scispace - formally typeset
Search or ask a question

Showing papers by "Kyushu University published in 1997"


Journal ArticleDOI
TL;DR: Novel strategies for cavity design using calix[n]arene skeletons, strategies that are intended to allow complexation of specific molecular targets or metal ions are described.
Abstract: Calixarenes are macrocyclic molecules, like crown ethers and cyclodextrins.1-7 Calixarenes made up of phenol and methylene units have many conformational isomers because of two possible rotational modes of the phenol unit: the oxygen-through-theannulus rotation and the para-substituent-throughthe-annulus rotation (Figure 1). The conformational isomers thus yielded afford a great number of unique cavities with the different size and the different shape. Recently, a number of strategies have been exploited by which not only the conformation of calix[4]arenes, but also those of calix[6]arenes and calix[8]arenes, can be immobilized. This means that our group can now design various calixarene-based receptors that show high selectivity for guest molecules and metal cations. In this review article, our group describe novel strategies for cavity design using calix[n]arene skeletons, strategies that are intended to allow complexation of specific molecular targets or metal ions.

1,216 citations


Journal ArticleDOI
TL;DR: In this article, the development of an ultra-fine grain size during equal-channel angular (ECA) pressing of high purity aluminum with an initial grain size of ∼1.0 mm was investigated.

759 citations


Journal ArticleDOI
TL;DR: Angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms.
Abstract: Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, the underlying mechanism by which TNF-alpha mediates angiogenesis is not completely understood. In this study, we assessed whether TNF-alpha-induced angiogenesis is mediated through TNF-alpha itself or indirectly through other TNF-alpha-induced angiogenesis-promoting factors. Cellular mRNA levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors were increased after the treatment of human microvascular endothelial cells with TNF-alpha (100 U/ml). TNF-alpha-dependent tubular morphogenesis in vascular endothelial cells was inhibited by the administration of anti-IL-8, anti-VEGF, and anti-bFGF antibodies, and coadministration of all three antibodies almost completely abrogated tubular formation. Moreover, treatment with Sp1, NF-kappaB, and c-Jun antisense oligonucleotides inhibited TNF-alpha-dependent tubular morphogenesis by microvascular endothelial cells. Administration of a NF-kappaB antisense oligonucleotide almost completely inhibited TNF-alpha-dependent IL-8 production and partially abrogated TNF-alpha-dependent VEGF production, and an Sp1 antisense sequence partially inhibited TNF-alpha-dependent production of VEGF. A c-Jun antisense oligonucleotide significantly inhibited TNF-alpha-dependent bFGF production but did not affect the production of IL-8 and VEGF. Administration of an anti-IL-8 or anti-VEGF antibody also blocked TNF-alpha-induced neovascularization in the rabbit cornea in vivo. Thus, angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms.

675 citations


Journal ArticleDOI
TL;DR: It is demonstrated that Rho-kinase directly modulates smooth muscle contraction through myosin light chain phosphorylation, independently of the Ca2+-calmodulin-dependent myos in light chain kinase pathway.

594 citations


Journal ArticleDOI
12 Nov 1997-Langmuir
TL;DR: In this paper, an alternating layer-by-layer assembly of colloidal SiO2 particles with polycations has been investigated by quartz crystal microbalance (QCM), scanning electron microscopy, and atomic force microscopy (AFM).
Abstract: Alternate layer-by-layer assembly of colloidal SiO2 particles with polycations has been investigated by quartz crystal microbalance (QCM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). QCM measurement confirmed the high regularity and reproducibility of the assembling process that depends on particle concentration, particle size, and ionic strength. The individual adsorption step was completed within 15 s. The thickness of adsorbed layers increased with increasing SiO2 concentrations at the three particle sizes used (45, 25, and 78 nm in diameter), unlike the case for other polyion assemblies. It also increased with increasing ionic strength of aqueous SiO2 dispersions. According to SEM observation, the assembled film possessed surprisingly flat surfaces at optimized ionic strengths. AFM observation revealed that SiO2 particles were not closely packed. The neutralization ratio of SiO2 and PDDA was estimated by turbidity measurement. Comparison of turbidity and QCM data indicated t...

