PubMed Health⌕ Search

Biomedical subjects

T Ueki

Publications and source records attributed to T Ueki.

At least 19 recordsLinked to original sources
PubMed2006

Expression of Golf in the rat placenta: Possible implication in olfactory receptor transduction.

Olfactory receptors are G-protein coupled receptors and are encoded by an extremely large and diverse family of genes in mammals. There is increasing evidence that olfactory receptors are widely distributed in many organs, suggesting that olfactory receptors do not only recognize airborne odorants but also play important roles in chemotaxis or organ construction in embryo. In this study, we investigated whether olfactory receptors and their transduction molecule, Golf are expressed in the rat placenta. By RT-PCR, we identified 11 different olfactory receptor genes, which are all members of class II, in the rat placenta cDNAs, and our results suggested that particular members of the olfactory receptor gene family might be preferentially expressed in the placenta. By western blot analysis, we demonstrated that Golf protein is expressed in the placenta and its expression levels are developmentally regulated. We found that Golf immunoreactivity is exclusively localized to giant cell trophoblasts and spongiotrophoblast cells. These findings raised a possibility that a particular subset of olfactory receptors might be coupled with Golf and function in giant cell trophoblasts and spongiotrophoblast cells.

Animals↗
PubMed2004

Sub-genomic replicons of Tick-borne encephalitis virus.

We constructed three sub-genomic replicons of Tick-borne encephalitis virus (TBEV) (Oshima REP, Oshima REP-GFP and Oshima REP-Neo) by deleting genes coding for structural proteins without or with insertion of green fluorescent protein (GFP) or Neo genes, respectively. BHK cells transfected with Oshima REP expressed the viral non-structural antigens in immunofluorescent and western blot analyses. GFP and viral antigens were co-expressed in the transfected cells with Oshima REP-GFP. G418-resistant cells harboring Oshima REP-Neo consistently expressed the antigens without showing any apparent CPE. These replicons constructed in this study will be useful in studies on the replication, assembly and packaging of TBEV, and to develop vaccines and gene-delivering systems.

Animals↗
PubMed2004

Clinical success of Neoral absorption profile.

We investigated the clinical benefits of cyclosporine microemulsion preconcentrate (CyA-MEPC; Neoral) in 16 de novo renal transplant recipients. The dose of CyA-MEPC was managed from AUC(0-4h), with serial target values of AUC(0-4h) at 5000-->4000-->3000-->2000 ng. hr/mL. The frequency of acute rejection episodes was 25%. The decreased renal function reached a low value of 12.5%, and creatinine was stable. Therefore, setting the target AUC(0-4h) value in the early phase at 5000 ng.hr/mL is an effective strategy to prevent acute rejection episodes. The single dose of Neoral given immediately after the renal transplant was 6 mg/kg (making a daily dose of 12 mg/kg). Thereafter, the dose-normalized AUC(0-4h) was set at a constant value to 4 weeks posttransplant. At week 4, the single dose was decreased to 4 mg/kg twice daily (a daily dose of 8 mg/kg). From these studies a daily dose of 12 mg/kg is suggested to be the appropriate amount for the first dose immediately after transplant. The renal biopsy performed at 6 months posttransplant showed neither cyclosporine-induced renal impairments, nor findings of chronic rejection, suggesting that 2000 ng.hr/mL is an appropriate target AUC(0-4h) value in the maintenance phase. These results suggest that it is possible to set the target value of C2 monitoring in the maintenance phase to a value slightly lower than that proposed from other studies.

Adult↗
PubMed2002

Importance of transition zone biopsies in patients undergoing ultrasound-guided prostate systemic biopsies for the first time.

INTRODUCTION: We analyze the efficacy of routine transition zone biopsies in patients undergoing ultrasound-guided systemic prostate biopsies for the first time because of a suspicious digital rectal examination or an elevated serum prostate-specific antigen (PSA) level. PATIENTS AND METHODS: During systemic prostate biopsy two or four additional transition zone biopsies were performed in 192 consecutive patients: in 182 because of a serum PSA concentration >4.1 ng/ml and in 10 because of a suspicious digital rectal examination and a serum PSA level <4.0 ng/ml. RESULTS: The overall prostate cancer detection rate was 37.5% (72/192). In 24 patients (33.3%), cancer was only detected in the peripheral zone, in 3 (4.2%) only in the transition zone, and in 45 (62.5%) in both zones. CONCLUSION: Transition zone biopsies performed at the first time of systemic prostate biopsy seem to have a low efficacy.

