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M Hattori

Publications and source records attributed to M Hattori.

At least 37 records · Page 2Linked to original sources
PubMed2001

Whole genome sequencing of meticillin-resistant Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is one of the major causes of community-acquired and hospital-acquired infections. It produces numerous toxins including superantigens that cause unique disease entities such as toxic-shock syndrome and staphylococcal scarlet fever, and has acquired resistance to practically all antibiotics. Whole genome analysis is a necessary step towards future development of countermeasures against this organism. METHODS: Whole genome sequences of two related S aureus strains (N315 and Mu50) were determined by shot-gun random sequencing. N315 is a meticillin-resistant S aureus (MRSA) strain isolated in 1982, and Mu50 is an MRSA strain with vancomycin resistance isolated in 1997. The open reading frames were identified by use of GAMBLER and GLIMMER programs, and annotation of each was done with a BLAST homology search, motif analysis, and protein localisation prediction. FINDINGS: The Staphylococcus genome was composed of a complex mixture of genes, many of which seem to have been acquired by lateral gene transfer. Most of the antibiotic resistance genes were carried either by plasmids or by mobile genetic elements including a unique resistance island. Three classes of new pathogenicity islands were identified in the genome: a toxic-shock-syndrome toxin island family, exotoxin islands, and enterotoxin islands. In the latter two pathogenicity islands, clusters of exotoxin and enterotoxin genes were found closely linked with other gene clusters encoding putative pathogenic factors. The analysis also identified 70 candidates for new virulence factors. INTERPRETATION: The remarkable ability of S aureus to acquire useful genes from various organisms was revealed through the observation of genome complexity and evidence of lateral gene transfer. Repeated duplication of genes encoding superantigens explains why S aureus is capable of infecting humans of diverse genetic backgrounds, eliciting severe immune reactions. Investigation of many newly identified gene products, including the 70 putative virulence factors, will greatly improve our understanding of the biology of staphylococci and the processes of infectious diseases caused by S aureus.

Animals↗
PubMed2001

Effect of pre-and postoperative plasmapheresis on posttransplant recurrence of focal segmental glomerulosclerosis in children.

BACKGROUND: Posttransplant recurrence is frequent in patients who received renal transplantation for focal segmental glomerulosclerosis (FSGS). The recurrence has been ascribed to a circulating permeability factor or factors. We have used plasmapheresis (PP) to treat recurrent FSGS and also studied whether preoperative PP is effective in preventing recurrence of FSGS. METHODS: We retrospectively analyzed 21 allografts of 20 patients with nephrotic syndrome and biopsyproven FSGS. They were divided into two groups depending on whether they had prophylactic PP; a prophylactic (n=15) and a nonprophylactic group (n=6). PP was performed two to three times prophylactically and therapeutically until proteinuria was markedly reduced. In each session, 50-75 ml/kg of the patient's plasma was exchanged with 5-8% albumin. RESULTS: FSGS recurred in 9 of 21 allografts, 4 of 6 in the nonprophylactic group, and 5 of 15 in the prophylactic group. Therapeutic PP was performed in seven of nine recurrent patients without definite adverse effect, with satisfactory results except in one patient. Children lost proteinuria after 6 to > 100 sessions of PP and the number correlated with the pretreatment level of proteinuria. The mean follow-up periods were 62.7 and 41.6 months for the prophylactic and nonprophylactic groups, respectively. At the last follow-up, 66.7% of relapsing and 81.8% of nonrelapsing patients had a functioning graft. CONCLUSION: PP appears to be effective for the prevention and treatment of posttransplant recurrence of FSGS, although further consideration of cost/benefit and risks is required before a conclusive judgement can be made.

Child↗
PubMed2001

A comprehensive two-hybrid analysis to explore the yeast protein interactome.

