Search PubMed⌕ Search

Biomedical subjects

T Mori

Publications and source records attributed to T Mori.

At least 253 records · Page 14Linked to original sources
PubMed2000

Identification and characterization of TMEFF2, a novel survival factor for hippocampal and mesencephalic neurons.

We have identified a novel mammalian gene, TMEFF2, that encodes a putative transmembrane protein containing two follistatin-like domains and one epidermal growth factor (EGF)-like domain. The TMEFF2 gene is predominantly expressed in the brain. In situ hybridization analysis revealed that TMEFF2 is widely expressed in the brain, including hippocampal cornu ammonis, dentate gyrus, and substantia nigra pars compacta. We evaluated the survival effect of TMEFF2 using primary cultured neurons from several regions of fetal rat brain following treatment with a recombinant TMEFF2 protein fragment consisting of the putative extracellular domain. TMEFF2 increased survival of neurons from the hippocampus and midbrain, but not from the cerebral cortex, indicating that the survival effects of TMEFF2 are specific to certain cell types. Recombinant TMEFF2 also promoted survival of mesencephalic dopaminergic neurons. Together, these findings suggest that TMEFF2 may be a novel survival factor for hippocampal and mesencephalic, but not for cortical, neurons.

Amino Acid Sequence↗
PubMed2000

Identification of fractalkine, a CX3C-type chemokine, as a direct target of p53.

Fractalkine is a CX3C-type chemokine that induces chemotaxis of monocytes and cytotoxic T cells. Using the differential display method for examining gene expression in p53-defective cells transfected by adenovirus containing wild-type p53, we observed that fractalkine was induced by ectopic expression of p53. An electrophoretic mobility shift assay showed that a potential p53-binding site present in the promoter of the fractalkine gene could bind to p53 protein. Moreover, a heterogeneous reporter assay indicated that this promoter sequence possessed p53-dependent transcriptional activity. The strong induction of fractalkine when p53 protein was expressed by a wild-type transgene in p53-defective cells brought to light a novel role for p53; that is, potential elimination of damaged cells by the host immune response system through transcriptional regulation of fractalkine. Our results imply a pivotal role of p53 in immunosurveillance to prevent cells from undergoing malignant transformation.

Adenoviridae↗
PubMed2000

Vasopressin receptor subtypes on mesenteric and cremasteric arterioles in rat.

We studied the effects of a selective vasopressin V(1A) receptor antagonist [1-(1-(4-(3-acetylaminopropoxy)benzoyl)-4-piperidyl)-3, 4-dihydro-2(1H)-quinolinone (OPC-21268)] and a selective vasopressin V(2) receptor antagonist [5-dimethylamino-1(4-(2-methylbenzoylamino)benzoyl)-2,3,4, 5-tetrahydro-1H-benzazepine (OPC-31260)] on vasopressin-induced contraction of mesenteric and cremasteric arterioles in urethane-anaesthetized rats. Vasopressin was infused intravenously for 60 min or applied topically to arterioles directly. Vasopressin infusion (50, 100 or 500 ng/kg/min) decreased the diameter of both mesenteric and cremasteric arterioles. Vasopressin (500 ng/kg/min)-induced vasoconstriction was antagonized by OPC-21268 (0. 2, 1.0 and 5.0 mg/kg, i.v.), dose-dependently, but not by OPC-31260. Topically applied vasopressin (4.6x10(-10)-4.6x10(-8) M) dose-dependently constricted both microvessels. Pre-administration of OPC-21268 (5.0 mg/kg, i.v.) completely inhibited topically applied vasopressin-induced vasoconstriction in both microvessels, and OPC-31260 partially inhibited it in cremasteric arterioles. These results suggest that vasopressin induces vasoconstriction in rat mesenteric and cremasteric arterioles mainly by stimulating vasopressin V(1A) receptors, while vasoconstriction in cremasteric arterioles is partly associated with stimulation of vasopressin V(2) receptors.

Animals↗
PubMed2000

Pyruvate dehydrogenase activity and energy metabolite levels following bilateral common carotid artery occlusion in rat brain.

