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Biomedical subjects

A Sugimoto

Publications and source records attributed to A Sugimoto.

At least 55 records · Page 3Linked to original sources

Myeloperoxidase positive acute lymphoblastic leukemia cell lines, NALM-30, NALM-31 and NALM-32, carrying Philadelphia chromosome with biphenotypic characteristics.

We established three sister cell lines, NALM-30, NALM-31 and NALM-32, with biphenotypic features carrying myeloperoxidase mRNA and protein with complex Philadelphia (Ph) chromosome, t(9;22;10)(q34;q11;q22), from a patient with Ph-positive acute leukemia in relapse. Epstein-Barr virus nuclear antigen was negative. The morphological appearance of the cell lines is that of immature lymphoid cells. Expression of myeloid- and lymphoid-associated surface membrane antigens on these cells was detected allowing for the classification of "biphenotypic" leukemia. Immunophenotypically, the established cell lines reported here fulfill the European Group for the Immunological Characterization of Leukemias (EGIL) criteria for B-lineage derivation, however, surface and cytoplasmic immunoglobulin chains were negative. Whereas TGF-beta R (CD105), MCSFR (CD115), SCFR (CD117), IL-4R/IL-13R (CD124) and IL-6R (CD126) were not expressed, the cell lines were mostly positive for IFN-gamma R (CD119), IL-7R (CD127) and FLT-3R (CD135). The NALM-30, NALM-31 and NALM-32 cell lines together with their serial sister cell lines NALM-27 and NALM-28 which were established from the same patient at diagnosis provide unprecedented opportunities for studying a multitude of biological aspects related to normal and neoplastic immature B-lymphocytes.

Adult↗

[An abnormality of facial nerve conduction velocity distribution (FNCVD) in Bell's palsy patients].

We studied bilateral facial nerve conduction velocity distribution (FNCVD) of 8 Bell's palsy patients in their paretic and recovered state and unilateral FNCVD of 13 normal control using collision method. Dual supramaximal stimuli were adapted to marginalis mandibulae branch of facial nerve and compound muscle action potential (CMAP) was recorded from the surface of mentalis muscles. Peak of FNCVD in normal control was present at 22-23 m/sec. In Bell's palsy patients, there was no significant change in FNCVD either at paretic or recovery state. Peak of involved side FNCVD of Bell's palsy patient was almost normal but its amplitude was low. However, in healthy side of Bell's palsy patient, peak of FNCVD was present at 18-19 m/sec. This finding shows that facial nerve diameter distribution in the healthy side of Bell's palsy patient has smaller peak than that of normal control.

Action Potentials↗

Efficient virus transmission from dendritic cells to CD4+ T cells in response to antigen depends on close contact through adhesion molecules.

Monocyte-derived cultured dendritic cells (DCs) are potent antigen-presenting cells (APCs) and are susceptible to HIV-1Lai infection. Compared to the low level of virus production by HIV-1-infected DCs alone, a level of virus two to three orders of magnitude higher was produced by cocultivation of HIV-1-infected DCs with autologous resting CD4+ T cells in the presence of a nominal antigen. In this coculture system, direct contact of HIV-1-infected DCs with T cells was crucial for efficient virus transmission and subsequent virus production. Blocking of the LFA-1/ICAM-1 or LFA-3/CD2 interaction between these cells substantially reduced virus production, without influence or IL-2 production by activated T cells. In contrast, cell-cell transmission of HIV between non-APCs and activated T cells was not blocked by an antibody against LFA-3. Since a low level of virus production by HIV-infected DCs was upregulated by cross-linking of CD40, it was suggested that not only focal adhesion, but also mutual activation of HIV-infected DCs and T cells through adhesion molecules, may potentiate virus transmission and production and that such activation signals to HIV may be distinct from signals responsible for IL-2 production in activated T cells.

Antigen Presentation↗

end-1 encodes an apparent GATA factor that specifies the endoderm precursor in Caenorhabditis elegans embryos.

