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T Morio

Publications and source records attributed to T Morio.

At least 19 recordsLinked to original sources
PubMed2006

Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team.

We retrospectively analyzed our results of 30 patients with three distinctive primary immunodeficiency diseases (PIDs)--severe combined immunodeficiency (SCID, n = 11), Wiskott-Aldrich syndrome (WAS, n = 11) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n = 8)--who underwent hematopoietic SCT (HSCT) during the past 20 years. Until 1995, all donors were HLA-haploidentical relatives with T-cell depletion (TCD) (n = 8). Since 1996, the donors have been HLA-matched related donors (MRD) (n = 8), unrelated BM (UR-BM) (n = 7) and unrelated cord blood (UR-CB) (n = 7). Twenty-seven of 30 patients had various pre-existing infections with or without organ damages before HSCT. Conditioning regimen and GVHD prophylaxis were determined according to disease, donor and pretransplant status. Although one of eight patients transplanted with TCD is alive with full engraftment, the other seven died. On the other hand, 18 of 22 patients transplanted without TCD are alive and well, including six of eight transplanted from MRD, seven of seven from UR-BM and five of seven from UR-CB. All 19 survivors did not require Ig supplementation after HSCT. These results indicate that UR-CBT as well as UR-BMT provides good results for PID comparable to MRD-SCT, and that early diagnosis, HSCT at early stage, careful supportive therapy and monitoring for various pathogens are important for the successful HSCT.

Adolescent↗
PubMed2005

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗
PubMed2001

FebA: a gene for eukaryotic translation initiation factor 4E-binding protein (4E-BP) in Dictyostelium discoideum.

We have identified a gene encoding a eukaryotic initiation factor 4E-binding protein (4E-BP) in the EST database of the Dictyostelium cDNA project. The Dictyostelium 4E-BP, designated febA (four e-binding), showed significant similarity to mammalian 4E-BPs. Northern blot analysis revealed that febA was expressed at a high level in the vegetative growth phase but the level of expression decreased during late development. The gene was shown to be non-essential since disruption of the gene had no severe effect; the null mutant proliferated normally and formed normal fruiting bodies. However, strains overexpressing the gene could not be established, suggesting that an excess of FebA protein may have a lethal effect on the cells.

Amino Acid Sequence↗
PubMed2001

Spatial expression patterns of genes involved in cyclic AMP responses in Dictyostelium discoideum development.

The spatial expression patterns of genes involved in cyclic adenosine monophosphate (cAMP) responses during morphogenesis in Dictyostelium discoideum were analyzed by in situ hybridization. Genes encoding adenylyl cyclase A (ACA), cAMP receptor 1, G-protein alpha2 and beta subunits, cytosolic activator of ACA (CRAC and Aimless), catalytic subunit of protein kinase A (PKA-C) and cAMP phosphodiesterases (PDE and REG-A) were preferentially expressed in the anterior prestalk (tip) region of slugs, which acts as an organizing center. MAP kinase ERK2 (extracellular signal-regulated kinase-2) mRNA, however, was enriched in the posterior prespore region. At the culmination stage, the expression of ACA, CRAC and PKA-C mRNA increased in prespore cells in contrast with the previous stage. However, no alteration in the site of expression was observed for the other mRNA analyzed. Based on these findings, two and four classes of expression patterns were catalogued for these genes during the slug and culmination stages, respectively. Promoter analyses of genes in particular classes should enhance understanding of the regulation of dynamic and coordinated gene expression during morphogenesis.

Animals↗
PubMed2001

Specific but variable expression of h-caldesmon in leiomyosarcomas: an immunohistochemical reassessment of a novel myogenic marker.

h-Caldesmon is considered a novel specific marker for tumors with smooth muscle differentiation. To reassess its diagnostic use, the authors evaluated the immunohistochemical expression of h-caldesmon and other myogenic markers (calponin, alpha-smooth muscle actin, HHF35, and desmin) in 30 leiomyosarcomas (external soft tissues [15], retroperitoneum [8], uterus [5], other sites [2]), 26 myofibroblastic lesions, and 26 fibrohistiocytic tumors of varying biologic potential and histology. In contrast with previous data, h-caldesmon was expressed only in 11 (36%) of the 30 leiomyosarcomas analyzed, whereas they consistently expressed actins and frequently expressed calponin (86%) and desmin (76%). Leiomyosarcomas with the expression of h-caldesmon were well or moderately differentiated and primarily confined to the retroperitoneum or uterus. All but one leiomyosarcomas in the external soft tissues examined were negative for h-caldesmon, and the h-caldesmon-negative tumors showed moderately to poorly differentiated morphology. All myofibroblastic lesions examined were negative for h-caldesmon despite their constant expressions of at least one of the other markers. h-Caldesmon was not expressed in fibrohistiocytic tumors either, although focal positivity for the other markers was seen in subsets of the tumors. Thus, h-caldesmon can be regarded as a specific myogenic marker. However, one should be aware that the expression of h-caldesmon in leiomyosarcomas can be more variable according to their locations and/or extent of smooth muscle differentiation than considered previously.

