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1.
Chem Commun (Camb) ; 54(45): 5648-5673, 2018 May 31.
Article in English | MEDLINE | ID: mdl-29691533

ABSTRACT

Zeolite-templated carbons (ZTCs) are ordered microporous carbons synthesized by using zeolite as a sacrificial template. Unlike well-known ordered mesoporous carbons obtained by using mesoporous silica templates, ZTCs consist of curved and single-layer graphene frameworks, thereby affording uniform micropore size (ca. 1.2 nm), developed microporosity (∼1.7 cm3 g-1), very high surface area (∼4000 m2 g-1), good compatibility with chemical modification, and remarkable softness/elasticity. Thus, ZTCs have been used in many applications such as hydrogen storage, methane storage, CO2 capture, liquid-phase adsorption, catalysts, electrochemical capacitors, batteries, and fuel cells. Herein, the relevant research studies are summarized, and the properties as well as the performances of ZTCs are compared with those of other materials including metal-organic frameworks, to elucidate the intrinsic advantages of ZTCs and their future development.

2.
J Neuroendocrinol ; 30(3): e12570, 2018 03.
Article in English | MEDLINE | ID: mdl-29356182

ABSTRACT

Development of the anterior pituitary proceeds via spatiotemporal patterning of transcription factors and signalling molecules. Among them, retinoic acid (RA) functions as an important signalling molecule for vertebrate organogenesis in many tissues. However, little is known regarding the target genes in the developing pituitary. The present study aimed to clarify the relationship between endogenous RA signalling and mRNA expression of the pituitary-specific transcription factor Prop1 in the pituitary primordium of Rathke's pouch. Gene expression analysis and in situ hybridisation demonstrated that retinaldehyde dehydrogenases (Raldhs) and all types of RA receptors (Rars) are expressed at the level of transcription in the rat Rathke's pouch. Ex vivo organ culture using Rathke's pouch and an in vitro reporter assay demonstrated that RA signalling increases the expression level of Prop1 via RARα. Moreover, a reporter assay using serial truncated constructs of the 5'-upstream region of mouse Prop1 revealed a predicted cis-regulatory element of RARα. This is the first report of a relationship between RA signalling and Prop1-expression during early pituitary development.


Subject(s)
Gene Expression Regulation, Developmental , Homeodomain Proteins/metabolism , Pituitary Gland/metabolism , Signal Transduction/physiology , Tretinoin/metabolism , Animals , Homeodomain Proteins/genetics , Mice , Pituitary Gland/embryology , Rats , Rats, Wistar , Receptors, Retinoic Acid/genetics , Receptors, Retinoic Acid/metabolism , Retinoid X Receptors/genetics , Retinoid X Receptors/metabolism
3.
Science ; 357(6354): 928-932, 2017 09 01.
Article in English | MEDLINE | ID: mdl-28860386

ABSTRACT

NAD+ (oxidized form of NAD:nicotinamide adenine dinucleotide)-reducing soluble [NiFe]-hydrogenase (SH) is phylogenetically related to NADH (reduced form of NAD+):quinone oxidoreductase (complex I), but the geometrical arrangements of the subunits and Fe-S clusters are unclear. Here, we describe the crystal structures of SH in the oxidized and reduced states. The cluster arrangement is similar to that of complex I, but the subunits orientation is not, which supports the hypothesis that subunits evolved as prebuilt modules. The oxidized active site includes a six-coordinate Ni, which is unprecedented for hydrogenases, whose coordination geometry would prevent O2 from approaching. In the reduced state showing the normal active site structure without a physiological electron acceptor, the flavin mononucleotide cofactor is dissociated, which may be caused by the oxidation state change of nearby Fe-S clusters and may suppress production of reactive oxygen species.