The influence of chronic cerebral hypoperfusion on cerebral energy metabolism was studied. The bilateral common carotid arteries of Wistar rats were occluded for 0, 2, 7, and 28 days. Cerebral energy metabolism was evaluated by assaying adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate levels and measuring pyruvate dehydrogenase (PDH) activity (each time point, n = 6). Pathological changes were assessed light-microscopically by Klüver-Barrera staining and immunohistochemical labeling for astroglia (each time point, n = 3). There were no changes in ATP and PCr levels or PDH activity; there was slight but significant transient lactate accumulation at 2 days. Myelin pallor and increase in immuno-reactive astroglia were only observed at 28 days. These results indicate that chronic cerebral hypoperfusion induces delayed white matter changes in the corpus callosum of rat brain, but does not affect energy production.

Adenosine Triphosphate↗
PubMed2000

Circadian clock-protein expression in cyanobacteria: rhythms and phase setting.

The cyanobacterial gene cluster kaiABC encodes three essential circadian clock proteins: KaiA, KaiB and KaiC. The KaiB and KaiC protein levels are robustly rhythmical, whereas the KaiA protein abundance undergoes little if any circadian oscillation in constant light. The level of the KaiC protein is crucial for correct functioning of the clock because induction of the protein at phases when the protein level is normally low elicits phase resetting. Titration of the effects of the inducer upon phase resetting versus KaiC level shows a direct correlation between induction of the KaiC protein within the physiological range and significant phase shifting. The protein synthesis inhibitor chloramphenicol prevents the induction of KaiC and blocks phase shifting. When the metabolism is repressed by either translational inhibition or constant darkness, the rhythm of KaiC abundance persists; therefore, clock protein expression has a preferred status under a variety of conditions. These data indicate that rhythmic expression of KaiC appears to be a crucial component of clock precession in cyanobacteria.

Bacterial Proteins↗
PubMed2000

Destabilization of nucleosomes by an unusual DNA conformation adopted by poly(dA) small middle dotpoly(dT) tracts in vivo.

Poly(dA) small middle dotpoly(dT) tracts are common and often found upstream of genes in eukaryotes. It has been suggested that poly(dA) small middle dotpoly(dT) promotes transcription in vivo by affecting nucleosome formation. On the other hand, in vitro studies show that poly(dA) small middle dotpoly(dT) can be easily incorporated into nucleosomes. Therefore, the roles of these tracts in nucleosome organization in vivo remain to be established. We have developed an assay system that can evaluate nucleosome formation in yeast cells, and demonstrated that relatively longer tracts such as A(15)TATA(16) and A(34) disrupt an array of positioned nucleosomes, whereas a shorter A(5)TATA(4) tract is incorporated in positioned nucleosomes of yeast minichromosomes. Thus, nucleosomes are destabilized by poly(dA) small middle dotpoly(dT) in vivo in a length-dependent manner. Furthermore, in vivo UV footprinting revealed that the longer tracts adopt an unusual DNA structure in yeast cells that corresponds to the B' conformation described in vitro. Our results support a mechanism in which a unique poly(dA) small middle dot poly(dT) conformation presets chromatin structure to which transcription factors are accessible.

Base Sequence↗
PubMed2000

Ring-expansion of thioacetal ring via bicyclosulfonium ylide. Effect Of protic nucleophile on ylide intermediate

The reaction of 2-(3-diazo-2-oxopropane-1-yl)-2-methyldithiolane 9a, 2-(4-diazo-3-oxobutane-2-yl)-2-methyldithiolane 9c, and 2-(3-diazo-2-oxopropane-1-yl)-2-methyl-1,3-dithiane 9b with Rh(2)(OAc)(4) gave three-carbon ring-expansion products dithiocan-2-en-1-ones 13a, 13c and dithionan-2-en-1-one 13b, respectively. 2-(5-Diazo-4-oxopentyl)-2-methyldithiolane 9e also gave the five-carbon ring-expansion products dithionan-3-en-1-one 13e and 5-methylenedithionane-1-one 13'e. On the other hand, reaction of 2-(4-diazo-3-oxobutyl)-2-methyldithiolane 9d in the presence of AcOH gave the four-carbon ring-expansion product 16d substituted by an acetoxyl group. In addition, the reaction of 2-(3-diazo-2-oxopropyl)-2-methyl-3-oxathiolane 9f in the absence of AcOH gave 4-oxa-7-thiocan-2-en-1-one 19 via a sulfonium ylide intermediate, whereas, in the presence of AcOH, an alternative regioisomer 20 was also formed competitively with 19 via an oxonium ylide intermediate.

Journal Article↗
PubMed2000

Pancreatic duct cell carcinomas express high levels of high mobility group I(Y) proteins.

