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Biomedical subjects

S Yamanaka

Publications and source records attributed to S Yamanaka.

At least 19 recordsLinked to original sources
PubMed2006

Genome-wide profiling of promoter methylation in human.

DNA methylation in the promoter region of a gene is associated with a loss of that gene's expression and plays an important role in gene silencing. The inactivation of tumor-suppressor genes by aberrant methylation in the promoter region is well recognized in carcinogenesis. However, there has been little study in this area when it comes to genome-wide profiling of the promoter methylation. Here, we developed a genome-wide profiling method called Microarray-based Integrated Analysis of Methylation by Isoschizomers to analyse the DNA methylation of promoter regions of 8091 human genes. With this method, resistance to both the methylation-sensitive restriction enzyme HpaII and the methylation-insensitive isoschizomer MspI was compared between samples by using a microarray with promoter regions of the 8091 genes. The reliability of the difference in HpaII resistance was judged using the difference in MspI resistance. We demonstrated the utility of this method by finding epigenetic mutations in cancer. Aberrant hypermethylation is known to inactivate tumour suppressor genes. Using this method, we found that frequency of the aberrant promoter hypermethylation in cancer is higher than previously hypothesized. Aberrant hypomethylation is known to induce activation of oncogenes in cancer. Genome-wide analysis of hypomethylated promoter sequences in cancer demonstrated low CG/GC ratio of these sequences, suggesting that CpG-poor genes are sensitive to demethylation activity in cancer.

Adenocarcinoma↗
PubMed2006

Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after a 3-6-week exposure to certain drugs, including anticonvulsants. There are some reports showing that serum IgG levels often decrease at the early stage of DIHS. Reactivation of human herpesvirus (HHV)-6 has been reported in patients with DIHS, and some other DIHS patients showed reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV). OBJECTIVES: To determine whether reactivation of HHV-6, HHV-7, CMV and/or EBV occurs in patients with DIHS. METHODS: Titres of IgG and IgM antibodies to HHV-6 and HHV-7 were determined using an indirect immunofluorescence antibody assay on admission and at various times after admission. Anti-CMV IgG and IgM antibody titres and anti-EBV capsid antigen IgG, IgA, IgM, and EBV nuclear antigen and EBV early antigen IgG titres were determined by enzyme immunoassay. Polymerase chain reaction (PCR) procedures for HHV-6, HHV-7, CMV and EBV DNAs were performed using serum samples. IgG antibody titres to HHV-6, HHV-7, CMV and EBV were increased after the onset in seven, six, seven and two of seven patients, respectively. IgG antibody titres to HHV-6 and HHV-7 were elevated simultaneously 21-38 days after the onset. RESULTS: IgG antibody titres to CMV and EBV were elevated 10-21 days after the elevation of HHV-6 and HHV-7 antibody titres. PCR showed that HHV-6, HHV-7, CMV and EBV DNAs became positive in six, five, seven and two of seven patients, respectively. HHV-6 and HHV-7 DNAs were detected 21-35 days after the onset, and CMV DNA was detected 10-21 days after detection of HHV-6 and HHV-7 DNAs. CONCLUSION: The present study suggests that in addition to HHV-6 reactivation, reactivation of HHV-7, CMV and/or EBV may also occur following drug eruption in some patients with DIHS.

Adult↗
PubMed2006

The characteristics and measuring technique of refractory dissolved organic substances in urban runoff.

It is considered that refractory dissolved organic substances have caused an increase in the COD concentration in Lake Biwa in recent years. We investigated the organic matter in the first flush of stormwater runoff from a road in the watershed area of the lake, and studied the possibility of improvement in the water environment from that aspect. After percolating the stormwater through soil, we analyzed organic substances fractionated by using GPC-TC. And we examined the effect of removal of organic substances by comparing the peak height before and after percolation. In the result of the experiments, we found that soil infiltration reduced the refractory dissolved organic substance and we successfully designed a system for a simple and easy experimental facility to treat urban runoff.

Biodegradation, Environmental↗
PubMed2005

Role of the phosphoinositide 3-kinase pathway in mouse embryonic stem (ES) cells.

Mouse ES (embryonic stem) cells maintain pluripotency with robust proliferation in vitro. ES cells share some similarities with cancer cells, such as anchorage-independent growth, loss of contact inhibition and tumour formation. After differentiation, ES cells lose pluripotency and tumorigenicity. Recent studies showed that the PI3K (phosphoinositide 3-kinase) pathway is important for proliferation, survival and maintenance of pluripotency in ES cells. The PI3K pathway is activated by growth factors and cytokines including insulin and leukaemia inhibitory factor. In addition to these exogenous factors, the PI3K pathway is endogenously activated by the constitutively active Ras family protein ERas (ES cell-expressed Ras). The PI3K pathway utilizes multiple downstream effectors including mTOR (mammalian target of rapamycin), which we have shown to be essential for proliferation in mouse ES cells and early embryos.