Subject(s)
Bacterial Proteins/chemistry , Hydrogenase/chemistry , NAD/chemistry , Binding Sites , Oxidation-Reduction , Protein Conformation , Protein Subunits/chemistry , Solubility
5.
Oncogene ; 35(30): 3932-43, 2016 07 28.
Article in English | MEDLINE | ID: mdl-26640147

ABSTRACT

Synovial sarcoma accounts for almost 10% of all soft tissue sarcomas, and its prognosis is poor with 5-year survival rates at 36%. Thus, new treatments and therapeutic targets for synovial sarcoma are required. Tumor-initiating cells have been defined by the ability for self-renewal and multipotent differentiation, and they exhibit higher tumorigenic capacity, chemoresistance and radiation resistance, expecting to be a new therapeutic target. In synovial sarcoma, the presence of such stemness remains largely unclear; thus, we analyzed whether synovial sarcoma possessed tumor-initiating cells and explored specific markers, and we discovered that synovial sarcoma cell lines possessed heterogeneity by way of containing a sphere-forming subpopulation highly expressing NANOG, OCT4 and SOX2. By expression microarray analysis, CXCR4 was identified to be highly expressed in the sphere subpopulation and correlated with stem-cell-associated markers. Inhibition of CXCR4 suppressed the cell proliferation of synovial sarcoma cell lines in vitro. The tumor-initiating ability of CXCR4-positive cells was demonstrated by xenograft propagation assay. CXCR4-positive cells showed higher tumorigenicity than negative ones and possessed both self-renewal and multipotent differentiation ability. Immunohistochemical analysis of 39 specimens of synovial sarcoma patients revealed that CXCR4 strongly correlated with poor prognosis of synovial sarcoma. Thus, we conclude that CXCR4 is the marker of synovial sarcoma-initiating cells, a new biomarker for prognosis and a new potential therapeutic target.


Subject(s)
Neoplastic Stem Cells/chemistry , Receptors, CXCR4/analysis , Sarcoma, Synovial/pathology , Animals , Biomarkers, Tumor/analysis , Cell Line, Tumor , Female , Humans , Mice , Oncogene Proteins, Fusion/physiology , Prognosis , Receptors, CXCR4/physiology , Sarcoma, Synovial/immunology
6.
Photosynth Res ; 126(2-3): 237-47, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25899392

ABSTRACT

Global energy demand is increasing rapidly and due to intensive consumption of different forms of fuels, there are increasing concerns over the reduction in readily available conventional energy resources. Because of the deleterious atmospheric effects of fossil fuels and the uncertainties of future energy supplies, there is a surge of interest to find environmentally friendly alternative energy sources. Hydrogen (H2) has attracted worldwide attention as a secondary energy carrier, since it is the lightest carbon-neutral fuel rich in energy per unit mass and easy to store. Several methods and technologies have been developed for H2 production, but none of them are able to replace the traditional combustion fuel used in automobiles so far. Extensively modified and renovated methods and technologies are required to introduce H2 as an alternative efficient, clean, and cost-effective future fuel. Among several emerging renewable energy technologies, photobiological H2 production by oxygenic photosynthetic microbes such as green algae and cyanobacteria or by artificial photosynthesis has attracted significant interest. In this short review, we summarize the recent progress and challenges in H2-based energy production by means of biological and artificial photosynthesis routes.


Subject(s)
Chlorophyta/physiology , Cyanobacteria/physiology , Hydrogen/metabolism , Oxygen/metabolism , Photosynthesis , Energy Metabolism , Nanotechnology , Photobiology
7.
Placenta ; 35(12): 974-80, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25465707

ABSTRACT

INTRODUCTION: Autophagy has not been studied extensively in the human placenta. This study was performed to determine whether autophagy is increased in the placentas of women with hypertensive disorders in pregnancy compared to normotensive pregnancies. METHODS: LC3-II and p62 protein expression were examined by quantitative Western blotting analysis in 40 placentas from women not experiencing labor pains. The 40 placentas were from 13, 8, and 19 women with preeclampsia, gestational hypertension, and normal pregnancy, respectively. Hypertensive disorders in pregnancy included preeclampsia and gestational hypertension. RESULTS: LC3-II expression was significantly increased, while that of p62 was significantly reduced in 21 placentas of women with hypertensive disorders compared to those with normal blood pressure irrespective of the presence or absence of fetal growth restriction (FGR). LC3-II expression was also significantly increased in 13 placentas of women with preeclampsia irrespective of the presence or absence of FGR. DISCUSSION: The results of this study suggested that autophagy is active in the placenta of hypertensive disorders even in the absence of FGR.