The high mobility group I (HMGI) family of proteins in mammals belongs to a group of nonhistone nuclear proteins known as architectural transcriptional factors. They function in vivo as both structural components of chromatin and auxiliary gene transcription factors. In an earlier study (N. Abe et al, Cancer Res., 59: 1169-1174, 1999), we demonstrated that the expression level of the HMGI(Y) gene/proteins was significantly increased in colorectal adenocarcinoma and colorectal adenoma with severe cellular atypia. In the current study, we analyzed HMGI(Y) expression in several human pancreatic lesions to investigate (a) whether HMGI(Y) overexpression is also observed in pancreatic carcinoma, and (b) the role of HMGI(Y) in the diagnosis of pancreatic neoplasms. To this end, HMGI(Y) expression was determined at the protein level by immunohistochemistry using a HMGI(Y)-specific antibody in 6 surgically resected specimens of nonneoplastic tissue (4 specimens of normal pancreatic tissue and 2 specimens of chronic pancreatitis tissue), 8 pancreatic cystic neoplasms (5 intraductal papillary mucinous adenomas, 1 serous cystadenoma, and 2 solid pseudopapillary tumors), and 15 duct cell carcinomas of the pancreas. Immunohistochemical analysis revealed intense nuclear staining in the pancreatic carcinoma cells, whereas only very faint nuclear staining was seen in the nonneoplastic cells. There was a strong correlation between HMGI(Y) protein overexpression and a diagnosis of carcinoma (P = 0.000018). Thus, an increased expression level of the HMGI(Y) proteins was clearly associated with the malignant phenotype in pancreatic tissue. In addition, a low level of protein expression was also apparent in two of the cystic neoplasms that exhibited cellular atypia, but not in those that did not exhibit cellular atypia. Based on these findings, we propose that the HMGI(Y) proteins could be closely associated with tumorigenesis in the pancreas and that HMGI(Y) could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignancies unambiguously from normal tissue or benign lesions.

Carcinoma↗
PubMed2000

Estrogen-induced vasoprotection is estrogen receptor dependent: evidence from the balloon-injured rat carotid artery model.

BACKGROUND: Previous studies have shown that estrogen (E2) is vasoprotective in multiple animal models of vascular injury, including mice with homologous disruptions of either the alpha or beta isoforms of the estrogen receptor (ER) gene, calling into question the ER dependency of the vasoprotective effect. This study used ICI 182,780, a nonselective ER antagonist, to test the hypothesis that the vasoprotective effect of E2 in the rat carotid injury model is ER mediated. METHODS AND RESULTS: Intact female Sprague-Dawley rats were divided into 4 groups and treated with the nonselective ER antagonist ICI 182,780 (ICI; 0.5, 1.5, or 5 mg. kg(-1). d(-1), subcutaneously [S.C.]) or vehicle, beginning before balloon injury of the right common carotid artery and continuing for 14 days afterward. Four groups of ovariectomized rats (OVX) were treated with 17beta estradiol (E2) (20 microgram. kg(-1). d(-1), S.C.) alone or combined with ICI 5 mg. kg(-1). d(-1), S.C.; with ICI 5 mg. kg(-1). d(-1) alone; or with vehicle according to a similar protocol. Two weeks after injury, rats were killed, and the carotid arteries were evaluated for neointima formation using morphometric analysis. ICI 182,780 blunted the E2-related protective effect and increased neointima formation in injured carotid arteries of intact female rats in a dose-dependent fashion. ICI had no effect on neointima formation in OVX, but addition of ICI to E2 in OVX blocked the inhibitory effect of exogenous E2 on neointima formation. CONCLUSIONS: These results indicate that the vasoprotective effect of E2 in the balloon-injured rat carotid artery model is mediated by ER.

Animals↗
PubMed2000

Hemophagocytosis by leukemic blasts in 7 acute myeloid leukemia cases with t(16;21)(p11;q22): common morphologic characteristics for this type of leukemia.

