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Biomedical subjects

I Uchiyama

Publications and source records attributed to I Uchiyama.

At least 19 recordsLinked 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

The flip side of perception-action coupling: locomotor experience and the ontogeny of visual-postural coupling.

The possible role of motor development on psychological function is once again a topic of great theoretical and practical importance. The revival of this issue has stemmed from a different approach to the topic, away from Gesell's interest in the long-term prediction of psychological functions from early motoric assessments, toward an attempt to understand how the acquisition of motor skills orchestrates psychological changes. This paper describes how the acquisition of one motor skill, prone locomotion, has been linked to developmental changes in an infant's ability to regulate posture based on information available in patterns of optic flow. It is argued that the onset of prone locomotion presses the infant to differentiate spatially delimited regions of optic flow to effectively and efficiently control the important subtasks nested within the larger task of locomotion, namely, steering, attending to the surface of support, and maintaining postural control. Following this argument, a research program is described that aims to determine if locomotor experience is causally linked to improvements in the ability to functionalize peripheral optic flow for postural control or whether locomotor experience is merely a maturational forecaster of such improvements. Finally, a hypothesis is put forward that links the emergence of wariness of heights to infants' ability to regulate posture on the basis of peripheral optic flow. The paper's overarching theoretical point is the principle of probabilistic epigenesis, which states that one developmental acquisition produces experiences that bring about a host of new developmental changes in the same and different domains.

Humans↗
PubMed2000

Diversity of restriction-modification gene homologues in Helicobacter pylori.

The complete genome sequences of two Helicobacter pylori strains have recently become available. We have searched them for homologues of restriction-modification genes. One strain (26695) carried 52 such homologues, and the other (J99) carried 53. Their sequence alignments were arranged in the form of a phylogenetic tree and compared with the tree based on rRNA. The trees showed that the homologues are scattered among diverse groups of bacteria. They also revealed high polymorphism within the species--there are 42 pairs with high homology, 10 specific to 26695, and 11 specific to J99. Many of the restriction-modification homologues were characterized by a GC content lower than that of the average gene in the genome. Some of the restriction-modification homologues showed a different codon use bias from the average genes. These observations are interpreted in terms of horizontal transfer of the restriction-modification genes.

Base Composition↗
PubMed2000

Insertion with long target duplication: a mechanism for gene mobility suggested from comparison of two related bacterial genomes.

The complete genome sequences of two closely related organisms--two Helicobacter pylori strains--have recently become available. Comparison of these genomes at single base pair level has suggested the presence of a mechanism for bacterial gene mobility--insertion with long target duplications. This mechanism is formally similar to classical transposon insertion, but the duplication is much longer, often in the range of 100bp. Restriction and/or modification enzyme genes are often within or adjacent to the insertion. A similar process may have mediated insertion of the cag(+) pathogenicity island in H. pylori. A similar structure was identified in comparisons between Neisseria meningitidis and Neisseria gonorrhoeae genomes. We hypothesize that this mechanism, as well as two other types of polymorphism linked with restriction-modification genes (insertion accompanied by target deletion and a tripartite structure composed of substitution/inversion/deletion), have resulted from attack by restriction enzymes on the chromosome.

Base Sequence↗
PubMed2000

Comparison between Pyrococcus horikoshii and Pyrococcus abyssi genome sequences reveals linkage of restriction-modification genes with large genome polymorphisms.

Recent work suggests that restriction-modification gene complexes are mobile genetic elements that insert themselves into the genome and cause various genome rearrangements. In the present work, the complete genome sequences of Pyrococcus horikoshii and Pyrococcus abyssi, two species in a genus of hyperthermophilic archaeon (archaebacterium), were compared to detect large genome polymorphisms linked with restriction-modification gene homologs. Sequence alignments, GC content analysis, and codon usage analysis demonstrated the diversity of these homologs and revealed a possible case of relatively recent acquisition (horizontal transfer). In two cases out of the six large polymorphisms identified, there was insertion of a DNA segment with a modification gene homolog, accompanied by target deletion (simple substitution). In two other cases, homologous DNA segments carrying a modification gene homolog were present at different locations in the two genomes (transposition). In both cases, substitution (insertion/deletion) in one of the two loci was accompanied by inversion of adjacent chromosomal segment. In the fifth case, substitution by a DNA segment carrying type I restriction, modification, and specificity gene homologs was likewise accompanied by adjacent inversion. In the last case, two homologous DNA segments, were found at different loci in the two genomes (transposition), but only one of them had insertion of a modification homolog and an unknown ORF. The possible relationship of these polymorphisms to attack by restriction enzymes on the chromosome will be discussed.