Subject(s)
Autophagy/physiology , Hypertension, Pregnancy-Induced/metabolism , Placenta/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adult , Biomarkers/metabolism , Female , Humans , Hypertension, Pregnancy-Induced/pathology , Microtubule-Associated Proteins/metabolism , Placenta/pathology , Pregnancy , Sequestosome-1 Protein
8.
Oncogenesis ; 2: e40, 2013 Mar 25.
Article in English | MEDLINE | ID: mdl-23552883

ABSTRACT

Ovarian cancer is one of the most aggressive female reproductive tract tumors. Paclitaxel (PTX) is widely used for the treatment of ovarian cancer. However, ovarian cancers often acquire chemotherapeutic resistance to this agent. We investigated the mechanism of chemoresistance by analysis of microRNAs using the ovarian cancer cell line KFr13 and its PTX-resistant derivative (KFr13Tx). We found that miR-31 was downregulated in KFr13Tx cells, and that re-introduction of miR31 re-sensitized them to PTX both in vitro and in vivo. miR-31 was found to bind to the 3'-UTR of mRNA of MET, and the decrease in MET correlated to higher sensitivity to PTX. Furthermore, co-treatment of KFr13Tx cells with MET inhibitors sensitized the tumor cells to PTX both in vitro and in vivo. In addition, lower levels of miR31 and higher expression of MET in human ovarian cancer specimens were significantly correlated with PTX chemoresistance and poor prognosis. This study demonstrated miR31-dependent regulation of MET for chemoresistance of ovarian cancer, raising the possibility that combination therapy with a MET inhibitor and PTX will increase PTX efficacy.

9.
J Oral Rehabil ; 40(5): 368-74, 2013 May.
Article in English | MEDLINE | ID: mdl-23438017

ABSTRACT

Gender-related risk factors in the survival of transplanted teeth with complete root formation have not yet been identified. The purpose of this study was to investigate gender differences in tooth autotransplantation at dental clinics. We asked participating dentists to provide information on transplantations they had undertaken from 1 January 1990 to 1931 December 2010. The data were screened to exclude patients who underwent more than one transplantation, smokers or those whose smoking habits were unknown, patients under 30 or who were 70 years old and over, cases where the transplanted teeth had incomplete root formation or multiple roots and those with fewer than 20 present teeth post-operation. We analysed 73 teeth of 73 males (mean age, 47.2 years) and 106 teeth of 106 females (mean age, 45.3 years) in this study. The cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method. The cumulative survival rate for males was 88.3% at the 5-year mark, 64.8% at 10 years and 48.6% at 15 years; for females, it was 97.2% at the 5-year mark, 85.9% at 10 years and 85.9% at 15 years. A log-rank test indicated the difference between males and females to be significant (P = 0.011). There was also a significant difference in the main causes for the loss of transplanted teeth: males lost more transplanted teeth due to attachment loss than females (P < 0.05). These results indicate that males require more attention during the autotransplantation process, particularly at the stage of pre-operation evaluation and that of follow-up maintenance.


