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T Shiina

Publications and source records attributed to T Shiina.

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

Genomic and phylogenetic analysis of the human CD1 and HLA class I multicopy genes.

The human CD1 proteins belong to a lipid-glycolipid antigen-presenting gene family and are related in structure and function to the MHC class I molecules. Previous mapping and DNA hybridization studies have shown that five linked genes located within a cluster on human chromosome 1q22-23 encode the CD1 protein family. We have analyzed the complete genomic sequence of the human CD1 gene cluster and found that the five active genes are distributed over 175,600 nucleotides and separated by four expanded intervening genomic regions (IGRs) ranging in length between 20 and 68 kb. The IGRs are composed mostly of retroelements including five full-length L1 PA sequences and various pseudogenes. Some L1 sequences have acted as receptors for other subtypes or families of retroelements. Alu molecular clocks that have evolved during primate history are found distributed within the HLA class I duplicated segments (duplicons) but not within the duplicons of CD1. Phylogeny of the alpha3 domain of the class I-like superfamily of proteins shows that the CD1 cluster is well separated from HLA class I by a number of superfamily members including MIC (PERB11), HFE, Zn-alpha2-GP, FcRn, and MR1. Phylogenetically, the human CD1 sequences are interspersed by CD1 sequences from other mammalian species, whereas the human HLA class I sequences cluster together and are separated from the other mammalian sequences. Genomic and phylogenetic analyses support the view that the human CD1 gene copies were duplicated prior to the evolution of primates and the bulk of the HLA class I genes found in humans. In contrast to the HLA class I genomic structure, the human CD1 duplicons are smaller in size, they lack Alu clocks, and they are interrupted by IGRs at least 4 to 14 times longer than the CD1 genes themselves. The IGRs seem to have been created as "buffer zones" to protect the CD1 genes from disruption by transposable elements.

Antigens, CD1↗
PubMed2001

The absence of disease-specific polymorphisms within the HLA-B51 gene that is the susceptible locus for Behçet's disease.

Behçet's disease is known to be associated with HLA-B51 in many different populations. Genetic evidence supports that the susceptible gene for Behçet's disease is the HLA-B51 allele at the HLA-B locus. This study was aimed to determine the HLA-B51 nucleotide sequence variation in three Behçet's disease patients and three healthy controls in order to elucidate if any disease specific mutations or polymorphisms may exist in the HLA-B51 gene of patients. Long-range polymerase chain reaction (PCR) was first carried out to give a PCR-amplified product of 9.5 kb which was then used as a template for nested PCR to give a final amplified product of 4.2 kb. This final product containing the 1.3-kb promoter/enhancer region and the entire HLA-B gene except for a 363-bp 3' terminal end segment encoding the 3' untranslated region was subcloned by the BP cloning technique and sequenced. The sequencing results showed that all the patients possessed the HLA-B*51011 allele, and there were no differences in the exonic nucleotide sequences between the three Behçet's disease patients and the three healthy controls. The HLA-B*51011 intronic and promoter/enhancer nucleotide sequences from the three patients had 22 single nucleotide polymorphisms (SNPs), a single insertion of 6 bp and a single deletion of 2 bp. On the other hand, the three healthy controls had 24 SNPs in their intronic and promoter/enhancer regions. However, none of these polymorphisms in the patients were specific for the disease. Therefore, these results clearly demonstrate that the HLA-B exonic sequence that encodes the HLA-B51 allele is the real pathogenic factor in Behçet's disease.

5' Flanking Region↗
PubMed2001

HLA-B*51 allele analysis by the PCR-SBT method and a strong association of HLA-B*5101 with Japanese patients with Behçet's disease.

