Multiple class I loci expressed by the quail Mhc.
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Amino Acid Sequence↗
Biomedical subjects
T Shiina
Publications and source records attributed to T Shiina.
Isolation and characterization of a pig major histocompatibility complex (SLA) class II DNA cDNA clone.
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Amino Acid Sequence↗
MIC-A polymorphism in Japanese and a MIC-A-MIC-B null haplotype.
A polymorphic gene, MIC-A, is one of the MIC family of genes which is composed of a group of homologous genes interspersed in the class III and class I regions of the major histocompatibility complex. MIC-A is located 46 kilobases (kb) centromeric of HLA-B, and is preferentially expressed in the epithelial cells and intestinal mucosa. Recently, MIC-A and the closely related MIC-B were reported as the molecules that conferred specificity in the recognition by the Vdelta1gammadeltaT cells. In the present study, polymorphic exons 2, 3, and 4 of the MIC-A gene were analyzed using the polymerase chain reaction-single-strand conformation polymorphism method. The number of patterns found in exons 2, 3, and 4 were 5, 6, and 4, respectively, in 114 healthy Japanese subjects. Eight MIC-A alleles were observed in Japanese individuals, among which one, tentatively named MIC-AMW, has not previously been reported. There was a strong linkage disequilibrium between MIC-A and HLA-B loci: each MIC-A allele showed strong association with a particular HLA-B group. In contrast, B*3901 showed association with multiple MIC-A alleles. Furthermore, the existence of a MIC-A-MIC-B null haplotype, which is associated with HLA-B*4801, was identified. In this haplotype, a large-scale deletion (of approximately 100 kb) including the entire MIC-A gene was indicated and the MIC-B gene possessed a stop codon.
Alleles↗
New polymorphic microsatellite markers in the human MHC class I region.
The human major histocompatibility complex (MHC) class I region is believed to contain a large number of genes encoding susceptible factors for diseases such as Behcet's disease, Graves disease and psoriasis vulgaris. To identify the causative genes of those diseases, we have conducted large-scale genomic sequencing and determined the 1.8 Mb entire HLA class I region from the MICB gene to the HLA-F gene. During the course of genomic sequencing, a total of 731 microsatellite sequences with dinucleotide to pentanucleotide repeats were found in this region. Previously, we reported that 26 microsatellites between MICB and S on the most centromeric side of the class I region, and between HSR1 and HLA-92/L in the midst of the class I region were highly polymorphic, and served as excellent genetic markers. In this paper, in order to fill the gaps with no known polymorphic microsatellites available in the HLA class I region, 12 new polymorphic microsatellite markers were recruited from the 1.8 Mb region including the remaining class I segments, namely between S and HSR1, and between HLA-92/L and HLA-F The average number of alleles at these new microsatellite loci was 8.2 with a polymorphism content value (PIC) of 0.63. These 38 markers in total almost uniformly interspersed in the HLA class I region will enable us to search precisely for the location of disease susceptible loci within the HLA class I region by association and for linkage analyses.
DNA↗
Developmental stage-specific multi-subunit plastid RNA polymerases (PEP) in wheat.
Most photosystem I and II plastid genes are transcribed by a plastid encoded Escherichia coli-like RNA polymerase (PEP). In this study, we show that both promoter selectivity and light-dependency of PEP change dramatically during development in wheat leaves. In the leaf tip, psbA and psbD promoter activities are light induced, whilst psbC, psbE and 16S rRNA promoters do not function efficiently irrespective of light conditions. In contrast to the leaf tip, in the basal portion all PEP promoters studied function in the dark as well as the light, except for psbD. Using in vitro transcription, we found that PEP in the illuminated leaf tip can initiate transcription from the -35 destructed psbA promoter, but the -35 element is essential for transcription in the basal portion. There is an extended -10 element in the psbA promoter, recognized by the PEP in the illuminated leaf tip or purified sigma 70-type Escherichia coli RNA polymerase but not by the PEP in the leaf base. These results suggest that during wheat leaf development, PEP in the leaf base that is functional for most PEP promoters even in the dark is replaced by the light-dependent PEP selectively transcribing the psbA and psbD promoters.
Base Sequence↗
The critical region for Behçet disease in the human major histocompatibility complex is reduced to a 46-kb segment centromeric of HLA-B, by association analysis using refined microsatellite mapping.
The HLA-B51 allele is known to be associated with Behçet disease. Recently, we found a higher risk for Behçet disease in the MICA gene, 46 kb centromeric of HLA-B, by investigation of GCT repetitive polymorphism within exon 5 of MICA. The pathogenic gene causing Behçet disease, however, has remained uncertain. Here, eight polymorphic microsatellite markers, distributed over a 900-kb region surrounding the HLA-B locus, were subjected to association analysis for Behçet disease. Statistical studies of associated alleles detected on each microsatellite locus showed that the pathogenic gene for Behçet disease is most likely found within a 46-kb segment between the MICA and HLA-B genes. The results of this mapping study, and the results of an earlier study of ours, suggest that MICA is a strong candidate gene for the development of Behçet disease.
