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Akira Okano

Publications and source records attributed to Akira Okano.

At least 19 recordsLinked to original sources
PubMed2006

Tumor necrosis factor-alpha induces apoptosis in cultured porcine luteal cells.

Some studies in mammalian species recently demonstrated that tumor necrosis factor (TNF)-alpha plays an important role for corpus luteum (CL) function by way of apoptosis during the estrous cycle. The objectives of this study were to clarify the induction of apoptosis in cultured porcine luteal cells by TNF-alpha treatment. Luteal cells prepared from porcine ovaries collected from crossbred mature gilts on Days 10-14 of the estrous cycle were isolated and examined as follows: 1) Flow cytometric analysis was carried out to determine apoptosis in cultured luteal cells. 2) Single-cell gel electrophoresis (comet assay) was performed to investigate apoptotic DNA fragmentation in luteal cells. The results of the flow cytometric analysis and comet assay demonstrated coincidentally that TNF-alpha induces DNA fragmentation in luteal cells causing apoptosis. These results revealed that TNF-alpha is an inducing factor of apoptosis in luteal cells.

Animals↗
PubMed2006

Effect of decrease in both postprandial blood glucose (PBG) and fasting blood glucose (FBG) levels in normal beagle dogs with nateglinide enteric coated granules and immediate release tablets.

Nateglinide is a new quick action/short duration (QRSD) type of oral blood glucose regulator, and nateglinide immediate release tablets are used for patients with mild diabetes under the trade name of Fastic((R)) tablets. In this study, we attempted to determine if it was possible to control both post-prandial blood glucose level (PBG) and fasting blood glucose level (FBG) for moderate or severe diabetes through controlled release of nateglinide. Enteric coated granules were selected for the administration form for controlled release of nateglinide, and three types of enteric coated granules were prepared having dissolution pH values of 5.5, 6.5 and 7.2. The three types of enteric coated granules were each administered separately or the enteric coated granules having an dissolution pH of 6.5 were administered simultaneous to administration of nateglinide immediate release tablets to normal beagle dogs just before feeding followed by measurement of plasma nateglinide concentration, plasma insulin concentration and blood glucose level. In the case of administering enteric coated granules alone (nateglinide: 9 mg/kg), the absorption of nateglinide was confirmed to tend to be delayed as the dissolution pH increased. In the case of an dissolution pH of 5.5, decreases in both PBG and FBG were observed. In the case of dissolution pH values of 6.5 and 7.2, only decrease in FBG was observed. In case of nateglinide immediate release tablets (nateglinide: 9 mg/kg), only decrease in PBG was observed. Decreases in both PBG and FBG were observed in the case of simultaneous administration of dissolution pH 6.5 enteric coated granules and nateglinide immediate release tablets just before feeding (nateglinide: 90 mg/head+60 mg/head). A correlation was observed between plasma nateglinide concentrations and blood glucose levels. On the other hand, there were no correlations observed between changes in plasma insulin concentrations and blood glucose levels. In case of nateglinide immediate release tablets (nateglinide: 150 mg/head), Decreases in both PBG and FBG were observed. However, the nateglinide controlled release formulation is more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, or of easy control of both PBG and FBG. On the basis of these results, the design of a controlled release formulation that contains nateglinide was suggested to enable control of both PBG and FBG for moderate and severe diabetes patients.

Administration, Oral↗
PubMed2005

Establishment of a specific radioimmunoassay for bovine interferon tau.

A radioimmunoassay (RIA) was developed for quantification of bovine interferon (bIFN) tau, conceptus secretory protein, which allows for the maintenance of the corpus luteum during early pregnancy. A cDNA coding bIFN tau was derived from cultured trophoblast cells (TBs). Recombinant (r) bIFN tau was produced in a baculovirus expression system with two different viruses. The RIA was a double-antibody competitive binding assay that used anti-bIFN tau antiserum (raised in rabbits) as the primary antibody, a radioiodinated derivative of bIFNtau as the radioactive tracer, and goat anti-rabbit IgG as the secondary antibody. The antibody did not cross-react with rbIFN alpha, recombinant human IFN beta or recombinant ovine IFN tau. The correct recovery of amounts of rbIFN tau indicated good accuracy. Serially concentrated TB conditioned media, paralleled the standard curve for bIFN tau. The intra-assay and inter-assay coefficients of variation at bIFN tau levels of 7.8 and 15.6 ng/mL were 7.1 and 8.1%, and 11.0 and 8.5%, respectively. bIFN tau was directly detected in uterine flushings obtained from cows at Day 16 of pregnancy. In summary, this assay was suitable for the measurement of bIFN tau.

