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S Maeda

Publications and source records attributed to S Maeda.

At least 181 records · Page 10Linked to original sources

Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats.

Thiazolidinedione (TZD) compounds are widely used as oral hypoglycemic agents. Herein, we provide evidence showing that troglitazone, one of the TZD compounds, is able to prevent glomerular dysfunction in diabetic rats through a novel mechanism independent of its insulin-sensitizing action. We examined the effect of troglitazone on functional and biochemical parameters of glomeruli in streptozotocin-induced diabetic rats. Troglitazone was able to prevent not only diabetic glomerular hyperfiltration and albuminuria, but an increase in mRNA expression of extracellular matrix proteins and transforming growth factor-beta1 in glomeruli of diabetic rats, without changing blood glucose levels. Biochemically, an increase in diacylglycerol (DAG) contents and the activation of the protein kinase C (PKC)-extracellular signal-regulated kinase (ERK) pathway in glomeruli of diabetic rats were abrogated by troglitazone. The activation of DAG-PKC-ERK pathways in vitro in mesangial cells cultured under high glucose conditions was also inhibited by troglitazone. Troglitazone enhanced the activities of DAG kinase, which could metabolize DAG to phosphatidic acid, in both glomeruli of diabetic rats and mesangial cells cultured under high glucose conditions. Surprisingly, pioglitazone, another TZD compound without alpha-tocopherol moiety in its structure, also prevented the activation of the DAG-PKC pathway and activated DAG kinase in mesangial cells cultured under high glucose conditions. These results may identify the TZDs as possible new therapeutic agents for diabetic nephropathy that prevent glomerular dysfunction through the inhibition of the DAG-PKC-ERK pathway.

Albuminuria↗

Isolation of rat mitochondrial transcription factor A (r-Tfam) cDNA.

We have isolated rat mitochondrial transcription factor A (Tfam; formerly known as mtTFA) cDNA clones from a rat cerebellum cDNA library using human Tfam cDNA as a probe. The deduced amino acid sequence of r-Tfam shows 62% and 89% overall identity to human and mouse Tfam, respectively. We also show the presence of two r-Tfam isoforms in testis as for mouse. Our findings suggest that the mechanisms underlying transcription of mitochondrial genes are conserved among rat, mouse, and human.

Amino Acid Sequence↗

The role of S100A4 gene encoding an S100-related calcium-binding protein in human bile duct adenocarcinoma cell lines: correlation of S100A4 expression and invasive growth in Matrigel Matrix.

S100A4, one of the tandemly arranged S100 genes at chromosome 1q21, has been suggested to play a functional role in cell motility and invasiveness of tumor cell growth. We investigated the expression of S100A4 and the in vitro invasiveness of 4 human bile duct adenocarcinoma cell lines by the Matrigel assay. S100A4 was abundantly expressed in 2 adenocarcinoma cell lines whose growth pattern was highly invasive. Induction of antisense S100A4 into one of the cell lines decreased S100A4 mRNA levels and reduced invasiveness. In contrast, induction of sense S100A4 expression into non-invasive KMBC adenocarcinoma cells, which originally lacked S100A4 expression, resulted in apparent invasive potential in the transfected cells compared with the cells with the vector alone. These results suggest that S100A4 expression is well correlated with the invasiveness of human bile duct adenocarcinomas.

Adenocarcinoma↗

Evaluation of two different homogeneous assays for LDL-cholesterol in lipoprotein-X-positive serum.

BACKGROUND: The purpose of this study was to evaluate the performance of two homogeneous assays for LDL-cholesterol (LDL-C), a polyethylene/cyclodextrin (PC) assay and a detergent (D) assay, which are based on different principles, in cholestatic serum. METHODS: We compared serum LDL-C concentrations determined by the two assays for healthy normolipidemic subjects (n = 42) and cholestatic patients (n = 51). LDL-C concentrations obtained with the homogeneous assays were also compared with those obtained by HPLC for patients' sera. In the interference study, conjugated bile acids were added to normal serum, and their effects on the two assays were examined. The effects of lipoprotein-X (LP-X), intermediate-density lipoprotein (IDL), and apolipoprotein (apo) E-rich HDL on the LDL-C assays were also investigated by adding these lipoproteins to normal serum. RESULTS: The LDL-C concentrations obtained with the D assay were higher than those obtained with the PC assay in the serum with high LP-X. The bias for LDL-C vs LP-X in cholestatic serum correlated with LP-X concentration (r = 0.582; P: <0.0001; n = 51). In the interference study, no effect of bile acids on the LDL-C assays was observed. However, the D assay measured 51.0% of the cholesterol in LP-X, whereas no reactivity was observed for LP-X in the PC assay. In addition, the D assay and the PC assay measured IDL-cholesterol at 31.2% and 52.4%, respectively, and measured apo E-rich HDL-C at 7.6% and 17.8%, respectively. CONCLUSIONS: Although both homogeneous LDL-C assays are suitable for most cases, the present study showed that each homogeneous assay has a different limitation for cholestatic serum with gross alterations in lipoproteins.