Aged↗
PubMed2001

Developmental changes in PSD-95 and Narp mRNAs in the rat olfactory bulb.

Glutamate is the main neurotransmitter in the olfactory bulb. Recently, postsynaptic-density 95 (PSD-95) and neuronal activity-regulated pentraxin (Narp) have been reported to be pivotal for targeting and clustering of NMDA receptors and AMPA receptors, respectively. We thus investigated the expressions of PSD-95 and Narp mRNAs in the rat developing olfactory bulb. PSD-95 mRNA was already expressed in most neurons on the first postnatal day (P1). On the other hand, Narp mRNA expression was weakly seen only in mitral cells on P1. Thereafter, we found initial expression of Narp mRNA on P7 in periglomerular cells, and on P14 in granular cells, indicating that in the developing olfactory bulb PSD-95 mRNA expression precedes Narp mRNA expression, and that the expression pattern of Narp mRNA seems to be well correlated with the maturation of the neurons. These results indicate that PSD-95 and Narp play important roles in making efficient excitatory synapses in the developing rat olfactory bulb, and suggest that olfactory neurons might first express PSD-95 for making efficient NMDA receptors and thereafter express Narp for efficient AMPA receptors.

Animals↗
PubMed2001

Identification and characterization of differentially methylated CpG islands in pancreatic carcinoma.

To identify CpG islands differentially methylated in pancreatic adenocarcinoma, we used methylated CpG island amplification (MCA) coupled with representational difference analysis. Of 42 CpG islands identified by MCA/representational difference analysis, 7 CpG islands [methylated in carcinoma of the pancreas (MICP)] were differentially methylated in a panel of eight pancreatic cancer cell lines compared with normal pancreas. In a larger panel of 75 pancreatic adenocarcinomas, these 7 MICPs (ppENK, Cyclin G, ZBP, MICP25, 27, 36, and 38) were methylated in 93, 3, 9, 15, 48, 19, and 41% of cancers, respectively, by methylation-specific PCR but not in any of 15 normal pancreata. In pancreatic cancer cell lines, methylation of ppENK, a gene with known growth suppressive properties, was associated with transcriptional silencing that was reversible with 5-aza-2'-deoxycytidine treatment. Relationships between the methylation patterns of pancreatic adenocarcinomas and their clinicopathological features were also determined. Larger pancreatic cancers and those from older patients (P = 0.017) harbored more methylated loci than smaller tumors and those from younger patients (P = 0.017). ppENK, MICP25, and 27 were variably methylated in normal gastric, duodenal, and colonic mucosae. These data indicate that aberrant methylation of ppENK and its transcriptional repression is a common event in pancreatic carcinogenesis.

Adenocarcinoma↗
PubMed2001

Developmental changes in gephyrin and collybistin mRNA expressions in the rat olfactory bulb.

GABA and glycine are inhibitory neurotransmitters in the olfactory bulb. Recently, gephyrin, a receptor-associated peripheral membrane protein, and collybistin, a gephyrin-binding protein have been shown to be pivotal for the formation of postsynaptic glycine and GABA(A) receptor clusters. In this study, we, thus, examined expressions of gephyrin and collybistin mRNAs in the developing olfactory bulb using in situ hybridization. Although collybistin has two splice variants, we found only collybistin 1 isoform mRNA in the developing olfactory bulb. On the first postnatal day (P1), mitral cells abundantly expressed gephyrin and collybistin 1 mRNAs. However, their expressions were weak or not detected in the other regions. On P3, we first detected both transcripts in granule cells. It was on P7 when periglomerular cells first showed hybridization signals for gephyrin and collybistin mRNAs. The sequence of their expressions was well correlated with that of the maturation of individual neurons, suggesting that gephyrin and collybistin 1 mRNA expressions are induced when neurons arrive at their final destinations and ready for synaptogenesis, and that they are indispensable to make efficient inhibitory synapses in the developing rat olfactory bulb.

