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Biomedical subjects

T Endo

Publications and source records attributed to T Endo.

At least 361 records · Page 20Linked to original sources
PubMed1998

Granisetron, a 5-HT3 receptor antagonist, inhibited cisplatin-induced 5-hydroxytryptamine release in the isolated ileum of ferrets.

We investigated the influence of granisetron, a 5-HT3 receptor antagonist, on the increase in 5-hydroxytryptamine (5-HT) release induced by cisplatin from the isolated ileum of the ferret, a species known to vomit in response to cisplatin. 2-Methyl-5-HT, a selective 5-HT3 receptor agonist, increased the release of 5-HT from the ferret ileum in a concentration-dependent manner within the range of 10(-7) to 10(-6)M. The 5-HT release induced by 2-methyl-5-HT was significantly inhibited by a concomitant perfusion with granisetron (10(-6)M). Cisplatin also increased the 5-HT release from the ferret ileum within the range of 10(-8) to 10(-6)M, in a concentration-dependent manner. Granisetron (10(-6)M) also significantly inhibited the cisplatin-induced 5-HT release. Since the cisplatin-induced 5-HT release was significantly inhibited by tetrodotoxin, the possible involvement of an interneuron pathway in the cisplatin-induced 5-HT release mechanism was suggested in the ileal tissue. It is likely that granisetron inhibited the cisplatin-induced 5-HT release from the gut EC cells by producing blockade of an EC cell 5-HT3 receptor.

Animals↗
PubMed1998

Flare response seen in therapy for osteomalacia.

We report an interesting case of osteomalacia in which flare response was seen during therapy. The first 99mTc-methylene diphosphonate bone scan showed increased bilateral and symmetric uptake in the ribs, clavicles and iliac bones. Thoracic CT showed symmetric radiolucent seams (Looser's zones) in both ribs, which were pathognomonic of osteomalacia. After initiation of therapy with vitamin D, the patient's subjective symptoms gradually were relieved. On a second bone scan 4 mo. after initiation of therapy, the hot spots in the ribs remained unchanged. Uptake in the bilateral clavicles had become more intense, and new hot spots were recognized in the right lower ribs and left tibia. A third bone scan after 10 mo. demonstrated an obvious decrease in the number and intensity of the hot spots. Increased uptakes in the second scan were thought to be a flare response caused by therapy.

Aged↗
PubMed1998

Differential effects of systemic morphine on responses elicited by tooth pulp stimulation of nociceptive neurons in lateral and medial thalamic nuclei.

The effects of intravenous morphine on responses of feline thalamic nociceptive neurons receiving afferent input from the tooth pulp (TP) were investigated. Morphine suppressed responses to TP stimulation in both tooth pulp specific (TPS) and wide dynamic range (WDR) neurons with TP input recorded from the nucleus ventralis posteromedialis (VPM). However, there was scant morphine effect on responses to stimulation of trigeminothalamic tract (TTT) fibers in the trigeminal medial lemniscus. Furthermore, in nociceptive neurons with TP input recorded from nucleus centralis lateralis (CL) and parafascicularis (Pf) of the intralaminar nuclei, intravenous morphine suppressed responses both to stimulation of the mesencephalic reticular formation (MRF) as well as TP stimulation. The suppressive action of morphine on responses elicited by TP stimulation of VPM, CL and Pf neurons was antagonized by intravenous naloxone (1 mg/kg). Results suggest that intravenous morphine suppresses synaptic transmission of nociceptive impulses in the intralaminar nuclei as well as in the lower brain stem but not in the VPM.

Analgesics, Opioid↗
PubMed1998

Changes in the weight of the thymus after birth and in pregnancy in mice.

The changes in the weight of thymus with age (days after birth) and effects of pregnancy on the weight of thymus were examined using mice. The weight of thymus increased after birth, and reached the maximum (107.5 mg) at the age of 40 days. It started to decrease, and became 48.9 mg at the age of 100 days. Thus, age-related involution of the thymus in the female mice had started 50 days after birth. The weight of thymus was markedly reduced by pregnancy. The weight of thymus at the age of 60 days was 74.8 mg in the intact mice and 19.7 mg in the pregnant mice. Pregnancy greatly affects the weight of the thymus.

