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Biomedical subjects

Satoshi Ueno

Publications and source records attributed to Satoshi Ueno.

51 records · Page 3Linked to original sources

Ruthenium-catalyzed functionalization of aryl carbon-oxygen bonds in aromatic ethers with organoboron compounds.

The ruthenium-catalyzed reaction of aryl ethers having a carbonyl group at the ortho position to the ether group with organoboronates (R-B(OCH2CMe2CH2O), R = aryl, alkenyl, and alkyl) resulted in site-selective C-C bond formation. Among the transition metal complexes screened, the RuH2(CO)(PPh3)3 complex showed the highest activity. Several aromatic ketones having methoxy or phenoxy groups at the ortho position can also be used in this coupling reaction. A variety of arylboronates containing electron-donating (NMe2, OMe, methyl, and vinyl) and -withdrawing (F and CF3) groups reacted with methoxy ketones to give the corresponding coupling products in high yields.

Journal Article↗

[Diffuse large B-cell lymphoma of the knee occurring 70 years after tuberculous arthritis].

A 72-year-old woman presented with a progressive swollen and painful left knee over a period of a month. The patient had a history of tuberculous arthritis of the left knee joint at the age of 1-2 years. Since then the knee showed a deformity and contraction. MRI scan demonstrated a soft tissue tumor measuring 7 x 8 x 6 cm in the front of the knee, a biopsy specimen taken from which revealed large B-cell lymphoma. The tumor cells showed a phenotype of CD3- CD5- CD10- CD20+ CD21- BCL2+, and surface immunoglobulin M-kappa. Since the lymphoma cells were found to be negative for Epstein-Barr virus encoded RNA by means of in situ hybridization, the DLBCL in this patient was thought to be caused by a different mechanism from pyothorax-associated lymphoma. The patient was treated with chemotherapy (CHOP) followed by radiotherapy, and obtained partial remission. There is no evidence of progression seven months after diagnosis.

Aged↗

Induction of ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptides by bacterial injection: novel members of ASABF in the nematode Ascaris suum.

Recently, invertebrate models have been widely used for the study of innate immunity. Nematodes are novel potential candidates because of the experimental advantages of Caenorhabditis elegans. However, whether nematodes have active immune responses is still ambiguous. Previously, we reported ASABF (Ascaris suum antibacterial factor)-type antimicrobial peptides in the parasitic nematode Ascaris suum and the genetic model nematode C. elegans. Further screening of a cDNA library and an expressed-sequence-tag database search detected five novel members of ASABF (ASABF-beta, -gamma, -delta, - epsilon and -zeta) in A. suum. The transcripts for ASABF-alpha, -beta, -gamma, and -delta clearly increased in the body wall, and also in the intestine for ASABF-delta, 4 h after injection of heat-killed bacteria into the pseudocoelom (body cavity), suggesting that these peptides are inducible in the acute phase of immune response. These results also suggest that the nematodes can recognize bacteria in the pseudocoelomic fluid and evoke an active immune response.

Amino Acid Sequence↗

Microarray reveals differences in both tumors and vascular specific gene expression in de novo CD5+ and CD5- diffuse large B-cell lymphomas.

Malignant lymphoma is a heterogeneous disease with different clinical features. Among diffuse large B-cell lymphomas (DLBCLs), a unique subtype has been identified recently based on cell surface marker CD5 and clinicopathological features. These de novo CD5(+) DLBCLs account for approximately 10% of all of the DLBCLs and have poorer prognosis. To additionally understand this subtype of DLBCLs at the molecular level and to find genes that are differentially expressed in de novo CD5(+) DLBCLs, CD5(-) DLBCLs, and mantle cell lymphomas, which also have poor prognosis, we performed gene expression profiling using cDNA microarray technology. Data from a total of 9 samples of CD5(-) DLBCLs, 11 samples of de novo CD5(+) DLBCLs, and 10 samples of mantle cell lymphomas were acquired. A series of genes were identified that distinguish these three types of lymphomas. Among DLBCL cases, integrin beta1 and/or CD36 adhesion molecules were overexpressed in most cases of CD5(+) DLBCL. An immunohistochemical confirmation study revealed that integrin beta1 was expressed on lymphoma cells, which may account for the high extranodal involvement and poor prognosis of CD5(+) DLBCLs. In contrast, CD36 was overexpressed on vascular endothelia in CD5(+) DLBCLs, although there was no difference in vascularity detected by von Wilbrand factor antibody between CD5(+) and CD5(-) DLBCLs. Those results suggest that CD5(+) and CD5(-) DLBCLs have different gene expression signatures in both tumor cells and their vascular systems.

Aged↗

Two novel spliced presenilin 2 transcripts in human lymphocyte with oxidant stress and brain.