Subject(s)
Tooth Root/anatomy & histology , Tooth/transplantation , Adult , Aged , Bicuspid/pathology , Bicuspid/transplantation , Female , Follow-Up Studies , Graft Survival , Humans , Male , Middle Aged , Molar/pathology , Molar/transplantation , Odontogenesis/physiology , Periodontal Attachment Loss/complications , Prognosis , Retrospective Studies , Risk Factors , Sex Factors , Time Factors , Tooth Loss/etiology , Transplantation, Autologous , Treatment Outcome
10.
J Oral Rehabil ; 40(2): 112-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23134328

ABSTRACT

The aim of this study was to investigate risk factors with age in the long-term prognosis of autotransplantation of teeth with complete root formation at dental clinics. Participating dentists were asked to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. The data were screened to exclude patients who were under 25 or 70 years of age and over, those who were smokers or whose smoking habits were unknown, those whose transplanted teeth had incomplete root formation or multiple roots and those with fewer than 25 present teeth post-operation. The participants in this study were 71 men (74 teeth) and 100 women (107 teeth) ranging from 25 to 69 years of age. Third molars were used as donor teeth in 89·0% of the cases. The participants were divided into three age groups of 25-39, 40-54 and 55-69. Survival analysis was conducted using the Kaplan-Meier method, and a log-rank test revealed that there were no significant differences in age groups for men or women. Cox regression analysis indicated that the survival of transplanted teeth was not influenced by age. However, although not statistically significant, the clinical success rate was lower in the 55-69-year-old group than that in the younger groups. These results indicate that if suitable donor teeth are available and the conditions are right, autotransplantation is a viable treatment for missing teeth regardless of the age of the patient.


Subject(s)
Tooth Root/growth & development , Tooth/transplantation , Adult , Age Factors , Aged , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Molar, Third/transplantation , Prognosis , Proportional Hazards Models , Transplantation, Autologous
11.
J Oral Rehabil ; 40(1): 33-42, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22943482

ABSTRACT

The aim of this study was to compare the prognosis of separated and non-separated tooth autotransplantation of the upper first and second molars with complete root formation undertaken at dental clinics. The participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. This study analysed 35 separated teeth and 22 non-separated teeth of 47 participants ranging from 27 to 76 years of age (mean age: 55·0 years) after data screening and elimination. The cumulative post-transplantation survival rate at 10 years was 77·1% for separated teeth and 63·6% for non-separated teeth as calculated with the Kaplan-Meier method. There were no significant differences between separated teeth and non-separated teeth in a log rank test (P = 0·687). Separated-tooth autotransplantation can help fill narrow recipient sites and increase occlusal supporting zones, but the clinical success rate was only 48·6%. Although transplantation of teeth with complete root formation has limited prognosis, transplantation of upper first and second molars, whether separated or non-separated, is a viable option to replace missing teeth.


Subject(s)
Jaw, Edentulous, Partially/surgery , Molar/transplantation , Oral Surgical Procedures/methods , Tooth Root/transplantation , Adult , Aged , Female , Humans , Male , Maxilla/surgery , Middle Aged , Prognosis , Transplantation, Autologous/methods
12.
J Oral Rehabil ; 39(11): 821-9, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22672336

ABSTRACT

The aim of this study was to investigate the risk factors affecting long-term prognosis of autotransplantation of third molars with complete root formation in males at dental clinics. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. After data screening and elimination, participants of this study consisted of 183 teeth of 171 males ranging from 20 to 72 years of age (mean age, 44·8 years). The cumulative survival rate was 86·0% at the 5-year mark, 59·1% at 10 years and 28·0% at 15 years. The mean survival time was 134·5 months, as calculated by the Kaplan-Meier method. Single factor analysis using the log-rank test showed that the following factors had significant influence (P < 0·05) on survival of transplanted teeth: periodontal disease as the reason for recipient site tooth extraction, fewer than 25 present teeth and Eichner index Groups B1 to C. Cox regression analysis examined five factors: age, smoking habit, recipient site extraction caused by periodontal disease, fewer than 25 present teeth and Eichner index. This analysis showed that two of these factors were significant: fewer than 25 present teeth was 2·63 (95% CI, 1·03-6·69) and recipient site extraction caused by periodontal disease was 3·80 (95% CI, 1·61-9·01). The results of this study suggest that long-term survival of transplanted teeth in males is influenced not only by oral bacterium but also by occlusal status.