Aging↗
PubMed1997

Evolutionary significance of intra-genome duplications on human chromosomes.

Phylogenetic analyses indicated that a series of paralogous gene pairs, found in two extensive regions on human chromosomal bands 6p21.3 and 9q33-34, were created by at least two independent duplications. The duplicated genes on chromosomal band 6p21.3 include the genes for type 11 collagen alpha2 subunit (COL11A2), NOTCH4 (mouse int-3 homologue), 70 kDa heat shock protein (HSPA1A, HSPA1B, and HSPA1L), valyl-tRNA synthetase 2 (VARS2), complement components (C2 and C4), pre-B cell leukemia transcription factor 2 (PBX2), retinoid X receptor beta (RXRB), NAT/RING3, and four other proteins. Their paralogous genes on chromosomal band 9q33-34 are genes for type 5 collagen alpha1 subunit (COL5A1), NOTCH1, 78 kDa glucose-regulated protein (HSPA5), valyl-tRNA synthetase 1 (VARS1), complement component V (C5), PBX3, retinoid X receptor alpha (RXRA), ORFX/RING3L, and others. Among these, the genes for collagen, complement components, NAT/RING3, PBX, and RXR appear to have been duplicated around the time of vertebrate emergence, supporting the idea that they were duplicated simultaneously at that time. Another group of genes that includes NOTCH and HSP appear to have diverged long before that time. A comparison of the physical maps of these two regions revealed that the genes which duplicated in the same period were arranged in almost the same order in the two regions, with the assumption of a few chromosomal rearrangements. We propose a possible model for the evolution of these regions, taking into account the molecular mechanisms of regional duplication, gene duplication, translocation, and inversion. We also propose that a comparative mapping of paralogous genes within the human genome would be useful for identifying new genes.

Animals↗
PubMed1997

A novel gastric-cancer-associated mucin antigen defined by a monoclonal antibody A3D4.

De-glycosylation of mucins may expose new tumor-associated core protein epitopes. In this study, to attempt to develop useful markers for gastric cancers, we have purified and de-glycosylated gastric mucin and tried to establish monoclonal antibodies (MAbs). A MAb designated A3D4 among established MAbs was shown to react with gastric cancer with high frequency, but not with normal gastric epithelium. Among normal digestive organs, only the colon and gall bladder were positive for MAb A3D4. The incidence of positivity in gastric cancer was 75% for intestinal-type adenocarcinoma (n = 28), 40% for solid-type adenocarcinoma (n = 5) and 33% for signet/scirrhous-type adenocarcinoma (n = 15). Interestingly, adenoma and intestinal metaplasia (IM) with chronic gastritis or peptic ulcer were negative for MAb A3D4, whereas 8 out of 13 cases (62%) of IM with gastric cancer was positive. Western-blot analysis using the lysate from normal colon tissues revealed a high-molecular-weight (> 300-kDa) smear-like band. Immunohistochemical analysis indicated that the reactivity of MAb A3D4 was clearly increased when tissue sections were pre-treated with periodic acid or O-glycanase, while it was decreased by pre-treatment with trypsin or protease V8. There was no reactivity with the synthetic peptide encompassing the tandem-repeat sequence of MUC2 or MUC3. These data suggest that MAb A3D4 detects a novel gastric-cancer-associated mucin antigen whose epitope may be peptide in nature.

Adenocarcinoma↗
PubMed1997

New missense mutation in the alpha-sarcoglycan gene in a Japanese patient with severe childhood autosomal recessive muscular dystrophy with incomplete alpha-sarcoglycan deficiency.