Behcet Syndrome↗
Association analysis using refined microsatellite markers localizes a susceptibility locus for psoriasis vulgaris within a 111 kb segment telomeric to the HLA-C gene.
The HLA-Cw6 antigen has been associated with psoriasis vulgaris despite racial and ethnic differences. However, it remains unclear whether it is the HLA-Cw6 antigen itself or a closely linked, hitherto unidentified, locus that predisposes to the disease. Here, in order to map the susceptibility locus for psoriasis vulgaris precisely within the HLA class I region, 11 polymorphic microsatellite markers distributed throughout a 1060 kb segment surrounding the HLA-C locus were subjected to association analysis in Japanese psoriasis vulgaris patients. Statistical analyses of the distribution and deviation from Hardy-Weinberg equilibrium of the allelic frequency at each micro-satellite locus revealed that the pathogenic gene for psoriasis vulgaris is located within a reduced interval of 111 kb spanning 89-200 kb telomeric of the HLA-C gene. In addition to three known genes, POU5F1, TCF19 and S, this 111 kb fragment contains four new, expressed genes identified in the course of our genomic sequencing of the entire HLA class I region. Therefore, these seven genes are the potential candidates for susceptibility to psoriasis vulgaris.
Adult↗
Genome sequencing analysis of the 1.8 Mb entire human MHC class I region.
The human MHC class I region spans 1.8 Mb from the MICB gene to the HLA-F gene at the telomeric end of the HLA region. There are fewer genes recognized in this region than in the class II or class III region, probably because this region remained uncharacterized for genomic organization. Based on the 1,796,938 bp genomic sequence of the entire class I region determined in our laboratory, the complete gene structure of this region has finally emerged. This region embraces as many as 118 genes (73 known and 45 new genes) with a gene density of one gene every 15.2 kb, which is comparable to that of the gene-rich class III region. The GC content is fairly uniform throughout the class I region, being 45.8% on average, which corresponds to the isochore H1. By investigation of genetic polymorphisms in 26 out of 758 microsatellite repeats identified in the class I region, we could reduce the critical region for Behçet's disease (associated with B51) and psoriasis vulgaris (associated with Cw6) to approximately 50 kb segments, between MICA and HLA-B and between TCF19 and S, respectively. Thus, systematic large-scale genomic sequencing provides an efficient way of identifying genes and of mapping disease-susceptible genes in the genome.
Animals↗
Assignment of the human alpha 1,3-fucosyltransferase IX gene (FUT9) to chromosome band 6q16 by in situ hybridization.
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Chromosome Mapping↗
Species differences in the transport activity for organic anions across the bile canalicular membrane.
Species differences in the transport activity mediated by canalicular multispecific organic anion transporter (cMOAT) were examined using temocaprilat, an angiotensin-converting enzyme inhibitor whose biliary excretion is mediated predominantly by cMOAT, and 2,4-dinitrophenyl-S-glutathione, a typical substrate for cMOAT, in a series of in vivo and in vitro experiments. Temocaprilat was infused to examine the biliary excretion rate at steady-state. The in vivo transport clearance values across the bile canalicular membrane, defined as the biliary excretion rate divided by the hepatic unbound concentrations, were 9.8, 39.2, 9.2, 1.1, and 0.8 ml/min/kg for mouse, rat, guinea pig, rabbit, and dog, respectively. The K(m) and V(max) values for ATP-dependent uptake of 2, 4-dinitrophenyl-S-glutathione into canalicular membrane vesicles were 15.0, 29.6, 16.1, 55.8, and 30.0 microM and 0.38, 1.90, 0.15, 0. 47, and 0.23 nmol/min/mg protein, yielding the in vitro transport clearance across the bile canalicular membrane (V(max)/K(m)) of 25.5, 64.2, 9.4, 8.4, and 7.7 for mouse, rat, guinea pig, rabbit, and dog, respectively. A close in vivo and in vitro correlation was observed among animal species for the transport clearance across the bile canalicular membrane. These results suggest that the uptake experiments with canalicular membrane vesicles can be used to quantitatively predict in vivo excretion across the bile canalicular membrane.
Animals↗
Nucleotide sequencing analysis of the 146-kilobase segment around the IkBL and MICA genes at the centromeric end of the HLA class I region.