Adult↗

Mycobacterium leprae typing by genomic diversity and global distribution of genotypes.

The genetic diversity and related global distribution of 51 Mycobacterium leprae isolates were studied. Isolates were obtained from leprosy patients from 12 geographically distinct regions of the world and two were obtained from nonhuman sources. Polymerase chain reaction (PCR) followed by DNA sequencing was performed targeting the rpoT gene of M. leprae. Isolates were classified into two groups based on the number of tandem repeats composed of 6 base pairs in the rpoT gene. Isolates from Japan (except Okinawa) and Korea belonged to one group, while those from Southeast Asian countries, Brazil, Haiti and Okinawa in Japan belonged to a second genotype. M. leprae obtained from two nonhuman sources (an armadillo and a mangabey monkey) revealed the latter genotype. These results demonstrate the genetic diversity of M. leprae and the related genotype-specific distribution in the world.

Bacterial Proteins↗

[A case of primary renal carcinoid tumor].

The patient was a 44-year-old woman in whom a mass of the right kidney was found when she underwent abdominal ultrasonography in a physical checkup. The computed tomography of abdomen and the magnetic resonance imaging of abdomen revealed a 3 x 3 cm solid mass at the right kidney. Excretory urograms showed a deformity of the right collecting system due to a mass lesion. The specimen of the resected tumor showed a cellular arrangement specific to carcinoid tumor and positive reaction of Grimelius stain. Electron microscopy confirmed the presence of dense-core granules in the tumor cells. Gastrointestinal investigation after the operation revealed no particular findings suggesting a carcinoid syndrome. No evidence of metastasis or recurrence was noted for 5 months after the operation. This was a very rare case of primary renal carcinoid tumor, representing the 12th case in the literature in Japan.

Adult↗

[Food allergy].

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Allergens↗

A new member of the GTPase superfamily that is upregulated in highly metastatic cells.

Two sublines of B16 melanoma cells, F10 and BL6, are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. We found a new member of the GTPase superfamily, namely TIB929, which displayed an induction of expression in BL6 cells. It conserved three consensus sequences for GTP-binding site motifs and showed a significant homology to the yeast Gtr2 gene throughout the coding sequence. TIB929 was expressed ubiquitously in human tumor cells, with a marked expression in highly metastatic cells. TIB929 was mapped on mouse chromosome 4D, syntenic to human chromosome 1p. The results suggested an involvement of TIB929 in malignant progression.

Amino Acid Sequence↗

rDLG6: a novel homolog of Drosophila DLG expressed in rat brain.

Drosophila DLG (Discs Large Tumor Suppresser Protein) is a component of septate junctions, and disruption of its gene leads to over growth of imaginal discs. Homologs of Drosophila DLG recently isolated from mammalian tissue have been classified as members of the MAGUK (Membrane Associated GUanylate Kinase) superfamily of proteins. Using a modified RT-PCR method applied to rat tissues, we have isolated cDNA clones encoding a novel MAGUK family member that we have named rDLG6. Immunoblot and immunohistochemical analyses revealed that rDLG6 protein is predominantly expressed in brain. GST pull-down assays showed that the PDZ domain of rDLG6 protein binds to the C-terminus of the AMPA (alpha-Amino-3-hydroxy-5-Methyl-isoxazole-4-Propionic Acid) receptor GluR2 subunit.

Amino Acid Sequence↗

Telomerase activity in hybrids between telomerase-negative and telomerase-positive immortal human cells is repressed in the different complementation groups but not in the same complementation group of immortality.

The expression of telomerase is essential for cells to be immortalized, and most immortal cell lines possessed telomerase activity. Using the cell fusion technique, it has been shown that mortal and telomerase-negative phenotypes of normal cells are dominant over immortal and telomerase-positive phenotypes, suggesting that the normal cells possessed dominant repressor-type activity for telomerase expression. Several telomerase-negative immortal human cell lines were reported, in which telomerase-independent mechanisms was supposed to maintain telomere length. We aimed at seeing whether the telomerase-negative phenotype of these immortal cells is dominant over telomerase-positive phenotype of other immortal cells in correlation with cellular mortality. Results showed that, when telomerase-positive and -negative immortal parental cell lines belonging to the different complementation groups were fused, telomerase-negative mortal hybrid clones arose, i.e. telomerase-negative phenotype was dominant as well as mortal phenotype. However, when immortal hybrid cells arose from telomerase-positive and -negative immortal parents belonging to either the same or different complementation groups, they were all telomerase-positive, i.e. telomerase-negative phenotype appeared to be recessive. Telomerase-negative immortal hybrid was never established from any combinations between telomerase-negative and -positive immortal parental cells.