Protein-protein interactions play crucial roles in the execution of various biological functions. Accordingly, their comprehensive description would contribute considerably to the functional interpretation of fully sequenced genomes, which are flooded with novel genes of unpredictable functions. We previously developed a system to examine two-hybrid interactions in all possible combinations between the approximately 6,000 proteins of the budding yeast Saccharomyces cerevisiae. Here we have completed the comprehensive analysis using this system to identify 4,549 two-hybrid interactions among 3,278 proteins. Unexpectedly, these data do not largely overlap with those obtained by the other project [Uetz, P., et al. (2000) Nature (London) 403, 623-627] and hence have substantially expanded our knowledge on the protein interaction space or interactome of the yeast. Cumulative connection of these binary interactions generates a single huge network linking the vast majority of the proteins. Bioinformatics-aided selection of biologically relevant interactions highlights various intriguing subnetworks. They include, for instance, the one that had successfully foreseen the involvement of a novel protein in spindle pole body function as well as the one that may uncover a hitherto unidentified multiprotein complex potentially participating in the process of vesicular transport. Our data would thus significantly expand and improve the protein interaction map for the exploration of genome functions that eventually leads to thorough understanding of the cell as a molecular system.

Fungal Proteins↗
PubMed2001

Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12.

Escherichia coli O157:H7 is a major food-borne infectious pathogen that causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Here we report the complete chromosome sequence of an O157:H7 strain isolated from the Sakai outbreak, and the results of genomic comparison with a benign laboratory strain, K-12 MG1655. The chromosome is 5.5 Mb in size, 859 Kb larger than that of K-12. We identified a 4.1-Mb sequence highly conserved between the two strains, which may represent the fundamental backbone of the E. coli chromosome. The remaining 1.4-Mb sequence comprises of O157:H7-specific sequences, most of which are horizontally transferred foreign DNAs. The predominant roles of bacteriophages in the emergence of O157:H7 is evident by the presence of 24 prophages and prophage-like elements that occupy more than half of the O157:H7-specific sequences. The O157:H7 chromosome encodes 1632 proteins and 20 tRNAs that are not present in K-12. Among these, at least 131 proteins are assumed to have virulence-related functions. Genome-wide codon usage analysis suggested that the O157:H7-specific tRNAs are involved in the efficient expression of the strain-specific genes. A complete set of the genes specific to O157:H7 presented here sheds new insight into the pathogenicity and the physiology of O157:H7, and will open a way to fully understand the molecular mechanisms underlying the O157:H7 infection.

Bacterial Proteins↗
PubMed2001

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗
PubMed2001

CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of Rap1.

CD98 is a multifunctional heterodimeric membrane protein involved in the regulation of cell adhesion as well as amino acid transport. We show that CD98 cross-linking persistently activates Rap1 GTPase in a LFA-1-dependent manner and induces LFA-1/ICAM-1-mediated cell adhesion in lymphocytes. Specific phosphatidylinositol-3-kinase (PI3K) inhibitors suppressed both LFA-1 activation and Rap1GTP generation, and abrogation of Rap1GTP by retroviral over-expression of a specific Rap1 GTPase activating protein, SPA-1, totally inhibited the LFA-1/ICAM-1-mediated cell adhesion. These results suggest that CD98 cross-linking activates LFA-1 via the PI3K signaling pathway and induces accumulation of Rap1GTP in a LFA-1-dependent manner, which in turn mediates the cytoskeleton-dependent cell adhesion process.

Androstadienes↗
PubMed2001

A novel superoxide-producing NAD(P)H oxidase in kidney.

During phagocytosis, gp91(phox), the catalytic subunit of the phagocyte NADPH oxidase, becomes activated to produce superoxide, a precursor of microbicidal oxidants. Currently increasing evidence suggests that nonphagocytic cells contain similar superoxide-producing oxidases, which are proposed to play crucial roles in various events such as cell proliferation and oxygen sensing for erythropoiesis. Here we describe the cloning of human cDNA that encodes a novel NAD(P)H oxidase, designated NOX4. The NOX4 protein of 578 amino acids exhibits 39% identity to gp91(phox) with special conservation in membrane-spanning regions and binding sites for heme, FAD, and NAD(P)H, indicative of its function as a superoxide-producing NAD(P)H oxidase. The membrane fraction of kidney-derived human embryonic kidney (HEK) 293 cells, expressing NOX4, exhibits NADH- and NADPH-dependent superoxide-producing activities, both of which are inhibited by diphenylene iodonium, an agent known to block oxygen sensing, and decreased in cells expressing antisense NOX4 mRNA. The human NOX4 gene, comprising 18 exons, is located on chromosome 11q14.2-q21, and its expression is almost exclusively restricted to adult and fetal kidneys. In human renal cortex, high amounts of the NOX4 protein are present in distal tubular cells, which reside near erythropoietin-producing cells. In addition, overexpression of NOX4 in cultured cells leads to increased superoxide production and decreased rate of growth. The present findings thus suggest that the novel NAD(P)H oxidase NOX4 may serve as an oxygen sensor and/or a regulator of cell growth in kidney.