Behçet's disease (BD) is known to be associated with human leukocyte antigen (HLA) B51 in many different ethnic groups. An increased incidence of HLA-B51 in the patient group has also been reported in a Japanese population. Recently, the B51 antigen has been identified to comprise 21 alleles, B*5101-B*5121. Further, not only HLA-B*5101 but also HLA-B*5108 were found to be relatively increased in the patient groups among Italian and Saudi Arabian populations. Therefore, we performed HLA-B*51 allele genotyping by the polymerase chain reaction-sequencing based typing (PCR-SBT) method in order to investigate whether there is any correlation of one particular B51-associated allele with Japanese BD. Ninety-six Japanese patients with BD and 132 healthy Japanese volunteers were enrolled in this study. As a result, the phenotype frequency of the B51 antigen was confirmed to be remarkably increased in the patient group as compared to the ethnically matched control group (59.4% in patients vs. 13.6% in controls; Pc=0.0000000000098, R.R.=9.3). In the B*51 allele genotyping, 56 out of 57 B51-positive patients were defined as B*5101 and the remaining one was B*5102. In contrast, all of 18 B51-positive normal controls were B*5101. None of the Japanese patients and healthy controls carried the HLA-B*5108 allele. This study revealed that B*51 allelic distribution in Japanese was different from those in Italian and Saudi Arabian populations, and that the significantly high incidence of the HLA-B51 antigen in the Japanese BD patient group was mostly caused by the significant increase of the HLA-B*5101 allele.

Alleles↗
PubMed2001

cDNA cloning and genetic polymorphism of the swine major histocompatibility complex (SLA) class II DMA gene.

cDNA clones corresponding to the swine histocompatibility complex (SLA: swine leucocyte antigen)-DM alpha chain were isolated using the polymerase chain reaction (PCR) products from the third exon in the human HLA-DMA gene as a probe. Amino acid comparative analysis revealed that these clones were more closely related to the bovine and human DMA genes than to the other swine class II genes alpha chain genes, DRA, DQA and DOA. These results suggest that the SLA-DMA gene is expressed and may function, like HLA-DM, as an important modulator in class II restricted antigen processing in swine. Furthermore, based on the sequences and PCR-restriction fragment length polymorphism (PCR-RFLP) patterns in the SLA-DMA gene, no allelic variation was recognized in the second exon, but five allelic variations were recognized in the third exon in five different breeds of swine. These DMA alleles were defined by variation at four nucleotide positions. Two of these alleles resulted in an amino acid substitution. These results suggest that SLA-DMA has little polymorphism as observed in HLA-DMA and mouse H2-Ma.

Alleles↗
PubMed2001

Genomic anatomy of a premier major histocompatibility complex paralogous region on chromosome 1q21-q22.

Human chromosomes 1q21-q25, 6p21.3-22.2, 9q33-q34, and 19p13.1-p13.4 carry clusters of paralogous loci, to date best defined by the flagship 6p MHC region. They have presumably been created by two rounds of large-scale genomic duplications around the time of vertebrate emergence. Phylogenetically, the 1q21-25 region seems most closely related to the 6p21.3 MHC region, as it is only the MHC paralogous region that includes bona fide MHC class I genes, the CD1 and MR1 loci. Here, to clarify the genomic structure of this model MHC paralogous region as well as to gain insight into the evolutionary dynamics of the entire quadriplication process, a detailed analysis of a critical 1.7 megabase (Mb) region was performed. To this end, a composite, deep, YAC, BAC, and PAC contig encompassing all five CD1 genes and linking the centromeric +P5 locus to the telomeric KRTC7 locus was constructed. Within this contig a 1.1-Mb BAC and PAC core segment joining CD1D to FCER1A was fully sequenced and thoroughly analyzed. This led to the mapping of a total of 41 genes (12 expressed genes, 12 possibly expressed genes, and 17 pseudogenes), among which 31 were novel. The latter include 20 olfactory receptor (OR) genes, 9 of which are potentially expressed. Importantly, CD1, SPTA1, OR, and FCERIA belong to multigene families, which have paralogues in the other three regions. Furthermore, it is noteworthy that 12 of the 13 expressed genes in the 1q21-q22 region around the CD1 loci are immunologically relevant. In addition to CD1A-E, these include SPTA1, MNDA, IFI-16, AIM2, BL1A, FY and FCERIA. This functional convergence of structurally unrelated genes is reminiscent of the 6p MHC region, and perhaps represents the emergence of yet another antigen presentation gene cluster, in this case dedicated to lipid/glycolipid antigens rather than antigen-derived peptides.