A new homozygous alpha-sarcoglycan (adhalin) gene mutation was found in a Japanese patient with severe childhood autosomal recessive muscular dystrophy (SCARMD). Muscle biopsy specimens from the patient showed marked reduction but not complete deficiency of alpha-sarcoglycan. The sequence of part of exon 3 of the alpha-sarcoglycan gene exhibited a cytosine to thymidine substitution at nucleotide position 220. Since the same mutation was not found in 100 normal control samples, this new alpha-sarcoglycan gene mutation is not a polymorphism but is presumed to be responsible for the marked reduction of alpha-sarcoglycan in skeletal muscle. Most patients with homozygous alpha-sarcoglycan gene mutation were reported to show complete alpha-sarcoglycan deficiency. Present case showed the homozygous missense mutation of alpha-sarcoglycan and associated with incomplete alpha-sarcoglycan deficiency and severe clinical phenotype.

Action Potentials↗
PubMed1997

Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton.

During an attempt to elucidate regulatory mechanisms of skeletal muscle cell differentiation, we cloned cDNAs encoding a novel small GTPase from cDNA libraries of the mouse skeletal muscle cell line C2 and rat brain. It was designated as M-Ras due to the structural similarity to Ras family proteins. M-Ras contained conserved motifs for GDP/GTP-binding and GTPase activities, whereas it varied from the other Ras family proteins at several amino acids within the extended effector domain. From the C-terminal sequence, M-Ras is presumed to be anchored to the cell membrane with a geranylgeranyl group in combination with a polybasic region. Bacterially expressed recombinant M-Ras exerted the GTP-binding and GTPase activities. A mutant M-RasG22V was unable to hydrolyze bound GTP, indicating that it serves as a constitutively active form. Epitope-tagging experiments showed that M-Ras was concentrated on certain plasma membrane-associated structures. Transfection of M-Ras cDNA and microinjection of the M-RasG22V protein into fibroblasts induced formation of the peripheral microspikes. In addition, the actin stress fibers disappeared and instead numerous actin foci were formed in the injected cells. The transfected cells eventually exhibited dendritic appearances with microspikes. Consequently, M-Ras is likely to participate in reorganization of the actin cytoskeleton.

3T3 Cells↗
PubMed1997

Transcription of the thyroid transcription factor-1 (TTF-1) gene from a newly defined start site: positive regulation by TTF-1 in the thyroid.

Regulation of the thyroid transcription factor-1 (TTF-1) gene expression in the thyroid was investigated. We identified a new transcription start site as nucleotide (nt) -1917, 1700 bp upstream of previously described site, and the region encompassing nt -1242 to -14 as the first intron. Although a probe targeting exon 2 hybridized to both 3.7 and 2.7 kp transcripts, a probe targeting newly identified exon 1 mainly reacted with 3.7 kb transcript, indicating that there exsits a transcript from -1917. Chloramphenicol acetyltransferase (CAT) reporter gene assays demonstrated that 5'-flanking region of the start site exhibited promoter activity in FRTL-5 cells but not in rat liver cells, suggesting that this region confers the thyrocyte-selective expression of the gene. Two consensus TTF-1 binding motifs were detected in this promoter region, and electrophoretic mobility-shift assays showed that oligonucleotide probes, each containing one of these motifs, formed a complex with the recombinant TTF-1 homeodomain. Moreover, recombinant TTF-1 increased the transcriptional activity in FRT cells which do not express TTF-1. These results suggest that transcription from the newly identified start site in the TTF-1 gene is positively regulated by TTF-1 in the thyroid.

Animals↗
PubMed1997

Structural identification of the myo-inositol 1,4,5-trisphosphate-binding domain in rat brain inositol 1,4,5-trisphosphate 3-kinase.