Adult↗
PubMed2001

Architecture and anatomy of the genomic locus encoding the human leukemia-associated transcription factor RUNX1/AML1.

The RUNX1 gene on human chromosome 21q22.12 belongs to the 'runt domain' gene family of transcription factors (also known as AML/CBFA/PEBP2alpha). RUNX1 is a key regulator of hematopoiesis and a frequent target of leukemia associated chromosomal translocations. Here we present a detailed analysis of the RUNX1 locus based on its complete genomic sequence. RUNX1 spans 260 kb and its expression is regulated through two distinct promoter regions, that are 160 kb apart. A very large CpG island complex marks the proximal promoter (promoter-2), and an additional CpG island is located at the 3' end of the gene. Hitherto, 12 different alternatively spliced RUNX1 cDNAs have been identified. Genomic sequence analysis of intron/exon boundaries of these cDNAs has shown that all consist of properly spliced authentic coding regions. This indicates that the large repertoire of RUNX1 proteins, ranging in size between 20-52 kDa, are generated through usage of alternatively spliced exons some of which contain in frame stop codons. The gene's introns are largely depleted of repetitive sequences, especially of the LINE1 family. The RUNX1 locus marks the transition from a ~1 Mb of gene-poor region containing only pseudogenes, to a gene-rich region containing several functional genes. A search for RUNX1 sequences that may be involved in the high frequency of chromosomal translocations revealed that a 555 bp long segment originating in chromosome 11 FLI1 gene was transposed into RUNX1 intron 4.1. This intron harbors the t(8;21) and t(3;21) chromosomal breakpoints involved in acute myeloid leukemia. Interestingly, the FLI1 homologous sequence contains a breakpoint of the t(11;22) translocation associated with Ewing's tumors, and may have a similar function in RUNX1.

3' Untranslated Regions↗
PubMed2001

Inhibitory effects of Korean plants on HIV-1 activities.

In the search for novel anti-human immunodeficiency virus type 1 (anti-HIV-1) agents from natural sources, 49 MeOH extracts of Korean plants were screened for their inhibitory effects against RNA-dependent DNA polymerase (RT) and ribonuclease H (RNase H) activities of HIV-1 reverse transcriptase and HIV-1 protease, and anti-HIV-1 activity. Regarding the HIV-1 reverse transcriptase, Agrimonia pilosa (whole plant), Cornus kousa (stem and leaf), Limonium tetragonum (root) and Mallotus japonicus (stem) showed significant inhibitory activity on RT activity with 50% inhibitory activity (IC(50)) of 8.9, 6.3, 7.5 and 11.9 microg/mL, respectively, whereas Agrimonia pilosa was also active against RNase H activity (IC(50) = 98.4 microg/mL). Four plants, namely Agrimonia pilosa (whole plant), Atractylodes japonica (root), Clematis heracleifolia (whole plant) and Syneilesis palmata (whole plant), were appreciably active (<35%) against recombinant HIV-1 protease at a concentration of 100 microg/mL. Crinum asiaticum var. japonicum (root) showed significant anti-HIV-1 activity (ED(50) = 12.5 microg/mL) with a favourable SI value of 16.

Anti-HIV Agents↗
PubMed2001

In vivo antiviral activity of Stephania cepharantha against herpes simplex virus type-1.

The antiviral activity of a MeOH extract of Stephania cepharantha (root tubers), its CHCl3-soluble fraction (alkaloid fraction) and the major alkaloid FK-3000 (1) were investigated in BALB/c mice cutaneously infected with HSV-1 strain 7401H. At doses of 125 and 250 mg/kg body weight, p.o., the MeOH extract significantly delayed skin lesion on score 2 (vesicles in the local region), limited the development of further lesions on score 6 (mild zosteriform lesion) and prolonged the mean survival time of HSV-1 infected mice. After p.o. administration of the CHCl3-soluble fraction at doses of 25 and 50 mg/kg or FK-3000 (1) at 10 and 25 mg/kg, similar results were obtained. Although the alkaloid improved the survival of infected mice, it had a narrow therapeutic index.

Alkaloids↗
PubMed2001

Relaxation behavior of laser-polarized (129)Xe gas: size dependency and wall effect of the T(1) relaxation time in glass and gelatin bulbs.