Antigens, CD1↗
PubMed2001

Genetic variations and polymorphisms of G protein-coupled receptors: functional and therapeutic implications.

G protein-coupled receptors (GPCRs) represent a major class of proteins in the genome of many species, including humans. In addition to the mapping of a number of human disorders to regions of the genome containing GPCRs, a growing body of literature has documented frequently occurring variations (i.e. polymorphisms) in GPCR loci. In this article, we use a domain-based approach to systematically examine examples of genetic variation in the coding and noncoding regions of GPCR loci. Data to date indicate that residues in GPCRs are involved in ligand binding and coupling to G proteins and that regulation can be altered by polymorphisms. Studies of GPCR polymorphisms have also uncovered the functional importance of residues not previously implicated from other approaches that are involved in the function of GPCRs. We predict that studies of GPCR polymorphisms will have a significant impact on medicine and pharmacology, in particular, by providing new means to subclassify patients in terms of both diagnosis and treatment.

Animals↗
PubMed2000

Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors.

The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.

Adenylyl Cyclases↗
PubMed2000

Gene structure and promoter for Crad2 encoding mouse cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase isozyme.

Cis-retinol/androgen dehydrogenase type 2 (CRAD2) has been shown to catalyze the dehydrogenation of retinols, including 9-cis retinol, and also to exhibit 3alpha- and 17beta- hydroxysteroid dehydrogenase activities. To examine the function of this enzyme and regulation of its gene, the Crad2 gene was cloned from a mouse genomic DNA library and characterized. The complete mouse CRAD2-coding region was found in four exons spanning an approximately 5kb region. The nucleotide sequences of the exons encoding 316 amino acids were identical to those of the previously reported mouse Crad2 cDNA. Primer extension analysis and RNase protection assay were used to map the major transcription initiation sites to the positions lying 87 and 89 base pairs upstream of the ATG translation start codon. The region proximal to the initiation sites exhibited the absence of both TATAA and CAAT boxes. This region had hepatocyte nuclear factor binding sites, consistent with its predominant expression in the liver. Computer analysis of an approximately 7.5kb 5'-flanking region also suggested the presence of binding sites for AP-1, SREBP1, HSF2, c-Rel, c-Myc, CREBP, GATA, Ets, E2F, and Oct-1, suggesting that various factors including retinoic acid, cholesterol, various kinds of stress, the cell cycle, and cyclic AMP may regulate the expression of this gene. Fluorescence in-situ hybridization analysis showed that Crad2 is located at the terminus of mouse chromosome 10, an area that corresponds to band 10D3, suggesting that RDH-related SDRs may be located together in the cluster locus. Northern blot hybridization and RT-PCR analysis demonstrated that CRAD2 was expressed not in early embryonic stages, and not in embryonic stem cells, but instead in the gastrointestinal tract during later embryonic development and adult stage. In conclusion, we have presented the first complete structural analysis, including that of the promoter and chromosomal location, of a member of the retinol/androgen dehydrogenase subfamily of the group of the short-chain dehydrogenase/reductase (SDR) isozymes. Our findings will provide the basis for in-vitro or in-vivo studies concerning the regulation of retinol and androgen metabolism and enable determination of the mechanism of diseases related to retinol, retinal, retinoic acid, and androgen.

Alcohol Oxidoreductases↗
PubMed2000

Genetic polymorphisms in the cell growth regulated gene, SC1 telomeric of the HLA-C gene and lack of association of psoriasis vulgaris.

