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Mari Nakamura

Publications and source records attributed to Mari Nakamura.

18 recordsLinked to original sources
PubMed2006

Sequence comparison of distal and proximal ribosomal DNA arrays in rice (Oryza sativa L.) chromosome 9S and analysis of their flanking regions.

Rice (Oryza sativa ssp. japonica cv. Nipponbare) harbors a ribosomal RNA gene (rDNA) cluster in the nucleolar-organizing region at the telomeric end of the short arm of chromosome 9. We isolated and sequenced two genomic clones carrying rice rDNA fragments from this region. The rice rDNA repeat units could be classified into three types based on length, which ranged from 7,928 to 8,934 bp. This variation was due to polymorphism in the number of 254-bp subrepeats in the intergenic spacer (IGS). Polymerase chain reaction (PCR) analysis suggested that the rDNA units in rice vary widely in length and that the copy number of the subrepeats in the IGS ranges from 1 to 12 in the rice genome. PCR and Southern blot analyses showed that most rDNA units have three intact and one truncated copies of the subrepeats in the IGS, and distal (telomere-side) rDNA units have more subrepeats than do proximal (centromere-side) ones. Both genomic clones we studied contained rDNA-flanking DNA sequences of either telomeric repeats (5'-TTTAGGG-3') or a chromosome-specific region, suggesting that they were derived from the distal or proximal end, respectively, of the rDNA cluster. A similarity search indicated that retrotransposons appeared more frequently in a 500-kb portion of the proximal rDNA-flanking region than in other subtelomeric regions or sequenced regions of the genome. This study reveals the repetitive nature of the telomeric end of the short arm of chromosome 9, which consists of telomeric repeats, an rDNA array, and a retrotransposon-rich chromosomal region.

Base Sequence↗
PubMed2006

Genome-wide analysis of mammalian promoter architecture and evolution.

Mammalian promoters can be separated into two classes, conserved TATA box-enriched promoters, which initiate at a well-defined site, and more plastic, broad and evolvable CpG-rich promoters. We have sequenced tags corresponding to several hundred thousand transcription start sites (TSSs) in the mouse and human genomes, allowing precise analysis of the sequence architecture and evolution of distinct promoter classes. Different tissues and families of genes differentially use distinct types of promoters. Our tagging methods allow quantitative analysis of promoter usage in different tissues and show that differentially regulated alternative TSSs are a common feature in protein-coding genes and commonly generate alternative N termini. Among the TSSs, we identified new start sites associated with the majority of exons and with 3' UTRs. These data permit genome-scale identification of tissue-specific promoters and analysis of the cis-acting elements associated with them.

3' Untranslated Regions↗
PubMed2006

Effects of the angiotensin receptor blocker candesartan on arterial stiffness and markers of extracellular matrix metabolism in patients with essential hypertension.

Laboratory studies have shown that angiotensin receptor blockers (ARBs) can affect extracellular matrix (ECM) metabolism and thereby have a beneficial effect on vascular remodeling. The aim of this study was to examine the clinical effects of the ARB candesartan cilexetil on serum markers of synthesis and degradation of ECM, as well as their relation to changes in arterial stiffness in hypertensive patients. Twenty-three patients with essential hypertension were recruited for this study. Markers related to ECM synthesis and degradation (procollagen type 1 propeptide [PIP], procollagen type III propeptide [PIIIP], matrix metalloproteinase-3 [MMP-3, stromelysin-1], tissue inhibitor of matrix metalloproteinases [TIMP-1], and hyaluronic acid [HA]) were examined both before and after one year of treatment with candesartan. Pulse-wave velocity [PWV] and ankle-brachial pressure index [ABI] were measured two months (i.e., after achieving blood pressure reduction) and one year after the initiation of therapy. PWV values after one year of treatment with ARB were significantly decreased compared to previous values, whereas ABI values were unchanged. Treatment with ARB was also associated with a significant decrease in serum PIIIP values and an increase in serum stromelysin-1, whereas changes in PIP, TIMP-1, and HA did not achieve statistical significance. A significant relationship was found between the changes in PWV and the changes in stromelysin-1 levels after correction for blood pressure and heart rate (p = 0.02). These results suggest that the treatment for just one year with ARB results in significant changes in markers of ECM metabolism as well as PWV. These effects on ECM metabolism could have a beneficial effect in decreasing vascular pathology in patients with essential hypertension.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

[Combination chemotherapy with carboplatin and weekly Paclitaxel in patients with advanced non-small cell lung cancer].

BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity of carboplatin plus weekly paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Forty-nine patients were analyzed retrospectively. Every 4 weeks patients received 70 mg/m(2)paclitaxel on days 1, 8, and 15, and AUC 5-6 carboplatin on day 1. RESULTS: A median of four cycles (range, 1-7) was administered. Twenty-four patients had a partial response, and the overall response rate was 48.9%. The median survival time was 12.8 months and the 1-year survival was 50.7%. Overall toxicities were mild. The most common toxicity was neutropenia, grade 3/4 in 32% of the patients. Grade 3/4 hematologic toxicities included anemia (16%) and thrombocytopenia (8%). Grade 3/4 non-hematologic toxicities included febrile neutropenia (2%), pneumonia (10%) and interstitial pneumonia (2%). Grade 2 peripheral neuropathy was seen in one patient (2%). CONCLUSIONS: These results demonstrate that this regimen is an active and tolerable treatment for patients with advanced NSCLC. It is suggested that this weekly regimen should be considered as one of the standard therapies for future chemotherapy in advanced NSCLC.

Adult↗
PubMed2006

[Effectiveness of pneumococcal polysaccharide vaccine in older patients with chronic respiratory diseases].

To evaluate effectiveness of pneumococcal polysaccharide vaccine, we recommended 1378 outpatients aged over 60 with chronic respiratory diseases to be vaccinated from August to October 2002, and 647 patients were vaccinated from August to November 2002. In the 1229 patients without respiratory failure, the incidence of antimicrobial treatment for bacterial respiratory infections in 547 vaccinated patients significantly decreased from 7.9% in the 2001/02 winter season to 5.7% in the 2002/03 winter season, although that in the 682 unvaccinated patients increased from 3.8% to 5.7%. The incidence of antimicrobial treatment for bacterial respiratory infections in 229 vaccinated patients with pneumococcal and influenza vaccines together significantly decreased from 10.5% in the 2001/02 winter season to 5.2% in 2002/03 winter season although that in 110 subjects vaccinated with influenza vaccine only increased from 2.7% to 7.2%. These findings suggest the effectiveness of the pneumococcal polysaccharide vaccine for the prevention of bacterial respiratory infections and the additive effectiveness of pneumococcal and influenza vaccines together.

Aged↗
PubMed2005

[Eighty cases of chronic respiratory failure treated with home noninvasive positive pressure ventilation].

We studied the clinical features and efficacy of home noninvasive positive pressure ventilation (NPPV) therapy in 80 patients to ascertain its indications and problems. The causes of chronic respiratory failure were restrictive thoracic diseases of post-tuberculosis sequelae (40 cases) and kyphoscoliosis (9 cases), COPD (8 cases), bronchiectasis (7 cases), and interstitial pneumonia (4 cases). One year survival rate of the patients with post-tuberculosis sequelae was 76% and most of the patients who started NPPV at their acute exacerbation died within several months. About half of the patients of COPD improved their quality of life (QOL) through NPPV. However, their survival rate 3 months later was only 69%. More than half of the patients with bronchiectasis felt that their QOL was improved by NPPV. Most of the patients with interstitial pneumonia died within 3 months indicating that NPPV is less useful for improving QOL of interstitial pneumonia PaCO2, after home NPPV, decreased significantly in the responder group (70.0 +/- 15.4 vs. 57.6 +/- 10.7[SD]Torr, p < 0.05), while PaCO2 in the non-responder group was unchanged (65.4 +/- 12.1 vs. 64.2 - 10.4 [SD] Torr). Body Mass Index (BMI) in the responder group tended to be higher than in the non-responder group. In conclusion, the restrictive thoracic diseases with post-tuberculosis sequelae and kyphoscoliosis are a good indication for NPPV and the therapy is also useful for patients with bronchiectasis who can dispose of their sputum by themselves. Home NPPV is suitable for patients whose PaCO2 decreases through NPPV and whose BMI is relatively high. QOL of interstitial pneumonia barely improves through NPPV, because interstitial pneumonia with hypercapnia is at the terminal stage.

Aged↗
PubMed2004

Libraries enriched for alternatively spliced exons reveal splicing patterns in melanocytes and melanomas.