The endoderm in the nematode Caenorhabditis elegans is clonally derived from the E founder cell. We identified a single genomic region (the endoderm-determining region, or EDR) that is required for the production of the entire C. elegans endoderm. In embryos lacking the EDR, the E cell gives rise to ectoderm and mesoderm instead of endoderm and appears to adopt the fate of its cousin, the C founder cell. end-1, a gene from the EDR, restores endoderm production in EDR deficiency homozygotes. end-1 transcripts are first detectable specifically in the E cell, consistent with a direct role for end-1 in endoderm development. The END-1 protein is an apparent zinc finger-containing GATA transcription factor. As GATA factors have been implicated in endoderm development in other animals, our findings suggest that endoderm may be specified by molecularly conserved mechanisms in triploblastic animals. We propose that end-1, the first zygotic gene known to be involved in the specification of germ layer and founder cell identity in C. elegans, may link maternal genes that regulate the establishment of the endoderm to downstream genes responsible for endoderm differentiation.

Amino Acid Sequence↗

Type II myosin heavy chain encoded by the myo2 gene composes the contractile ring during cytokinesis in Schizosaccharomyces pombe.

We cloned the myo2 gene of Schizosaccharomyces pombe, which encodes a type II myosin heavy chain, by virtue of its ability to promote diploidization in fission yeast cells. The myo2 gene encodes 1,526 amino acids in a single open reading frame. Myo2p shows homology to the head domains and the coiledcoil tail of the conventional type II myosin heavy chain and carries putative binding sites for ATP and actin. It also carries the IQ motif, which is a presumed binding site for the myosin light chain. However, Myo2p apparently carries only one IQ motif, while its counterparts in other species have two. There are nine proline residues, which should break alpha-helix, in the COOH-terminal coiled-coil region of Myo2p. Thus, Myo2p is rather unusual as a type II myosin heavy chain. Disruption of myo2 inhibited cell proliferation. myo2Delta cells showed normal punctate distribution of interphase actin, but they produced irregular actin rings and septa and were impaired in cell separation. Overproduction of Myo2p was also lethal, apparently blocking actin relocation. Nuclear division proceeded without actin ring formation and cytokinesis in cells overexpressing Myo2p, giving rise to multinucleated cells with dumbbell morphology. Analysis using tagged Myo2p revealed that Myo2p colocalizes with actin in the contractile ring, suggesting that Myo2p is a component of the ring and responsible for its contraction. Furthermore, genetic evidence suggested that the acto-myosin system may interact with the Ras pathway, which regulates mating and the maintenance of cell morphology in S. pombe.

Amino Acid Sequence↗

Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding ascorbic acid in a rat mutant unable to synthesize ascorbic acid.

We examined the possibility that bilirubin oxidation is provoked in vivo by using scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. In ODS-od/od rats fed an ascorbic-acid-free diet, the concentration of bilirubin metabolites in urine was increased 7.0-fold at 3 h after injection of lipopolysaccharide and 4.4-fold at 10 h compared to the control rats injected with saline. The dietary supplement of ascorbic acid, the physiological antioxidant, suppressed the increase in bilirubin metabolites in urine after lipopolysaccharide injection: concentrations of biotripyrrin-a and biotripyrrin-b in urine collected 6.5-10 h after the injection were lower in rats fed an ascorbic-acid-supplemented diet than in rats fed an ascorbic-acid-free diet. Moreover, feeding of ascorbic acid suppressed the hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with lipopolysaccharide. These findings indicate that bilirubin oxidation is markedly stimulated in lipopolysaccharide-treated rats and suggest that bilirubin and ascorbic acid have physiologically protective effects against oxidative stress.

Animals↗

Structure of the zinc endoprotease from Streptomyces caespitosus.