Animals↗
PubMed2005

CD5+ Epstein-Barr virus-positive intravascular large B-cell lymphoma in the uterus co-existing with huge myoma.

A 42-year-old female underwent hysterectomy because of a huge uterine mass. Histologically, she was diagnosed as having intravascular lymphoma co-existing with myoma uteri. Lymphoma cells were large in size and were positive for CD5, CD20, CD45, CD79a, lambda light chain, and EBV but were negative for CD3 and cyclin D1. No other organs except for the adjoining bilateral ovaries seemed to be affected by the lymphoma cells. She received the combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) together with rituximab and has been well without definite disease progression. So far, this is the first case of CD5+ EBV+ intravascular large B-cell lymphoma (CD5+ EBV+ IVLBL) in the uterus of a patient who was incidentally diagnosed and successfully treated.

Adult↗
PubMed2005

Unique three-way translocation, t(3;14;18)(q27;q32;q21), in follicular lymphoma.

A 43-year-old woman was diagnosed as having stage IV follicular lymphoma. Phenotypically, the lymphoma cells were CD5(-), CD10(+), CD19(+), CD20(+), CD23(-), HLA-DR(+), and IgM-lambda(+). Conventional chromosomal analysis showed a three-way t(3;14;18)(q27;q32;q21) in the lymphoma cells, which was confirmed by spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH). Immunohistochemistry revealed that both BCL2 and BCL6 proteins were expressed in the lymphoma cells, whereas only the BCL6 gene, and not the BCL2 gene, was rearranged by Southern blotting. The patient received combination chemotherapy and has been well for 3 years. This is the first reported case showing a three-way translocation involving 2 major lymphoma-specific abnormalities, 3q27 and t(14;18)(q32;q21).

Adult↗
PubMed2005

Malignant lymphoma presenting as a cardiac tumor and superior vena caval syndrome successfully treated by haploidentical stem cell transplantation.

A 16 year-old male with B-cell non-Hodgkin's lymphoma presenting as a cardiac tumor and superior vena caval (SVC) syndrome received a haploidentical stem cell transplant (SCT) from his mother after conventional and salvage chemotherapy. He received additional radiation therapy for the residual tumor and is alive and well on day 640 after transplantation. Malignant lymphoma presenting as a cardiac tumor, including primary cardiac lymphoma, is rare. Although many reports have shown the poor prognosis of cardiac lymphoma, our case suggests that allogeneic haploidentical SCT might be useful for the treatment of aggressive cardiac lymphoma.

Adolescent↗
PubMed2005

Nitrogen-containing bisphosphonate incadronate augments the inhibitory effect of farnesyl transferase inhibitor tipifarnib on the growth of fresh and cloned myeloma cells in vitro.

RAS gene mutations occur in 30 - 40% of multiple myeloma (MM) patients. Farnesylation is the first step in the post-translational modification of RAS proteins. Tipifarnib is a potent farnesyl transferase inhibitor, and incadronate prevents post-translational prenylation of GTP-binding proteins such as RAS proteins. We examined the effect of tipifarnib in combination with incadronate on the growth of fresh and cloned myeloma cells in vitro. Tipifarnib inhibited the growth of myeloma cells, and this inhibition was intensified when tipifarnib was combined with incadronate. Tipifarnib, in combination with incadronate, may have some benefits in MM patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal myristoylation and palmitoylation, and interacts with alpha, but not beta, subunit of Ca/calmodulin-dependent protein kinase II.

We cloned a rat BAALC 1-6-8 isoform cDNA (GenBank Accession No. AB073318) that encoded a 22-kDa protein, and identified endogenous BAALC 1-6-8 protein in the brain. The gene was expressed widely in the frontal part of the brain, and the protein was localized to the synaptic sites and was increased in parallel with synaptogenesis. The protein interacted with the alpha, but not beta, subunit of Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIalpha). The interaction occurred between the N-terminal 35-amino-acid region of BAALC 1-6-8 protein and the C-terminal end of the regulatory domain of CaMKIIalpha, which contains alpha isoform-specific sequence. Thus, the interaction may be CaMKIIalpha-specific. We also found that BAALC 1-6-8 protein, as well as CaMKIIalpha, was localized to lipid rafts and that both myristoylation and palmitoylation of BAALC 1-6-8 N-terminal portion were required for targeting of the protein into lipid rafts. These findings suggest that BAALC 1-6-8 protein play a synaptic role at the postsynaptic lipid raft possibly through interaction with CaMKIIalpha.