To elucidate the complete gene structure and to identify new genes involved in the development of HLA class I antigen-associated diseases in the class I region of the human major histocompatibility complex on chromosome 6, a YAC clone (745D12) covering the 146-kb segment around the IkBL and MICA loci was isolated from a YAC library constructed from the B-cell line, BOLETH. A physical map of this region was constructed by isolation of overlapping cosmid clones derived from 745D12. Of these, five contiguous cosmids were chosen for DNA sequencing by the shotgun strategy to give a single contig of 146,601 bp from 2.8 kb telomeric of the IkBL gene to exon 6 of MICA. This region was confirmed to contain five known genes, IkBL, BAT1, MICB, P5-1, and HLA-X (class I fragment), from centromere to telomere, and their exon-intron organizations were determined. The 3.8-1 homologue gene (3.8-1-hom) showing 99.7% identity with the 3.8-1 cDNA clone, which was originally isolated using the 3.8-kb EcoRI fragment between the HLA-54/H and the HLA-G genes, was detected between MICA and MICB and was suggested to represent the cognate 3.8-1 genomic sequence from which the cDNA clone was derived. No evidence for the presence of expressed new genes could be obtained in this region by homology and EST searches or coding and exon prediction analyses. One TA microsatellite repeat spanning 2545 bases with as many as 913 repetitions was found on the centromeric side of the MICA gene and was indicated to be a potential hot spot for genetic recombination. The two segments of approximately 35 kb upstream of the MICA and MICB genes showed high sequence homology (about 85%) to each other, suggesting that segmental genome duplication including the MICA and MICB genes must have occurred during the evolution of the human MHC.
Carrier Proteins↗
Circadian-regulated transcription of the psbD light-responsive promoter in wheat chloroplasts.
The level of mRNAs derived from the plastid-encoded psbD light-responsive promoter (LRP) is controlled by a circadian clock(s) in wheat (Triticum aestivum). The circadian oscillations in the psbD LRP mRNA level persisted for at least three cycles in continuous light and for one cycle in continuous dark, with maxima in subjective morning and minima in subjective early night. In vitro transcription in chloroplast extracts revealed that the circadian cycles in the psbD LRP mRNA level were dominantly attributed to the circadian-regulated transcription of the psbD LRP. The effects of various mutations introduced into the promoter region on the psbD LRP activity in vitro suggest the existence of two positive elements located between -54 and -36, which generally enhance the transcription activity, and an anomalous core promoter structure lacking the functional "-35" element, which plays a crucial role in the circadian fluctuation and light dependency of psbD LRP transcription activity.
Base Sequence↗
rbcL Transcript levels in tobacco plastids are independent of light: reduced dark transcription rate is compensated by increased mRNA stability.
The plastid rbcL gene, encoding the large subunit of ribulose-1, 5-bisphosphate carboxylase, in higher plants is transcribed from a sigma70 promoter by the eubacterial-type RNA polymerase. To identify regulatory elements outside of the rbcL -10/-35 promoter core, we constructed transplastomic tobacco plants with uidA reporter genes expressed from rbcL promoter derivatives. Promoter activity was characterized by measuring steady state levels of uidA mRNA on RNA gel blots and by measuring promoter strength in run-on transcription assays. We report here that the rbcL core promoter is sufficient to obtain wild-type rates of transcription. Furthermore, the rates of transcription were up to 10-fold higher in light-grown leaves than in dark-adapted plants. Although the rates of transcription were lower in the dark, rbcL mRNA accumulated to similar levels in light-grown and dark-adapted leaves. Accumulation of uidA mRNA from most rbcL promoter deletion derivatives directly reflected the relative rates of transcription: high in the light-grown and low in the dark-adapted leaves. However, uidA mRNA accumulated to high levels in a light-independent fashion as long as a segment encoding a stem-loop structure in the 5' untranslated region was included in the promoter construct. This finding indicates that lower rates of rbcL transcription in the dark are compensated by increased mRNA stability.
Base Sequence↗
Twenty-six new polymorphic microsatellite markers around the HLA-B, -C and -E loci in the human MHC class I region.
The human major histocompatibility complex (MHC) class I region is believed to contain a large number of disease-related loci for diseases such as Behçet's disease and psoriasis vulgaris. Although many novel genes have recently been identified in this region, it still appears to be difficult to relate any of these new genes to MHC class I-associated diseases as causative genetic factors. During the course of large-scale genomic sequencing of the human MHC class I region, we identified 262 microsatellite sequences with dinucleotide to pentanucleotide repeats around the HLA-B, -C and HLA-E genes. Of these, 26 microsatellites were investigated for repeat polymorphism using 60 HLA homozygous B-cell lines and 60 healthy random individuals. The average number of alleles at these microsatellite loci was 9.6 with a PIC (polymorphism content value) of 0.69. These new polymorphic microsatellite markers will probably be very useful for precise mapping of disease-related genes within the HLA class I region in linkage analysis. Moreover, they will provide a powerful tool to study recombination events in this region, which contributes to haplotypic diversification.
