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S Akiyoshi

Publications and source records attributed to S Akiyoshi.

10 recordsLinked to original sources
PubMed2001

Targets of transcriptional regulation by transforming growth factor-beta: expression profile analysis using oligonucleotide arrays.

Transforming growth factor-betas (TGF-betas) are potent inhibitors of cell proliferation, and disruption of components of the TGF-beta signaling pathway leads to tumorigenesis. Mutations of transmembrane receptors and Smads mediating intracellular signaling have been reported in various cancers. To identify transcriptional targets of TGF-beta, we conducted an expression profile analysis. HaCaT cells derived from human keratinocytes and highly sensitive to TGF-beta were treated with TGF-beta in the absence or presence of cycloheximide (CHX). mRNAs extracted from the HaCaT cells were used for hybridization of oligonucleotide arrays representing approximately 5600 human genes. TGF-beta increased the expression of PAI-1, junB, p21 cdk inhibitor, Smad7, betaIG-H3, and involucrin that have been reported to be up-regulated by TGF-beta, validating the usefulness of this approach. The induction of betaIG-H3 by TGF-beta was completely abolished by CHX, suggesting that the transcription of betaIG-H3 is not directly regulated by TGF-beta. Unexpectedly, we identified more genes down-regulated by TGF-beta than up-regulated ones. TGF-beta repressed the expression of epithelial specific Ets that may be involved in breast and lung tumorigenesis, which could contribute to tumor suppression by TGF-beta. Among a panel of cell cycle regulators, TGF-beta induced the expression of p21 cdk inhibitor; however, the induction of other cdk inhibitors was not significant in the present study. Taken together, the results suggest that TGF-beta may suppress tumorigenesis through positive and negative regulation of transcription.

Cell Cycle↗
PubMed2000

A genetic linkage map of the MSM Japanese wild mouse strain with restriction landmark genomic scanning (RLGS).

A high-resolution genetic map of the Mus musculus molossinus (MSM) Japanese wild mouse strain was constructed with restriction landmark genomic scanning (RLGS) and compared with that of the laboratory strain C3H. MSM is phylogenetically 1 million years apart from common laboratory mouse strains and is distinctly resistant to chemical carcinogenesis. Since it exhibits frequent genetic polymorphisms with laboratory mice but can still be easily crossed with laboratory strains, hybrids between MSM and carcinogen-sensitive laboratory mouse strains provide excellent materials for analysis of modifier genes and genetic changes during carcinogenesis. We have generated MSM backcross progeny with the C3H strain, which is extremely sensitive to hepatocarcinogenesis, to construct the present map. RLGS profiles with two combinations of restriction enzymes (NotI-PvuII-PstI, NotI-PstI-PvuII) yielded more than 2000 spots each. The polymorphism rate was about 39.2%, and of a total of 1732 polymorphic spot loci identified, 1371 could be assigned to specific chromosomes by comparison with 79 microsatellite marker loci. Thus, 1450 loci, on all chromosomes except for Y, effectively mapped 90% of the genome (1431.7 cM length). Although some spots might be derived from the same NotI site, each NotI site potentially generating two fragments, the presence of at least 515 loci groups with different progeny distribution patterns dispersed through the genome with an average spacing of 3 cM, means that this genetic map should be useful for analysis of various biological phenomena, including carcinogenesis and ontogenesis, at the gene level.

Animals↗
PubMed2000

Reduction of carotid arterial blood flow in ventricular septal defect associated with severe congestive heart failure.

After diagnosing abnormality of cardiac and carotid-cerebral circulation in an infant with isolated ventricular septal defect (VSD) associated with severe congestive heart failure, the authors measured the carotid arterial blood flow volume (CABF). At 3 months, the patient was not thriving and had dyspnea because of severe congestive heart failure. The authors measured the VSD size/body surface area (BSA) ratio relative to the predicted value of the left ventricular end-diastolic dimension (%LVEDd), left-to-right shunt ratio (Qp/Qs), and the small stroke volume (SV)/BSA using echocardiography and cardiac catheterization. The mean, maximum, and minimum CABF (mean CABF, maxCABF, and minCABF) among R-R intervals on electrocardiogram were measured by Doppler flowmetry in this patient and 5 healthy age-matched control children. The patient had a large VSD size/BSA ratio (37.9 mm/m2), %LVEDd (164%), and Qp/Qs (3.8), and a small SV/BSA ratio (18 mL/m2). The mean CABF, maxCABF, and minCABF were significantly lower than those of control children (VSD patient vs. controls; 2.7 +/- 0.4 vs. 4.5 +/- 0.6, 6.1 +/- 0.9 vs. 12.0 +/- 2.1, 1.2 +/- 0.2 vs. 1.7 +/- 0.4 mL/sec (mean +/- S.D.)), respectively (p < 0.01). The authors' results showed abnormal cardiac and carotid-cerebral circulation in an infant with large VSD associated with severe congestive heart failure.

Blood Volume↗
PubMed2000

[Diagnostic accuracy of carotid ultrasonography in screening for coronary artery disease].