BACKGROUND: In a previous study of a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22), which displayed hemophagocytosis by leukemic blasts, the authors mentioned that the same type of morphology had been cited in the literature for 4 other cases of acute myeloid leukemia (AML) with the same translocation. This observation prompted the authors to examine more cases of AML with t(16;21)(p11;q22) for this morphology. METHODS: The authors reviewed bone marrow smears for the presence of hemophagocytosis in 7 patients with AML identified as having t(16;21)(p11;q22). RESULTS: The leukemias belonged to the FAB-M1/M7 (n = 5), M5b (n = 2), and contained phagocytic blasts in various percentages (< 0.2-36.7%). The blasts contained either single or multiple cytoplasmic vacuoles, in some of which the phagosomes were visible. The engulfed hemopoietic cells (red cells, erythroblasts, lymphocytes, and thrombocytes) were also noted in their cytoplasm. These observations confirmed that hemophagocytosis by leukemic blasts is a common and characteristic feature of this type of leukemia. CONCLUSIONS: The study of 12 cases (the 7 cases described here and the previous 5 cases) strongly supports the hypothesis that hemophagocytosis by leukemic blasts is common and characteristic in this type of leukemia, which may be related to the specific chromosome aberration of t(16;21)(p11;q22).

Adolescent↗
PubMed2000

Respective roles of cyclobutane pyrimidine dimers, (6-4)photoproducts, and minor photoproducts in ultraviolet mutagenesis of repair-deficient xeroderma pigmentosum A cells.

The role of UV light-induced photoproducts in initiating base substitution mutation in human cells was examined by determining the frequency and spectrum of mutation in a supF tRNA gene in a shuttle vector plasmid transfected into DNA repair deficient cells (xeroderma pigmentosum complementation group A). To compare the role of two major UV-induced photoproducts, cis-syn cyclobutane-type pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), each photoproduct was removed from UV-irradiated plasmid by photoreactivation before transfection. Removal of either CPDs or 6-4PPs by in vitro photoreactivation reduced the mutation frequency while keeping the mutation distribution and the predominance of G:C-A:T transitions as UV-irradiated plasmid without photoreactivation, indicating that both cytosine-containing CPDs and 6-4PPs were premutagenic lesions for G:C-A:T transitions. On the other hand, A:T-G:C transitions were not recovered from plasmids after the removal of 6-4PPs, whereas this type of mutation occurred at a significant level (11%) after the removal of CPDs. Thus, the premutagenic lesions for the A:T-G:C transition are 6-4PPs. Removal of both CPDs and 6-4PPs resulted in the disappearance of mutational hot spots and random distribution of mutation as observed in unirradiated control plasmids. However, the mutational spectrum of photoreactivated plasmids differed significantly from that of unirradiated plasmids. A characteristic feature is a high portion of A:T-T:A transversions (11%) in the photoreactivated plasmid. This mutation is due to nondipyrimidinic "minor" photoproducts, and the mutation spectrum suggests that TA*, the major photoproduct of thymidylyl-(3'-5')-deoxyadenosine, is the premutagenic lesion for this mutation. This is the first report revealing the distinct mutagenic roles of the major UV photoproducts and "minor" photoproducts by the use of (6-4)photolyase.

Base Sequence↗
PubMed2000

Lobe specific effects of testosterone and estrogen on 3,2'-dimethyl-4-aminobiphenyl-induced rat prostate carcinogenesis.

We have previously shown that chronic administration of a pharmacological dose of testosterone propionate (TP) after treatment with the carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMAB), results in development of invasive and metastatic adenocarcinomas arising from the dorso-lateral and anterior prostate, as well as the seminal vesicles. Co-administration of ethinyl estradiol (EE) with TP increased the yield of carcinomas in the lateral and anterior lobes. In the present experiment, male F344 rats were treated with DMAB for 20 weeks and then co-administered a pharmacological dose of TP together with various doses of EE for 40 weeks. Without hormone(s) administration, carcinomas were confined to the ventral prostate and all were of intra-acinar type. TP administration suppressed development of the ventral prostate carcinomas but caused invasive carcinomas of the lateral and anterior lobes and of seminal vesicles and intra-acinar carcinomas in the dorsal prostate. The appearance of carcinomas in the lateral and anterior prostate was increased by co-administration of EE in a dose-related fashion but carcinomas of the seminal vesicles were inversely reduced. The suppressive influence of TP on ventral carcinoma development was overcome by only the highest dose of EE. It is concluded that estrogen can modify the enhancing effects of TP on induction of rat prostate and seminal vesicle carcinomas in a dose-related fashion with lobe specificity.

Aminobiphenyl Compounds↗
PubMed2000

Activation of caspase-3 in molt4 cells by apoptosis-inducing nucleosides from CD57(+)HLA-DR(bright) natural suppressor cell line.