Cell Line↗
Geranylgeranylpyrophosphate plays a key role for the G1 to S transition in vascular smooth muscle cells.
Pravastatin, a HMG-CoA reductase inhibitor was found to inhibit DNA synthesis of vascular smooth muscle cells (VSMC) in a dose-dependent manner. Flow cytometric analysis demonstrated that pravastatin induced G1 arrest. Mevalonate restored the inhibitory effect of pravastatin on DNA synthesis and on cell cycle progression, suggesting the importance of mevalonate itself and/or its metabolites in VSMC proliferation. The major intermediate metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP), farnesyl pyrophosphate (FPP) and IPP (isopentenyl pyrophosphate) were prepared in the form of liposomes, and the effects of GGPP, FPP and IPP on pravastatin induced inhibition of VSMC proliferation and G1 arrest were examined. Only GGPP restored the pravastatin-induced inhibition of DNA synthesis and G1 arrest. Pravastatin inhibited translocation of Rho small GTPase from cytosol to membrane. By the addition of GGPP, Rho small GTPase are geranylgeranylated and translocated to membranes during G1/S transition. These data suggest that GGPP, rather than FPP or IPP, is an essential metabolite among mevalonic acid metabolites for VSMC proliferation and the G1/S transition.
Animals↗
[Ultrasound scattering properties of Albunex microspheres].
In Japan, clinical and basic investigations of Albunex were started from 1989, and was firstly approved by the government as a commercially available contrast agent for the cardiovascular disorders. Although it has recently evacuated from the market, its acoustic properties proven by the many investigators were valuable for preparation of the second generation of contrast agents. Therefore, we summarized our data of the ultrasonic properties of Albunex both in vitro and experimental dog studies using RF signals. In conclusion, Albunex was a extremely sensitive blood flow tracer in evaluating intracardiac blood flow as well as intramyocardial perfusion.
Albumins↗
[Review: the overviews of contrast echocardiography in cardiovascular disorders].
The contrast echocardiography used to be applied for the diagnosis of congenital heart diseases, analysis of right side heart hemodynamics, and the evaluation of peripheral blood flow profiles. Recently, myocardial contrast echocardiography is evoked for estimating regional coronary blood flow as a parallel procedure of interventional therapy for ischemic patients. Advanced technology such as harmonic imaging, rf signal processing and digital storage of the data are extremely supportive for the quantitative evaluation of myocardial blood flow. In addition, new contrast agents which enable interpretation of myocardial contrast could be administered by peripheral injection.
Aged↗
Electron paramagnetic resonance and mutational analyses revealed the involvement of photosystem II-L subunit in the oxidation step of Tyr-Z by P680+ to form the Tyr-Z+P680Pheo- state in photosystem II.
To reveal the molecular mechanism of involvement of photosystem II (PSII)-L protein in the electron transfer in PSII, effects of mutations in PSII-L on the photochemistry of PSII were investigated by means of electron paramagnetic resonance (EPR) and flash photolysis. Wild type and a series of mutant versions of PSII-L were overproduced in Escherichia coliand chromatographically purified. Plastoquinone 9 (PQ-9) depleted PSII reaction center core complex consisting of CP47/D1/D2/Cytb-559/PSII-I/PSII-W was prepared and reconstituted with the wild type and each mutant version of PSII-L together with or without PQ-9. EPR signal indicating the formation of Tyr-Z+P680Pheo- state upon room-temperature illumination disappeared in CP47/D1/D2/Cytb-559/PSII-I/PSII-W, and it was recovered when the complex was reconstituted with the wild-type PSII-L. Mutation of a few amino acid residues in the carboxyl-terminal region of PSII-L, such as substitution of a triad of Tyr34, Phe35, and Phe36 by Leu, selectively resulted in the loss of the capability of PSII-L to recover the light-induced formation of Tyr-Z+P680Pheo- state in the reconstituted complex. Hydropathy profile of PSII-L suggests that it spans the membrane once by a hydrophobic stretch of the carboxyl-terminal side as its carboxyl end to face to the lumen. If this is the case, the amino acid residues essential for PSII-L to function are expected to be located close to the donor side of P680, suggesting the interaction of PSII-L with Tyr-Z (and/or Tyr-D) or P680 to facilitate the oxidation of Tyr-Z by P680+ to form Tyr-Z+P680Pheo- state in PSII. Evidence against PSII-L being involved in the electron transfer from Pheo- to QA was obtained by the flash photolysis experiments.
Amino Acid Sequence↗