Size dependency of the relaxation time T(1) was measured for laser-polarized (129)Xe gas encapsulated in different sized cavities made by glass bulbs or gelatin capsules. The use of laser-polarized gas enhances the sensitivity a great deal, making it possible to measure the longer (129)Xe relaxation time in quite a short time. The size dependency is analyzed on the basis of the kinetic theory of gases and a relationship is derived in which the relaxation rate is connected with the square inverse of the diameter of the cavity. Such an analysis provides a novel parameter which denotes the wall effect on the relaxation rate when a gas molecule collides with the surface once in a second. The relaxation time of (129)Xe gas is also dependent on the material which forms the cavity. This dependency is large and the relaxation study using polarized (129)Xe gas is expected to offer important information about the state of the matter of the cavity wall.

Journal Article↗
PubMed2001

Molecular cloning and characterization of a gene expressed in mouse developing tongue, mDscr5 gene, a homolog of human DSCR5 (Down syndrome Critical Region gene 5).

For understanding the pathogenesis of Down syndrome (DS), it is important to identify and characterize the genes on Chromosome (Chr) 21, especially those in the Down syndrome critical region (DSCR) on Chr 21q22.2. Recently we have determined 33.5 Mb (more than 99%) of DNA sequence of Chr 21 and, from these sequence data, we identified a novel gene, DSCR5 (transcript = 0.8 kb), from DSCR by combination of computational gene prediction and cDNA screening. For functional analysis of DSCR5, we identified a mouse homolog of the DSCR5 cDNA, and termed it mDscr5 (transcript length = 0.8 kb). The gene was mapped to mouse Chr 16 C3-C4, the syntenic region of human Chr 21, and encodes an amino acid of 132 residues with 90% identity to DSCR5. In situ hybridization showed that mDscr5 is predominantly expressed in the developing tongue. To our best knowledge, no other gene in DSCR is reported to be expressed in tongue, so that DSCR5 may be the first candidate to elucidate the pathophysiology of tongue malformation observed in DS.

Amino Acid Sequence↗
PubMed2001

Primary lung cancer occurring concomitantly with the cicatrized and calcified ova of a parasite: report of a case.

We report herein a rare case of primary lung cancer that occurred concomitantly with the calcified ova of a parasite. A 58-year-old man was referred to our department after a pulmonary abnormal shadow had been seen on a chest X-ray done at mass screening. A transbronchial lung biopsy (TBLB) revealed the calcified ova of a parasite. Because the possibility of concomitant lung cancer could not be ruled out, a lung biopsy was taken via video-assisted thoracic surgery (VATS). The pathological diagnosis was squamous cell carcinoma, and a left upper lobectomy was serially performed through a posterolateral thoracotomy. The patient recovered uneventfully and has remained in good health without any sign of recurrence for over 9 months. Following this case report, we review three other cases of this unusual disease combination documented in the literature.

Calcinosis↗
PubMed2001

The genomic structure and expression of MJD, the Machado-Joseph disease gene.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder that is clinically characterized by cerebellar ataxia and various associated symptoms. The disease is caused by an unstable expansion of the CAG repeat in the MJD gene. This gene is mapped to chromosome 14q32.1. To determine its genomic structure, we constructed a contig composed of six cosmid clones and eight bacterial artificial chromosome (BAC) clones. It spans approximately 300kb and includes MJD. We also determined the complete sequence (175,330bp) of B445M7, a human BAC clone that contains MJD. The MJD gene was found to span 48,240bp and to contain 11 exons. Northern blot analysis showed that MJD mRNA is ubiquitously expressed in human tissues, and in at least four different sizes; namely, 1.4, 1.8, 4.5, and 7.5kb. These different mRNA species probably result from differential splicing and polyadenylation, as shown by sequences of the 21 independent cDNA clones isolated after the screening of four human cDNA libraries prepared from whole brain, caudate, retina, and testis. The sequences of these latter clones relative to the MJD gene in B445M7 indicate that there are three alternative splicing sites and eight polyadenylation signals in MJD that are used to generate the differently sized transcripts.

Alternative Splicing↗
PubMed2001

Five saponins from the root bark of Aralia elata.

