Biomedical subjects

Satoshi Tanaka

Publications and source records attributed to Satoshi Tanaka.

At least 73 records · Page 4Linked to original sources

PubMed2005

[Regulatory T cell and autoimmune diseases].

CD25+CD4+ regulatory T cells are naturally anergic and suppressive. They differentiate through thymus as professional regulator to control immunological self-tolerance in the periphery. When they are depleted from normal animals, various organ-specific autoimmune diseases spontaneously develop, and reconstitution of regulatory T cells prevents the diseases. Transcriptional factor FoxP3 is the master gene for differentiation and function of regulatory T cells. Mutation of FoxP3 gene causes development of autoimmune disease in both human and mouse. There are accumulating reports that regulatory T cells are abnormal in their number or function in several animal models and also patients with autoimmune diseases. These findings indicate that regulatory T cells are involved in the pathogenesis of many autoimmune diseases. Regulatory T cells can also be employed for the treatment of autoimmune diseases. Further studies of regulatory T cells, especially the detection of their specific markers and the development of the method to propagate them in an antigen-specific manner, will facilitate their clinical application.

Animals↗

PubMed2005

Glioblastoma multiforme metastasis to the axis. Case report.

Extracranial bone metastasis from glioblastoma multiforme (GBM) has rarely been reported in the literature, and most metastatic GBMs are multiple bone metastases. The authors describe the first case of a GBM with metastasis only to the axis. This 42-year-old man presented with a 2-month history of headache, nausea, vomiting, and disorientation. Magnetic resonance imaging demonstrated a right temporal tumor, which was diagnosed as a GBM based on tumor resection. The patient was treated using radiation (6000 cGy) and the intravenous administration of nimustine hydrochloride. Eighteen months thereafter, he experienced the sudden onset of neck pain. Magnetic resonance studies revealed a tumor in the axis that was diagnosed as GBM based on biopsy procedure.

Adult↗

PubMed2005

[A case of intraosseous meningioma with extracranial progression having difficulty in making a preoperative diagnosis].

Intraosseous meningioma is very rare and is often confused preoperatively with a primary bone tumor of the skull. We report a case of intraosseous meningioma with hyperostosis for which preoperative diagnosis was difficult. A 78-year-old female with a slowly growing hard mass in the left parietal bone was admitted. Neurological findings were normal. Plain skull radiograph showed a 6 x 6 cm hyperostotic lesion in the left parietal bone. Bone window CT scan showed thickening and hyperostosis in the same area. MRI using Gd-DTPA showed heterogeneous enhancement of the intraosseous mass, and homogenous enhancement of the dura matter. And angiogram showed a tumor stain fed by the bilateral superficial temporal artery and the It-occipital artery. The tumor and the underlying dura mater were totally removed. Preoperative diagnosis was an osteogenic tumor, but histological examination revealed a transitional meningioma. We discussed the development and the classification of an ectopic meningioma and the mechanism of hyperostosis. We should be aware of the existence of intraosseous menigiomas mimicking osteogenic tumors.

Aged↗

PubMed2005

[The effects of postoperative continuous epidural analgesia after laparoscopy-assisted distal gastrectomy].

BACKGROUND: This study was conducted to evaluate the effects of continuous epidural analgesia on the postoperative pain and the early recovery after laparoscopy-assisted gastrectomy (LAG). METHODS: A total of 66 patients undergoing elective LAG were investigated for postoperative pain score and other variables retrospectively. RESULTS: Forty-four patients who had received epidural analgesia (E group) showed significantly lower pain scores for 2, 12 and 48 hours after surgery, compared with 22 patients who had received analgesics intramuscularly or transrectally (C group). The patients in the E group needed significantly less supplemental analgesics than those in C group for 2 and 12 hours after the operation. The early recovery and the incidence of postoperative complications were not significantly different between the two groups. CONCLUSIONS: These results show that postoperative continuous epidural analgesia is effective for postoperative pain relief in patients after laparoscopy-assisted gastrectomy.