Alternative Splicing↗
PubMed2005

In vitro attachment of bovine hatched blastocysts on fibronectin is mediated by integrin in a RGD dependent manner.

We investigated the effect of extracellular matrix protein on in vitro attachment and outgrowth of bovine hatched blastocysts. In vitro produced bovine hatched blastocysts were cultured on a fibronectin- or laminin-coated Petri dishes. Hatched blastocysts adhered and outgrew on the fibronectin-coated dish whereas no attachment was observed on the laminin-coated dish. The attachment and outgrowth on fibronectin were significantly inhibited in the presence of synthetic peptides containing the Arg-Gly-Asp (RGD) sequence, which interacts with the fibronectin receptor (integrin alpha5beta1), but were not inhibited by the control peptides containing the Arg-Gly-Glu (RGE) sequence. Addition of anti-fibronectin receptor (integrin alpha5beta1) antibody to the culture medium also inhibited the attachment and outgrowth on fibronectin-coated Petri dishes. Subsequently we examined mRNA expression and protein expression of alpha5 and beta1 integrin subunit in the hatched blastocyst by reverse transcription-polymerase chain reaction (RT-PCR) and immunostaining, respectively. Expression of both mRNA and protein were detected in blastocysts. These results indicate that trophectoderm cells of bovine hatched blastocysts have already acquired the ability to adhere and outgrow on fibronectin in vitro by an integrin- mediated manner.

Animals↗
PubMed2005

Plasmacytoma of the urinary bladder in a renal transplant recipient.

A 28-year-old woman underwent renal transplantation in 1993. Eight years later, she experienced macroscopic hematuria, and Epstein-Barr virus-negative solitary extramedullary plasmacytoma (EMP) of the urinary bladder was diagnosed. After the reduction of immunosuppressive therapy, she received combined chemotherapy, resulting in complete tumor disappearance. However, 10 months later, she relapsed with aggressive multiple EMP and died of disease progression in 2003. This report is the first of a case of solitary EMP of the urinary bladder appearing as posttransplantation plasma cell dyscrasias after renal transplantation.

Adult↗
PubMed2005

Combination therapy with thalidomide, incadronate, and dexamethasone for relapsed or refractory multiple myeloma.

The feasibility and efficacy of a combination of thalidomide, incadronate, and dexamethasone (TID) were studied in 12 patients with relapsed or refractory multiple myeloma. The protocol, consisting of 300 mg/day of thalidomide administered orally, intravenous incadronate (10 mg/day) administered weekly, and 12 mg/day dexamethasone for 4 days, was repeated every 3 weeks. Evaluations of efficacy and toxicity were carried out every 3 weeks and were continued for 3 cycles. Three patients were excluded during the study because of apnea, severe somnolence, and pancytopenia. Of 9 evaluated patients, the partial responses achieved in 3 patients and the minor responses achieved in 4 patients corresponded to a response rate of 78% according to the criteria of the European Group for Blood and Marrow Transplantation. In addition, painful osteolytic symptoms improved rapidly after 1 cycle of TID therapy in the 10 patients evaluated. These data suggest that TID is a feasible and promising therapeutic approach for refractory and relapsed multiple myeloma.

Aged↗
PubMed2004

NIDD, a novel DHHC-containing protein, targets neuronal nitric-oxide synthase (nNOS) to the synaptic membrane through a PDZ-dependent interaction and regulates nNOS activity.

Targeting of neuronal nitric-oxide synthase (nNOS) to appropriate sites in a cell is mediated by interactions with its PDZ domain and plays an important role in specifying the sites of reaction of nitric oxide (NO) in the central nervous system. Here we report the identification and characterization of a novel nNOS-interacting DHHC domain-containing protein with dendritic mRNA (NIDD) (GenBank accession number AB098078), which increases nNOS enzyme activity by targeting the nNOS to the synaptic plasma membrane in a PDZ domain-dependent manner. The deduced NIDD protein consisted of 392 amino acid residues and possessed five transmembrane segments, a zinc finger DHHC domain, and a PDZ-binding motif (-EDIV) at its C-terminal tail. In vitro pull-down assays suggested that the C-terminal tail region of NIDD specifically interacted with the PDZ domain of nNOS. The PDZ dependence was confirmed by an experiment using a deletion mutant, and the interaction was further confirmed by co-sedimentation assays using COS-7 cells transfected with NIDD and nNOS. Both NIDD and nNOS were enriched in synaptosome and synaptic plasma membrane fractions and were present in the lipid raft and postsynaptic density fractions in the rat brain. Co-localization of these proteins was also observed by double staining of the proteins in cultured cortical neurons. Thus, NIDD and nNOS were co-localized in the brain, although the colocalizing regions were restricted, as indicated by the distribution of their mRNA expression. Most important, co-transfection of NIDD and nNOS increased NO-producing nNOS activity. These results suggested that NIDD plays an important role in the regulation of the NO signaling pathway at postsynaptic sites through targeting of nNOS to the postsynaptic membrane.

