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Biomedical subjects

Satoshi Hara

Publications and source records attributed to Satoshi Hara.

At least 19 recordsLinked to original sources
PubMed2026

Beckwith-Wiedemann spectrum exhibiting a 46,XY karyotype caused by genome-wide paternal uniparental heterodisomy: a case report.

BACKGROUNDS: Patients with genome-wide paternal uniparental disomy (GWpUPD) usually exhibit clinical features of Beckwith-Wiedemann syndrome (BWS) and a 46,XX karyotype, with all chromosomes showing isodisomy. To date, male patients with GWpUPD and a complete 46,XY karyotype, specifically involving heterodisomy, have not been described. RESULTS: We report a male infant exhibiting classical BWS clinical features. DNA methylation analyses showed paternal-specific methylation across multiple imprinted loci, suggesting GWpUPD. Genetic analysis of autosomes and sex chromosomes indicated two distinct paternal genomes in peripheral blood leukocytes, whereas a normal biparental genome was detected in other tissues under chimeric conditions. These findings indicated that the patient had genome-wide paternal uniparental heterodisomy (GWpUPhD). The SNP array revealed the presence of one copy of the X chromosome and one copy of the Y chromosome, the patient is a chimera composed of 46,XY biparental cells (with maternal X) and 46,XY GWpUPhD cells (with paternal X). CONCLUSIONS: This is the first report of a male patient with a GWpUPhD chimera. We propose a potential mechanism of GWpUPhD formation. Our findings expand the molecular spectrum of GWpUPD and provide valuable insights into its pathogenesis in chimeric conditions. Furthermore, the potential for clinical manifestations unique to 46,XY heterodisomy warrants careful long-term follow-up.

Humans↗
PubMed2006

Thioredoxin-h1 reduces and reactivates the oxidized cytosolic malate dehydrogenase dimer in higher plants.

Cytosolic malate dehydrogenase (cytMDH) was captured by thioredoxin affinity chromatography as a possible target protein of cytosolic thioredoxin (Yamazaki, D., Motohashi, K., Kasama, T., Hara, Y., and Hisabori, T. (2004) Plant Cell Physiol. 45, 18-27). To further dissect this interaction, we aimed to determine whether cytMDH can interact with the cytosolic thioredoxin and whether its activity is redox-regulated. We obtained the active recombinant cytMDH that could be oxidized and rendered inactive. Inactivation was reversed by incubation with low concentrations of dithiothreitol in the presence of recombinant Arabidopsis thaliana thioredoxin-h1. Inactivation of cytMDH was found to result from formation of a homodimer. By cysteine mutant analysis and peptide mapping analysis, we were able to determine that the cytMDH homodimer occurs by formation of a disulfide bond via the Cys(330) residue. Moreover, we found this bond to be efficiently reduced by the reduced form of thioredoxin-h1. These results demonstrate that the oxidized form cytMDH dimer is a preferable target protein of the reduced form thioredoxin-h1 as suggested by thioredoxin affinity chromatography.

Arabidopsis↗
PubMed2006

Successful treatment of multi-agent chemotherapy with rituximab for IgM plasma cell leukemia.

A 67-year-old woman presented with impaired general performance, suffering from fatigue, dyspnea on exertion, and paresthesia of the finger tips. The laboratory findings showed increased white blood cells at 11.37 x 10(3)cells/microl with 26.5% abnormal cells, low haemoglobin and, elevated creatinine, although serum lactate dehydrogenase and calcium levels were normal. Serum immunofixation was positive for monoclonal IgM-kappa paraprotein. Total serum protein and the IgM component were elevated. X-ray examination of the skeleton was normal. Bone marrow aspiration showed 59.5% infiltration of abnormal cells that were characterized by typical mature plasmacytoid morphology. Abnormal cells expressed surface CD20, surface CD138, and cytoplasmic IgM, but not surface CD56 nor surface IgM by flow cytometric immunophenotyping with CD38 gating. Immunohistochemistry showed surface CD38, surface CD20, and cytoplasmic IgM. The clinical findings led to the diagnosis of the IgM Plasma cell leukemia (PCL). The patient received multi-agent chemotherapy (VAD and EDAP with rituximab). The clinical symptoms disappeared, leading to the tumor load reduction. To the best of our knowledge, this is the first report of successful treatment of multi-agent chemotherapy with rituximab for IgM PCL.