467 citations


Journal ArticleDOI
TL;DR: The thermoelectric properties of a mixed oxide were investigated in terms of materials for high-temperature thermal conversion in this paper, showing metallic behavior and the electrical conductivity of the oxide increases on Al-doping by more than three orders of magnitude up to ca.
Abstract: The thermoelectric properties of a mixed oxide (Zn 1-x Al x )O (x=0, 0.005, 0.01, 0.02, 0.05) are investigated in terms of materials for high-temperature thermoelectric conversion. The electrical conductivity, σ, of the oxide increases on Al-doping by more than three orders of magnitude up to ca. 10 3 S cm -1 at room temperature, showing metallic behaviour. The Seebeck coefficient, S, of (Zn 1-x Al x )O (x>0) shows a general trend in which the absolute value increases gradually from ca. -100 µV K -1 at room temperature to ca. -200 µV K -1 at 1000 °C. As a consequence, the power factor, S 2 σ, reaches ca. 15×10 -4 W m -1 K -2 , the largest value of all reported oxide materials. The thermal conductivity, κ, of the oxide decreases with increasing temperature, owing to a decrease in the lattice thermal conductivity which is revealed to be dominant in the overall κ. In spite of the considerably large values of κ, the figure of merit, Z=S 2 σ/κ, reaches 0.24×10 -3 K -1 for (Zn 0.98 Al 0.02 )O at 1000 °C. The extremely large power factor of (Zn 1-x Al x )O compared to other metal oxides can be attributed to the high carrier mobility revealed by the Hall measurements, presumably resulting from a relatively covalent character of the Zn–O bond owing to a fairly small difference of the electronegativities of Zn and O. The dimensionless figure of merit,ZT, of 0.30 attained by (Zn 0.98 Al 0.02 )O at 1000 °C demonstrates the potential usefulness of the oxide.

420 citations


Journal ArticleDOI
TL;DR: In this paper, a review is given of several important defect production and accumulation parameters for irradiated ceramics including alumina, magnesia, spinel, silicon carbide, silicon nitride, aluminum nitride and diamond.

414 citations


Journal ArticleDOI
TL;DR: In this paper, a porous α-alumina support tube, polished with a finely powdered X-type zeolite for use as seeds, was placed vertically in an autoclave containing an aqueous mixture of water glass and sodium aluminate.
Abstract: A porous α-alumina support tube, polished with a finely powdered X-type zeolite for use as seeds, was placed vertically in an autoclave containing an aqueous mixture of water glass and sodium aluminate. Hydrothermal synthesis was carried out at 90 °C for 24 h. A polycrystalline layer of Y-type zeolite was thus formed on the outer surface of the support tube. After washing and drying in air, permeances of single components and mixtures of CO2 and N2, as well as CH4, C2H6, and SF6, were determined. The CO2 permeance was higher than that of N2 at temperatures of 30−130 °C. When an equimolar mixture of CO2 and N2 was fed into the feed side, the CO2 permeance was nearly equal to that for the single-component system and the N2 permeance for the mixture was greatly decreased, especially at lower permeation temperatures. This was due to selective adsorption of CO2 in subnanometer micropores of the membrane. At 30 °C, the permeance of CO2 was higher than 10-7 mol·m-2·s-1·Pa-1, and the permselectivity of CO2 to N2 ...

387 citations


Journal ArticleDOI
TL;DR: The spatial structure modifies the condition for the development of cooperation in two different ways: it facilitates the evolution of cooperation due to spontaneously formed positive correlation between neighbors, but it also inhibits cooperation because of the advantage of being spiteful by killing neighbors and then replacing them.

326 citations


Journal ArticleDOI
TL;DR: A nationwide epidemiological survey was conducted in 1995 to estimate an annual number of patients treated for Moyamoya disease in Japan and to describe the clinico-epidemiological features, and the present findings were quite comparable with those obtained in the previous nationwide Epidemiological survey in 1990.

323 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present nucleosynthesis results from relatively slow deflagration (1.5 − 3 % of the sound speed) to constrain the rate of accretion from the companion star.