Chromosome Inversion↗
PubMed2000

The role of p16-cyclin d/CDK-pRb pathway in the tumorigenesis of endometrioid-type endometrial carcinoma.

We analysed p16 gene alteration and p16, cyclin-dependent kinase 4 (CDK4), CDK6, cyclin D1, cyclin D2, cyclin D3 and retinoblastoma protein (pRb) expression in ten normal endometriums (PE), 18 endometrial hyperplasias (EH) and 35 endometrial cancers (EC). Two of ten PE (20%), nine of 18 EH (50.0%) and 29 of 35 EC (82.9%) exhibited p16 nuclear staining. p16 expression was significantly higher in EC than EH (P = 0.0119). In the six p16 (-) EC, one was considered to have reduced gene dosage consistent with possible homozygous deletion of the CDKN2 gene and three had methylation in 5'CpG island in the promoter region of the p16 gene, whereas none showed such reduced gene dosage and four had methylation in the nine p16 (-) EH. Strong CDK4 staining was observed in 12 of 35 EC (34.3%) and one of 18 EH (5.6%). The strong expression of CDK4 was higher in EC than in EH (P = 0.0399). The expression of CDK4 was higher in EH than PE (P = 0.0054). The abnormalities of p16-cyclin D/CDK-pRb pathway were detected in 18 of 35 EC (51.4%). In conclusion, the expression of p16 and CDK4 may be an early event in the neoplastic transformation of endometrial cancer.

Base Sequence↗
PubMed2000

Relations of empathy and social responsibility to guilt feelings among undergraduate students.

Empathy and social responsibility as related to guilt feelings were investigated among undergraduate students. Subjects (337 men and 353 women) were assessed for guilt feelings, empathy, and social responsibility. The Guilt Inventory was used to assess guilt feelings. Analysis indicated that scores on the two empathy subscales, Fantasy and Personal Distress, were related to rated Trait Guilt and State Guilt, whereas Social Responsibility scores were associated with those on Moral Stan dards of the Guilt Inventory.

Adolescent↗
PubMed1999

Significant differences in the frequency of transcriptional units, types and numbers of repetitive elements, GC content, and the number of CpG islands between a 1010-kb G-band genomic segment on chromosome 9q31.3 and a 1200-kb R-band genomic segment on chromosome 3p21.3.

We determined the nucleotide sequence of the entire 1,010,525-bp insert contained in CEPH YAC clone 867e8. This human genomic segment was derived from chromosome 9q31.3 and corresponds to a G-band region. We compared this segment, in terms of structure, with a previously characterized 1,201,033-bp sequence in CEPH YAC936c1 that had come from a portion of human chromosome 3p21.3 corresponding to an R-band region. The two segments were significantly different with respect to the frequency of transcriptional units, the types and numbers of repetitive elements present, their GC content, and the number of CpG islands. Alu elements, GC content, and CpG islands all showed positive correlations with the abundance of exons, but the distribution of LINE1s did not. These observations might reflect an influence of the first three of these features on the functions or expression of genes in the respective regions. In addition to a novel gene (F36) lying at the centromeric end of the 9q segment, we found a cluster of placenta-specific genes within a small section (about 400 kb) on the telomeric side of YAC867e8. This cluster consisted of four apparently unrelated ESTs and two genes, pregnancy-associated plasma protein-A (PAPP-A) and a novel gene (tentatively named EST-YD1). Our characterization of the two chromosomal regions provided evidence that genes are not evenly distributed throughout the human genome, and that gene richness is correlated with the GC content and with the frequency of either Alu elements or CpG islands.

Alu Elements↗
PubMed1999

Characterization of a 1200-kb genomic segment of chromosome 3p22-p21.3.