Animals↗
PubMed2005

Possible role of autoantibodies against nephrin in an experimental model of chronic graft-versus-host disease.

Nephrin, a product of the NPHS1 gene, is a component of the slit diaphragms that are found between glomerular foot processes and is a crucial element for glomerular filtration barrier. Recently, nephrin has been focused in a number of studies of proteinuria development including various types of acquired glomerular diseases including minimal change nephrotic syndrome and membranous nephropathy. However, the precise role of nephrin in such acquired glomerular diseases is still unknown. To analyse the role of nephrin further, two kinds of anti-nephrin antibodies were raised in the rabbits and applied to an experimental mouse model of chronic graft-versus-host disease, in which (C57BL/10 x DBA/2) F1 mice developed clinically apparent severe proteinuria with significant glomerular lesions 7 weeks after parental DBA/2 cell transfer. Antibody-sandwich ELISA detected anti-nephrin antibodies during week 2 to week 6, with the peak at week 2 or week 4. Colocalization of nephrin and IgG on week 4, week 6, and week 8 was revealed by confocal microscopic analysis, suggesting that in situ immune complex formation with nephrin in glomerular lesion. Taken together, it seems to be suggested nephrin and its autoantibody have a certain role in the development of glomerular lesion in our model mice.

Animals↗
PubMed2005

Experimental study on pathogenesis and histomorphology of early carcinoma of the extrahepatic bile duct in the Syrian hamster.

To elucidate the pathogenesis of carcinomas in the extrahepatic bile duct, we investigated the histomorphological characteristics of adenomas and early carcinomas induced in the extrahepatic bile duct of hamsters. Syrian hamsters underwent a cholecystoduodenostomy along with a dissection of the common duct, while also being administered N-nitrosobis(2-oxopropyl)amine (BOP). The tumors that arose from the extrahepatic bile duct included 10 adenomas and 55 early carcinomas in 56 of the 156 hamsters sacrificed. All the adenomas were found to be polypoid in shape. The early carcinomas, which were restricted within the mucosal layer of the bile duct, showed the following three different growth patterns: (1) protruding type in 41 (75%), consisting of 27 polypoid and 14 papillary tumors; (2) superficial spreading type in 9 (16%); and (3) periductal glandular type in 5 (9%). There were no depressed tumors observed. Carcinomas existing either alone or associated with adenomas were evident in 12 (22%) tumors, and 11 of these were polypoid. Atypical papillary hyperplasia within the tumor mass was noted in 22 early carcinomas (40%) and was particularly prominent in papillary type tumors. These results support the concept of an adenoma-carcinoma sequence in the majority of polypoid tumors of the extrahepatic bile duct. Atypical papillary hyperplasia might also be premalignant, and these precursor lesions should reflect the growth patterns of tumors, at least in the early stage of tumorigenesis.

Adenoma↗
PubMed2003

Superconductivity in doped sp3 semiconductors: the case of the clathrates.

We present a joint experimental and theoretical study of the superconductivity in doped silicon clathrates. The critical temperature in Ba(8)@Si-46 is shown to strongly decrease with applied pressure. These results are corroborated by ab initio calculations using MacMillan's formulation of the BCS theory with the electron-phonon coupling constant lambda calculated from perturbative density functional theory. Further, the study of I(8)@Si-46 and of gedanken pure silicon diamond and clathrate phases doped within a rigid-band approach show that the superconductivity is an intrinsic property of the sp(3) silicon network. As a consequence, carbon clathrates are predicted to yield large critical temperatures with an effective electron-phonon interaction much larger than in C60.

Journal Article↗
PubMed2003

Mechanism of superconductivity in the polyhedral-network compound Ba8Si46.

The silicon clathrates--materials composed of metal-doped Si(20) dodecahedra--were identified as the first superconductors based on pure silicon networks. The mechanism of superconductivity in these materials can be obtained by studying their phonon modes, as modified by isotope substitution, and specific-heat measurements. Here, we present experimental studies that provide strong evidence that superconductivity in Ba(8)Si(46) is explained in the framework of phonon-mediated Bardeen-Cooper-Schriefer theory. Analyses using the McMillan approximation of the Eliashberg equation indicate that the superconducting mechanism is in the medium coupling regime, but at the high-end limit. The large density of states at the Fermi level, which arises from hybridization of the Si(20) cluster and Ba orbitals, is responsible for the unexpectedly high superconducting temperature. The temperature evolution of the specific heat unambiguously shows that this is an s-wave symmetry superconductor.