Adult↗
PubMed2001

Characterization of soluble CD40 ligand released from human activated platelets.

We report here that soluble CD40 ligand (sCD40L) is released from human platelets when activated with collagen or thrombin. The sCD40L was detectable in the culture supernatants of platelets within 30 min after stimulation in vitro, and reached maximal levels in 3 h. The release was blocked by the metalloproteinase inhibitor, KB8301, indicating that the soluble CD40L is made by cleaving the membrane bound CD40L expressed on activated platelets. The sCD40L was undetectable in the supernatant of the activated platelets obtained from patients with X-linked hyper IgM syndrome (XHIM), who have defects in CD40L gene. Since sCD40L has been shown to have biologic function on the activation of vascular endothelial cells and B cells, these findings suggest that platelets play some roles in both inflammation and humoral immune response by releasing soluble CD40L.

Antibody Formation↗
PubMed2000

A syntaxin 7 homologue is present in Dictyostelium discoideum endosomes and controls their homotypic fusion.

Endo-phagocytic activity is prominent in Dictyostelium discoideum and makes it a good model organism to study the molecular organization of membrane traffic in this pathway. We have identified a syntaxin 7 homologue (26% identity and 54% similarity to human syntaxin 7) in Dictyostelium cDNA and genomic data banks. In addition to the Habc and H3 helices and the C-terminal transmembrane domain characteristic of syntaxins, this protein contains a repetitive N-terminal extension of 68 amino acids. We first showed that Dictyostelium syntaxin 7 was able to form a complex with N-ethylmaleimide-sensitive fusion protein and alpha- and gamma-soluble N-ethylmaleimide-sensitive fusion protein attachment protein. Its intracellular localization was then studied by cell fractionation techniques and magnetic purification of the endocytic compartments. Most of D. discoideum syntaxin 7 is contained in endosomes. Finally, an in vitro endosome homotypic fusion assay (Laurent, O., Bruckert, F., Adessi, C., and Satre, M. (1998) J. Biol. Chem. 273, 793-799) was used to study a possible role for syntaxin 7 in this process. Purified anti-syntaxin 7 antibodies and a recombinant soluble fragment of syntaxin 7 both strongly inhibited fusion activity, indicating that this protein was necessary for endosome-endosome fusion. These results demonstrate the importance of this syntaxin 7 homologue in the early phases of Dictyostelium endo-phagocytic pathway.

Amino Acid Sequence↗
PubMed2000

Developmental changes in the spatial expression of genes involved in myosin function in Dictyostelium.

We analyzed the spatial expression patterns of the genes involved in myosin function by in situ hybridization at the tipped aggregate and early culmination stages of Dictyostelium. Myosin heavy chain II mRNA was enriched in the anterior prestalk region of the tipped aggregates, whereas it disappeared from there and began to appear in both upper and lower cups of the early culminants. Similarly, mRNAs for essential light chain, regulatory light chain, myosin light chain kinase A, and myosin heavy chain kinase C were enriched in the prestalk region of the tipped aggregates. However, expression of these genes was distinctively regulated in the early culminants. These findings suggest the existence of mechanisms responsible for the expression of particular genes.

Animals↗
PubMed2000

Loss of a member of the aquaporin gene family, aqpA affects spore dormancy in Dictyostelium.

We isolated and characterized a gene from Dictyostelium discoideum, which encodes a protein of 279 amino acids (30.6kDa) containing six transmembrane domains with two highly conserved motifs of asparagine-proline-alanine (NPA) found in the aquaporin family of water-channel proteins, although the second motif of the protein has been modified into NPV (asparagine-proline-valine). The deduced amino acid sequence of the gene, which we have named aqpA, is 39% identical to D. discoideum WacA, 26% identical to human Aqp5, 26% identical to Oryza sativa PIP2a, 25% identical to yeast Aqy1 and 24% identical to E.coli AqpZ. Southern analyses indicated that aqpA is present as a single copy in the genome. Northern blot analysis showed that the developmentally regulated 1kb mRNA transcript first appears at the tight mound stage (12h), and is abundant in fingers (16h) and late culminants (20h). In-situ hybridization of slugs revealed that aqpA mRNA accumulated in cells of the prespore region but not in those of the prestalk region. Disruption of aqpA by homologous recombination did not significantly affect growth or developmental morphogenesis. Although mutant spores were viable, when assayed soon after encapsulation, they became permeable to propidium iodide and lost viability after a week on the top of a fruiting body. Thus, AqpA is essential to maintain spore dormancy perhaps through the regulation of water flow.