Subject(s)
Molar, Third/transplantation , Adult , Age Factors , Aged , Crowns , Dental Abutments , Dental Caries/etiology , Follow-Up Studies , Humans , Male , Middle Aged , Periodontal Attachment Loss/etiology , Periodontitis/complications , Postoperative Complications , Retrospective Studies , Risk Factors , Root Canal Therapy , Root Resorption/etiology , Sex Factors , Smoking , Survival Analysis , Tooth Ankylosis/etiology , Tooth Extraction , Tooth Fractures/etiology , Tooth Root/injuries , Tooth Socket/surgery , Transplantation, Autologous , Treatment Outcome , Young Adult
13.
Br J Cancer ; 107(1): 137-42, 2012 Jun 26.
Article in English | MEDLINE | ID: mdl-22644300

ABSTRACT

BACKGROUND: Mesothelin is expressed in various types of malignant tumour, and we recently reported that expression of mesothelin was related to an unfavourable patient outcome in pancreatic ductal adenocarcinoma. In this study, we examined the clinicopathological significance of the mesothelin expression in gastric cancer, especially in terms of its association with the staining pattern. METHODS: Tissue specimens from 110 gastric cancer patients were immunohistochemically examined. The staining proportion and intensity of mesothelin expression in tumour cells were analysed, and the localisation of mesothelin was classified into luminal membrane and/or cytoplasmic expression. RESULTS: Mesothelin was positive in 49 cases, and the incidence of mesothelin expression was correlated with lymph-node metastasis. Furthermore, luminal membrane staining of mesothelin was identified in 16 cases, and the incidence of luminal membrane expression was also correlated with pT factor, pStage, lymphatic permeation, blood vessel permeation, recurrence, and poor patient outcome. Multivariate analysis showed that luminal membrane expression of mesothelin was an independent predictor of overall patient survival. CONCLUSION: We described that the luminal membrane expression of mesothelin was a reliable prognostic factor in gastric cancer, suggesting the functional significance of membrane-localised mesothelin in the aggressive behaviour of gastric cancer cells.


Subject(s)
GPI-Linked Proteins/metabolism , Stomach Neoplasms/metabolism , Aged , Biomarkers, Tumor/metabolism , Epithelial Cells/metabolism , Female , Humans , Immunohistochemistry , Lymph Nodes/metabolism , Lymphatic Metastasis , Male , Mesothelin , Middle Aged , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Analysis
14.
Perception ; 41(9): 1027-30, 2012.
Article in English | MEDLINE | ID: mdl-23409368

ABSTRACT

David Marr came to MIT's Artificial Intelligence (AI) Lab in the early 1970s and energized the study of vision at the intersection of computer science, psychology, and neuroscience. As one of his first graduate students, I had the privilege of getting to know him and working with him during that heady period of AI research.


Subject(s)
Vision, Ocular , Boston , History, 20th Century , Humans , Neurosciences/history
15.
J Oral Rehabil ; 39(1): 37-43, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21793869

ABSTRACT

The aim of this study was to investigate the usage of tooth autotransplantation in dental clinics which offer the treatment and evaluate its practicality. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. A total of 614 teeth from 552 patients (37 dentists) ranging in age from 17 to 79 (mean age: 44·1) were examined. Cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method, and log rank test was used for analysis of factors. The mean number of autotransplantation patients per clinic per year was 1·4. Upper third molars constituted 36·8% of donor teeth, while 37·1% were lower third molars. The lower first molar region was the most common recipient site at 32·6%, followed by the lower second molar region (28·0%). Prosthodontic treatment of transplanted teeth involved coverage with a single crown (72·5%) and abutment of bridge (18·9%). A total of 102 transplanted teeth were lost owing to complications such as attachment loss (54·9%) and root resorption (25·7%). The cumulative survival rate in cases where donor teeth had complete root formation was 90·1% at 5 years, 70·5% at 10 years and 55·6% at 15 years. The mean survival time was 165·6 months. Older age was a significant risk factor (P < 0·05) for survival. In cases where suitable donor teeth are available, autotransplantation of teeth may be a plausible treatment option for dealing with missing teeth in dental clinics.