Journal ArticleDOI
TL;DR: Three cases of the suspected autoimmune pancreatitis are found in Japan, in which ERP revealed diffuse narrowing of the main pancreatic duct with an irregular wall, and pancreatitis dramatically improved morphologically and enzymatically.
Abstract: The most common forms of chronic pancreatitis are related to alcohol ingestion, whereas the entity of non-alcohol-associated (idiopathic) pancreatitis is poorly understood. Autoimmunity has been suggested as a possible etiologic factor of idiopathic chronic pancreatitis. A total of 362 Japanese patients underwent endoscopic retrograde pancreatography (ERP) for suspected pancreatic disease, and 161 were diagnosed with chronic pancreatitis. Among them, we found three cases (1.86% incidence) of unique chronic pancreatitis, in which ERP revealed diffuse narrowing of the main pancreatic duct with an irregular wall. We diagnosed these three patients as having pancreatitis associated with an autoimmune mechanism morphologically and biochemically and started them on steroid therapy. The characteristics of the these three patients were as follows: hypergammaglobulinemia, eosinophilia, ultrasonography showing hypoehoic diffuse swelling in the pancreas (sausage-like appearance), ERP showing diffuse narrowing of the main pancreatic duct with irregular like thumbprint-like marks, reversible exocrine insufficiency, and positive anti-carbonic anhydrase II antibody. After one month of the treatment with steroids, pancreatitis dramatically improved morphologically and enzymatically. Here we describe these cases of the suspected autoimmune chronic pancreatitis. We must recognize the concept and the features of autoimmune pancreatitis in order to avoid unnecessary surgery as pancreatic cancer.

Journal ArticleDOI
TL;DR: The results showed that the contribution of EDHF to endothelium-dependent relaxations is significantly larger in microvessels than in large arteries; the nature of ED HF may not be a product of cytochrome P450 pathway, while EDHF-induced hyperpolarization is partially mediated by calcium-activated K channels; and aging and hypercholesterolemia significantly impair ED HF-mediated relaxations.
Abstract: The endothelium plays an important role in maintaining the vascular homeostasis by releasing vasodilator substances, including prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). Although the former two substances have been investigated extensively, the importance of EDHF still remains unclear, especially in human arteries. Thus we tested our hypothesis that EDHF plays an important role in human arteries, particularly with reference to the effect of vessel size, its vasodilating mechanism, and the influences of risk factors for atherosclerosis. Isometric tension and membrane potentials were recorded in isolated human gastroepiploic arteries and distal microvessels (100-150 microm in diameter). The contribution of PGI2, NO, and EDHF to endothelium-dependent relaxations was analyzed by inhibitory effects of indomethacin, NG-nitro- L-arginine, and KCl, respectively. The nature of and hyperpolarizing mechanism by EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K channels. The effects of atherosclerosis risk factors on EDHF-mediated relaxations were also analyzed. The results showed that (a) the contribution of EDHF to endothelium-dependent relaxations is significantly larger in microvessels than in large arteries; (b) the nature of EDHF may not be a product of cytochrome P450 pathway, while EDHF-induced hyperpolarization is partially mediated by calcium-activated K channels; and (c) aging and hypercholesterolemia significantly impair EDHF-mediated relaxations. These results demonstrate that EDHF also plays an important role in human arteries.

Journal ArticleDOI
TL;DR: These findings support a scheme wherein ΔFosB, expressed as a 33 kDa protein, is modified to form highly stable isoforms of 35 and 37 kDa, which gradually accumulate in the brain with repeated treatments to mediate forms of long-lasting neural and behavioral plasticity.
Abstract: Fos family transcription factors are believed to play an important role in the transcriptional responses of the brain to a variety of stimuli. Previous studies have described 35 and 37 kDa Fos-like proteins, termed chronic Fos-related antigens (FRAs), that are induced in brain in a region-specific manner in response to several chronic perturbations, including chronic electroconvulsive seizures, psychotropic drug treatments, and lesions. We show in this study that the chronic FRAs are isoforms of ΔFosB, a truncated splice variant of FosB that accumulate in brain after chronic treatments because of their stability. ΔFosB cDNA encodes the expression of 33, 35, and 37 kDa proteins that arise from a single AUG translation start site. The 35 and 37 kDa proteins correspond to the chronic FRAs that are induced in brain by chronic treatments, whereas the 33 kDa protein corresponds to a Fos-like protein that is induced in brain by acute treatments, findings based on migration on one- and two-dimensional Western blots with anti-FRA and anti-FosB antibodies. Using cells in which ΔFosB or FosB expression is under the control of a tetracycline-regulated gene expression system, we show that the 37 kDa ΔFosB protein exhibits a remarkably long half-life, the 35 kDa ΔFosB protein exhibits an intermediate half-life, and the 33 kDa ΔFosB protein and all FosB-derived proteins exhibit relatively short half-lives. Moreover, we show that the 33 kDa ΔFosB protein is the first to appear after activation of ΔFosB expression. Finally, ΔFosB proteins are shown to possess DNA-binding activity and to exert potent transactivating effects in reporter gene assays. Together, these findings support a scheme wherein ΔFosB, expressed as a 33 kDa protein, is modified to form highly stable isoforms of 35 and 37 kDa. As a result, these stable isoforms gradually accumulate in the brain with repeated treatments to mediate forms of long-lasting neural and behavioral plasticity.