Analgesia, Epidural↗

PubMed2005

Down-regulation of O6-methylguanine-DNA methyltransferase gene expression in gliomas by platinum compounds.

Forty-two patients with malignant gliomas that had received two courses of chemotherapy more than 2 months apart were examined. Among these 42 patients, 31 were treated with 1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), and 11 were treated with platinum compounds such as cis-platinum (CDDP) or carboplatin (CBDCA), as the first-line chemotherapy. The response rate of the second chemotherapy in the 31 patients treated first with ACNU was significantly lower than that in the 11 patients treated with platinum compounds, regardless of the type of the second chemotherapy (P=0.0292 by Fisher's exact probability test). O(6)-methylguanine-DNA methyltransferase (MGMT) mRNA expression was measured twice by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using Sybr-Green I in 16 of 42 patients. The relative quantitation value (RQV) of MGMT mRNA normalized to the level of 2-microglobulin decreased after chemotherapy in all 5 patients treated with platinum compound. U373MG and A172 human glioma cells were cultured for 5 days with 1 microM of CDDP or 4 microM of CBDCA. The RQV of MGMT in these cells treated with platinum compounds obviously decreased, and these cells were more sensitive to ACNU than the control cells based on colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Both the clinical findings and laboratory results suggest that platinum compounds may play a role in the down-regulation of MGMT mRNA expression and up-regulation of the sensitivity to ACNU. Platinum compounds may be strong candidates for use as first-line chemotherapeutic agents against malignant gliomas.

Adult↗

PubMed2004

Non-coding RNA directed DNA demethylation of Sphk1 CpG island.

The formation of DNA methylation patterns is one of the epigenetic events that underlie mammalian development. The Sphk1 CpG island is a target for tissue-dependent DNA methylation as well as a template for generating multiple subtypes. The number of mammalian non-coding RNA genes is rapidly expanding. In this study, we found endogenous antisense transcripts, Khps1 subtypes with different sizes (600-20,000nt). A subtype, Khps1a, was a 1290-bp, non-coding, 5'-capped and 3'-polyadenylated RNA that originated from the CpG island and overlapped with a tissue-dependent differentially methylated region (T-DMR) of Sphk1. Intriguingly, overexpression of two fragments of Khps1 caused demethylation of CG sites in the T-DMR. Furthermore, this RNA-directed demethylation was associated with DNA methylation at three CC(A/T)GG sites in the T-DMR. The link between the RNA-directed CG demethylation and non-CG methylation provides a novel mechanism of epigenetic regulation and potential tool for epigenetic manipulation of mammalian cells.

Animals↗

PubMed2004

Skewed X-inactivation in cloned mice.

In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P<0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders.

Animals↗

PubMed2004

Mechanisms of sustained cutaneous vasodilation induced by spinal cord stimulation.

This study was performed to investigate whether spinal cord stimulation (SCS) at intensities below motor threshold prolongs cutaneous vasodilation and whether sustained vasodilation by SCS is mediated through sympathetic inhibition and/or antidromic activation of sensory fibers. SCS was applied to the dorsal surface of the L2-L3 spinal cord of anesthesized rats with stimulus parameters used clinically (i.e., 50 Hz, 0.2 ms duration, and stimulus intensity at 30%, 60%, or 90% of motor threshold). Peripheral vasodilation induced by 5-min SCS was not attenuated by hexamethonium, an autonomic ganglion-blocking agent, but was abolished by dorsal rhizotomy. SCS at < or = 60% of motor threshold increased cutaneous blood flow to the level similar to that obtained at 90% of motor threshold, but the vasodilation did not last for 5 min. SCS-induced vasodilation at 90% of motor threshold persisted for the entire stimulation period up to 30 min, and the vasodilation was not attenuated by hexamethonium. It is concluded that sustained vasodilation, which is induced by SCS at only 90% of motor threshold, in this study was mediated via antidromic activation of sensory fibers.

