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Hitoshi Ohno

Publications and source records attributed to Hitoshi Ohno.

At least 19 recordsLinked to original sources
PubMed2006

Increased susceptibility to Staphylococcus aureus colonization of the skin of the NOA mouse: a potentially useful animal model for evaluating antiseptic effects.

Isolation of bacteria from wet skin lesions was attempted using Naruto Research Institute Otsuka Atrichia (NOA) mice, which develop such lesions spontaneously at a high rate. As a result, Staphylococcus aureus was demonstrated to have colonized the wet skin lesions at high density. In addition, the isolated S. aureus was found to be similar to the strain of S. aureus thought to colonize the eczematous lesions seen in humans with atopic dermatitis. Furthermore, a survey of the S. aureus colonization status of NOA mice with no wet skin lesions confirmed colonization at higher density than in HR-1 mice as control, indicating that the skin of the NOA mouse has the novel characteristic of increased susceptibility to S. aureus colonization. Thus, by using changes in S. aureus counts as an index, the NOA mouse can be expected to serve as a useful animal model for evaluating the effects of topical antiseptics. The antiseptic effects of an ointment and a lotion containing chlorhexidine gluconate were confirmed using this animal model.

Administration, Topical↗
PubMed2006

Pathogenetic and clinical implications of non-immunoglobulin ; BCL6 translocations in B-cell non-Hodgkin's lymphoma.

Chromosomal translocations affecting band 3q27, where BCL6 gene is located, are among the most common genetic abnormalities in non-Hodgkin's lymphoma of B-cell type (B-NHL). The BCL6 gene encodes a BTB/POZ zinc finger transcription factor, which exerts repressive activity by recruiting corepressor molecules. The 3q27/BCL6 translocation is unique in that it can involve not only immunoglobulin (Ig) genes but also non-Ig chromosomal loci as a partner. To date, around 20 non-Ig partner genes have been identified. As a result of non-Ig ; BCL6 translocations, many types of regulatory sequences of each partner gene substitute for the 5' untranslated region of BCL6, and the rearranged BCL6 comes under the control of the replaced promoter. The introduction of non-Ig ; BCL6 constructs into transformed cells led to high-level Bcl-6 protein expression in the nucleus, while BCL6 mRNA levels in clinical materials of diffuse large B-cell lymphoma (DLBCL) with non-Ig ; BCL6 translocations were unexpectedly low. A comparative study suggested that non-Ig ; BCL6 translocation and a low level of BCL6 mRNA expression are concordant indicators of a poor clinical outcome in cases of DLBCL. The coexistence of a non-Ig ; BCL6 translocation with t(14 ; 18)(q32 ; q21) in a single clone did not significantly affect the clinical features of follicular lymphoma. The pathogenetic and clinical implications of non-Ig ; BCL6 translocations in B-NHL subtypes may not be identical to those of Ig ; BCL6.

Animals↗
PubMed2005

Stimulation of CD30 in anaplastic large cell lymphoma leads to production of nuclear factor-kappaB p52, which is associated with hyperphosphorylated Bcl-3.

Anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) express CD30 at high levels, but stimulation of this molecule has been reported to induce contradictory effects. To elucidate the molecular mechanism of CD30-mediated apoptosis of ALCL, we compared the gene expression profiles of t(2;5)(p23;q35)-positive ALCL with those of HL altered by CD30 agonistic stimulation. The results showed that BCL3, the high-level expression of which in ALCL was previously reported, was further upregulated in response to CD30 stimulation, along with several pro-apoptotic genes. Bcl-3 protein was present as an intermediate phospho-form in the resting-state ALCL, becoming hyperphosphorylated (Bcl-3P) upon stimulation. We next found that the stimulation promoted de novo synthesis of the nuclear factor (NF)-kappaB2/p100 precursor as well as processing to p52, and a series of immunoprecipitation and western blotting analyses consistently showed association of Bcl-3P with p52 in CD30-stimulated ALCL. An electrophoretic mobility shift assay revealed the induction of kappaB binding activity of the p52 homodimer, and nuclear colocalization of Bcl-3 and p52 was demonstrated in anaplastic lymphoma kinase-positive ALCL tumor tissues by immunohistochemistry. As Bcl-3 can act as an anti-repressor or transactivator or both, we propose that the (p52)2/Bcl-3P ternary complex, which is specifically induced in CD30-stimulated ALCL, can modulate expression of apoptosis-related genes regulated by NF-kappaB, thereby accounting for CD30-mediated apoptosis of ALCL.