Journal ArticleDOI
TL;DR: Increased local ACE expression may be important in the pathogenesis of cardiovascular remodeling in this model, as vascular and myocardial remodeling were characterized by increased tissue ACE activities and immunodetectable ACE in those tissues.
Abstract: The long-term administration of N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, produces coronary vascular remodeling and myocardial hypertrophy in animals. This study used a rat model to investigate the role of angiotensin I converting enzyme (ACE) in the pathogenesis of such changes. We studied the following groups, all of which received drug treatment in their drinking water: untreated controls, and those administered L-NAME, L-NAME, and an ACE inhibitor (ACEI), and L-NAME and hydralazine. Cardiovascular structural changes and tissue ACE activities were evaluated after the first, fourth, and eighth week of treatment. In rats treated with L-NAME alone, vascular remodeling was evident at the fourth and eighth week, and myocardial hypertrophy was present at the eighth week of treatment. The vascular and myocardial remodeling were characterized by increased tissue ACE activities and immunodetectable ACE in those tissues. These changes were markedly reduced by ACEI, but not by hydralazine treatment. Increased local ACE expression may thus be important in the pathogenesis of cardiovascular remodeling in this model.

Journal ArticleDOI
01 Jan 1997-Carbon
TL;DR: In this article, pitch-based active carbon fibers (ACFs) were analyzed by a FTIR micro-ATR technique by introducing a very thin KBr layer on their surfaces.

Journal ArticleDOI
01 Oct 1997-Oncogene
TL;DR: A novel p53-inducible gene that encodes a 1584-amino-acid product containing five thrombospondin type 1 (TSP-type 1) repeats and is specifically expressed in the brain is isolated, suggesting BAI1 plays a significant role in angiogenesis inhibition, as a mediator of p53.
Abstract: The genetic alteration of p53 is associated with neovascularization during progression of glioma to its more malignant form, glioblastoma. Hence, one or more of the genes transactivated by p53 is likely to function as an angiogenesis inhibitors. We isolated a novel p53-inducible gene that encodes a 1584-amino-acid product containing five thrombospondin type 1 (TSP-type 1) repeats and is specifically expressed in the brain. A recombinant protein corresponding to the TSP-type 1 repeats of this gene product inhibited in vivo neovascularization induced by bFGF in the rat cornea. The expression of this gene, designated BAI1 (brain-specific angiogenesis inhibitor 1) was absent or significantly reduced in eight of nine glioblastoma cell lines, suggesting BAI1 plays a significant role in angiogenesis inhibition, as a mediator of p53.