Five saponins, 3-O-[beta-D-glucopyranosyl (1-->2)-[beta-D-glucopyranosyl (1-->3)]-beta-D-glucopyranosyl]-oleanolic acid 28-O-beta-D-glucopyranosyl ester (aralia-saponin V), 3-O-[beta-D-glucopyranosyl (1-->2)-[beta-D-glucopyranosyl (1-->3)]-beta-D-glucopyranosyl]-echinocystic acid 28-O-beta-D-glucopyranosyl ester (aralia-saponin VI), 3-O-beta-D-glucopyranosyl (1-->2)-[beta-D-glucopyranosyl (1-->3)]-beta-D-glucopyranosyl]-hederagenin 28-O-beta-D-glucopyranosyl ester (aralia-saponin VII), 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->3)-[beta-D-glucopyranosyl-(1-->2)]-beta-D-glucopyranosyl]-caulophyllogenin 28-O-beta-D-glucopyranosyl ester (aralia-saponin VIII), 3-O-[beta-D-glucopyranosyl (1-->2)-[beta-D-glucopyranosyl(1-->3)]-alpha-L-arabinopyranosyl]-hederagenin 28-O-beta-D-glucopyranosyl ester (aralia-saponin IX), were isolated from the root bark of Aralia elata (Miq.) Seem., together with four known compounds. Their structures were determined on the basis of chemical and spectroscopic methods.

Magnoliopsida↗
PubMed2001

Reduced immunogenicity of beta-lactoglobulin by conjugation with carboxymethyl dextran differing in molecular weight.

To reduce the immunogenicity of beta-lactoglobulin (beta-LG), two beta-LG-carboxymethyl dextran (CMD) conjugates (Conj. 40 and Conj. 162) were prepared by using water-soluble carbodiimide (EDC). The molar ratios of beta-LG to CMD in Conj. 40 and Conj. 162 were 8:1 and 7:1, respectively. Each conjugate maintained approximately 50% of the retinol binding activity of beta-LG. Structural analyses by intrinsic fluorescence, CD spectra, and ELISA with monoclonal antibodies indicated that the surface of beta-LG in each conjugate was covered by CMD without great disruption of native conformation. By conjugation with CMD, the antibody response to beta-LG was reduced in BALB/c, C3H/He, and C57BL/6 mice, which was eminent in Conj. 162. The results of B cell epitope scanning using overlapping synthesized peptides showed that the linear epitope profiles of the conjugates were similar to those of beta-LG, whereas the antibody response to each epitope was reduced, which was eminent in Conj. 162. It was concluded that conjugation with CMD of higher molecular weight is effective in reducing the immunogenicity of beta-LG and that masking of epitopes by CMD is responsible for the reduced immunogenicity.

Animals↗
PubMed2001

Inherited factor H dysfunction and complement-associated glomerulonephritis in renal grafts of first and second transplantations.

A 38-yr-old man with factor H dysfunction and unknown glomerular disease received first and second renal transplantations (Tx) from living-related donors. His examination showed a low percentage activity of factor H (31%). Factor H dysfunction has been known to be associated with type II or III membranoproliferative glomerulonephritis (MPGN), haemolytic uraemic syndrome and IgA GN. The first graft from his mother showed diffuse mesangial deposit of IgA. His son has had IgA GN and his data also revealed a low percentage activity of factor H (33%). He and his son both showed a low activity of C3. Moreover, his father, who was the donor of the second Tx, had a low percentage activity of factor H (25%), and presented with mild glomerular deposit of C3 at operation, while he has been healthy through his entire 67 yr of life. Each of them had a low percentage activity of factor H. These findings through three generations suggested the inheritance of factor H dysfunction. The patient presented with proteinuria 3 months after the first Tx. At the first biopsy 30 months after the first Tx, light microscopy revealed minor glomerular abnormalities with electron dense deposits in subepithelial, intramembranous and mesangial regions, while immunofluorescence showed massive glomerular deposits of C3. In the second biopsy 51 months after the first Tx, the glomerulonephritis developed mesangial proliferation and crescent formation, accompanied by more massive C3 deposit and intramembranous, mesangial and subepithelial dense deposits. He then required redialysis. At the second and third biopsies within 2 months after the second Tx, the renal graft showed similar findings to the first biopsy after the first Tx. He perhaps presented with a recurrence of complement-associated GN, showing an atypical form of MPGN after Tx. These findings suggest that factor H dysfunction may play an important role of a certain pathogenesis of GN.

Adult↗