B-Cell Lymphoma 3 Protein↗
PubMed2005

Spontaneous recovery from renal infarction resulting from renal artery dissection.

A 31-year-old, previously normotensive healthy man developed right flank pain and was admitted to a medical service. Right renal infarction was suspected by enhanced abdominal computed tomography (CT) and arteriography. Fourteen days after the onset, he was transferred to the Oita University Hospital, Oita, Japan. Renal angiography revealed an isolated renal artery dissection causing renal atrophy due to main stem narrowing of the right renal artery. Renogram and renal scintigram with (99m)Tc-diethylene triamine pentaacetic acid revealed a remarkable decline in the glomerular filtration rate and almost no uptake in the right kidney. Four months later, in spite of our belief that functional recovery could not be expected, intravenous pyelography and enhanced abdominal CT scans revealed a functioning right kidney that had spontaneously recovered from the renal artery dissection through conservative management.

Adult↗
PubMed2005

Polyclonal proliferation of plasma cells associated with marked hypergammaglobulinemia in an elderly patient.

We describe an 89-year-old woman who presented with prominent plasmacytosis mimicking plasma cell leukemia. The apparent serum M-protein level of > 7 g/dL of gamma mobility was revealed to be a polyclonal increase of immunoglobulins. The plasma cells in the peripheral blood expressed polyclonal surface/cytoplasmic immunoglobulins as well as CD19, CD30, CD38, and CD138 antigens but lacked CD10, CD20, CD25, and CD56. The bone marrow plasma cells showed the CD45+, CD19+, CD56-, MPC-1(-/+), and CD49e- immunophenotype, which was in clear contrast with the immunophenotypes of the neoplastic myeloma cells. Abdominal lymphadenopathy, splenomegaly, and a high level of soluble interleukin 2 receptor may have been reflections of an underlying lymphoproliferative disorder, potentially leading to the polyclonal proliferation of plasma cells.

Aged↗
PubMed2005

Reappraisal of BCL3 as a molecular marker of anaplastic large cell lymphoma.

The BCL3 gene was initially discovered through its involvement in a recurring translocation, t(14;19)(q32;q13), which is found in some patients with B-cell chronic lymphocytic leukemia (B-CLL). The translocation leads to the juxtaposition of BCL3 to the immunoglobulin heavy chain gene locus, resulting in high-level expression of the BCL3 transcript. The Bcl-3 protein includes 7 tandem copies of the ankyrin repeat element in the central domain, a structure that is characteristic of the IkappaB family of inhibitors of the nuclear factor kappaB transcription factors. Anaplastic large cell lymphoma (ALCL) is a subtype of aggressive non-Hodgkin's lymphoma that is characterized by expression of CD30 and the NPM/ALK chimeric protein, which is generated by t(2;5)(p23;q35). We compared the gene expression profiles of ALCL with those of another CD30+ neoplasm, Hodgkin's disease (HD), and found that BCL3 is expressed at higher levels in ALCL than in HD. A comparison by real-time polymerase chain reaction assay revealed that t(2;5)+ ALCL expresses a high level of BCL3 messenger RNA relative to the levels expressed in other hematologic tumors, and the level in ALCL is comparable to or even higher than that in t(14;19)+ B-CLL. An immunohistochemical analysis of ALCL tumor tissues showed that the lymphoma cells exhibited strong nuclear staining by a monoclonal antibody against Bcl-3. We suggest that Bcl-3 sequestrates the (p50)2 homodimer to the nucleus and that the kappaB sites are occupied by the (p50)2/Bcl-3 ternary complex. Future studies should identify the relationships among the 3 independent molecules (ie, NPM/ALK, CD30, and Bcl-3) that are activated in t(2;5)+ ALCL.