A zinc endoprotease produced by Streptomyces caespitosus (ScNP) specifically hydrolyzes the peptide bond at the imino side of aromatic residues and is the smallest protease found to date. Although ScNP carries the zinc-binding sequence HEXXH, its primary structure of 132 amino acid residues differs from those of other known zinc metalloendoproteases. X-ray structural analysis of ScNP at 1.6 A resolution revealed that despite a lack of sequence homology, the common topological feature of main-chain folding and a beta-turn containing methionine, which is a feature of the zinc metalloendoprotease superfamily of metzincins, is conserved in ScNP. The zinc atom of ScNP is tetrahedrally ligated by the two histidines in the HEXXH sequence, an aspartate residue and a water molecule. Thus, ScNP represents a novel subfamily of metzincins with a HEXXHXXGXXD zinc-binding sequence. A plausible substrate recognition pocket to which aromatic residues bind is located near the catalytic zinc ion.

Amino Acid Sequence↗

Correlation of middle latency auditory evoked potentials and cerebral blood flow changes.

The purpose of this study is to find the correlation between middle latency auditory evoked potentials (MLAEP) and sound activated single photon emission computed tomography (SPECT) studies. This study was performed on six normal right-handed volunteers with a mean age of 35.2 +/- 7.6 years, using the split-dose technique. First, a SPECT study was performed on subjects in blinded, awake and silent states. After bilateral ears were stimulated with a click sound, MLAEP and a second SPECT study were performed. Subtraction of the first SPECT from the second SPECT revealed a statistically significant increase of cerebral blood flow (CBF) in the bilateral superior temporal region. Bilateral Na amplitudes of MLAEP had a statistically significant and good correlation with the percentages of CBF changes in the bilateral superior temporal region. The superior temporal cerebral blood flow activation can be expressed by electrophysiological activation. Moreover, correlation during the left Na components and left frontal and occipital lobe are discussed.

Adult↗

The major allergen of Dendropanax trifidus Makino.

Dendropanax trifidus Makino (family Araliaceae, syn. Gilibertia trifida Makino) has been reported as causing allergic contact dermatitis in Japan. To identify the major allergen, fractionated extracts of fresh leaves of Dendropanax trifidus were patch tested on 2 patients with hypersensitivity to the plant. Cis-9,17-octadecadiene-12,14-diyne-1, 16-diol (I), an analog of falcarinol, was identified as an active component. 18 normal control subjects were patch tested with the leaf of Dendropanax trifidus and I diluted to 0.05% in pet. 4 of them showed active sensitization to the leaf of Dendropanax trifidus and I. Our results suggest that I is the major allergen of Dendropanax trifidus and is a strong sensitizer. The results of patch testing on patients and control subjects with the leaves of Fatsia japonica Decne. et Planch. and Hedera helix L., which also belong to the Araliaceae family, and urushiol are also shown.

Adult↗

A useful method for measuring daily physical activity by a three-direction monitor.

The purpose of this study was to investigate whether a three-direction accelerometer is useful for measuring daily physical activity. Physical activity, being an important part of human behavior, may be related to various aspects of health and disease. In this study, the relationship between the intensity of each action and the three-direction accelerometer (Actigraph) output was compared in 10 healthy subjects under free-living conditions. Subjects wore the Actigraph on their non-dominant wrist and filled out a physical activity check list (self-report) throughout the daytime. Daily physical activities were classified into six categories according to different intensities. The differences of the Actigraph output among each of the six categories were significant by the Kruskal-Wallis analysis (p = 0.001). The Actigraph output appeared to correlate highly with the intensity of actions by the Spearman Rank test (r = 0.95, p < 0.05). The Actigraph output was over-estimated while the subjects were typing, driving and being a passenger in a motor vehicle. The Actigraph was shown to be a useful and convenient device for measuring daily physical activity.

Acceleration↗

Epitope of 24G7 anti-bilirubin monoclonal antibody.