Animals↗

PubMed2004

Lack of histamine alters gastric mucosal morphology: comparison of histidine decarboxylase-deficient and mast cell-deficient mice.

Histamine plays an important role in the regulation of gastric acid secretion; however, its role in maintenance of gastric morphology remains unclear. To clarify the necessity of histamine for gastric mucosal development and maintenance, we evaluated two different kinds of mice that lacked either mast cells (one of the gastric histamine-producing cell types) or histidine decarboxylase (HDC; a histamine-synthesizing enzyme). Measurements of stomach weight, intragastric pH, mucosal histamine levels, as well as serum gastrin and albumin levels were performed in mice. Gastric mucosal appearance was examined by immunohistochemical techniques. Although gastric mucosal histamine levels in mast cell-deficient mice were half of those observed in the wild-type mice, intragastric pH, serum gastrin levels, and gastric morphology at 12 mo were unchanged compared with the wild-type mice. In contrast, HDC-deficient mice possessed no detectable gastric histamine, but did exhibit hypergastrinemia, as well as marked increases in intragastric pH and stomach weight compared with the wild-type mice. Histological analysis revealed that 9-mo-old HDC-deficient mice demonstrated hyperplasia in the oxyntic glandular base region, as well as increased numbers of parietal and enterochromaffin-like cells. These results indicate that enterochromaffin-like cell-derived histamine is potentially involved in gastric mucosal morphology regulation.

Achlorhydria↗

PubMed2004

Isolation of a new member of group 3 late embryogenesis abundant protein gene from a halotolerant green alga by a functional expression screening with cyanobacterial cells.

By a functional expression screening with cyanobacterial cells, a new member of group 3 late embryogenesis abundant protein genes (designated cw80lea3) was isolated from the cDNA library of halotolerant green alga Chlamydomonas sp. strain W80. The principle of the screening method was based on the acquisition of NaCl salt-tolerance of the fresh water cyanobacterial cells carrying the halotolerant algal gene. The expression of cw80lea3 gene in the C. W80 cells was induced by salt- and cold-stresses, but not by abscisic acid treatment.

Amino Acid Sequence↗

PubMed2004

DNA methylation-mediated control of Sry gene expression in mouse gonadal development.

DNA methylation at CpG sequences is involved in tissue-specific and developmentally regulated gene expression. The Sry (sex-determining region on the Y chromosome) gene encodes a master protein for initiating testis differentiation in mammals, and its expression is restricted to gonadal somatic cells at 10.5-12.5 days post-coitum (dpc) in the mouse. We found that in vitro methylation of the 5'-flanking region of the Sry gene caused suppression of reporter activity, implying that Sry gene expression could be regulated by DNA methylation-mediated gene silencing. Bisulfite restriction mapping and sodium bisulfite sequencing revealed that the 5'-flanking region of the Sry gene was hypermethylated in the 8.5-dpc embryos in which the Sry gene was not expressed. Importantly, this region was specifically hypomethylated in the gonad at 11.5 dpc, while the hypermethylated status was maintained in tissues that do not express the Sry gene. We concluded that expression of the Sry gene is under the control of an epigenetic mechanism mediated by DNA methylation.

Animals↗

PubMed2004

Epigenetic control of mouse Oct-4 gene expression in embryonic stem cells and trophoblast stem cells.