A series of key amino acids involved in Ins(1,4,5)P3 (InsP3) binding and catalytic activity of rat brain InsP3 3-kinase has been identified. The catalytic domain is at the C-terminal end and restricted to a maximum of 275 amino acids [Takazawa and Erneux (1991) Biochem. J. 280, 125-129]. In this study, newly prepared 5'-deletion and site-directed mutants have been compared both for InsP3 binding and InsP3 3-kinase activity. When the protein was expressed from L259 to R459, the activity was lost but InsP3 binding was conserved. Another deletion mutant that had lost only four amino acids after L259 had lost InsP3 binding, and this finding suggests that these residues (i.e. L259DCK262) are involved in InsP3 binding. To further support the data, we have produced two mutants by site-directed mutagenesis on residues C261 and K262. The two new enzymes were designated M4 (C261S) and M5 (K262A). M4 showed similar Vmax and Km values for InsP3 and ATP to wild-type enzyme. In contrast, M5 was totally inactive but had kept the ability to bind to calmodulin-Sepharose. C-terminal deletion mutants that had lost five, seven or nine amino acids showed a large decrease in InsP3 binding and InsP3 3-kinase activity. One mutant that had lost five amino acids (M2) was purified to apparent homogeneity: Km values for both substrates appeared unchanged but Vmax was decreased approx. 40-fold compared with the wild-type enzyme. The results indicate that (1) a positively charged amino acid residue K262 is essential for InsP3 binding and (2) amino acids at the C-terminal end of the protein are necessary to act as a catalyst in the InsP3 3-kinase reaction.

Amino Acid Sequence↗
PubMed1997

Organization of a large gene cluster encoding ribosomal proteins in the cyanobacterium Synechococcus sp. strain PCC 6301: comparison of gene clusters among cyanobacteria, eubacteria and chloroplast genomes.

The structure of a large gene cluster containing 22 ribosomal protein (r-protein) genes of the cyanobacterium Synechococcus sp. strain PCC6301 is presented. Based on DNA and protein sequence analyses, genes encoding r-proteins L3, L4, L23, L2, S19, L22, S3, L16, L29, S17, L14, L24, L5, S8, L6, L18, S5, L15, L36, S13, S11, L17, SecY, adenylate kinase (AK) and the alpha subunit of RNA polymerase were identified. The gene order is similar to that of the E. coli S10, spc and alpha operons. Unlike the corresponding E. coli operons, the genes for r-proteins S4, S10, S14 and L30 are not present in this cluster. The organization of Synechococcus r-protein genes also resembles that of chloroplast (cp) r-protein genes of red and brown algal species. This strongly supports the endosymbiotic theory that the cp genome evolved from an ancient photosynthetic bacterium.

Amino Acid Sequence↗
PubMed1997

Analysis of the functional domain of the rat liver mitochondrial import receptor Tom20.

Tom20 is an outer mitochondrial membrane protein and functions as a component of the import receptor complex for the cytoplasmically synthesized mitochondrial precursor proteins. It consists of the N-terminal membrane-anchor segment, the tetratricopeptide repeat (TPR) motif, a charged amino acids-rich linker segment between the membrane anchor and the TPR motif, and the C-terminal acidic amino acid cluster. To assess the functional significance of these segments in mammalian Tom20, we cloned rat Tom20 and expressed mutant rat Tom20 proteins in Deltatom20 yeast cells and examined their ability to complement the defects of respiration-driven growth and mitochondrial protein import. Tom20N69, a mutant consisting of the membrane anchor and the linker segments, was targeted to mitochondria and complemented the growth and import defects as efficiently as wild-type Tom20, whereas a mutant lacking the linker segment did not. In vitro protein import into mitochondria isolated from the complemented yeast cells revealed that the precursor targeted to yeast Tom70 was efficiently imported into the mitochondria via rat Tom20N69. Thus the linker segment is essential for the function of rat Tom20, whereas the TPR motif and the C-terminal acidic amino acids are not.

Amino Acid Sequence↗
PubMed1997

Decreased sensitivity of carcinoembryonic antigen cDNA-transfected cells to adriamycin.