We examined an antigenic epitope recognized by an anti-bilirubin monoclonal antibody designated 24G7 (Shimizu, S., Izumi, Y., Yamazaki, M., Shimizu, K., Yamaguchi, T., and Nakajima, H. (1988) Biochim. Biophys. Acta 967, 255-260). The reactivity of bilirubin-IX alpha, its analogues (III alpha, XIII alpha, and mesobilirubin-IX alpha) and related azo compounds, with 24G7 was compared by means of an enzyme-linked immunosorbent assay (ELISA). The order of reactivity was as follows: (a) aniline azopigment > ethyl anthranilate azopigment > sulfanilic acid azopigment, (b) bilirubin-XIII alpha > bilirubin-IX alpha > bilirubin-III alpha, (c) bilirubin-IX alpha = mesobilirubin-IX alpha. These findings indicated that the epitope is present in (a) the dipyrrolic moiety of the endovinyl (correspond to N-21 and N-22 of bilirubin), or exovinyl types (N-23 and N-24); (b) the dipyrrolic moiety of the endovinyl type, which contains (c) a methyl group (C-2) but not a vinyl group (C-3) in the dipyrrolic moiety of endovinyl type. Therefore, we concluded that the epitope was the region containing the oxo group at C-1, the methyl group at C-2, C-(4,5,6,9), and the N-21 and -22 of bilirubin-IX alpha.

Antibodies, Monoclonal↗

dad-1, an endogenous programmed cell death suppressor in Caenorhabditis elegans and vertebrates.

Programmed cell death (apoptosis) is a normally occurring process used to eliminate unnecessary or potentially harmful cells in multicellular organisms. Recent studies demonstrate that the molecular control of this process is conserved phylogenetically in animals. The dad-1 gene, which encodes a novel 113 amino acid protein, was originally identified in a mutant hamster cell line (tsBN7) that undergoes apoptosis at restrictive temperature. We have identified a dad-1 homologue in Caenorhabditis elegans (Ce-dad-1) whose predicted product is > 60% identical to vertebrate DAD-1. A search of the sequence databases indicated that DAD-1-like proteins are also expressed in two plant species. Expression of either human dad-1 or Ce-dad-1 under control of a C.elegans heat-shock-inducible promoter resulted in a reduction in the number of programmed cell death corpses visible in C.elegans embryos. Extra surviving cells were present in these animals, indicating that both the human and C.elegans dad-1 genes can suppress developmentally programmed cell death. Ce-dad-1 was found to rescue mutant tsBN7 hamster cells from apoptotic death as efficiently as the vertebrate genes. These results suggest that dad-1, which is necessary for cell survival in a mammalian cell line, is sufficient to suppress some programmed cell death in C.elegans.

Amino Acid Sequence↗

Schizosaccharomyces pombe pac2+ controls the onset of sexual development via a pathway independent of the cAMP cascade.

The Schizosaccharomyces pombe pac2 gene encodes a protein of 235 amino acids not similar to any protein of known function. Cells over-expressing pac2 were poor in mating and sporulation. Expression of ste11, which encodes a key transcription factor for sexual development, was not inducible by nitrogen starvation in these cells. Cells defective in pac2 could express ste11 and enter sexual development under incomplete starvation conditions. Although expression of ste11 is regulated primarily by the cAMP cascade, genetic analysis indicated that this cascade and pac2 can partially compensate for each other in the regulation of sexual development, and that neither of them is epistatic over the other. Thus, Pac2 appears to control ste11 expression via a signaling pathway independent of the cAMP cascade.

Amino Acid Sequence↗

Induction of heparin-binding growth-associated molecule expression in reactive astrocytes following hippocampal neuronal injury.