We identified two novel spliced human presenilin 2 (PS2) transcripts. The first, PS2deltaEx3-7, lacked part ofexon 3, all of exons 4, 5, and 6, and part of exon 7, resulting in an in-frame shift and inclusion of the natural start codon and proteolytic region. This transcript was detected in cerebral cortex and peripheral lymphocytes. The second transcript, PS2deltaEx4, lacked exon 4, resulting in a frame shift and inclusion of the natural start codon, and was transcribed in peripheral lymphocytes and heart but not in brain. Quantitative RT-PCR analysis revealed that the PS2deltaEx3-7 significantly increased in lymphocytes treated with H2O2, suggesting that this transcript is a novel genetic marker that can be used to study the pathogenesis of Alzheimer's disease.

Amino Acid Sequence↗

Humanin improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes.

Humanin (HN) has been reported to be an endogenous peptide that exerts highly selective neuroprotection against cell death induced by various types of Alzheimer's disease-related insults. We previously proposed the much broader cytoprotective potential of HN from the result that HN suppressed serum-deprivation-induced death of rat pheochromocytoma cells. In this study, we showed that HN also suppressed death of human lymphocytes cultured under serum-deprived condition. Further, we revealed, by assaying metabolic activity and survival rate, that HN was a potent factor capable of increasing the metabolic activity of individual serum-deprived lymphocytes. To our knowledge, there is no report described about a rescue factor that increases the metabolic activity of individual serum-deprived cells and prolongs their survival. This novel feature of HN may enable us to apply this peptide for the management of diseases involving poor metabolic activity, such as mitochondria-related disorders and brain ischemia.

Adult↗

Axial type self-bearing motor for axial flow blood pump.

An axial self-bearing motor is proposed which can drive an axial blood pump without physical contact. It is a functional combination of the bi-directional disc motor and the axial active magnetic bearing, where it actively controls single degree-of-freedom motion, while other motions such as lateral vibration are passively stable. For application to a blood pump, the proposed self-bearing motor has the advantages of simple structure and small size. Through the finite element method (FEM) analysis and the experimental test, its good feasibility is verified. Finally, the axial flow pump is fabricated using the developed magnetically suspended motor. The pump test is carried out and the results are discussed in detail.

Equipment Design↗

Characteristic brain distribution of 1-(14)C-octanoate in a rat model of focal cerebral ischemia in comparison with those of (123)I-IMP and (123)I-iomazenil.

UNLABELLED: 1-(11)C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-(11)C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-(14)C-octanoate and compared it with N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) distribution (cerebral blood flow), (123)I-iomazenil ((123)I-IMZ) distribution (neuronal viability based on (123)I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia. METHODS: The right middle cerebral artery of each rat was occluded intraluminally. The brain distribution of 1-(14)C-octanoate and (123)I-IMP (or (123)I-IMZ) was determined 4 and 24 h after the insult using a dual-tracer autoradiographic technique (n = 4-7 in each group). Coronal brain sections adjacent to those used for autoradiography were stained with hematoxylin and eosin. Regions of interest (ROIs) were determined for 3 coronal slices, and asymmetry indices (AIs, lesion/normal hemisphere) of the tracer uptake were calculated. ROIs on the hemisphere with the lesion were classified into 4 groups: In region A, widespread necrotic cells were observed; in region B, necrotic cells were occasionally observed; in region C1, no morphologic changes were observed and the AIs for (123)I-IMP (or (123)I-IMZ) were 0.8. RESULTS: 1-(14)C-Octanoate uptake decreased in the regions where morphologic changes were observed (regions A and B) but was relatively preserved in the surrounding region without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake (region C1). In the region without morphologic changes (region C1), AIs for 1-(14)C-octanoate were significantly higher than those for (123)I-IMP (4 h, 0.73 +/- 0.23 for 1-(14)C-octanoate and 0.37 +/- 0.20 for (123)I-IMP, P < 0.0001; 24 h, 0.84 +/- 0.11 for 1-(14)C-octanoate and 0.44 +/- 0.15 for (123)I-IMP, P < 0.0001) and those for (123)I-IMZ (4 h, 0.83 +/- 0.19 for 1-(14)C-octanoate and 0.57 +/- 0.13 for (123)I-IMZ, P < 0.0001; 24 h, 0.91 +/- 0.13 for 1-(14)C-octanoate and 0.73 +/- 0.06 for (123)I-IMZ, P < 0.0001). CONCLUSION: 1-(14)C-Octanoate uptake was relatively preserved in the regions without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake. 1-(11)C-Octanoate may provide further functional information on the pathophysiology of ischemic stroke, reflecting astroglial function based on fatty acid metabolism.

Animals↗

Identification of signature genes by microarray for acute myeloid leukemia without maturation and acute promyelocytic leukemia with t(15;17)(q22;q12)(PML/RARalpha).