Apoptosis-inducing nucleosides (AINs), which were released and isolated from CD57(+)HLA-DR(bright) natural suppressor (57.DR-NS) cell line derived from human decidual tissue, induced apoptosis in Molt4 cells. The addition of caspase-3 inhibitor into the reaction blocked the cleavage of caspase-3 and apoptosis in Molt4 cells treated with AINs, detected by flow cytometrical or spectrofluorometrical analysis and DNA fragmentation assay. Furthermore, by means of immunoblotting, the processing of caspase-3 was shown with the appearance of their catalytically active subunits of 20 and 11 kDa during the generation of apoptosis in Molt4 cells treated with AINs. This processing of caspase-3 into active subunits was also blocked by the addition of caspase-3 inhibitor. Thus, it was definitely revealed that the activation of caspase-3 was a key feature in the caspase cascade of AINs-induced apoptosis in Molt4 cells.

Apoptosis↗
PubMed2000

SN-1, a novel leukemic cell line with t(11;16)(q23;p13): myeloid characteristics and resistance to retinoids and vitamin D3.

The MLL gene is fused with the cAMP-responsive element binding protein-binding protein (CBP) gene in t(11;16)(q23;p13), which has been reported to be associated with therapy-related acute leukemia. We established a novel myeloid cell line, SN-1, from a patient with T-cell acute lymphoblastic leukemia with t(11;16)(q23;p13) having in-frame MLL-CBP fusion transcripts. The majority of the SN-1 cells were positive for myeloperoxidase when examined using an electron microscope and expressed CD13, CD33, CD56, and HLA-DR antigens, but not CD7, CD10, CD19, CD34, or CD41 antigens, suggesting that these cells are of myeloid origin. SN-1 cells underwent functional and morphological differentiation when treated with actinomycin D or sodium butyrate, but not with all-trans-retinoic acid (ATRA) or 1alpha,25-dihydroxyvitamin D3 (VD3). Exposure of SN-1 cells to ATRA hardly affected cell growth and differentiation, whereas the growth of HL-60 and NB4 cells treated with ATRA was effectively inhibited, and differentiation into mature granulocytes was induced. SN-1 cells were relatively insensitive to VD3 with respect to inhibiting the cell growth and inducing the ability to reduce nitroblue tetrazolium, lysozyme activity, and morphological differentiation, although the expression of CD11b was slightly induced by VD3. These results suggest that the cell line was impaired in the signal transduction systems of ATRA and VD3. This cell line should be useful for the study of the role of CBP as a transcriptional regulator in leukemia differentiation and for the functional analysis of the MLL-CBP fusion gene, which will provide new insights into leukemogenesis caused by 11q23 translocations.

Amino Acid Sequence↗
PubMed2000

Calcium ion-independent recognition of sialyl and nonsialyl N-acetyllactosamine and Le(x) structures by boar sperm.

Recognition of defined carbohydrate structures by boar sperm was studied on the basis of oligosaccharide structures of porcine zona pellucida glycoproteins so far elucidated. Boar sperm abundantly adhered to fetuin-Sepharose beads, moderately to asialofetuin-Sepharose beads, but not at all to galactosidase (beta1-4-linkage-specific)-digested asialofetuin-Sepharose beads. The sperm also adhered to Le(x) oligosaccharide probe-coupled avidin-Sepharose beads. These adhesive activities were retained in the medium containing EDTA instead of calcium ion but abolished after induction of acrosome reaction by preincubation of sperm with calcium ionophore. Inhibition study of sperm adhesion to the beads by soluble ligands demonstrated that boar sperm express at least two kinds of carbohydrate recognition molecules, one recognizing both sialyl and nonsialyl N-acetyllactosamines but not the Le(x) structure and the other recognizing the Le(x) structure but not N-acetyllactosamines. Sperm binding to the zona pellucida on fixed porcine oocytes was inhibited by N-glycans of fetuin and their asialo form but not by the asialo, agalacto-N-glycans. Finally, dextran-based multivalent oligosaccharide polymers were prepared and their inhibitory activities in sperm-oocyte binding were examined. The result indicated that the polymer composed of fetuin N-glycans, its asialo-N-glycans, or lacto-N-fucopentaose III causes a remarkable inhibition at the oligosaccharide-based concentration of 50 microM. Thus, boar sperm are suggested to express multiple carbohydrate recognition molecules which may be involved in the sperm-egg interaction.

Amino Sugars↗