Animals↗
PubMed2001

Epidermal growth factor down-regulates connexin-43 expression in cultured rat cortical astrocytes.

Astrocytes are coupled via gap junction channels, predominantly formed by connexin-43 (Cx43), and contribute to neuronal function in the normal and diseased brain. In this study, we demonstrate that epidermal growth factor (EGF), applied to cortical astrocytes, results in a decrease in the expression of Cx43 mRNA and protein. We have further shown that the decrease is associated with the receptor tyrosine kinase pathway and the MEK inhibitor prevents EGF-stimulated down-regulation of Cx43 expression. These findings demonstrate a previously unknown function of EGF on cultured astrocytes, which may be relevant to the regulation of astrocytic growth and differentiation.

Animals↗
PubMed2001

Retrovirus-mediated gene therapy for hepatocellular carcinoma with reversely oriented therapeutic gene expression regulated by alpha-fetoprotein enhancer/promoter.

In the present study, to achieve more selective and efficient therapeutic gene expression in hepatoma cells, we compared the therapeutic efficacies of the retroviral vectors expressing the herpes simplex virus thymidine kinase (HSV-tk) gene by the alpha-fetoprotein (AFP) enhancer/promoter in the forward (LNAFE0.3TK) and reverse (LN[AFE0.3TK]R) orientation to the vector long terminal repeats. By Northern blotting, the level of the HSV-tk mRNA in LN[AFE0.3TK]R-infected HepG2 human hepatoma cells was much higher than that in LNAFE0.3TK-infected cells. Consistent with this, LN[AFE0.3TK]R infection into HepG2 cells caused a greater cytotoxicity by ganciclovir exposure together with a stronger bystander effect than LNAFE0.3TK infection. In an animal model, intratumorous injection of LN[AFE0.3TK]R with ganciclovir treatment resulted in pronounced growth inhibition of HepG2 tumor. Thus, the reversely oriented therapeutic gene expression under the control of AFP enhancer/promoter is a possible candidate for the retrovirus-mediated gene therapy for hepatocellular carcinoma.

Animals↗
PubMed2001

Synthetic study of macquarimicins: highly stereoselective construction of the AB-ring system.

The highly stereoselective synthesis of the AB-ring system of macquarimicins, a novel class of microbial metabolites with inhibitory activity for neutral sphingomyelinase, has been achieved. The present synthesis features the highly stereocontrolled construction of the cis-tetrahydroindan structure via the intramolecular Diels-Alder reaction of an (E,Z,E)-1,6,8-nonatriene derived from D-glyceraldehyde acetonide. Reaction: see text.

Anti-Bacterial Agents↗
PubMed2001

Molecular predictors of survival after adjuvant chemotherapy for colon cancer.

BACKGROUND: Adjuvant chemotherapy improves survival among patients with stage III colon cancer, but no reliable molecular predictors of outcome have been identified. METHODS: We evaluated loss of chromosomal material (also called loss of heterozygosity or allelic loss) from chromosomes 18q, 17p, and 8p; cellular levels of p53 and p21(WAF1/CIP1) proteins; and microsatellite instability as molecular markers. We analyzed tumor tissue from 460 patients with stage III and high-risk stage II colon cancer who had been treated with various combinations of adjuvant fluorouracil, leucovorin, and levamisole to determine the ability of these markers to predict survival. RESULTS: Loss of heterozygosity at 18q was present in 155 of 319 cancers (49 percent). High levels of microsatellite instability were found in 62 of 298 tumors (21 percent), and 38 of these 62 tumors (61 percent) had a mutation of the gene for the type II receptor for transforming growth factor beta1 (TGF-beta1). Among patients with microsatellite-stable stage III cancer, five-year overall survival after fluorouracil-based chemotherapy was 74 percent in those whose cancer retained 18q alleles and 50 percent in those with loss of 18q alleles (relative risk of death with loss at 18q, 2.75; 95 percent confidence interval, 1.34 to 5.65; P=0.006). The five-year survival rate among patients whose cancer had high levels of microsatellite instability was 74 percent in the presence of a mutated gene for the type II receptor for TGF-beta1 and 46 percent if the tumor did not have this mutation (relative risk of death, 2.90; 95 percent confidence interval, 1.14 to 7.35; P=0.03). CONCLUSIONS: Retention of 18q alleles in microsatellite-stable cancers and mutation of the gene for the type II receptor for TGF-beta1 in cancers with high levels of microsatellite instability point to a favorable outcome after adjuvant chemotherapy with fluorouracil-based regimens for stage III colon cancer.