Journal ArticleDOI
TL;DR: Evidence is presented that repeated inhalation of anti-FAs antibody mimicking Fas-Fas ligand crosslinking induces excessive apoptosis and inflammation, which results in pulmonary fibrosis in mice.
Abstract: Fas antigen is a cell surface protein that mediates apoptosis, and it is expressed in various cells and tissues. Fas ligand binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Malfunction of the Fas-Fas ligand system causes lymphoproliferative disorders and autoimmune diseases, whereas its exacerbation may cause tissue destruction. We hypothesize that excessive apoptosis mediated by Fas-Fas ligand interaction may damage alveolar epithelial cells and result in pulmonary fibrosis. Mice were allowed to inhale repeatedly an aerosolized anti-Fas antibody for 14 days. The nuclei of bronchial and alveolar epithelial cells were positively stained by in situ DNA nick end labeling. Electron microscopy demonstrated apoptotic changes in bronchial and alveolar epithelial cells. Histologic findings and hydroxyproline content showed the development of pulmonary fibrosis, which was dependent on the dose of anti-Fas antibody. The repeated inhalation of control antibody (isotype-matched control hamster IgG) did not induce apoptosis of epithelial cells or pulmonary fibrosis. The expression of TGF-beta mRNA was upregulated from day 7 to day 28 in lung tissues of anti-Fas antibody-treated mice but not in those of control mice. In this report, we present the evidence that repeated inhalation of anti-Fas antibody mimicking Fas-Fas ligand crosslinking induces excessive apoptosis and inflammation, which results in pulmonary fibrosis in mice.

Journal ArticleDOI
TL;DR: A simple sufficient condition for such a class of maps to produce a fair Bernoulli sequence, that is, a sequence of independent and identically distributed (i.i.d.) binary random variables.
Abstract: Statistical properties of binary sequences generated by a class of ergodic maps with some symmetric properties are discussed on the basis of an ensemble-average technique. We give a simple sufficient condition for such a class of maps to produce a fair Bernoulli sequence, that is, a sequence of independent and identically distributed (i.i.d.) binary random variables. This condition is expressed in terms of binary function, which is a generalized version of the Rademacher function for the dyadic map.

Journal ArticleDOI
TL;DR: In this article, forced modulation scanning force microscopic (SFM) and lateral force microscopic measurements of the monodisperse polystyrene (PS) films were carried out at 293 K in order to reveal surface molecular motion.
Abstract: Forced modulation scanning force microscopic (SFM) and lateral force microscopic (LFM) measurements of the monodisperse polystyrene (PS) films were carried out at 293 K in order to reveal surface molecular motion. Surface dynamic storage modulus, E‘, and surface loss tangent, tan δ, of the monodisperse PS films were evaluated on the basis of forced modulation SFM measurement. It was revealed that the magnitudes of surface E‘ and surface tan δ were lower and higher than those for its bulk state, respectively, in the case of the number-average molecular weight (Mn) lower than 26.6k. Based on forced modulation SFM measurements, the surface of the PS film with Mn lower than 26.6k was in a glass−rubber transition state even at 293 K, in spite of that the bulk Tg was far above 293 K. LFM measurements for the PS films revealed that the magnitude of lateral force was dependent on the scanning rate of the cantilever tip in the case of Mn lower than 40.4k. The scanning rate dependence of lateral force appeared in t...

Journal ArticleDOI
TL;DR: It is shown that there might be a correlation between the expression levels of the EWS-Fli1 fusion gene and the proliferative activities of Ewing's sarcoma and primitive neuroectodermal tumor cells, and the E WS-Fali1 fusion RNA could be used as a target to inhibit the growth of Ewings' sarcomA and primitive Neuroectoder mal tumor with the specific antisense oligonucleotide.
Abstract: The translocation t(11;22) is a common chromosomal abnormality detected both in Ewing's sarcoma and in primitive neuroectodermal tumor cells. The translocation results in an EWS-Fli1 fusion gene, made up of the 5' half of the EWS gene on chromosome 22 fused to the 3' half of the Fli1 gene on chromosome 11. Recent studies have evaluated possible roles of the fusion gene products. However, the biological significance of EWS-Fli1 is still unknown. Using a competitive polymerase chain reaction technique, we show here that there might be a correlation between the expression levels of the EWS-Fli1 fusion gene and the proliferative activities of Ewing's sarcoma and primitive neuroectodermal tumor cells. When the EWS-Fli1 expression is inhibited by antisense oligodeoxynucleotides against the fusion RNA, the growth of the tumor cells is significantly reduced both in vitro and in vivo. The data further indicate the growth inhibition of the cells by the antisense sequence might be mediated by G0/G1 block in the cell cycle progression. These results suggest that EWS-Fli1 may play an important role in the proliferation of the tumor cells, and the EWS-Fli1 fusion RNA could be used as a target to inhibit the growth of Ewing's sarcoma and primitive neuroectodermal tumor with the specific antisense oligonucleotide.