It is becoming increasingly clear that alternative splicing enables the complex development and homeostasis of higher organisms. To gain a better understanding of how splicing contributes to regulatory pathways, we have developed an alternative splicing library approach for the identification of alternatively spliced exons and their flanking regions by alternative splicing sequence enriched tags sequencing. Here, we have applied our approach to mouse melan-c melanocyte and B16-F10Y melanoma cell lines, in which 5,401 genes were found to be alternatively spliced. These genes include those encoding important regulatory factors such as cyclin D2, Ilk, MAPK12, MAPK14, RAB4, melastatin 1 and previously unidentified splicing events for 436 genes. Real-time PCR further identified cell line-specific exons for Tmc6, Abi1, Sorbs1, Ndel1 and Snx16. Thus, the ASL approach proved effective in identifying splicing events, which suggest that alternative splicing is important in melanoma development.

Alternative Splicing↗
PubMed2004

Identification of region-specific transcription factor genes in the adult mouse brain by medium-scale real-time RT-PCR.

We established a medium-scale real-time RT-PCR system focusing on transcription factors and applied it to their expression profiles in the adult mouse 11 brain regions (http://genome.gsc.riken.jp/qRT-PCR/). Almost 90% of the examined genes showed significant expression in at least one region. We successfully extracted 179 region-specific genes by clustering analysis. Interestingly, the transcription factors involved in the development of the pituitary were still expressed in the adult pituitary, suggesting that they also play important roles in maintenance of the pituitary. These results provide unique molecular markers that may account for the molecular basis of the unique functions of specific brain regions.

Aging↗
PubMed2004

Composition and structure of the centromeric region of rice chromosome 8.

Understanding the organization of eukaryotic centromeres has both fundamental and applied importance because of their roles in chromosome segregation, karyotypic stability, and artificial chromosome-based cloning and expression vectors. Using clone-by-clone sequencing methodology, we obtained the complete genomic sequence of the centromeric region of rice (Oryza sativa) chromosome 8. Analysis of 1.97 Mb of contiguous nucleotide sequence revealed three large clusters of CentO satellite repeats (68.5 kb of 155-bp repeats) and >220 transposable element (TE)-related sequences; together, these account for approximately 60% of this centromeric region. The 155-bp repeats were tandemly arrayed head to tail within the clusters, which had different orientations and were interrupted by TE-related sequences. The individual 155-bp CentO satellite repeats showed frequent transitions and transversions at eight nucleotide positions. The 40 TE elements with highly conserved sequences were mostly gypsy-type retrotransposons. Furthermore, 48 genes, showing high BLAST homology to known proteins or to rice full-length cDNAs, were predicted within the region; some were close to the CentO clusters. We then performed a genome-wide survey of the sequences and organization of CentO and RIRE7 families. Our study provides the complete sequence of a centromeric region from either plants or animals and likely will provide insight into the evolutionary and functional analysis of plant centromeres.

Base Composition↗
PubMed2004

Absolute expression values for mouse transcripts: re-annotation of the READ expression database by the use of CAGE and EST sequence tags.

The RIKEN expression array database (READ) provides comprehensive gene expression data for the mouse, which were obtained as relative values from microarray double-staining experiments with E17.5 mRNA as common reference. To assign absolute expression values for mouse transcripts within READ, we applied the E17.5 reference sample to CAGE (cap analysis of gene expression) and expressed sequence tag (EST) high-throughput tag sequencing. Newly assigned values within the READ database were validated by comparison to expression data from serial analysis of gene expression, CAGE and EST experiments. These experiments confirmed the great significance of the absolute expression values within the improved READ database. The new Absolute READ database on absolute expression data is available under.

Animals↗
PubMed2004

[A pilot study of trastuzumab and vinorelbine-combined therapy for metastatic breast cancer].

We performed combined therapy with trastuzumab-vinorelbine for 6 HER2 positive metastatic breast cancer patients from which informed consent was obtained. As the initial dosage, we administered 4 mg/kg of trastuzumab, followed by a dosage of 2 mg/kg every week thereafter. At the same time, 25 mg/m2 of vinorelbine was administered for 2 weeks, followed by a week of rest. Total administration frequency of trastuzumab was 13-34 times (median: 27 times) and vinorelbine was 8-22 times (median: 17 times). A partial response was seen in 4 patients and no change in 2, for a response rate of 66%. A fixed period effect was recognized in each case, and the TTP was 112-274 days (median: 205 days). The side effects recognized were leukopenia of grade 3 in 1 patient, but she recovered during a withdrawal period. After that, continuous administration was possible. Trastuzumab-vinorelbine combined therapy expanded treatment alternatives for HER2 positive metastatic breast cancer patients and might prolong life.