Aged↗
PubMed2001

Isolation of Dlx and Emx gene cognates in an agnathan species, Lampetra japonica, and their expression patterns during embryonic and larval development: conserved and diversified regulatory patterns of homeobox genes in vertebrate head evolution.

Agnathan cognates of vertebrate homeobox genes, Emx and Dlx, were isolated from embryonic cDNA of a Japanese marine lamprey, Lampetra japonica. Analyses of amino acid sequences indicated that the Dlx cognate was closely related to the common ancestor of gnathostome Dlx1 and Dlx6 groups and termed LjDlx1/6. Southern blot analyses could not rule out the possibility that L. japonica possesses more than one paralog for both LjDlx1/6 and LjEmx, the lamprey cognate of Emx. Expression of LjDlx1/6 was regulated spatially as well as developmentally, and its transcripts were mainly found in the craniofacial and pharyngeal mesenchyme and in the forebrain. The expression pattern of LjEmx changed dramatically during embryogenesis; expression was seen initially in the entire neural tube and mesoderm, which were secondarily downregulated, and secondarily in cranial nerve ganglia and in the craniofacial mesenchyme. No specific expression of LjEmx was seen in the telencephalon. Comparisons of Dlx and Otx gene expression patterns suggested a shared neuromeric pattern of the vertebrate brain. Absence of Emx expression implied that the patterning of the lamprey telencephalon is not based on the tripartite plan that has been presumed in gnathostomes. Expression domains of LjDlx1/6 in the upper lip and of LjEmx in the craniofacial mesenchyme were peculiar features that have not been known in gnathostomes. Such differences in expression pattern may underlie distinct morphogenetic pathway of the mandibular arch between the agnathans and gnathostomes.

Amino Acid Sequence↗
PubMed2001

Silencing of the caspase-1 gene occurs in murine and human renal cancer cells and causes solid tumor growth in vivo.

Renal cell cancer is a unique solid tumor that occasionally shows spontaneous regression even at an advanced stage, of which the underlying mechanism is not well understood. To investigate a potential role of the pro-apoptotic molecule caspase-1 in the growth regulation of renal cell cancer, we created transfectants expressing exogenous caspase-1 from a murine renal cancer cell line, Renca. Overexpression of caspase-1 did not affect the growth of Renca cells in vitro at the exponential phase but induced apoptotic cell death at 50% to 75% confluence, whereas control cells underwent apoptosis only after reaching 100% confluence. When implanted into the flank of a syngeneic BALB/c mouse, caspase-1-overexpressing Renca cells did not effectively establish growth as a solid tumor, forming a measurable tumor in only 7 of 11 (64%) animals, whereas control cells formed a tumor in 6 of 6 (100%) animals. The growth of tumors from caspase-1-overexpressing cells slowed down markedly after the tumors reached 5 to 10 mm in diameter, and histological examination of such tumors revealed numerous apoptotic cells positively stained by TUNEL assay. Interestingly, endogenous caspase-1 was not detected in the tumors from control cells, which re-expressed caspase-1 when they were re-cultured and exposed to a demethylation reagent, 5-aza-2'-deoxycytidine. Furthermore, treatment of a human renal cancer cell line, ACHN, with 5-aza-2'-deoxycytidine also caused recovery of caspase-1 expression, which was not detected before treatment. These data suggest that silencing of caspase-1 through DNA methylation may be involved in the oncogenesis of some renal cell cancers growing as a solid tumor.