The first cell differentiation event in mammalian embryogenesis segregates inner cell mass lineage from the trophectoderm at the blastocyst stage. Oct-4, a member of the POU family of transcription factors, is necessary for the pluripotency of the inner cell mass lineage. Embryonic stem (ES) cells, which contribute to all of embryonic lineages, express the Oct-4 gene. Trophoblast stem (TS) cells, which have the ability to differentiate into trophoblast lineage in vitro, never contribute to embryonic proper tissues in chimeras and differentiate only into trophoblastic cells in the placenta. Expression of the Oct-4 gene was undetectable and severely repressed in trophoblastic lineage, including the stem cells. We found that the culture of TS cells with 5-aza-2'-deoxycytidine or trichostatin A caused the activation of the Oct-4 gene. Analysis of the DNA methylation status of mouse Oct-4 gene upstream region revealed that Oct-4 enhancer/promoter region was hypomethylated in ES cells but hypermethylated in TS cells. Furthermore, in vitro methylation suppressed Oct-4 enhancer/promoter activity in reporter assay. In the placenta of Dnmt1(n/n) mutant mice, most of the CpGs in the enhancer/promoter region were unmethylated, and Oct-4 gene expression was aberrantly detected. Chromatin immunoprecipitation assay revealed that Oct-4 enhancer/promoter region was hyperacetylated in ES cells compared with TS cells, thus demonstrating that DNA methylation status is closely linked to the chromatin structure of the Oct-4 gene. Here we propose that the epigenetic mechanism, consisting of DNA methylation and chromatin remodeling, underlies the developmental stage- and cell type-specific mechanism of Oct-4 gene expression.

Animals↗

PubMed2004

Inositol deacylation of glycosylphosphatidylinositol-anchored proteins is mediated by mammalian PGAP1 and yeast Bst1p.

The inositol moiety of mammalian glycosylphosphatidylinositol (GPI) is acylated at an early step in GPI biosynthesis. The inositol acylation is essential for the generation of mature GPI capable of attachment to proteins. However, the acyl group is usually absent from GPI-anchored proteins (GPI-APs) on the cell surface due to inositol deacylation that occurs in the endoplasmic reticulum (ER) soon after GPI-anchor attachment. Mammalian GPI inositol-deacylase has not been cloned, and the biological significance of the deacylation has been unclear. Here we report a GPI inositol-deacylase-deficient Chinese hamster ovary cell line established by taking advantage of resistance to phosphatidylinositol-specific phospholipase C and the gene responsible, which was termed PGAP1 for Post GPI Attachment to Proteins 1. PGAP1 encoded an ER-associated, 922-amino acid membrane protein bearing a lipase consensus motif. Substitution of a conserved putative catalytic serine with alanine resulted in a complete loss of function, indicating that PGAP1 is the GPI inositol-deacylase. The mutant cells showed a clear delay in the maturation of GPI-APs in the Golgi and accumulation of GPI-APs in the ER. Thus, the GPI inositol deacylation is important for efficient transport of GPI-APs from the ER to the Golgi.

Acylation↗

PubMed2004

Different molecular mechanisms underlie placental overgrowth phenotypes caused by interspecies hybridization, cloning, and Esx1 mutation.

To obtain a deeper insight into the genes and gene networks involved in the development of placentopathies, we have assessed global gene expression in three different models of placental hyperplasia caused by interspecies hybridization (IHPD), cloning by nuclear transfer, and mutation of the Esx1 gene, respectively. Comparison of gene expression profiles of approximately 13,000 expressed sequence tags (ESTs) identified specific subsets of genes with changed expression levels in IHPD, cloned, and Esx1 mutant placentas. Of interest, only one gene of known function and one EST of unknown function were found common to all three placentopathies; however, a significant number of ESTs were common to IHPD and cloned placentas. In contrast, only one gene was shared between IHPD and Esx1 mutant, and cloned and Esx1 mutant placentas, respectively. These genes common to different abnormal placental growth genotypes are likely to be important in the occurrence of placentopathy.

Animals↗

PubMed2004

Expression of L-histidine decarboxylase in granules of elicited mouse polymorphonuclear leukocytes.