Aged↗
PubMed2006

Bronchial infiltration with diffuse large B-cell lymphoma.

Non-Hodgkin's lymphoma (NHL) refers to a heterogeneous group of lymphoproliferative diseases with a diversity of clinical courses, including involvement in another organs. NHL frequently involves the thoracic structures, and particularly the mediastinum and lung parenchyma. Several clinical reports have described bronchial-associated lymphoid tissue (BALT) lymphoma as an endobronchial lesion, but endobronchial infiltration with diffuse large B-cell lymphoma is extremely rare. Here, we provide the first report of this condition confirmed by a histopathological study and the presence of an immunoglobulin heavy chain (IgH) gene rearrangement detected by a polymerase chain reaction (PCR).

Antibodies, Monoclonal↗
PubMed2006

[Septic shock induced by Serratia marcescens complicating adult T-cell leukemia (ATL)].

A 75-year-old woman was admitted with fever of unknown origin and liver damage, and treated with prednisolone. Hypercalcemia appeared when of the dose of prednisolone was reduced, and human T-cell lymphotropic virus type-I (HTLV-I) proviral DNA was detected in the leukemic cells by Southern blot analysis, and a diagnosis of acute adult T-cell lymphoma (ATL) was made. After chemotherapy with sobuzoxane was started, she went into septic shock caused by multiple resistant Serratia marcesense, and was treated with PMX-DHP and antibiotics. Although ner general condition and her serum cytokine leyels improved, the septic shock became more severe, and the patient died. Serratia marcesense expreses lipopolysaccharide (LPS), a biologically active substance that is present in gram-negative bacteria. Exposure to LPS leads to activation of cytokines, including TNF-alpha, IL-1beta, IL-6, and IFN-gamma. After treatment with PMX-DHP, the patient's general condition improved, but she died of septic shock. Bacterial infection may be a life-threatening complication in the immunocompromised hosts and elderly patients, particularly when granulocytopenia has been induced by chemotherapy, and thus such these patients require careful management.

Aged↗
PubMed2006

[Effective measurement of coronary flow velocity reserve (CFVR) with transthoracic Doppler echocardiography (TTDE) for plasma cell leukemia with hyperviscosity syndrome].

A 67-year-old woman was admitted with impaired general performance, suffering from fatigue, chest oppression on exertion, and paresthesia of the finger trips. The laboratory findings showed increased white blood cells with abnormal cells, and serum immunofixation test showed monoclonal IgM kappa paraprotein. On flow cytometric immunophenotyping with CD38 gating, most of the abnormal cells expressed surface CD20, CD138, cytoplasmic IgM, but neither surface CD56 nor surface IgM. Immunohistochemical staining of abnormal cells was positive for surface CD38, surface CD20 and cytoplasmic IgM. The final diagnosis was plasma cell leukemia IgM kappa type. Electrocardiography (ECG) on admission showed ST depression in II, III, aV(F), V4, V5, and V6. Coronary angiography (CAG) is invasive and difficult for patients with renal failure, therefore the patient underwent transthoracic Doppler echocardiography (TTDE), which revealed reduced coronary flow velocity reserve (CFVR). Two courses of VAD therapy were administered, then the condition improved, the serum IgM level decreased, abnormal cells were decreased in peripheral blood and bone marrow aspirates, and the creatinine levels improved. With the return of normal ECG findings and improved CFVR, the abnormal ECG and reduction in CFVR was thought to be associated with the hyperviscosity syndrome in PCL. Noninvasive assessment of CFVR by TTDE is significantly useful for the patients who have renal failure and need chemotherapy.

Aged↗
PubMed2006

[Acute pancreatitis during the treatment of relapsed acute promyelocytic leukemia with As2O3].

A 77-year-old man suffered from acute pancreatitis during the treatment of relapsed acute promyelocytic leukemia with As2O3. He presented with epigastralgia on day 25 during the treatment with As2O3. Pancreatic enzyme levels were elevated and the computed tomography scan of the abdomen showed swelling of the pancreas. As acute pancreatitis due to As2O3 was suspected, As2O3 was discontinued. Intravenous gabexate mesilate was administered, and the pancreatitis improved. Acute pancreatitis should be considered as a possible complication during treatment with As2O3.

