxorubicin-resistant K562 (K562/ADM) cells, and concatamer sequences were analyzed with SAGE 2000 software. We used 9792 tags in the identification of 1076 different transcripts, 296 of which were similarly expressed in K562 and K562/ADM cells. There were 343 genes more actively expressed in K562/ADM than in parental K562 cells and 437 genes expressed less often in K562/ADM cells. K562/ADM cells showed increased expression of well-known genes, including the genes for spectrin beta, eukaryotic translation initiation factor 1A (EIF1A), RAD23 homolog B, laminin receptor 1, and polyA-, RAN-, and PAI-1 messenger RNA-binding proteins. K562/ADM cells showed decreased expression of the genes for fatty acid desaturase 1 (FADS1), hemoglobin epsilon 1, N-myristoyltransferase 1, hemoglobin alpha 2, NADH dehydrogenase Fe-S protein 6, heat shock 90-kDa protein, and karyopherin beta 1. Quantitative reverse transcription-polymerase chain reaction analysis confirmed the increased expression of EIF1A and the decreased expression of FADS1 in K562/ADM cells. Prior to this investigation, such differences in the expression of these genes in doxorubicin-resistant leukemia cells were unknown. Although we do not provide any evidence in the present report for the potential roles of these genes in drug resistance, SAGE may provide a perspective into our understanding of drug resistance in human leukemia that is different from that provided by cDNA microarray analysis.

Delta-5 Fatty Acid Desaturase↗
PubMed2004

Contribution of Complementarity-Determining Region 3 of the T-Cell Receptor Vδ2 Chain to the Recognition of Aminobisphosphonates by Human γδ T-Cells.

Human gammadelta T-lymphocytes expressing Vgamma2Vdelta2 T-cell receptors (TCRs) can be stimulated by aminobisphosphonates and can kill certain tumor cells. Although germline-encoded lysine residues on the Jgamma1.2 segment have been demonstrated to be essential for the recognition of nonpeptide antigens by human gammadelta T-cells, the role of the junctional sequences of the TCR delta chain in the recognition of aminobisphosphonates by Vgamma2Vdelta2+ T-cells remains unknown. We examined the structure of complementarity-determining region 3 (CDR3) of Vdelta2 chains expressed by aminobisphosphonate-stimulated human gammadelta T-cells. CDR3 size-spectratyping analysis of Vdelta2 chains revealed that risedronate did not induce a CDR3 size distribution pattern of Vdelta2 cells that was distinct from that of Vdelta2 cells cultured without risedronate. The clonality of risedronate-expanded Vdelta2 T-cells was also determined by sequencing analysis, with the result that no particular consensus sequences were observed. However, most Vdelta2 T-cells freshly isolated from peripheral blood carried a distinctive junctional motif consisting of a hydrophobic amino acid residue (valine, leucine, or isoleucine [Val/Leu/Ile]) at conserved position 97, and this feature was not altered by risedronate stimulation. A significant proportion of Vdelta1 T-cells from the same individual had Leu at position 97, but Vdelta1 T-cells did not expand in response to risedronate. Moreover, Vdelta2 T-cells from the nonresponder against risedronate also carried a Val/Leu/Ile amino acid residue at position 97. These results suggest that the presence of a hydrophobic amino acid residue at position 97 in CDR3 of the TCR delta chain is not sufficient to account for the recognition of aminobisphosphonate by human gammadelta T-cells.

Amino Acid Sequence↗
PubMed2004

Gene expression profiling of human erythroid progenitors by micro-serial analysis of gene expression.

We compared the expression profiles of highly purified human CD34+ cells and erythroid progenitor cells by micro-serial analysis of gene expression (microSAGE). Human CD34+ cells were purified from granulocyte colony-stimulating factor-mobilized blood stem cells, and erythroid progenitors were obtained by cultivating these cells in the presence of stem cell factor, interleukin 3, and erythropoietin. Our 10,202 SAGE tags allowed us to identify 1354 different transcripts appearing more than once. Erythroid progenitor cells showed increased expression of LRBA, EEF1A1, HSPCA, PILRB, RANBP1, NACA, and SMURF. Overexpression of HSPCA was confirmed by real-time polymerase chain reaction analysis. MicroSAGE revealed an unexpected preferential expression of several genes in erythroid progenitor cells in addition to the known functional genes, including hemoglobins. Our results provide reference data for future studies of gene expression in various hematopoietic disorders, including myelodysplastic syndrome and leukemia.

Antigens, CD34↗
PubMed2004

49, XXXXY syndrome with unilateral renal aplasia, proteinuria, and venous thromboembolism.

A 28-year-old man presented with mental retardation, peculiar facial features, radioulnar synostosis, hypogonadism, aplasia of the right kidney, a moderate degree of proteinuria, and peripheral cyanosis. The activated partial thromboplastin time was shortened, and the level of plasma factor VIII was high. A chromosomal analysis revealed a 49, XXXXY karyotype. From the 10th hospital day, he suffered from sudden dyspnea following swelling of the left leg. He was diagnosed as having deep vein thrombosis and pulmonary embolism, and was successfully treated with anticoagulant therapy. This is the first case of the 49, XXXXY syndrome complicated with unilateral renal aplasia, proteinuria, and venous thromboembolism.

Abnormalities, Multiple↗