Journal ArticleDOI
03 Oct 1997-Science
TL;DR: Control of transcriptional fidelity by the ubiquitous MutT function has implications for evolution of RNA-based life, phenotypic expression, adaptive mutagenesis, and functional maintenance of nondividing cells.
Abstract: Oxidized guanine (8-oxo-7,8-dihydroguanine; 8-oxo-G) is a potent mutagen because of its ambiguous pairing with cytosine and adenine. The Escherichia coli MutT protein specifically hydrolyzes both 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) and 8-oxo-guanosine triphosphate (8-oxo-rGTP), which are otherwise incorporated in DNA and RNA opposite template A. In vivo, this cleaning of the nucleotide pools decreases both DNA replication and transcription errors. The effect of mutT mutation on transcription fidelity was shown to depend on oxidative metabolism. Such control of transcriptional fidelity by the ubiquitous MutT function has implications for evolution of RNA-based life, phenotypic expression, adaptive mutagenesis, and functional maintenance of nondividing cells.

Journal ArticleDOI
TL;DR: The results showed that a single instillation of bleomycin leads to the rapid appearance of apoptosis in bronchial and alveolar epithelial cells, which resolves within 1 day, and apoptosis reappears on day 7 and continues for over 14 days after bleomyin instillation.
Abstract: The incidence of apoptosis and the expression of Fas antigen (Fas)/Fas ligand (FasL) mRNA in bleomycin-induced pulmonary fibrosis in mice were examined. Male ICR mice were intratracheally instilled with bleomycin (5 U/kg of body weight). The controls were injected with sterile saline. The animals were anesthetized and killed at 1, 6, and 12 h, and 1, 3, 5, 7, 9, and 14 days after bleomycin instillation. We assessed the incidence of apoptosis in lung tissues by DNA fragmentation on agarose gel electrophoresis, terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling, and electron microscopy. The expression of Fas and FasL mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). The localization of Fas mRNA was analyzed by in situ hybridization and that of FasL mRNA was analyzed by RT in situ PCR. The results showed that (1) a single instillation of bleomycin leads to the rapid appearance of apoptosis in bronchial and alveolar epithelial cells, which resolves within...


Journal ArticleDOI
TL;DR: The existence of multiple, overlapping imprinted (maternally repressed) sense and antisense transcripts that are associated with a tandem repeat in the mouse Igf2 upstream region supports the proposal that tandem repeats act to target methylation to imprinted genetic loci.
Abstract: The mouse insulin-like growth factor 2 (Igf2) locus is a complex genomic region that produces multiple transcripts from alternative promoters. Expression at this locus is regulated by parental imprinting. However, despite the existence of putative imprinting control elements in the Igf2 upstream region, imprinted transcriptional repression is abolished by null mutations at the linked H19 locus. To clarify the extent to which the Igf2 upstream region contains autonomous imprinting control elements we have performed functional and comparative analyses of the region in the mouse and human. Here we report the existence of multiple, overlapping imprinted (maternally repressed) sense and antisense transcripts that are associated with a tandem repeat in the mouse Igf2 upstream region. Regions flanking the repeat exhibit tissue-specific parental allelic methylation patterns, suggesting the existence of tissue-specific control elements in the upstream region. Studies in H19 null mice indicate that both parental allelic methylation and monoallelic expression of the upstream transcripts depends on an intact H19 gene acting in cis. The homologous region in human IGF2 is structurally conserved, with the significant exception that it does not contain a tandem repeat. Our results support the proposal that tandem repeats act to target methylation to imprinted genetic loci.