Acute Disease↗
PubMed2005

Thioredoxin affinity chromatography: a useful method for further understanding the thioredoxin network.

Thioredoxin affinity chromatography can be used to recognize the target proteins of thioredoxin or thioredoxin-related proteins in whole cells or certain cellular compartments. In the last couple of years, many potential target proteins have been identified from various organelles and organisms by this method. Based on the information on the target proteins provided by these studies, the complete thioredoxin-related redox networks can now be efficiently described.

Chloroplasts↗
PubMed2005

Pulmonary parenchymal infiltrates in a patient with CD20-positive multiple myeloma.

A 53-yr-old woman developed a dry cough after the completion of multi-agent chemotherapy. The biopsy specimens showed diffuse infiltrates with multiple myeloma (MM) cells. Immunohistochemistry revealed positive staining in MM cells with surface CD20, surface CD38, and cytoplasmic IgG. This report represents the first reported case of pulmonary parenchymal infiltrates in a patient with CD20-positive MM.

ADP-ribosyl Cyclase↗
PubMed2005

Flow cytometric immunophenotyping of adult T-cell leukemia/lymphoma using CD3 gating.

Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative neoplasm of helper T lymphocytes caused by human T-cell leukemia virus type-1 (HTLV-1). The disease was first described in Kyushu, in southwestern Japan, and most frequently occurs in endemic areas, such as Japan, the Caribbean basin, West Africa, Brazil, and northern Iran. ATLL is essentially a disease of adults, characterized clinically by generalized lymphadenopathy, hepatosplenomegaly, skin lesions, and hypercalcemia. The prognosis of most patients is quite poor, with a median survival time of only 13 months, even if multiagent combination chemotherapy is given. In the present study, flow cytometric immunophenotyping with CD3 gating was performed on 30 samples from 26 patients who had been given a diagnosis of ATLL. The records of these patients also were reviewed retrospectively. In 14 of the 30 samples, an abnormal CD3(low) T-cell population was distinguishable from the normal T-cell populations by flow cytometric analysis. Herein we report a novel strategy for flow cytometric immunophenotyping of ATLL facilitated by CD3(low) gating.

Adult↗
PubMed2005

[Graft-versus-ATLL effect induced by abrupt discontinuation of immunosuppression following allogeneic bone marrow transplantation].

A 46-year-old man was admitted to our hospital with swelling of a neck lymph node in June, 2002, and was diagnosed with adult T-cell leukemia/lymphoma (ATLL). As ATLL cells were detected in the peripheral blood after two courses of multi-agent chemotherapy (LSG 15), the treatment was changed to biweekly CHOP therapy. After two courses, hematological remission was achieved. Allogeneic bone marrow transplant (allo-BMT) from HTLV- negative and HLA-matched sibling donor was performed (conditioned with cyclophosphamide 60 mg/kg x 2 and total body irradiation 12 Gy). Cyclosporine A (CsA) and short-term methotrexate (MTX) were used for graft-versus-host disease prevention. Though the HTLV- provirus DNA (Southern blot) disappeared, HTLV-I provirus DNA (real-time PCR) T-cell receptor ygammachain gene rearrangement DNA (Southern blot) were detected in bone marrow after allo-BMT. MRD disappeared after the withdrawal of CsA. After the allo-BMT transplant, a graft-versus-ATLL (GVATLL) effect may be induced by abrupt discontinuation of immunosuppression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Modulation of bcl-2 family proteins in MAPK independent apoptosis induced by a cdc25 phosphatase inhibitor Cpd 5 in renal cancer cells.