Aged↗
PubMed2003

Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage.

We introduce cap analysis gene expression (CAGE), which is based on preparation and sequencing of concatamers of DNA tags deriving from the initial 20 nucleotides from 5' end mRNAs. CAGE allows high-throughout gene expression analysis and the profiling of transcriptional start points (TSP), including promoter usage analysis. By analyzing four libraries (brain, cortex, hippocampus, and cerebellum), we redefined more accurately the TSPs of 11-27% of the analyzed transcriptional units that were hit. The frequency of CAGE tags correlates well with results from other analyses, such as serial analysis of gene expression, and furthermore maps the TSPs more accurately, including in tissue-specific cases. The high-throughput nature of this technology paves the way for understanding gene networks via correlation of promoter usage and gene transcriptional factor expression.

Animals↗
PubMed2003

Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia.

We report the construction of the mouse full-length cDNA encyclopedia,the most extensive view of a complex transcriptome,on the basis of preparing and sequencing 246 libraries. Before cloning,cDNAs were enriched in full-length by Cap-Trapper,and in most cases,aggressively subtracted/normalized. We have produced 1,442,236 successful 3'-end sequences clustered into 171,144 groups, from which 60,770 clones were fully sequenced cDNAs annotated in the FANTOM-2 annotation. We have also produced 547,149 5' end reads,which clustered into 124,258 groups. Altogether, these cDNAs were further grouped in 70,000 transcriptional units (TU),which represent the best coverage of a transcriptome so far. By monitoring the extent of normalization/subtraction, we define the tentative equivalent coverage (TEC),which was estimated to be equivalent to >12,000,000 ESTs derived from standard libraries. High coverage explains discrepancies between the very large numbers of clusters (and TUs) of this project,which also include non-protein-coding RNAs,and the lower gene number estimation of genome annotations. Altogether,5'-end clusters identify regions that are potential promoters for 8637 known genes and 5'-end clusters suggest the presence of almost 63,000 transcriptional starting points. An estimate of the frequency of polyadenylation signals suggests that at least half of the singletons in the EST set represent real mRNAs. Clones accounting for about half of the predicted TUs await further sequencing. The continued high-discovery rate suggests that the task of transcriptome discovery is not yet complete.

Animals↗
PubMed2003

Subtraction of cap-trapped full-length cDNA libraries to select rare transcripts.

The normalization and subtraction of highly expressed cDNAs from relatively large tissues before cloning dramatically enhanced the gene discovery by sequencing for the mouse full-length cDNA encyclopedia, but these methods have not been suitable for limited RNA materials. To normalize and subtract full-length cDNA libraries derived from limited quantities of total RNA, here we report a method to subtract plasmid libraries excised from size-unbiased amplified lambda phage cDNA libraries that avoids heavily biasing steps such as PCR and plasmid library amplification. The proportion of full-length cDNAs and the gene discovery rate are high, and library diversity can be validated by in silico randomization.

Gene Expression Profiling↗
PubMed2003

[A case of breast cancer with lung and bone metastasis treated successfully by oral combination chemotherapy of 5'-deoxy-5-fluorouridine and cyclophosphamide].

The patient was a 52-year-old woman who underwent left partial mastectomy on April 30, 1999. The stage was T0N1bM1 (bone). After operation, adjuvant therapy consisting of 6 cycles of CMF therapy and radiation was performed. On September 2000, the tumor marker (NCC-ST 439) was at a high level. On January 2001, chest CT examination revealed multiple lung metastases of the right lobe. Oral combination chemotherapy of 5'-deoxy-5-fluorouridine (5'-DFUR, 1,200 mg/day) and cyclophosphamide (CPA, 100 mg/day) was thus performed, and definite improvement resulted in the lung. No adverse reactions occurred except for anemia and thrombocytopenia of grade 1. It is suggested that this oral combination chemotherapy may be useful for advanced recurrent breast cancer patients and applicable in ambulatory chemotherapy administered with consideration for the patient's quality of life.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

The genome sequence and structure of rice chromosome 1.

The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence.

Arabidopsis↗