Heparin-binding growth-associated molecule is a potent neurotrophic factor. To obtain a better understanding of its role in the central nervous system, we studied the changes of its expression in adult rat brain after two types of neuronal injury. In the control hippocampus, expression of heparin-binding growth-associated molecule messenger RNA was confined to CA1 pyramidal neurons and some hilar cells. Following transient forebrain ischaemia, the messenger RNA expression decreased within the first two days. On day 4, however, both the messenger RNA level and the number of expression-positive cells markedly increased in the CA1 subfield, where the selective neuronal losses were seen following ischaemia. Double-staining with a heparin-binding growth-associated molecule complementary RNA probe and an anti-glial fibrillary acidic protein antibody revealed that most of the expressing cells were reactive astrocytes. Moreover, the protein induction of heparin-binding growth-associated molecule after neuronal injury was demonstrated by immunohistochemistry using the affinity-purified antibodies. This molecule was also induced after intraventricular kainate injection, which is known to cause selective pyramidal cell necrosis in the CA3 region. Four days after the insult, the number of cells expressing the messenger RNA prominently increased in the CA3 subfield ipsilateral to the injection. As observed after the ischaemic insult, most of the expression-positive cells were identified as astrocytes. The data presented here suggest that heparin-binding growth-associated molecule, produced by the reactive astrocytes, may play important roles in the repair process after neuronal injury.

Animals↗

Schizosaccharomyces pombe zfs1+ encoding a zinc-finger protein functions in the mating pheromone recognition pathway.

We isolated the Schizosaccharomyces pombe zfs1 gene as a multicopy suppressor of the sterility caused by overexpression of a double-stranded RNase. The deduced zfs1 gene product of 404 amino acids showed similarity to a mouse growth factor-inducible nuclear protein Nup475. Its C-terminal region carried two putative zinc-fingers, both of which should be intact for the protein to be functional as the suppressor. This protein appeared to localize in nuclei. Disruption of zfs1 was not lethal but conferred deficiency in mating and sporulation. Activation of transcription in response to the mating pheromone signaling was greatly reduced in the zfs1-disrupted cells. The mating deficiency of the zfs1-disruptant was suppressed partially by overexpression of either gpa1, ras1, byr1, or byr2, which are involved in the transmission of the pheromone signal. Disruption of zfs1 reduced both hypersensitivity of the ras1Val17 mutant to the mating pheromone and uncontrolled mating response caused by mutational activation of Gpa1, the G protein alpha subunit coupled to the mating pheromone receptors. However, overexpression of zfs1 could not bypass complete loss of function of either gpa1, ras1, byr1, or byr2. These observations indicate that the function of zfs1 is involved in the mating pheromone signaling pathway, and are consistent with its function being required to fully activate a factor in this pathway, either directly or indirectly.

Amino Acid Sequence↗

Accumulation of endogenous inhibitors for nitric oxide synthesis and decreased content of L-arginine in regenerated endothelial cells.

1. We examined regeneration of endothelial cells (ECs), neointima formation, decreased endothelium-dependent relaxation (EDR) and changes in the contents of L-arginine, NG-monomethyl-L-arginine (L-NMMA), asymmetrical NG, NG-dimethylarginine (ADMA) and symmetrical NG,NG-dimethylarginine (SDMA) in the regenerated ECs, 6 weeks after balloon denudation of the rabbit carotid artery. 2. Regeneration of ECs was completed in 6 weeks and a significant neointima formation accompanied by the decreased EDR was observed. 3. L-NMMA and ADMA contents in the regenerated ECs (23.5 +/- 4.3 and 21.2 +/- 2.0 pmol mg-1 DNA, respectively) were significantly (P < 0.05 and P < 0.01) higher than those in the control ECs (8.8 +/- 3.0 and 7.4 +/- 1.9 pmol mg-1 DNA, respectively), whereas L-arginine was significantly (P < 0.005) decreased in the regenerated ECs (31,470 +/- 1,050 pmol mg-1 DNA) as compared to that in the control ECs (47,870 +/- 1,890 pmol mg-1 DNA). SDMA content was below the assay limits. 4. L-NMMA and ADMA, but not SDMA, inhibited the EDR induced by acetylcholine in a concentration-dependent manner. The inhibition with L-NMMA and ADMA was prevented by an addition of L-arginine, but not by D-arginine. 5. These results suggest that the accumulation of endogenous inhibitors for nitric oxide synthesis and decreased L-arginine content are associated with decreased NO production/release from regenerated ECs and neointima formation.

Acetylcholine↗