Amino Acid Sequence↗
PubMed2000

The mitochondrial DNA of Dictyostelium discoideum: complete sequence, gene content and genome organization.

We present an overview of the gene content and organization of the mitochondrial genome of Dictyostelium discoideum. The mitochondria genome consists of 55,564 bp with an A + T content of 72.6%. The identified genes include those for two ribosomal RNAs (rn1 and rns), 18 tRNAs, ten subunits of the NADH dehydrogenase complex (nad1, 2, 3, 4, 4L, 5, 6, 7, 9 and 11), apocytochrome b (cytb), three subunits of the cytochrome oxidase (cox1/2 and 3), four subunits of the ATP synthase complex (atp1, 6, 8 and 9), 15 ribosomal proteins, and five other ORFs, excluding intronic ORFs. Notable features of D. discoideum mtDNA include the following. (1) All genes are encoded on the same strand of the DNA and a universal genetic code is used. (2) The cox1 gene has no termination codon and is fused to the downstream cox2 gene. The 13 genes for ribosomal proteins and four ORF genes form a cluster 15.4 kb long with several gene overlaps. (3) The number of tRNAs encoded in the genome is not sufficient to support the synthesis of mitochondrial protein. (4) In total, five group I introns reside in rnl and cox1/2, and three of those in cox1/2 contain four free-standing ORFs. We compare the genome to other sequenced mitochondrial genomes, particularly that of Acanthamoeba castellanii.

Animals↗
PubMed2000

Characterization of the gammac chain among 27 unrelated Japanese patients with X-linked severe combined immunodeficiency (X-SCID).

X-linked severe combined immunodeficiency (X-SCID) is a rare fatal disease that is caused by mutations in the gene encoding the gammac chain. In this study, 27 unrelated Japanese patients with X-SCID were examined in terms of their genetic mutations and surface expression of the gammac chain. Among 25 patients examined, excluding two patients with large deletions, 23 different mutations were identified in the IL2RG gene, including 10 novel mutations. One patient bearing an extracellular mutation and all three of the patients bearing intracellular mutations after exon 7 expressed the gammac chain on the cell surface. Overall, 84% of patients lacked surface expression of the gammac chain leading to a diagnosis of X-SCID.

Antibodies, Monoclonal↗
PubMed2000

A second functional delta5 fatty acid desaturase in the cellular slime mould Dictyostelium discoideum.

A cDNA with homology to fatty acid desaturases was selected by searching the cDNA data bank of Dictyostelium discoideum (http://www. csm.biol.tsukuba.ac.jp/cDNAproject.html) with conserved histidine box motifs. Using this sequence, genomic DNA encoding the Delta5 desaturase was amplified from the genomic DNA of D. discoideum, and its desaturase activity was confirmed by the overexpression mutation in D. discoideum and the gain-of-function mutation in yeast. The cloned cDNA is 1565 nucleotides in length, and the deduced amino-acid sequence comprised 467 amino-acid residues containing an N-terminal cytochrome b5 domain that shared 43% identity with cytochrome b5 of Oryza sativa. The whole sequence was 42% identical to the Delta5 desaturase of Mortierella alpina. This desaturase is a novel member of the cytochrome b5-containing Delta5 fatty acid desaturase. As we have already reported one other Delta5 desaturase in Dictyostelium, this organism is the first to be confirmed as having two functional Delta5 fatty acid desaturase genes. The substrate specificities of the two functional Delta5 desaturases of D. discoideum were also examined.

Amino Acid Sequence↗
PubMed2000

Mutations of the WASP gene in 10 Japanese patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency, and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this study, we identified mutations of the WASP gene in 10 Japanese patients from 9 unrelated families with WAS/XLT. All XLT patients (n = 3) and one WAS patient had a missense mutation at the PH domain of WASP. Two WAS patients had nonsense mutations. One WAS patient had exon 8 skipping caused by one nucleotide deletion at the acceptor site of intron 7. Three WAS patients had genomic deletions; one of the three had a large genomic deletion involving exons 3 to 7. Codons 45 and 86 seem to be the hot spots of the WASP mutation, because missense mutations in these codons have been reported previously in several WAS/XLT patients in addition to the patients in this report, and patients with the same mutation show a similar clinical phenotype. All other mutations are novel, indicating that the mutations of WASP are heterogeneous. EB virus-transformed cell lines from XLT patients expressed nearly normal amounts of WASP, whereas those from typical WAS patients expressed almost undetectable amounts of WASP. We conclude that the analysis of gene mutation and protein expression of WASP are useful together in assessing the severity of WAS.

Adult↗