B-Cell Lymphoma 3 Protein↗
PubMed2005

Development of dry skin in the NOA mouse under individual housing conditions: a potentially useful animal model for evaluating moisturizing effects.

In a previous study, we reported the development of grossly observable dry skin in all of the Naruto Research Institute Otsuka Atrichia (NOA) mice that were housed individually. In the present study, dermal physiological function tests were conducted and the usefulness of this dry skin model for evaluating the efficacy of topical moisturizers was assessed. As a result, we have confirmed a marked reduction in the water content of the stratum corneum in these animals. Therefore, the development of dry skin in the NOA mouse strain under individual housing conditions may be expected to serve as a useful animal model for evaluating topical moisturizers. Specifically, the water content of the stratum corneum was restored in proportion to the oil content of the ointment base used to treat the animals, and the moisturizing effects of urea were confirmed in animals treated with urea-containing ointment. In addition, when the animals that had been housed individually were returned to group housing conditions, the water content of the stratum corneum was restored, with a corresponding improvement in dry skin. This finding suggests that socio-psychological factors are involved in the etiology of dry skin in individually housed NOA mice.

Animal Husbandry↗
PubMed2004

Coexistent rearrangements of c-MYC, BCL2, and BCL6 genes in a diffuse large B-cell lymphoma.

We present a patient with stage III de novo diffuse large B-cell lymphoma. The lymphoma cells showed mature B-cell immunophenotype but lacked surface immunoglobulin (Ig) expression. Long-distance and long-distance inverse polymerase chain reaction assays to detect the oncogene/Ig gene rearrangement revealed that the cells carried 3 independent fusion genes, namely, c-MYC/Ig heavy chain gene (IgH), BCL2/IgH, and Ig lambda light chain gene/BCL6. Thus, the lymphoma cells concurrently carried t(8;14)(q24;q32), t(14;18)(q32;q21), and t(3;22)(q27;q11), which developed in association with class switching, V/D/J recombination, and somatic hypermutation, respectively. The lymphoma responded to chemoradiotherapy, and the patient has been well for 2 years, suggesting that multiple oncogene rearrangements may not necessarily be associated with poor clinical outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Extraosseous accumulation of 99mTc-MDP in lymph node metastases of small cell carcinoma of the esophagus.

We report a case of esophageal carcinoma that showed extraosseous accumulation of 99mTc-MDP in lymph node metastases to the cervical and paracardial lymph nodes. There are few cases showing abnormal extraosseous accumulation of 99mTc-MDP in esophageal cancer lesion. The patient was a 53-year-old man with advanced esophageal cancer. Bone scintigraphy demonstrated extraosseous accumulations in left supraclavicular and paracardial lymph node metastases. The histopathological diagnosis was small cell carcinoma of the esophagus, which is a rare disease with aggressive behavior and poor prognosis. Our patient underwent 2 courses of systemic chemotherapy (CDDP + VP16), but died of rapidly growing systemic metastases 5 months after the initial treatment.

Bone and Bones↗
PubMed2004

Successful allogeneic bone marrow transplantation for acute myelogenous leukemia after drug-induced cardiomyopathy.

Anthracycline derivatives often induce cardiomyopathy. Patients with seriously decreased cardiac function due to chemotherapeutic drugs cannot usually receive allogeneic hematopoietic stem cell transplantation (SCT) for hematologic disorders. We successfully performed allogeneic bone marrow transplantation (BMT) in a patient with severe cardiomyopathy. An 18-year-old woman with relapsed acute myelogenous leukemia had cardiomyopathy due to previous anthracycline administration. She underwent allogeneic BMT from her HLA-identical brother. Her preconditioning regimen was cytosine arabinoside, etoposide, total body irradiation, and high-dose cyclophosphamide. Congestive heart failure (CHF) was not present before BMT. Right heart pressures were monitored by a pulmonary arterial balloon catheter system (Swan-Ganz catheter). After BMT, she had severe CHF, which was controlled using pimobendan and amrinone. Patients with cardiomyopathy can receive allogeneic SCT under strict hemodynamic management.