OBJECTIVES: This study investigated the diagnostic accuracy of carotid ultrasonography in screening for significant coronary artery disease (% diameter stenosis > or = 75%). METHODS: Five hundred sixty patients (342 males, 218 females, mean age 66.4 years) underwent both coronary angiography and carotid ultrasonography. Gensini's coronary score was calculated as a quantitative parameter of coronary atherosclerosis. The most hypertrophic intimal-medial complex thickness (IMT) of the bilateral common carotid arteries (distal and proximal to the echo probe in each artery) was measured within 2 or 3 cm from the carotid bifurcation. The mean IMT (mean of these 4 sites), the maximum IMT (maximum of these 4 sites), and number of plaques (localized hypertrophy of IMT > or = 1.1 mm) were calculated as a quantitative parameter of carotid atherosclerosis. RESULTS: The screening parameters were determined as 0.85 mm mean IMT, 1.1 mm maximum IMT, and at least 2 sites of plaque. The sensitivity, specificity and accuracy rate for the detection of coronary artery disease were 57.3%, 61.6% and 59.6% for mean IMT, 43.5%, 71.1% and 58.6% for maximum IMT, and 60.8%, 70.5% and 66.1% for number of plaques. Furthermore, the overall results (except maximum IMT) were 73.3%, 49.2% and 60.2%. CONCLUSIONS: These results suggest that carotid ultrasonography is useful as a non-invasive and easy screening method for coronary artery disease. Furthermore, carotid ultrasonography will allow routine observations to follow the progression of coronary atherosclerosis.

Adult↗
PubMed1999

c-Ski acts as a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with smads.

Smads are intracellular signaling mediators of the transforming growth factor-beta (TGF-beta) superfamily that regulates a wide variety of biological processes. Among them, Smads 2 and 3 are activated specifically by TGF-beta. We identified c-Ski as a Smad2 interacting protein. c-Ski is the cellular homologue of the v-ski oncogene product and has been shown to repress transcription by recruiting histone deacetylase (HDAC). Smad2/3 interacts with c-Ski through its C-terminal MH2 domain in a TGF-beta-dependent manner. c-Ski contains two distinct Smad-binding sites with different binding properties. c-Ski strongly inhibits transactivation of various reporter genes by TGF-beta. c-Ski is incorporated in the Smad DNA binding complex, interferes with the interaction of Smad3 with a transcriptional co-activator, p300, and in turn recruits HDAC. c-Ski is thus a transcriptional co-repressor that links Smads to HDAC in TGF-beta signaling.

Acetyltransferases↗
PubMed1999

Application of the RLGS image analysis tool (RAT) to the construction of a genetic linkage map of recombinant inbred strain SMXA.

The construction of a genetic linkage map is the first, fundamental step to analyze the genetic properties of any organism. For this purpose, the restriction landmark genome scanning method (RLGS) can be used and has been shown to have high productivity in various genetic analyses. However, construction of a genetic linkage map by the RLGS method is laborious, because hundreds of spots must be scored, usually by visual observation. In order to reduce human involvement in the data processing, we developed an image analysis software, RAT (RLGS Analysis Tool). We evaluated its accuracy and feasibility by comparing the parental distribution patterns of RLGS spots obtained by RAT and by human observation, using Syrian hamster strain backcross progeny. We then used RAT to construct a genetic linkage map of the recombinant inbred strain SMXA. We were able to obtain 121 progenitor strain-specific spots that were assigned to a specific chromosome.

Animals↗
PubMed1998

An automatic image analysis system for RLGS films.

The RLGS (Restriction Landmark Genome Scanning) method was originally developed as a powerful method for enabling viewing of thousands of restriction landmarks. It offers a tool for obtaining information about genetic loci, with a single RLGS profile displaying approximately 2000 restriction landmarks as spots. One of the most useful applications is RLGS spot mapping, which allows the efficient, low-cost construction of the genetic map of any organism. However, analyses of the profiles depend mainly on human visual observation and are tedious and laborious. Although several commercially available image analyzing systems for profile comparison have been examined, they cannot be used for the RLGS spot mapping system owing to the background characteristics of the RLGS profiles, unsatisfactory rates of correspondence, and inefficient correction of informative genetic data. We therefore developed a novel automatic image analysis system for RLGS spot mapping, using an original algorithm based on the binary image transferred from the original RLGS profile. This system was employed for identifying non-polymorphic and parental strain-specific polymorphic spots of the F1 mouse profile and yielded efficient initial screening of RLGS profiles.

Animals↗
PubMed1998

Genetic profile of the SMXA recombinant inbred mouse strains revealed with restriction landmark genomic scanning.

We have applied the restriction landmark genomic scanning (RLGS) method to the SMXA recombinant inbred (RI) mouse strain set to reveal its detailed genetic profile. A total of 663 polymorphic RLGS spot loci were identified, 576 of which were assigned to chromosomes. Strain distribution patterns (SDPs) at 55 microsatellite marker loci were also obtained. As a result, the total number of loci with distinct SDPs on chromosomes increased to 400. These loci were dispersed on all chromosomes, except for the Chromosome (Chr) Y, and effectively covered the genome with an average spacing of 4 cM. The SMXA RI strain set, hereby, would be of value for genetic study.

Animals↗
PubMed1995

Hemodialysis patient regarded as a primary hyperoxaluria after long-term hemodialysis and renal transplantation.

Primary hyperoxaluria (PH) is a rare inborn error of oxalate metabolism resulted in autosomal recessive genetic defects. Clinical manifestations and end stage renal failure are developed during childhood in most cases, but occasionally they begin later in life. The diagnosis of PH is quite difficult due to diminished oxalate excretion after the renal function was declined. especially after initiation of hemodialysis therapy. We report here an adult case who was introduced into hemodialysis and subsequently regarded to have primary hyperoxaluria (PH). In clinical situations, this case had some peculiar clinical signs such as histories of frequent stone formations, impressive dental manifestations and destructive erosions of bones resembling renal osteodystrophy. There might be more PH patients among hemodialysis patients. PH should be considered in hemodialysis patients whenever curious bone changes and/or dental manifestations with history of frequent urolithiasis are recognized in the earlier course of hemodialysis therapy.

Adult↗