Journal Article↗
PubMed2003

Assessment of cytochrome P450 sequences offers a useful tool for determining genetic diversity in higher plant species.

To investigate and develop new genetic tools for assessing genome-wide diversity in higher plant-species, polymorphisms of gene analogues of mammalian cytochrome P450 mono-oxygenases were studied. Data mining on Arabidopsis thaliana indicated that a small number of primer-sets derived from P450 genes could provide universal tools for the assessment of genome-wide genetic diversity in diverse plant species that do not have relevant genetic markers, or for which, there is no prior inheritance knowledge of inheritance traits. Results from PCR amplification of 51 plant species from 28 taxonomic families using P450 gene-primer sets suggested that there were at least several mammalian P450 gene mammalian-analogues in plants. Intra- and inter- specific variations were demonstrated following PCR amplifications of P450 analogue fragments, and this suggested that these would be effective genetic markers for the assessment of genetic diversity in plants. In addition, BLAST search analysis revealed that these amplified fragments possessed homologies to other genes and proteins in different plant varieties. We conclude that the sequence diversity of P450 gene-analogues in different plant species reflects the diversity of functional regions in the plant genome and is therefore an effective tool in functional genomic studies of plants.

Arabidopsis↗
PubMed2003

[Clinical experience of gelatin-resorcin-formal (GRF) glue for acute empyema with bronchopleural fistula].

Gelatin-resorcin-formal (GRF) glue is a new biological adhesive agent with the advantage of sealing efficacy. We report a successful closure of bronchopleural fistula using this agent. A 77-year-old man underwent cavernostomy for lung aspergillosis. After surgery, he developed methicillin-resistant staphylococcus aureus (MRSA)-empyema with bronchopleural fistula. Thoracoplasty and muscular plombage were performed for filling up the cavity and closure of bronchial fistula. But the fistula relapsed 3 days after surgery. GRF glue was injected into the residual cavity, then air-leakage was completely disappeared with tight adhesion of cavity wall. We consider this agent is useful material for the closure of bronchopleural fistula.

Acute Disease↗
PubMed2003

[Pulmonary actinomycosis mimicking of mucosa-associated lymphoid tissue lymphoma by frozen section examination: report of a case].

A 59-year-old man was admitted to our hospital for hemoptysis. Chest X-ray films showed a mass shadow in the left lower lobe. Any definitive diagnosis could not be made after examinations including sputum culture and bronchial cytology. Exploratory thoracotomy was performed since malignancy was not excluded. During the operation, mucosa-associated lymphoid tissue (MALT) lymphoma was suspected based on the pathological findings of the frozen section. The permanent section of the resected specimen contained colonies of actinomycetes in the bronchus, and the peripheral region demonstrated marked infiltration of lymphocytes and plasma cells through the interstitium of alveolar walls and peri-bronchovascular sheath, with many lymphoid follicles. This case revealed pulmonary actinomycosis coexisted with lymphocytic interstitial pneumonia (LIP). We concluded that lymphoproliferative disease should be considered another candidate for the differential diagnosis from pulmonary actinomycosis.

Actinomycosis↗
PubMed2003

[Subdiaphragmatico-mediastinal lipoma through the foramen of Bochdalek; report of a surgical case].

A 53-year-old man was admitted to our hospital for evaluation of chest abnormal shadow at the left cardiophrenic angle. Computed tomography (CT) scan revealed a homogeneous mass of fatty density on the left diaphragm. Magnetic resonance imaging (MRI) demonstrated a well-demarcated tumor mass with a fatty signal intensity and, in the sagittal view, the mass showed continuity into the retroperitoneal fatty tissue. Extirpation of the tumor was performed under thoracoscopic procedure. The tumor was adhesive closely to diaphragm and extended into the retroperitoneal space through the foramen of Bochdalek. Pathologically the tumor was diagnosed as a mature lipoma. This tumor was considered to originated from the retroperitoneal fatty tissue under the diaphragm and to herniate into the mediastinum through the foramen of Bochdalek.

Humans↗
PubMed2003

[Catamenial pneumothorax due to diaphragmatic endometriosis; report of a surgical case].

A 27-year-old female was complained repeated right pneumothorax. Each episode was obviously related to the onset of menstruation, suggesting catamenial pneumothorax. Thoracoscope revealed the presence of several fistulas in the central tendon of the diaphragm. Partial resection of the diaphragm including these lesions was performed under thoracoscopic procedure. Microscopic examination of the excised specimen showed endometriosis. The patient was followed without hormonal therapy, but recurrent pneumothorax occurred. For the catamenial pneumothorax, hormonal treatment is considered necessary even after surgical treatment.