Adolescent↗
PubMed2003

Unrelated bone marrow transplantation for non-Hodgkin lymphoma: a study from the Japan Marrow Donor Program.

There is little information available regarding the outcome of unrelated bone marrow transplantation (BMT) for non-Hodgkin lymphoma (NHL). Therefore, we retrospectively analyzed the data of 124 patients who underwent unrelated BMT through the Japan Marrow Donor Program (JMDP) between July 1992 and August 2001. The overall survival (OS), progression-free survival (PFS), cumulative incidences of disease progression, and nonprogression mortality at 3 years after BMT were 49.7%, 42.6%, 24.5%, and 32.9%, respectively, with a median follow-up duration of 565 days among survivors. The incidence of grades II-IV acute graft-versus-host disease (GVHD) was 40.9%. Recipient age, previous history of autologous transplantation, and chemosensitivity at transplantation were independent prognostic factors for OS and PFS. The development of grades II-IV acute GVHD was associated with lower incidence of disease progression after transplantation, which suggested the existence of a graft versus lymphoma effect. Unrelated BMT should be considered as a treatment option for patients with high-risk NHL without an HLA-matched related donor.

Adolescent↗
PubMed2003

Gallium-67 demonstration of extensive soft-tissue involvement of multiple myeloma.

A 46-year-old woman with multiple myeloma presented with neurological symptoms in the right upper extremity. After MR imaging of the cervical spine failed to show the cause of her symptoms, Ga-67 scintigraphy demonstrated increased uptake in multiple areas including the right supraclavicular region and bilateral lower extremities. Histology of the specimen obtained from the left thigh proved soft-tissue involvement of myeloma, and extensive extramedullary involvement was diagnosed. Radiotherapy to the right supraclavicular mass relieved her symptoms. Although Ga-67 scintigraphy is generally considered of limited value in multiple myeloma, this modality contributed to the development of an appropriate strategy in this patient with extensive extramedullary involvement.

Citrates↗
PubMed2003

Comparison of gene expression profiles of lymphoma cell lines from transformed follicular lymphoma, Burkitt's lymphoma and de novo diffuse large B-cell lymphoma.

To determine the specific gene expression in B-cell lymphoma subtypes, we compared expression profiles of cell lines from transformed follicular lymphoma (tFL), Epstein-Barr virus-negative (EBV(-)) Burkitt's lymphoma (BL) and EBV(+)BL. Complementary DNAs were synthesized from these cell lines and hybridized with the Atlas Human 1.2 Array membrane. Hierarchical clustering analysis based upon the levels of 43 genes highlighted characteristic expression patterns of the 3 lymphoma subtypes. Genes expressed at higher levels in tFL than EBV(-)BL and EBV(+)BL included calcium/calmodulin-dependent protein kinase I (CAMK1) and mitogen-activated protein kinase 10 (MAPK10). EBV(-)BL was characterized by high-level expression of amyloid beta precursor protein (APP), heat shock 27 kD protein 1 (HSPB1) and mothers against decapentaplegic homolog 1 (MADH1). Gardner-Rasheed feline sarcoma viral oncogene homolog (FGR) was the most significant gene to delineate EBV(+)BL. A subtype prediction algorithm using 34 genes correctly classified 22 (92%) of 24 lymphomas into FL/tFL, EBV(-)BL or EBV(+)BL. By comparison with normal reference B-cell materials, the expression patterns of the selected genes were characteristic of lymphomas. We extended the clustering analysis to cell lines from de novo diffuse large B-cell lymphoma (DLBCL). The DLBCL cell lines were either separated from the former 3 lymphoma subtypes or segregated with EBV(+)BL, possibly reflecting variable genetic abnormalities. The associations of CAMK1 with tFL, APP and MADH1 with EBV(-)BL, FGR with EBV(+)BL, and BCL2 with tFL and DLBCL were confirmed by real-time quantitative reverse transcriptase-mediated polymerase chain reaction assays. This study has provided new molecular markers, expressions of which are closely associated with B-cell lymphoma subtypes.