Carcinoembryonic antigen (CEA) is a heavily glycosylated protein and is expressed at a high frequency in adenocarcinomas, which are known to be one of the cancers most resistant to chemotherapeutic agents. In this study, with the aim to elucidate whether CEA participates in drug resistance or not, we tested the adriamycin (ADR) sensitivity of CEA transfectants of H-ras-transformed NIH 3T3 cells in vitro and in vivo. The ADR sensitivity of CEA transfectants in vitro was evaluated as growth (% of control) when incubated with various concentrations of ADR, and showed that they were higher than those of mock transfectants. The decreased ADR sensitivity of CEA transfectants in vivo was also observed as an increase in tumor size after intraperitoneal administration of ADR into SCID mice. To define the mechanisms for resistance, the accumulation and efflux of ADR in transfectants was examined. The rate of ADR accumulation in CEA transfectants was reduced compared to mock transfectants, caused at least partly by an increased efflux out of the cells. Furthermore, the modification of N-glycan on CEA by deoxymannojirimycin, an N-glycosylation processing inhibitor, partially restored ADR sensitivity of CEA transfectants, suggesting an involvement of sugar chains. Our data suggest that CEA expression may decrease ADR sensitivity of cancer cells.

Animals↗
PubMed1997

A role of dystroglycan in schwannoma cell adhesion to laminin.

Dystroglycan is encoded by a single gene and cleaved into two proteins alpha- and beta-dystroglycan by posttranslational processing. Recently, alpha-dystroglycan was demonstrated to be an extracellular laminin-binding protein anchored to the cell membrane by a transmembrane protein beta-dystroglycan in striated muscle and Schwann cells. However, the biological functions of the dystroglycan-laminin interaction remain obscure, and in particular, it is still unclear if dystroglycan plays a role in cell adhesion. In the present study, we characterized the role of dystroglycan in the adhesion of schwannoma cells to laminin-1. Immunochemical analysis demonstrated that the dystroglycan complex, comprised of alpha- and beta-dystroglycan, was a major laminin-binding protein complex in the surface membrane of rat schwannoma cell line RT4. It also demonstrated the presence of alpha-dystroglycan, but not beta-dystroglycan, in the culture medium, suggesting secretion of alpha-dystroglycan by RT4 cells. RT4 cells cultured on dishes coated with laminin-1 became spindle in shape and adhered to the bottom surface tightly. Monoclonal antibody IIH6 against alpha-dystroglycan was shown previously to inhibit the binding of laminin-1 to alpha-dystroglycan. In the presence of IIH6, but not several other control antibodies in the culture medium, RT4 cells remained round in shape and did not adhere to the bottom surface. The adhesion of RT4 cells to dishes coated with fibronectin was not affected by IIH6. The known inhibitors of the interaction of alpha-dystroglycan with laminin-1, including EDTA, sulfatide, fucoidan, dextran sulfate, heparin, and sialic acid, also perturbed the adhesion of RT4 cells to laminin-1, whereas the reagents which do not inhibit the interaction, including dextran, chondroitin sulfate, dermatan sulfate, and GlcNAc, did not. Altogether, these results support a role for dystroglycan as a major cell adhesion molecule in the surface membrane of RT4 cells.

Animals↗
PubMed1997

The yeast JEM1p is a DnaJ-like protein of the endoplasmic reticulum membrane required for nuclear fusion.

DnaJ-like proteins are functional partners for Hsp70 molecular chaperones. Complete nucleotide sequencing of yeast chromosome X has revealed that an open reading frame YJL073w encodes a novel member of the DnaJ-like protein family. The open reading frame represents a protein of 692 amino acids with a J-domain and one putative membrane-spanning segment. An epitope-tagged version of the protein was anchored in the endoplasmic reticulum (ER) membrane and its J-domain faced the ER lumen. We therefore propose to designate this gene JEM1 (DnaJ-like protein of the ER membrane) and to designate its gene product JEM1p. The JEM1 gene is not essential for cell growth, but double disruption of the JEM1 gene and the SCJ1 gene, which encodes another DnaJ-like protein in the ER lumen, causes growth arrest at elevated temperature. The Deltajem1 mutant is defective in nuclear fusion, karyogamy, during mating. A mutant JEM1p carrying a mutation in the highly conserved His-Pro-Asp sequence in the J-domain could not complement either temperature-sensitive growth of the Deltajem1 Deltascj1 double mutant or defects in karyogamy of the Deltajem1 mutant. JEM1p likely assists the functions of BiP, Hsp70 in the ER, including karyogamy.

Cell Nucleus↗