Subject(s)
Oral Surgical Procedures/statistics & numerical data , Tooth/transplantation , Adolescent , Adult , Aged , Dental Clinics , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Transplantation, Autologous/statistics & numerical data , Treatment Outcome , Young Adult
16.
Appl Microbiol Biotechnol ; 59(6): 731-6, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12226733

ABSTRACT

We developed a method based on real-time PCR for the specific and rapid enumeration of a trichloroethylene-degrading methanotroph, Methylocystis sp. M, with the aim of monitoring the strain in groundwater. A primer set designed from the nucleotide sequence of the mmoC gene of a soluble methane monooxygenase (sMMO) gene cluster from Methylocystis sp. M was specific to amplify the DNA region from the strain and no PCR products were amplified with the sMMO gene clusters from six other methanotroph strains. The real-time PCR reliably quantified Methylocystis sp. M over at least five orders of magnitude (5x10(6) to 5x10(2 )cells/PCR tube, or 2x10(8) to 2x10(4 )cells/ml). Five cells of Methylocystis sp. M per PCR tube (2x10(2 )cells/ml) were detectable when the cells were suspended in distilled water. The concomitant presence of other methanotrophs in samples did not affect the reliability of enumeration; and recovery of the cells with a membrane filter enabled us to quantify cells of the strain in groundwater. This quantification procedure was completed within 3 h, including preparation time of environmental samples. We conclude that real-time PCR using the mmoC primer set can be used practically to analyze the behavior of Methylocystis sp. M at bioremediation sites.


Subject(s)
Fresh Water/microbiology , Proteobacteria/isolation & purification , Proteobacteria/metabolism , Trichloroethylene/metabolism , Water Pollutants, Chemical/metabolism , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Oxygenases/chemistry , Oxygenases/genetics , Polymerase Chain Reaction , Proteobacteria/genetics
18.
Inorg Chem ; 40(19): 4986-95, 2001 Sep 10.
Article in English | MEDLINE | ID: mdl-11531448

ABSTRACT

We synthesized azobenzene-conjugated bis(terpyridine) Ru(II) and Rh(III) mononuclear and dinuclear complexes and investigated their photochemical properties on excitation of the azo pi-pi band upon 366 nm light irradiation. The Ru mononuclear complex underwent trans-to-cis photoisomerization to reach the photostationary state with only 20% of the cis form, while the Ru dinuclear complex did not isomerize at all photochemically. On the other hand, the mononuclear and dinuclear Rh complexes showed almost complete trans-to-cis photoisomerization behavior. Cis forms of the Rh complexes thermally returned to the trans form at a much slower rate than those of organic azobenzenes, but they did not isomerize photochemically. The reduction potential of the cis forms was 80 mV more negative than that of the trans forms. The photoisomerization quantum yields of the Rh complexes were strongly dependent on the polarity, viscosity, and donor site of the solvents as well as the size of the counterions. We investigated the photoisomerization process of these complexes using femtosecond absorption spectroscopy. For the Rh complexes, we observed S(n) <-- S(2) and S(n) <-- S(1) absorption bands similar to those of organic azobenzenes. For the Ru complexes, we observed very fast bleaching of the MLCT band of the Ru complex, which indicated that the energy transfer pathway to the MLCT was the primary cause of the depressed photoisomerization. The electronic structures, which were estimated from ZINDO molecular orbital calculation, supported the different photochemical reaction behavior between the Ru and Rh complexes.