Acute myeloid leukemia (AML) has distinct subgroups characterized by different maturation and specific chromosomal translocation. In order to gain insight into the gene expression activities in AML, we carried out a gene expression profiling study with 21 AML samples using cDNA microarrays, focusing on acute promyelocytic leukemia with specific translocation t(15;17)(q22;q12) [French-American-British or FAB-M3 with t(15;17)] and AML without maturation (FAB-M1) characterized by morphologically and phenotypically immature AML blasts and no recurrent chromosomal abnormalities. Using a multivariate sigma-classifier algorithm, we identified 33 strong feature genes that distinguish FAB-M3 with t(15;17) from other AML samples, and 24 strong feature genes that classify FAB-M1. A direct comparison between FAB-M3 with t(15;17) and FAB-M1 led to selection of 13 strong feature genes. Those genes include some known to be related to leukemogenesis and cell differentiation. RIN1, a gene in the ras pathway, was up-regulated in FAB-M3 with t(15;17). Growth factor-binding protein 2 gene was down-regulated in FAB-M1. Huntingtin gene was up-regulated in FAB-M1. Others include syndecan 4, interleukin-2 receptor beta, folate receptor beta, low affinity immunoglobulin gamma, Fc receptor IIC precursor, insulin-like growth factor binding protein 2, and myeloperoxidase, which are involved in cell differentiation. Overexpression of myeloperoxidase in FAB-M3 cells with t(15;17) compared to FAB-M1 cells is consistent with the conventional cytochemical staining pattern. Thus, the study revealed that a morphologically-defined FAB-M1 subtype has a distinct gene expression signature that contributes to its cell differentiation and proliferation as well as FAB-M3 with a recurrent cytogenetic abnormality t(15;17)(q22;q12).

Algorithms↗

Expression of the costimulatory molecule BB-1 and its receptors in patients with scleroderma-polymyositis overlap syndrome.

We investigated expression of costimulatory molecules BB-1, B7-1 (CD80), B7-2 (CD86), and their counter-receptors CD28 and CTLA-4 (CD152) in muscle biopsy specimens of patients with scleroderma-polymyositis overlap syndrome (SSc-PM), primary polymyositis (PM), and other related diseases to examine whether the muscle fibers in patients with SSc-PM behave as antigen-presenting cells (APCs). The major histocompatibility (MHC) class II-positive muscle fibers of SSc-PM patients reacted with monoclonal antibodies (mAb) against BB-1 but not against B7-1 or B7-2. The CD4+ T cells expressed the counter-receptors CD28 and CTLA-4, and bound with the BB-1-positive muscle fibers in cell-to-cell contact. Our findings show that muscle fibers in patients with SSc-PM function as "professional" APCs in a way distinct from muscle fibers in patients with primary PM.

Abatacept↗

Daphmanidin A, a novel hexacyclic alkaloid from Daphniphyllum teijsmanii.

A novel alkaloid with an unprecedented fused-hexacyclic skeleton, daphmanidin A (1), and a new pentacyclic alkaloid, daphmanidin B (2), have been isolated from the leaves of Daphniphyllum teijsmanii, and the structures were elucidated on the basis of spectroscopic data. The relative and absolute stereochemistry of 1 was determined by combination of NOESY correlations and a modified Mosher method.

Alkaloids↗

Humanin inhibits cell death of serum-deprived PC12h cells.

Humanin (HN) and S14G HN (HNG) are recently discovered polypeptides that rescue cells from death induced by multiple different types of familial Alzheimer's disease genes and by amyloid-beta. However, the cytoprotective activity of these peptides against other cell death-inducing stimuli remains unclear. In this study, we demonstrated, using three different methods (MTS assay, caspase-3 assay, and detection of DNA fragmentation), that both HN and HNG protect PC12 cells from death elicited by serum deprivation. This implies the potential of the peptides to rescue cells from a broad spectrum, if not all, of cell death-inducing factors. Further investigations on HN may lead the possible application of this peptide as therapeutic agent for the treatment of other neurodegenerative diseases.

Animals↗

Bax-induction alone is sufficient to activate apoptosis cascade in wild-type Bax-bearing K562 cells, and the initiation of apoptosis requires simultaneous caspase activation.

It has been reported that expression of Bax by Tet-On system induces apoptosis in Jurkat cells. The parental Jurkat cells have mutation of Bax gene and do not express Bax protein. Wild-type Bax-bearing cells express endogenous Bax protein and it is still unclear whether overexpression of Bax alone can sufficiently induce apoptosis in these cells in the absence of any cytotoxic stimulus. To investigate this, wild-type Bax-bearing K562 cells were transfected with Tet-On Bax-inducible system (pTet-On and pTRE-Bax plasmids), and Bax-inducible stable cell lines were established. Overexpression of Bax in wild-type Bax-bearing K562 cells without any cyctotoxic signal resulted in increase of apoptotic cells, caspase-3 activation, mitochondrial release of cytochrome c, and mitochondrial membrane potential change. Western blotting and confocal microscopy revealed that overexpression of Bax was detected in mitochondria. A pancaspase inhibitor, zVAD-fmk, which has no effect on mitochondrial cytochrome c release and mitochondrial membrane potential change inhibited the apoptotic events in the presence of overexpressed Bax in mitochondria. These findings suggest that Bax protein, when present above a threshold level, is sufficient to trigger an apoptosis cascade, and its initiation requires simultaneous caspase activation probably not mediated by mitochondrial cytochrome c release and mitochondrial membrane potential change in K562 cells.

Apoptosis↗