Adult↗
PubMed2003

[The prevention and measures to complication of video-assisted thoracoscopic surgery for lung cancer patients].

Video-assisted thoracoscopic surgery (VATS) for patient with lung cancer is seemed to be more genetic in future. It is because of small wound, little ache and short hospitalization. However, dissection of lymph-nodes is necessary since it is lung cancer. Because the thoracoscopic lobectomy is performed in the limited space, troubles those we cannot predict can happen. So surgical techniques of to prevent troubles are important. And this is the first step to avoid postoperative complication. It is necessary that to grasps a state of the patient and not to leave perioperative troubles.

Adult↗
PubMed2002

Lysosomal storage results in impaired survival but normal neurite outgrowth in dorsal root ganglion neurones from a mouse model of Sandhoff disease.

Sandhoff disease is a heritable lysosomal storage disease resulting from impaired degradation of GM2 ganglioside and related substrates. A mouse model of Sandhoff disease created by gene targeting displays progressive neurological manifestations, similar to patients with the disease. In the present in vivo and in vitro studies, we examined morphological and functional abnormalities of dorsal root ganglion (DRG) neurones in Sandhoff disease mice at an asymptomatic stage (approximately 1 month of age). Light microscopic studies with Nissl staining and immunocytochemistry suggested extensive intracytoplasmic storage of GM2 ganglioside in the Sandhoff mouse DRG neurones. These findings were consistent with the results of electron microscopy, in which a huge number of pleomorphic inclusion bodies immunoreactive for GM2 ganglioside were present in the cytoplasm of the neurones. The inclusion bodies were also identified in satellite cells and Schwann cells in the Sandhoff mouse DRG. The survival ratios of DRG neurones after 1, 2, 4 and 6 days in culture were significantly lower in the Sandhoff mice than in the age-matched heterozygous mice. The ratio of neurite-bearing cells on poly-l-lysine-coated dishes after 2 days in culture was also lower by approximately 10% in the Sandhoff mice compared to the heterozygotes, but additional coating of laminin onto poly-l-lysine dramatically enhanced the neurite extension from the neurones in both groups of mice. These results indicate that accumulation of GM2 ganglioside in DRG neurones impairs the capability of the neurones to survive in vitro, although viable neurones from the Sandhoff mice in culture can regenerate neurites nearly as well as unaffected neurones.

Animals↗
PubMed2001

Unconventional superconductivity in electron-doped layered Li0.48(THF)yHfNCL.

We report magnetic susceptibility measurements on a layered superconductor Li0.48(THF)0.3HfNCl having Tc approximately 26 K. The present study revealed that (a) the Fermi level density of states is small, N*(EF) approximately 0.25 states/(eV spin f.u.), (b) mass enhancement is negligible, gamma; approximately 1, (c) electron-phonon coupling is weak, lambda(ep)<<1, (d) exchange enhancement is negligible, 1/(1+F(a)0) approximately 1, and (e) electronic density parameter is large, r(2D)s approximately 10.3 (i.e., low-carrier density). It is difficult to explain the origin of the high Tc in terms of the conventional phonon (BCS) mechanism of superconductivity.

Journal Article↗
PubMed2001

Quantitative assessment of DNA microarrays--comparison with Northern blot analyses.

DNA microarray is a powerful technology that provides the expression profile of thousands of genes. However, less attention has been paid to its quantitative aspect. In this study, we constructed a small-scale DNA microarray that contains 84 genes and characterized its quantitative aspect. Analyses with this microarray showed that 17 genes were induced, whereas 8 genes were suppressed at least twofold during the differentiation of mouse embryonic stem cells. When repeated with the same combination of fluorescent dyes for probe labeling, the microarray produced consistent data (correlation coefficient = 0.991). In contrast, data were less consistent when repeated with the reverse combination of dyes (correlation coefficient = 0.945). The effect of dye combination was particularly evident in several genes. Total RNA (15 microg) and poly(A) RNA (0.5 microg) showed comparable sensitivity and produced essentially identical data (correlation coefficient = 0.983). The sensitivity of the DNA microarrays was slightly inferior to that of Northern blot analyses. In most genes, data obtained with the two methods were consistent. However, in 4 of 46 genes compared, DNA microarrays failed to detect the expression changes that were revealed by Northern blot. These data demonstrated that DNA microarrays provide quantitative data comparable to Northern blot in general, but a few issues must be considered when analyzing data.

Animals↗