19.
J Biol Chem ; 276(48): 45137-44, 2001 Nov 30.
Article in English | MEDLINE | ID: mdl-11567024

ABSTRACT

The c-myc oncogene product (c-Myc) is a transcription factor that dimerizes with Max and recognizes the E-box sequence, and it plays key functions in cell proliferation, differentiation, and apoptosis. We previously showed that MM-1 bound to myc box II within the transactivation domain of c-Myc and repressed the E-box-dependent transcriptional activity of c-Myc. Here we report that MM-1 showed features of a tumor suppressor. In an EST data base search for cDNAs homologous to MM-1, we found a frequent substitution of amino acid 157 of MM-1, from alanine to arginine (A157R), and the substitution was observed more in tumor cells than in normal cells. A survey of the A157R mutation of MM-1 in 57 cultured cancer cells and 90 tissues from cancer patients showed that the A157R was present in about 50-60% of leukemia/lymphoma cells and in more than 75% of squamous cell carcinoma of tongue cancer. Although both the A157R and the wild-type MM-1 bound to c-Myc, only A157R lost the activities to repress both the E-box-dependent transcriptional activity of c-Myc and the myc/ras cooperative transforming activity in rat 3Y1 cells. Furthermore, the wild-type MM-1, but not A157R, arrested the growth of 3Y1 cells. The human MM-1 gene was mapped at chromosome 12q12-12q13, where many chromosome abnormalities in cancer cells have been reported. The results suggest that MM-1 is a novel candidate for a tumor suppressor that controls the transcriptional activity of c-Myc.


Subject(s)
Leukemia/metabolism , Lymphoma/metabolism , Repressor Proteins/metabolism , Repressor Proteins/physiology , Tongue Neoplasms/metabolism , 3T3 Cells , Amino Acids/chemistry , Animals , Blotting, Northern , Cell Cycle , Cell Division/drug effects , Cell Line , Chromosomes, Human, Pair 12 , Cloning, Molecular , DNA/metabolism , DNA, Complementary/metabolism , Exons , Expressed Sequence Tags , Fluorescent Antibody Technique, Indirect , HeLa Cells , Humans , In Situ Hybridization, Fluorescence , Leukemia/genetics , Luciferases/metabolism , Lymphoma/genetics , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Mutation , Plasmids/metabolism , Protein Binding , Protein Structure, Tertiary , Rats , Time Factors , Transcription Factors/metabolism , Transcription, Genetic , Transcriptional Activation , Transfection , Tumor Cells, Cultured
20.
Virology ; 286(1): 100-12, 2001 Jul 20.
Article in English | MEDLINE | ID: mdl-11448163

ABSTRACT

To investigate the early events of JC virus (JCV) infection, including attachment, penetration, transport to the nuclei, and replication of the virus, we analyzed the susceptibility of 15 different cell lines to infection using a semiquantitative polymerase chain reaction (PCR) assay, in situ hybridization, laser scanning confocal microscopy, and a viral replication assay. The cell lines examined were human permissive and nonpermissive cells as well as cells of monkey and mouse origin. JCV entry into the nuclei of the all cell lines was observed within 10 min after inoculation, demonstrating that the virus receptor is widely distributed among mammalian cells. Inhibition of viral entry by an anti-JCV VP1 antibody and sialidase treatment to remove sialic acid residues, which are considered a candidate for the JCV receptor, suggested that VP1 may interact with the cellular surface sialic acid. In addition, chlorpromazine, a clathrin-dependent pathway inhibitor, significantly suppressed entry of JCV into nuclei. In spite of the broad spectrum of cells susceptible to JCV entry, replication of the virus occurred exclusively in human neuroblastoma cell lines. These results suggest that whereas JCV can enter a wide variety of cell types and localize to the nuclei, cell-specific intranuclear mechanisms are required for virus replication.


Subject(s)
JC Virus/physiology , Leukoencephalopathy, Progressive Multifocal/virology , HeLa Cells , Humans , In Situ Hybridization , Organ Specificity , Polymerase Chain Reaction , Receptors, Virus/physiology , Virus Replication
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