Protein phosphatases have been classified into two basic types, namely protein serine/threonine phosphatase (PP), and protein tyrosine phosphatase (PTP). Cpd 5 is a selective inhibitor of cdc25 phosphatases, which belong to members of PTPs and regulate cell proliferation by controlling cyclin-dependent kinases (cdks). The present study was undertaken to investigate the potential utility of Cpd 5 as an anti-neoplastic agent for renal cell carcinomas (RCCs). Three renal cancer cell lines, 769P, Sw839, and A498 were used. The effects of Cpd 5 on the viability of renal cancer cell lines was analyzed using an Alamar Blue assay. Apoptosis was determined by flow cytometric TUNEL analysis. Changes in the expression of cdc25 phosphatases, mitogen-activated protein kinases (MAPKs), and bcl-2 family proteins were detected using Western blot analysis. The apoptosis-inducing effect of Cpd 5 on human RCC tissue was analyzed through TUNEL staining of organ cultures from RCCs. Cpd 5 showed a strong cytotoxicity against all renal cancer cell lines with an apoptosis-inducing effect. All cell lines treated with Cpd 5 resulted in a down-regulation of cdc25A, cdc25B, and cdc25C, however, the MAPK pathways were not affected. In addition, the up-regulation of bax, and the down-regulation of bcl-2 and bcl-xL, was observed. In organ cultures from RCCs, TUNEL-positive apoptotic nuclei were observed when treated with Cpd 5. Cpd 5 was thus found to effectively inhibit the proliferation of human renal cancer cells while also inducing apoptosis by inhibiting cdc25 phosphatases and modulating bcl-2 family proteins. The administration of Cpd 5 may thus be an effective therapeutic approach for RCCs.

Apoptosis↗
PubMed2005

[Intestinal bleeding during the treatment of chronic myeloid leukemia with imatinib mesylate].

A 35-year-old woman attended our hospital with chronic myeloid leukemia and was prescribed imatinib mesylate. She was admitted with lower abdominal pain, stomatitis, and hyposthenia after an increase in her dose of imatinib mesylate. When the treatment was changed to interferon-alpha and Ara-C, the lower abdominal pain, stomatitis, and hyposthenia improved, but bone marrow aspiration showed 36.4% blasts. After the treatment was changed back to an increased dose of imatinib mesylate (800 mg), the stomatitis deteriorated and intestinal bleeding reoccurred. Endoscopy demonstrated the presence of multiple ulcers in the ascending colon and 99mTc RBC scintigraphy demonstrated lesions of the large and small intestine. The patient declined any treatment except for transfusion and died suddenly after ten days. The present case suggests that we should carefully consider the possibility of intestinal bleeding when prescribing imatinib mesylate.

Adult↗
PubMed2005

[Successful treatment of refractory mantle cell lymphoma with irinotecan].

A 59-year-old man presented in January 2003 with generalized lymphadenopathy. An inguinal lymph node biopsy showed mantle cell lymphoma (MCL). After four courses of Rituximab-CHOP therapy were administered, complete response (CR) was achieved. However, in August 2003, he presented with neck lymphadenopathy and was found to have relapsed. Several salvage therapies (ESHAP, Hyper-CVAD/MTX-ara-C) were administered, but CR was not achieved. After two courses of single-agent chemotherapy with CPT-11 (40 mg/m2) were administered on days 1, 2, 3, 8, 9, and 10, CR was achieved. Several studies reveal that the long-term prognosis for MCL with conventional therapy is poor. This report describes CPT-11 therapy for MCL and provides evidence that CPT-11 is another therapeutic option in refractory cases of MCL.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Stratification of the biologic aggressiveness of non-small cell lung cancer using DNA flow cytometry and immunohistochemistry for the retinoblastoma protein.

DNA ploidy pattern and S-phase fraction (SPF) measured by flow cytometry and expression of the retinoblastoma gene product (pRB) estimated by immunohistochemistry were correlated with outcome in 114 patients who received a curative operation for primary non-small cell lung cancer (NSCLC). One hundred ten tumors yielded an adequate DNA histogram, and all tumors exhibited an assessable immunohistochemical stain. DNA diploidy was detected in 31 tumors and DNA aneuploidy in 79 tumors. The mean SPF was 14.1 +/- 6.4%. Eighty tumors were positively stained, and 34 tumors were negative for pRB. Multivariate analysis clarified that both TNM staging and DNA ploidy were prognostic factors after surgery. In 39 recurrent cases, the SPF value was inversely correlated with disease-free interval. With only supportive care after recurrence, high SPF tumors and pRB-negative tumors progressed rapidly, whereas active treatment yielded an equivalent effect on recurrent tumors regardless of the SPF or pRB expression. DNA ploidy is related to the risk of recurrence, while SPF is related to tumor growth rate and the impact of active treatment on recurrence. The utility of pRB expression was limited. The combination of DNA ploidy and SPF allows practical stratification of the biologic aggressiveness of NSCLC.

Adult↗