Psoriasis vulgaris is associated with the HLA-Cw6 and Cw7 antigens. We have previously narrowed down the critical region most likely to contain the psoriasis vulgaris gene to 111 kb spanning 89 kb to 200 kb telomeric of the HLA-C locus by microsatellite mapping. This segment includes three known genes (POU5F1, SC1 and S) and four new expressed genes. Among them, SC1 (TCF19) is the cell growth regulated gene possibly with trans-activator activity. Since psoriasis vulgaris is a common skin disorder characterized by hyperproliferation of epidermal cells, it is tempting to speculate that the SCI gene is one of the strong candidate genes responsible for the development of psoriasis vulgaris. Here, we investigated genetic polymorphisms in the SC1 gene by direct DNA sequencing and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) techniques. Three single nucleotide polymorphisms in exon 2, two of which are accompanied by amino-acid substitutions, were identified. Further, one 4-bp deletion polymorphism was detected around the acceptor site of the lariat-shaped structure necessary for RNA splicing in intron 2. No significant difference in the dimorphic or haplotypic distribution at these four polymorphic sites was observed between the patients with psoriasis vulgaris and healthy controls. This suggests that the susceptible gene for psoriasis vulgaris is not the SC1 gene itself, although a unique homozygous haplotype was identified in the patients.

Base Sequence↗
PubMed2000

Chloroplast tubules visualized in transplastomic plants expressing green fluorescent protein.

A fusion between the plastid psbA promoter and the green fluorescent protein gene (gfp) was introduced into the tobacco chloroplast genome by stable plastid transformation. GFP was synthesized actively and exclusively in the chloroplasts. Tubular projections filled with GFP but containing no chlorophyll were visualized for the first time in chloroplasts of these transplastomic plants. Occasionally, the tubules connect chloroplasts with each other, suggesting the possibility of the exchange of endogenous proteins. However, the fusion of protoplasts between the transplastomic and wild-type plants showed that such chloroplast connections might be rare in mesophyll protoplasts.

Chloroplasts↗
PubMed2000

Detection of characteristic waves of sleep EEG by neural network analysis.

In psychiatry, the sleep stage is one of the most important evidence for diagnosing mental disease. However, doctors require much labor and skill for diagnosis, so a quantitative and objective method is required for more accurate diagnosis since it depends on the doctor's experience. For this reason, an automatic diagnosis system must be developed. In this paper, we propose a new type of neural network (NN) model referred to as a sleep electroencephalogram (EEG) recognition neural network (SRNN) which enables us to detect several kinds of important characteristic waves in sleep EEG which are necessary for diagnosing sleep stages. Experimental results indicate that the proposed NN model was much more capable than other conventional methods for detecting characteristic waves.

Adult↗
PubMed2000

[Assessment of the new TNM classification for resected lung cancer].

To evaluate the revised TNM classification, we investigated the prognoses of 552 consecutive patients who had resection of non-small-cell lung cancer between April 1982 and March 1996. According to the new classification, the 5-year survival rate was 76.9% for stage I A, 57.2% for stage I B (I A versus I B, p < 0.0005), 47.7% for stage IIA, 49.8% for stage IIB, 18.6% for stage IIIA (IIB versus IIIA, p = 0.005), 16.7% for stage IIIB, and 7.9% for stage IV (IIIB versus IV, p = 0.02). Especially for patients in stage I A, there was significant difference in survival between patients with the tumor size within 1.5 cm and those with larger than 1.5 cm. The survival rate for T3N0M0 patients was significantly better than that for T3N1-2M0, but there was no significant difference between patients with T3N0M0 disease and those with T2N1M0 disease. Concerning the pm1 patients, the survival rate was significantly better than other stage IIIB patients. Our results supported the revision for dividing stage I and putting T3N0M0 into stage IIB. However, the classification is controversial about dividing stage II and putting pm1 as T4 disease. Furthermore, subgrouping of T1N0M0 disease by tumor size, T3 by tumor invaded organ will be necessary in the next revisions.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region.