Journal Article
TL;DR: Results suggest that cMOAT levels are inversely correlated with those of glutathione, and that c MOAT and its related genes may be involved in the sensitivity of cells to certain anticancer agents.
Abstract: The human cMOAT gene encodes a membrane protein involved in the ATP-dependent transport of hydrophobic compounds. To determine whether cMOAT is associated with drug sensitivity, we transfected an expression vector containing cMOAT antisense cDNA into the HepG2 human hepatic cancer cell line. We observed a reduction in cMOAT protein, as well as an enhanced level of glutathione, in the antisense transfectants. The transfectants displayed an increased sensitivity to cisplatin, vincristine, doxorubicin, and the camptothecin derivatives, (4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)carbonyl oxy]dione hydrochloride triethydrate and 7-ethyl-10-hydroxycamptothecin, but not to etoposide, 3-[4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosoure a, 5-fluorouracil, and mitomycin C. Results suggest that cMOAT levels are inversely correlated with those of glutathione, and that cMOAT and its related genes may be involved in the sensitivity of cells to certain anticancer agents.

Journal ArticleDOI
01 Aug 1997-Neuron
TL;DR: The TTX-3 LIM homeodomain protein is likely to regulate the expression of target genes required late in AIY differentiation for the function of this interneuron in the thermoregulatory pathway, showing that ttx-3 specifies AIY thermosensory information processing of both motor and autonomic outputs.


Journal ArticleDOI
TL;DR: This data indicates that TGFβ‐related genes such as lefty and nodal are L‐R asymmetrically expressed in developing mouse embryos, and may be involved in L-R determination.
Abstract: Background: Vertebrates have numerous lateral asymmetries in the position of their organs, but the molecular basis for the determination of left–right (L-R) asymmetries remains largely unknown. TGFβ-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in L-R determination. Results: We have identified two highly conserved genes, lefty-1 and lefty-2, in the mouse genome. These two genes are tightly linked on mouse chromosome 1. lefty-1 and lefty-2 are both expressed in a L-R asymmetric fashion in mouse embryos. However, the major expression domains of the two genes are different: lefty-1 expression is predominantly confied to the left side of ventral neural tube, whereas lefty-2 is strongly expressed in the lateral plate mesoderm on the left side. In embryos homozygous for the iv and inv mutation, which cause situs inversus, the expression sites of both genes are affected, either reversed or bilaterally, indicating that lefty-1 and lefty-2 are downstream of iv and inv. Although Lefty-1 and Lefty-2 prepro-proteins are not readily processed in cultured cells, BMP2-Lefty chimeric proteins can be processed to a secreted form. We have examined the activities of Lefty-1 and Lefty-2 in Xenopus embryos. In animal cap explants, Lefty-1 and Lefty-2 induce neural cells in the absence of mesoderm induction. The direct neuralizing activities of Lefty-1 and Lefty-2 thus seem remarkably similar to those of BMP antagonists such as noggin and chordin, suggesting that the action of Lefty-1 and Lefty-2 may be to locally antagonize BMP (bone morphogenic protein)-mediated signals in tissues positioned on the left side of the mouse embryos. Conclusion: There are two lefty genes in mice (lefty-1 and lefty-2), both of which are expressed in a L-R asymmetric fashion and are downstream of iv and inv. Lefty-1 and Lefty-2 possess direct neuralizing activity in Xenopus embryos, resembling the activities of BMP antagonists.

Journal ArticleDOI
TL;DR: VEGF derived from RPE cells, macrophages and Müller cells may play a role in the formation of choroidal neovascularization using an experimental primate model.
Abstract: • Background: Although the choroidal neovascularization (CNV) is a common pathologic feature of a number of different eye diseases, its pathological mechanisms have not been fully elucidated. We investigated the expression of vascular endothelial growth factor (VEGF) in CNV using an experimental primate model. • Method: CNV was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 1, 3, 7 or 14 days after photocoagulation and examined immunohistochemically for VEGF, macrophage antigen, von Willebrand factor and glial fibrillary acidic protein (GFAP). Expression of VEGF mRNA was examined byin situ hybridization. • Results: One day after photocoagulation, the normal structure of the outer portion of the retina and the inner portion of the choroid was destroyed. Three days after photocoagulation, choroidal vascular endothelial cells migrated into the subretinal space through the defect in Bruch's membrane. Increased expression of VEGF was detected in the accumulating macrophages, migrating retinal pigment epithelial (RPE) cells and Muller cells. Maximal expression of VEGF was observed between 3 and 7 days after wounding, and many newly formed vessels extended into the subretinal space 7–14 days after photocoagulation. • Conclusion: VEGF derived from RPE cells, macrophages and Muller cells may play a role in the formation of CNV.