Base Sequence↗

Transcriptional regulation of rat cyclin D1 gene by CpG methylation status in promoter region.

Cyclin D1, a G(1)/S cell cycle-regulating oncogene, is known to be transcriptionally regulated by numerous growth factors. We cloned and characterized the rat cyclin D1 gene 5'-flanking region and, by species- and subspecies-matched transient transfection studies, found that a basic promoter structure with a cAMP response element and two continuous Sp1-binding sites was crucial for the steady-state expression of the cyclin D1 gene. Furthermore, the methylation status especially around two continuous Sp1-binding sites was found to be an important epigenetical mechanism determining the steady-state expression level in rat leukemic cell lines K4D, K4DT, and K4D16. Whether or not epigenetic control of the cyclin D1 gene existed among normal rat tissues was further examined by high sensitivity mapping of the methylated cytosine. In normal rat tissues, the methylated cytosines at non-CpG loci within two continuous Sp1-binding sites were observed in uterine stromal cells of the basal layer and found to be demethylated in the functioning layer, possibly by a passive demethylation mechanism through cell division. Since in the passive demethylation process Sp1-binding sites remain methylated in a part of the cell population, methylated cytosines at Sp1-binding sites may be essential for keeping a number of the stromal cells in the basal layer live against estrogen-induced proliferation that leads to either apoptosis or compaction.

Animals↗

Sequence analysis of the Xestia c-nigrum granulovirus genome.

The nucleotide sequence of the Xestia c-nigrum granulovirus (XcGV) genome was determined and found to comprise 178,733 bases with a G+C content of 40.7%. It contained 181 putative genes of 150 nucleotides or greater that showed minimal overlap. Eighty-four of these putative genes, which collectively accounted for 43% of the genome, are homologs of genes previously identified in the Autographa californica multinucleocapsid nucleopolyhedrovirus (AcMNPV) genome. These homologs showed on average 33% amino acid sequence identity to those from AcMNPV. Several genes reported to have major roles in AcMNPV biology including ie-2, gp64, and egt were not found in the XcGV genome. However, open reading frames with homology to DNA ligase, two DNA helicases (one similar to a yeast mitochondrial helicase and the other to a putative AcMNPV helicase), and four enhancins (virus enhancing factors) were found. In addition, several ORFs are repeated; there are 7 genes related to AcMNPV orf2, 4 genes related to AcMNPV orf145/150, and a number of repeated genes unique to XcGV. Eight major repeated sequences (XcGV hrs) that are similar to sequences found in the Trichoplusia ni GV genome (TnGV) were found.

Amino Acid Sequence↗

Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene.

The nucleotide sequence analysis of the dihydropteroate synthase (DHPS) gene of six diaminodiphenylsulfone-resistant Mycobacterium leprae strains revealed that the mutation was limited at highly conserved amino acid residues 53 or 55. Though the mutation at amino acid residue 55 or its homologous site has been reported in other bacteria, the mutation at residue 53 is the first case in bacteria. This is the first paper which links the mutations in DHPS and sulfonamide resistance in M. leprae. This finding is medically and socially relevant, since leprosy is still a big problem in certain regions.

Dapsone↗

An aggressive familial amyloidotic polyneuropathy caused by a new variant transthyretin Lys 54.

Histologic examination of sural nerve of a 32-year-old man with an aggressive polyneuropathy associated with autonomic failure demonstrated amyloid deposition, and familial amyloidotic polyneuropathy (FAP) was diagnosed. Immunohistochemical staining showed transthyretin (TTR) staining of the amyloid deposits in nerve. Sequencing revealed G to A transition in the codon 54 causing TTR Lys 54. This is a new variant TTR associated with aggressive FAP.

Adult↗

Methylglyoxal modification of protein. Chemical and immunochemical characterization of methylglyoxal-arginine adducts.