The intensely studied MHC has become the paradigm for understanding the architectural evolution of vertebrate multigene families. The 4-Mb human MHC (also known as the HLA complex) encodes genes critically involved in the immune response, graft rejection, and disease susceptibility. Here we report the continuous 1,796,938-bp genomic sequence of the HLA class I region, linking genes between MICB and HLA-F. A total of 127 genes or potentially coding sequences were recognized within the analyzed sequence, establishing a high gene density of one per every 14.1 kb. The identification of 758 microsatellite provides tools for high-resolution mapping of HLA class I-associated disease genes. Most importantly, we establish that the repeated duplication and subsequent diversification of a minimal building block, MIC-HCGIX-3.8-1-P5-HCGIV-HLA class I-HCGII, engendered the present-day MHC. That the currently nonessential HLA-F and MICE genes have acted as progenitors to today's immune-competent HLA-ABC and MICA/B genes provides experimental evidence for evolution by "birth and death," which has general relevance to our understanding of the evolutionary forces driving vertebrate multigene families.

Base Pairing↗
PubMed1999

Alpha1,3-fucosyltransferase IX (Fuc-TIX) is very highly conserved between human and mouse; molecular cloning, characterization and tissue distribution of human Fuc-TIX.

The amino acid sequence of Fuc-TIX is very highly conserved between mouse and human. The number of non-synonymous nucleotide substitutions of the Fuc-TIX gene between human and mouse was strikingly low, and almost equivalent to that of the alpha-actin gene. This indicates that Fuc-TIX is under a strong selective pressure of preservation during evolution. The human Fuc-TIX (hFuc-TIX) showed a unique characteristics, i.e. hFuc-TIX was not activated by Mn2+ and Co2+, whereas hFuc-TIV and hFuc-TVI were activated by the cations. The hFuc-TIX transcripts were abundantly expressed in brain and stomach, and interestingly were detected in spleen and peripheral blood leukocytes.

Amino Acid Sequence↗
PubMed1999

Circadian-regulated expression of a nuclear-encoded plastid sigma factor gene (sigA) in wheat seedlings.

The activity of a light-responsive psbD promoter in plastids is known to be regulated by a circadian clock. However, the mechanism of the circadian regulation of the psbD light-responsive promotor, which is recognized by an Escherichia coli-type RNA polymerase, is not yet known. We examined the time course of mRNA accumulation of two E. coli-type RNA polymerase subunit genes, sigA and rpoA, under a continuous light condition after 12 h light/12 h dark entrainment. Accumulation of the sigA mRNA was found to be regulated by a circadian clock, while rpoA mRNA did not show any significant oscillation throughout the experiment.

Amino Acid Sequence↗
PubMed1999

Gene organization of the quail major histocompatibility complex (MhcCoja) class I gene region.

Class I genomic clones of the quail (Coturnix japonica) major histocompatibility complex (MhcCoja) were isolated and characterized. Two clusters spanning the 90.8 kilobase (kb) and 78.2 kb class I gene regions were defined by overlapping cosmid clones and found to contain at least twelve class I loci. However, unlike in the chicken Mhc, no evidence for the existence of any Coja class II gene was obtained in these two clusters. Based on comparative analysis of the genomic sequences with those of the cDNA clones, Coja-A, Coja-B, Coja-C, and Coja-D (Shiina et al. 1999), these twelve loci were assigned to represent one Coja-A gene, two Coja-B genes (Coja-B1 and -B2), four Coja-C genes (Coja-C1-C4), four Coja-D genes (Coja-D1-D4), and one new Coja-E gene. A class I gene-rich segment of 24.6 kb in which five of these genes (Coja-B1, -B2, -D1, -D2 and -E) are densely packed were sequenced by the shotgun strategy. All of these five class I genes are very compact in size [2089 base pairs (bp)-2732 bp] and contain no apparent genetic defect for functional expression. A transporter associated with the antigen processing (TAP) gene was identified in this class I gene-rich segment. These results suggest that the quail class I region is physically separated from the class II region and characterized by a large number of the expressible class I loci (at least seven) in contrast to the chicken Mhc, where the class I and class II regions are not clearly differentiated and only at most three expressed class I loci so far have been recognized.

ATP-Binding Cassette Transporters↗