We previously determined the nucleotide sequence and characterized the 685-kb proximal half of CEPH YAC936c1, which corresponds to a portion of human chromosome 3p21.3. In the study reported here, we characterized the remaining 515-kb of this YAC clone corresponding to the telomeric half of its human insert. The newly sequenced region contained a total of ten genes including six reported previously: phospholipase C delta 1 (PLCD1), human activin receptor type IIB (hActR-IIB), organic cation transporter-like 1 (OCTL1), organic cation transporter-like 2 (OCTL2), oxidative stress response 1 (OSR1), and human xylulokinase-like protein (XYLB). The remaining four genes present in the telomeric region included two known genes, MyD88 and ACAA, and two novel genes. One (designated ENGL) of the novel sequences was found to encode an amino-acid sequence homologous to the family of DNA/RNA endonucleases, especially endonuclease G. The other gene F56 revealed no significant homology to any known genes. These results disclosed complete physical and transcriptional maps of the 1200-kb region of 3p present in YAC 936c1.

Amino Acid Sequence↗
PubMed1999

Shaping the genome--restriction-modification systems as mobile genetic elements.

A restriction enzyme gene is often linked to a modification methylase gene the role of which is to protect a recognition site on DNA from breakage by the former. Loss of some restriction-modification gene complexes leads to cell death through restriction breakage in the genome. Their behavior as genomic parasites/symbionts may explain the distribution of restriction sites and clarify certain aspects of bacterial recombination repair and mutagenesis. A comparison of bacterial genomes supports the hypothesis that restriction-modification gene complexes are mobile elements involved in various genome rearrangements and evolution.

Bacteria↗
PubMed1998

DBGET/LinkDB: an integrated database retrieval system.

The integrated database retrieval system DBGET/LinkDB is the backbone of the Japanese GenomeNet service. DBGET is used to search and extract entries from a wide range of molecular biology databases, while LinkDB is used to search and compute links between entries in different databases. DBGET/LinkDB is designed to be a network distributed database system with an open architecture, which is suitable for incorporating local databases or establishing a specialized server environment. It also has an advantage of simple architecture allowing rapid daily updates of all the major databases. The WWW version of DBGET/LinkDB at GenomeNet is integrated with other search tools, such as BLAST, FASTA and MOTIF, and with local helper applications, such as RasMol. In addition to factual links between database entries, LinkDB is being extended to included similarity links and biological links toward computerization of logical reasoning processes.

Databases, Factual↗
PubMed1998

[E coli genomes].

Explore the source record for details and available documents.

Base Sequence↗
PubMed1997

Age-related changes in ventilatory and heart rate responses to acute ozone exposure in the conscious rat.

To evaluate the effect of age on toxicant-induced pulmonary and extrapulmonary changes, we examined the effect of inhalation exposure to oxone (O3) on the ventilatory and heart rate (HR) responses in 4-6 and 20-22-month-old male rats. The rats, chronically implanted with an electrocardiographic (ECG) electrodes, were placed in a head-out plethysmograph for continuous ventilatory measurements of tidal volume and breathing frequency. Simultaneous measurements of HR were also obtained. A 6-hr exposure of each rat to filtered air was followed 2 days later by a 5-hr exposure to 0.1 ppm O3, 5 days later by a 5-hr exposure to 0.3 ppm O3 and 10 days later by a 5-hr exposure to 0.5 ppm O3. Each of the O3 exposures was preceded by a 1-hr exposure to filtered air. Transient rapid shallow breathing with slightly increased HR appeared 1-2 min after the start of O3 exposure. It was suggested on the basis of the electroencephalographic (EEG) activity of the olfactory bulb that this transient response was mediated through olfactory sensation. Persistent rapid shallow breathing with a progressive decrease in HR occurred with a latent period of 1-2 hr. The last 90-min averaged values for relative minute ventilation tended to decrease with the increase in the level of exposure to O3 and these values for young rats were significantly lower than those for old rats. An exposure of young rats to 0.1 ppm O3 for shorter than 5 hr significantly decreased the tidal volume and HR and increased breathing frequency, but no significant changes were observed in old rats. There were no differences between young and old rats in non-observable-adverse-effect-levels (NOAELs) for the O3-induced persistent ventilatory and HR responses, when the NOAELs were determined by exposure to 0.3 and 0.5 ppm O3. The present results, as well as the reported decrease in body temperature and blood pressure, suggested that the age-related changes in patterns and magnitude of the persistent rapid shallow breathing with a progressive decrease in HR are mediated through some age-related defense mechanism acting against O3 inhalation. The validity of the occupational exposure limit for O3 in workplaces was discussed in the light of the present findings.

Aging↗
PubMed1997

Automatic construction of knowledge base from biological papers.