Animals↗
PubMed2001

Regulation of rat hippocampal neural cadherin in the kainic acid induced seizures.

Regulation of neural (N-) cadherin expression in the hippocampus was examined by in situ hybridization and immunohistochemistry methods in the rat model of kainic acid (KA) induced seizures. After 12 and 24 h of KA administration, mRNA expression level of N-cadherin decreased in the hippocampal CA1 and CA3 area in parallel with decrease of the number of neural cells. In contrast, after 48 h and 7 days, mRNA expression level recovered partially, although the number of neural cells remained small. In addition, immunohistochemical staining indicated that N-cadherin protein expression of survived neurons increased significantly after 48 h of KA administration. These results indicated that N-cadherin might be involved in neuronal reconstruction at the hippocampus.

Animals↗
PubMed2001

Effectiveness of endoscopic biliary drainage for unresectable hepatocellular carcinoma associated with obstructive jaundice.

Endoscopic biliary drainage (EBD) for unresectable hepatocellular carcinoma (HCC) associated with obstructive jaundice remains controversial because of the short survival of these patients. To evaluate the effectiveness of this procedure, we retrospectively studied 18 patients who had unresectable HCC with obstructive jaundice and underwent EBD with polyethylene stents, over a 10-year period. Nine patients with tumor thrombus involving the first branches of the portal vein or portal trunk (Vp3) formed group A and the other 9 (Vp0-Vp2) formed group B. The serum albumin level and serum total bililubin level differed significantly between the two groups (P < 0.05 and P < 0.005. Student's t-test), but prothrombin time did not. The obstructive jaundice was mainly caused by direct tumor invasion in 6 patients from group A and 3 from group B, by blood clots and/or tumor fragments in 2 patients from group A and 3 from group B, by the tumor protruding into the common hepatic duct in 2 patients from group B. and by tumor compression of the common bile duct in 1 patient from each group. Drainage was successful in 4 patients (44%) from group A and in all 9 patients (100%) from group B. Among the 5 patients with unsuccessful drainage in group A, 4 had obstruction of both the left and right hepatic ducts and 3 had multiple tumors in both lobes. The mean survival time (mean +/- SD) after EBD was 47 +/- 44 days in group A and 181 +/- 70 days in group B. In group A. the average survival time was only 85 days in the 4 patients with successful drainage. However, an improvement in the quality of life after EBD was observed in one-third of the Vp3 patients and in all of the Vp0-Vp2 patients. In summary, satisfactory palliation is possible with successful EBD, but this is difficult in most patients with Vp3 portal thrombus, direct tumor invasion involving both hepatic ducts, and multiple tumors in both lobes. It is important to determine the site, extent, and nature of the obstruction, as well as liver function and the presence of portal thrombus, before performing EBD.

Aged↗
PubMed2001

Subunit C of the vacuolar-type ATPase from the vanadium-rich ascidian Ascidia sydneiensis samea rescued the pH sensitivity of yeast vma5 mutants.

A vanadium-accumulating ascidian, Ascidia sydneiensis samea, expresses vacuolar-type H(+)-ATPases (V-ATPases) on the vacuole membrane of the vanadium-containing blood cells known as vanadocytes. Previously, we showed that the contents of their vacuoles are extremely acidic and that a V-ATPase-specific inhibitor, bafilomycin A(1), neutralized the contents of the vacuoles. To understand the function of V-ATPase in vanadocytes, we isolated complementary DNA encoding subunit C of V-ATPase from vanadocytes because this subunit has been known to be responsible for the assembly of V-ATPases and to regulate the ATPase activity of V-ATPases. The cloned cDNA was 1443 nucleotides in length, and encoded a putative 384 amino acid protein. By expressing the ascidian cDNA for subunit C under the control of a galactose-inducible promoter, the pH-sensitive phenotype of the corresponding vma5 mutant of a budding yeast was rescued. This result showed that the ascidian cDNA for subunit C functioned in yeast cells.

Journal Article↗
PubMed2001

STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas.

Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as well as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of some IPMNs.

AMP-Activated Protein Kinase Kinases↗