B-Lymphocytes↗
PubMed2002

High-level expression of BCL3 differentiates t(2;5)(p23;q35)-positive anaplastic large cell lymphoma from Hodgkin disease.

Anaplastic large cell lymphoma (ALCL) with t(2;5)(p23;q35) and Hodgkin disease (HD) share many cellular features, including expression of CD30. We compared gene expression profiles of 4 ALCL (Karpas 299, SU-DHL-1, DEL, SR-786) and 3 HD cell lines and found that BCL3, which encodes a nuclear protein belonging to the I kappa B family of inhibitors of nuclear factor-kappa B (NF-kappa B) transcriptional factors, was expressed at higher levels in ALCL than HD. Northern and Western blotting analyses confirmed the high-level expression of BCL3 in ALCL at both mRNA and protein levels. We established a real-time reverse transcriptase-mediated polymerase chain reaction assay to measure the BCL3 mRNA level and found a predominant level of BCL3 expression in t(2;5)(+) ALCL; the levels of cell lines and clinical materials were comparable to or higher than that of a B-cell chronic lymphocytic leukemia carrying t(14;19)(q32;q13). Southern blotting and fluorescence in situ hybridization disclosed that the BCL3 gene copies were amplified in SU-DHL-1, whereas Karpas 299 carried 4 BCL3 gene loci. The BCL3 gene contains 2 cytosine-guanine dinucleotide (CpG) islands, and the intragenic 3' CpG was entirely demethylated in SU-DHL-1 and DEL. In contrast to HD, in which NF-kappa B was constitutively activated, ALCL cells consistently showed (p50)(2) homodimer binding activity on electrophoretic mobility shift assay. It is suggested that the high-level nuclear Bcl-3 sequesters the (p50)(2) homodimer to the nucleus, which may account for the contradictory effect of CD30 stimulation on ALCL and HD. We propose that BCL3 is overexpressed by genetic and epigenetic modifications, potentially contributing to the development of t(2;5)(+) ALCL.

B-Cell Lymphoma 3 Protein↗
PubMed2002

Characterization of t(3;6)(q27;p21) breakpoints in B-cell non-Hodgkin's lymphoma and construction of the histone H4/BCL6 fusion gene, leading to altered expression of Bcl-6.

A recurrent translocation, t(3;6)(q27;p21), in non-Hodgkin's lymphoma results in fusion of BCL6 with a particular histone H4 gene on 6p21. We cloned five H4/BCL6 junctions from both der(3) and der(6) chromosomes. The breakpoints on H4 were distributed within the single exon or close to the terminal palindrome, and those on BCL6 were localized within or close to the translocation hypercluster. Deletions or duplications of variable numbers of nucleotides were identified at the junctions. A total of eight single nucleotide alterations were introduced into the translocation/mutation cluster of BCL6, whereas four single nucleotide substitutions were identified within a 360-bp region of H4. Thus, the somatic hypermutation mechanism is likely to target H4, resulting in a predisposition to the development of translocation with BCL6. Lymphoma cells carrying H4/BCL6 produced fusion transcripts containing both H4 and BCL6 messages; however, the cells expressed only moderate levels of BCL6 mRNA. We constructed expression plasmids that mimicked the H4/BCL6 fusion gene and transiently introduced them into COS-7 cells. H4/BCL6-transfected cells expressed markedly higher levels of Bcl-6 protein than cells transfected with a plasmid carrying BCL6 driven by its normal promoter and displayed bright nuclear staining with a characteristic punctate pattern with an anti-Bcl-6 antibody. Deletion analyses revealed that the high-level Bcl-6 expression was promoted by the H4 regulatory sequences. The levels of expression of activating transcription factor 3, prefoldin 4, and retinoblastoma-binding protein 7 significantly increased in accordance with that of BCL6, suggesting that Bcl-6 may act as a transcriptional activator. Our study suggested that t(3;6)(q27;p21) leads to BCL6 overexpression; however, the high-level BCL6 expression may not be required to maintain the malignant phenotype of lymphoma cells.

Animals↗