Infiltrating polymorphonuclear leukocytes (PMN) in the peritoneal cavity were found to express L-histidine decarboxylase (HDC), the rate-limiting enzyme of histamine synthesis, in a csein-induced peritonitis model. Expression of HDC was detected in the elicited PMN, but not in the peripheral blood leukocytes. The peritoneal lavage fluids in this model were found to augment histamine synthesis in PMN isolated from the bone marrow. Rapid post-translational processing of HDC was observed in PMN, and the dominant form of HDC was the mature 53-kDa form, which was found to co-localize with a granule enzyme, matrix metalloproteinase-9 (MMP-9). Treatment of PMN with the phorbol ester PMA, which stimulates the release of MMP-9, did not liberate the granular HDC. Immunofluorescence studies using an anti-HDC antibody strongly suggested that HDC is bound to the cytosolic side of the granule membranes. These observations suggest that HDC is induced upon infiltration of PMN into the mouse peritoneal cavity and that histamine is synthesized by HDC attached to the granule membranes of PMN.

Animals↗

PubMed2004

Virological significance of low-level hepatitis B virus infection in patients with hepatitis C virus associated liver disease.

The clinical and virological significance of low-level viremia by hepatitis B virus (HBV) in hepatitis C virus (HCV)-infected patients remains unclear. HBV-DNA and HCV-RNA were, therefore, quantitatively analyzed in livers and sera from co-infected patients. HBV-DNA and HCV-RNA were quantitated using real-time detection of polymerase chain reaction (RTD-PCR), based on Taq-Man chemistry, in 220 non-HCV-infected healthy volunteers and 93 HCV-infected patients without detectable HBsAg. Serum HBV-DNA was detected in 4 (1.8%) of 220 non-HCV-infected healthy volunteers and 32 (34.4%) of 93 HCV-infected patients without detectable HBsAg. HCV-infected patients displayed higher frequency of HBV infection than healthy volunteers (P < 0.0001). Hepatocellular carcinoma (HCC) was more frequent among co-infected patients than among HCV mono-infected patients (P < 0.001). However, quantities of HBV-DNA in sera from co-infected patients were very low (8-19,000 copies/ml). HBV-DNA was detected in liver tissue from co-infected patients at 2-20 copies per 100 hepatocytes, accounting for 1/1,000 to 1/10,000 of HBsAg positive patients. In livers of patients with HCC and HCV or HBV mono-infection, the viruses existed predominantly in non-cancerous tissue, with levels 10- to 1,000-fold and 1- to 100-fold higher than in cancerous tissue, respectively. In contrast, patients co-infected with HCV and HBV displayed decreased HBV levels in non-cancerous tissue, but no change in cancerous tissue. These results indicate that low-level HBV infection exists in HCV-infected patients. HCC was more common among HCV/HBV co-infected patients than among HCV mono-infected patients. HCV might initiate hepatocarcinogenesis, but does not necessarily determine progression to HCC.

Adult↗

PubMed2004

Adventitial cystic disease of the femoral vein: report of a case.

Adventitial cystic disease (ACD) of the veins is a rare phenomenon, and ACD of the femoral vein is particularly difficult to diagnose due to the similarity in symptoms to those of deep vein thrombosis. We report a case of ACD of the femoral vein, which was initially misdiagnosed as deep vein thrombosis, in a 48-year-old woman who presented with a painless swelling in her right lower leg. The extensive cystic involvement of the femoral vein was completely resected and reconstructed with an 8-mm ringed polytetrafluoroethylene vascular graft with good results.

Blood Vessel Prosthesis Implantation↗

PubMed2004

Rhabdoid transformation of recurrent meningioma in the cervical cord: a case report.

We report a case of persistent local recurrence of rhabdoid meningioma in the cervical spinal cord. Recently, the meningioma has been reported to be undergoing rhabdoid transformation, but the clinical course is still unclear. Histopathological examination of the tumor showed that it was composed of both meningothelial cells and rhabdoid cells. At each recurrence of the tumor, the population of the rhabdoid cells had increased and the ability to grow had also increased, confirmed by the MIB-1 labeling index. This case showed that phenotypic change of the cells with "rhabdoid" morphology may affect meningiomas and that such changes are associated with aggressive biological and clinical behavior. This newly classified tumor should be recognized in the differential diagnosis of meningioma.

Adult↗