Amino Acid Sequence↗
PubMed2004

CD5-negative chronic lymphocytic leukemia with indolent clinical course and autoimmune thrombocytopenia, successfully treated with rituximab.

A 59-year-old male with lymphocytosis and thrombocytopenia was asymptomatic without lymphadenopathy or hepatosplenomegaly over 10 years. He was admitted to our hospital because his thrombocytopenia had worsened. The clonal lymphocytes appeared as regular small mature lymphocytes on blood films, and bone marrow biopsy showed diffuse infiltration of mature lymphocytes. However, megakaryocytes also presented. The immunophenotypic analysis by flow cytometry revealed that the lymphocytes were positive for CD19, CD20, CD22, and surface membrane immunoglobulin (SmIg) M and D-lambda and were negative for CD5, CD10, CD11c, CD23, and other lineage markers. Expression levels of CD20 and SmIg were strong. The markers were consistent with CD5- CLL with autoimmune thrombocytopenia. He received rituximab, and a rapid decrease of lymphocytes with concomitant increase of platelets was observed. A few cases of CD5- CLL with a stable clinical course have been reported, thought to be B lymphocytosis of undetermined significance (MLUS). This is the first report of CD5- CLL with indolent clinical course associated with autoimmune thrombocytopenia, successfully treated with rituximab.

Antibodies, Monoclonal↗
PubMed2004

Human immunodeficiency virus (HIV)-negative, API2-MALT1 fusion-negative bronchus-associated lymphoid tissue (BALT) lymphoma in a young male.

A 22-year-old male presented with multiple bilateral nodular shadows in the lungs by chest radiograph. He had been asymptomatic and showed no significant abnormal findings in laboratory examinations. He underwent a diagnostic partial lobectomy, and was diagnosed as having primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma; i.e. bronchus-associated lymphoid tissue (BALT) lymphoma/BALToma. Neither t(11;18)(q21;q21) chromosomal translocation nor API2-MALT1 chimeric transcript was found at diagnosis. Epstein-Barr virus (EBV) was also not detected in lymphoma cells. He had been a nonsmoker, and had also never shown any associated autoimmune disorders, chronic inflammatory lung diseases or human immunodeficiency virus (HIV) infection. However, he had suffered from moderate atopic dermatitis on his arms from childhood. It appears necessary to clarify whether atopy might play a role in the pathogenesis of API2-MALT1(-) BALT lymphoma for HIV(-) young patients who do not exhibit any other antecedent chronic antigenic stimulations.

Adult↗
PubMed2004

Brain-specific potential guanine nucleotide exchange factor for Arf, synArfGEF (Po), is localized to postsynaptic density.

We cloned from a rat brain cDNA library a novel cDNA and named it a potential synaptic guanine nucleotide exchange factor (GEF) for Arf (synArfGEF (Po)) (GenBank Accession no. AB057643) based on its domain structure and localization. The cloned gene was 7410 bases long with a 3585-bp coding sequence encoding a protein of 1194 amino acids. The deduced protein contained a coiled-coil structure in the N-terminal portion followed by Sec7 and Plekstrin homology (PH) domains. Thus, the protein was a member of the Sec7 family of proteins, GEFs. Conservation of the ADP-ribosylation factor (Arf)-binding sequence suggested that the protein was a GEF for Arf. The gene was expressed specifically in the brain, where it exhibited region-specific expression. The protein was highly enriched in the postsynaptic density (PSD) fraction prepared from the rat forebrain. Uniquely, the protein interacted with PSD-95, SAP97 and Homer/Vesl 1/PSD-Zip45 via its C-terminal PDZ-binding motif and co-localized with these proteins in cultured cortical neurons. These results supported its localization in the PSD. The postsynaptic localization was also supported by immunohistochemical examination of the rat brain. The mRNA for the synArfGEF was also localized to dendrites, as well as somas, of neuronal cells. Thus, both the mRNA and the protein were localized in the postsynaptic compartments. These results suggest a postsynaptic role of synArfGEF in the brain.

ADP-Ribosylation Factors↗