We designed a system that acquires domain specific knowledge from human written biological papers, and we call this system IFBP (Information Finding from Biological Papers). IFBP is divided into three phases, Information Retrieval (IR), Information Extraction (IE) and Dictionary Construction (DC). We propose a query modification method using automatically constructed thesaurus for IR and a statistical keyword prediction method for IE. A dictionary of domain specific terms, which is one of the central knowledge sources for the task of knowledge acquisition, is also constructed automatically in the DC phase. IFBP is currently used for constructing the Transcription Factor DataBase (TFDB) and shows good performance. Since the model of knowledge base construction that is adopted into IFBP is carried out entirely automatically, this system can be easily ported across domains.

Algorithms↗
PubMed1996

Construction of a normalized directionally cloned cDNA library from adult heart and analysis of 3040 clones by partial sequencing.

Large-scale sequencing of clones from cDNA libraries derived from specific tissues is a rapid and efficient way of discovering novel genes expressed in those tissues. However, because the heart is continually contracting and relaxing, it strongly expresses muscle-contractile genes and/or mitochondrial genes, a bias that reduces the efficiency of this method. To improve the efficiency of identifying novel genes expressed in the heart, we constructed a normalized directionally cloned cDNA library from adult heart and partially sequenced 3040 clones. Comparisons of these sequence data with known DNA sequences in the database revealed that 57.1% of the clones matched human genes already known, 23.4% were identical or almost identical to human expressed sequence tags (ESTs), 14.2% bore no significant homology to any sequences in the database, and 1.2% represented repetitive sequences. The remaining 4.1% showed some homology with known genes, and Northern blot analysis of several clones in this category revealed that most of them were expressed mainly in the heart and skeletal muscle. After redundancy was excluded, the 3040 clones accounted for 1395 distinctive ESTs, 446 of which exhibited no match to any known sequence. Our results suggest that our normalized library is less redundant than standard libraries and is a useful resource for cataloging genes expressed in the heart.

Adult↗
PubMed1996

Construction and analysis of a profile library characterizing groups of structurally known proteins.

A new sequence motif library StrProf was constructed characterizing the groups of related proteins in the PDB three-dimensional structure database. For a representative member of each protein family, which was identified by cross-referencing the PDB with the PIR superfamily classification, a group of related sequences was collected by the BLAST search against the nonredundant protein sequence database. For every group, the motifs were identified automatically according to the criteria of conservation and uniqueness of pentapeptide patterns and with a dual dynamic programming algorithm. In the StrProf library, motifs are represented by profile matrices rather than consensus patterns to allow more flexible search capabilities. Another dynamic programming algorithm was then developed to search this motif library. When the computationally derived StrProf was compared with PROSITE, which is a manually derived motif library in the best consensus pattern representation, the numbers of identified patterns were comparable. StrProf missed about one third of the PROSITE motifs, but there were also new motifs lacking in PROSITE. The new library was incorporated in SMART (Sequence Motif Analysis and Retrieval Tool), a computer tool designed to help search and annotate biologically important sites in an unknown protein sequence. The client program is available free of charge through the Internet.

Algorithms↗
PubMed1995

Physiological reaction and manual performance during work in cold storages.

Subjects were 10 workers (Group R) working in two cold storages (air temperature was between -20 degrees C and -23.2 degrees C), and eight workers (Group C) working in a general storehouse (air temperature was between 12 degrees C and 15.2 degrees C). They were all male workers operating forklift-trucks. Average (SE) age for Group R was 41.4(1.3) years and for Group C was 47.3(1.6) years. Hand tremor, handgrip strength, pinch strength, counting task, flicker value, peak flow rate and blood pressure were measured five times (before work, at 10 a.m., before lunch, at 3 p.m. and after work) per day. Blood samples were collected before lunch. Free fatty acid (FFA) of Group R was significantly higher than that of Group C. There were no significant differences in handgrip strength, pinch strength, counting task, flicker value and peak flow rate between Group R and Group C. However, changes in hand tremor and diastolic blood pressure for Group R were significantly greater than those for Group C. Only for Group R, there was a significant relationship between FFA and the hand tremor values measured the second time. Work loads of Group R would be increased by not only the extreme coldness but also large temperature difference between the inside and the outside of the cold storages. The actual forklift work in these cold storages did not cause a distinct reduction in manual performance, but caused an increase in stress which would be expressed as an increase in catecholamine excretion.

Adaptation, Physiological↗