Methylglyoxal (MG), an endogenous metabolite that increases in diabetes and is a common intermediate in the Maillard reaction (glycation), reacts with proteins and forms advanced glycation end products. In the present study, we identify a novel MG-arginine adduct and also characterize the structure of a major fluorescent adduct. In addition, we describe the immunochemical study on the MG-arginine adducts using monoclonal antibody directed to MG-modified protein. Upon incubation of Nalpha-acetyl-L-arginine with MG at 37 degrees C, two nonfluorescent products and one fluorescent product were detected as the major products. The nonfluorescent products were identified as the Ndelta-(5-hydro-5-methyl-4-imidazolon-2-yl)-L-ornithine derivatives (5-hydro-5-methylimidazolone) and a novel MG-arginine adduct having a tetrahydropyrimidine moiety (Ndelta-(4-carboxy-4,6-dimethyl-5, 6-dihydroxy-1,4,5,6-tetrahydropyrimidine-2-yl)-L-ornithine). On the basis of the following chemical and spectroscopic evidence, the major fluorescent product, putatively identified as Ndelta-(5-methylimidazolon-2-yl)-L-ornithine (5-methylimidazolone), was found to be identical to Ndelta-(5-hydroxy-4, 6-dimethylpyrimidine-2-yl)-L-ornithine (argpyrimidine): (i) the low and high resolution fast atom bombardment-mass spectrometry gave a molecular ion peak at m/z of 297 (M+H) and a molecular formula of C10H25O6N4, respectively, which coincided with argpyrimidine; (ii) the 1H NMR spectrum of this product in d6-Me2SO showed a singlet at 2.10 ppm corresponding to six protons; (iii) the peak corresponding to the 5-methylimidazolone derivative was not detected by the liquid chromatography-mass spectrometry with the mode of selected ion monitoring; (iv) incubation of 5-hydro-5-methylimidazolone, a putative precursor of 5-methylimidazolone, at 37 degrees C for 14 days scarcely generated 5-methylimidazolone. On the other hand, as an immunochemical approach to the detection of these MG adducts, we raised the monoclonal antibodies (mAb3C and mAb6B) directed to the MG-modified protein and found that they specifically recognized the major fluorescent product, argpyrimidine, as the dominant epitope. The immunohistochemical analysis of the kidneys from diabetic patients revealed the localization of argpyrimidine in intima and media of small artery walls. Furthermore, the accumulation of argpyrimidine was also observed in some arterial walls of the rat brain after middle cerebral artery occlusion followed by reperfusion. These results suggest that argpyrimidine may contribute to the progression of not only long term diabetic complications, such as nephropathy and atherosclerosis, but also the tissue injury caused by ischemia/reperfusion.

Animals↗

Evidence for the collateral innervation of the esophagus and the heart from neurons in the compact formation of the nucleus ambiguus of the rat.

We investigated whether the heart receives collateral projections from the neurons which innervate the esophagus with a retrograde double-labeling method using two fluorescent tracers. Following injections of True Blue (TB) into the esophagus and Diamidino Yellow (DY) into the heart, about 21.9% of the labeled esophageal motoneurons in the compact formation of the nucleus ambiguus (AmC) were retrogradely double labeled. No single-labeled cardiac motoneurons were found in the AmC. The present results provide anatomical substrates for the esophagocardiac reflex.

Amidines↗

Morphine prevents peroxynitrite-induced death of human neuroblastoma SH-SY5Y cells through a direct scavenging action.

N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC12), a nitric oxide donor, 3-morpholinosydnonimine (SIN-1), a generator of peroxynitrite (ONOO-), and peroxynitrite induced cell death accompanied by DNA fragmentation in human neuroblastoma SH-SY5Y cell cultures. Morphine prevented the cell death induced by SIN-1 or peroxynitrite, but not that induced by NOC12. The protective effect of morphine was concentration-dependent (10-100 microM), but was not antagonized by naloxone. The selective ligands for opioid receptor subtypes, [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin (DAMGO, micro-opioid receptor agonist), [D-Pen2,5]enkephalin (DPDPE, delta-opioid receptor agonist) and trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)benze neacetamide (U-50488, kappa-opioid receptor agonist) even at the concentration of 100 microM did not prevent the cell death induced by SIN-1. From measurement of the absorbance spectrum of peroxynitrite, the decomposition of peroxynitrite in 0.25 M potassium phosphate buffer (pH 7.4) was very rapid and complete within seconds. However, the absorbance was very stable in the presence of morphine. In addition, morphine inhibited peroxynitrite-induced nitration of tyrosine in a concentration-dependent manner. These results indicate that morphine rapidly reacts with peroxynitrite. The present study showed that morphine prevented peroxynitrite-induced cell death through its direct scavenging action, suggesting that morphine can protect cells against damage caused by peroxynitrite.

Cell Death↗