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  • Mice  (322)
  • American Association for the Advancement of Science (AAAS)  (322)
  • 2000-2004  (322)
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  • American Association for the Advancement of Science (AAAS)  (322)
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  • 1
    Publication Date: 2002-06-01
    Description: The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mural, Richard J -- Adams, Mark D -- Myers, Eugene W -- Smith, Hamilton O -- Miklos, George L Gabor -- Wides, Ron -- Halpern, Aaron -- Li, Peter W -- Sutton, Granger G -- Nadeau, Joe -- Salzberg, Steven L -- Holt, Robert A -- Kodira, Chinnappa D -- Lu, Fu -- Chen, Lin -- Deng, Zuoming -- Evangelista, Carlos C -- Gan, Weiniu -- Heiman, Thomas J -- Li, Jiayin -- Li, Zhenya -- Merkulov, Gennady V -- Milshina, Natalia V -- Naik, Ashwinikumar K -- Qi, Rong -- Shue, Bixiong Chris -- Wang, Aihui -- Wang, Jian -- Wang, Xin -- Yan, Xianghe -- Ye, Jane -- Yooseph, Shibu -- Zhao, Qi -- Zheng, Liansheng -- Zhu, Shiaoping C -- Biddick, Kendra -- Bolanos, Randall -- Delcher, Arthur L -- Dew, Ian M -- Fasulo, Daniel -- Flanigan, Michael J -- Huson, Daniel H -- Kravitz, Saul A -- Miller, Jason R -- Mobarry, Clark M -- Reinert, Knut -- Remington, Karin A -- Zhang, Qing -- Zheng, Xiangqun H -- Nusskern, Deborah R -- Lai, Zhongwu -- Lei, Yiding -- Zhong, Wenyan -- Yao, Alison -- Guan, Ping -- Ji, Rui-Ru -- Gu, Zhiping -- Wang, Zhen-Yuan -- Zhong, Fei -- Xiao, Chunlin -- Chiang, Chia-Chien -- Yandell, Mark -- Wortman, Jennifer R -- Amanatides, Peter G -- Hladun, Suzanne L -- Pratts, Eric C -- Johnson, Jeffery E -- Dodson, Kristina L -- Woodford, Kerry J -- Evans, Cheryl A -- Gropman, Barry -- Rusch, Douglas B -- Venter, Eli -- Wang, Mei -- Smith, Thomas J -- Houck, Jarrett T -- Tompkins, Donald E -- Haynes, Charles -- Jacob, Debbie -- Chin, Soo H -- Allen, David R -- Dahlke, Carl E -- Sanders, Robert -- Li, Kelvin -- Liu, Xiangjun -- Levitsky, Alexander A -- Majoros, William H -- Chen, Quan -- Xia, Ashley C -- Lopez, John R -- Donnelly, Michael T -- Newman, Matthew H -- Glodek, Anna -- Kraft, Cheryl L -- Nodell, Marc -- Ali, Feroze -- An, Hui-Jin -- Baldwin-Pitts, Danita -- Beeson, Karen Y -- Cai, Shuang -- Carnes, Mark -- Carver, Amy -- Caulk, Parris M -- Center, Angela -- Chen, Yen-Hui -- Cheng, Ming-Lai -- Coyne, My D -- Crowder, Michelle -- Danaher, Steven -- Davenport, Lionel B -- Desilets, Raymond -- Dietz, Susanne M -- Doup, Lisa -- Dullaghan, Patrick -- Ferriera, Steven -- Fosler, Carl R -- Gire, Harold C -- Gluecksmann, Andres -- Gocayne, Jeannine D -- Gray, Jonathan -- Hart, Brit -- Haynes, Jason -- Hoover, Jeffery -- Howland, Tim -- Ibegwam, Chinyere -- Jalali, Mena -- Johns, David -- Kline, Leslie -- Ma, Daniel S -- MacCawley, Steven -- Magoon, Anand -- Mann, Felecia -- May, David -- McIntosh, Tina C -- Mehta, Somil -- Moy, Linda -- Moy, Mee C -- Murphy, Brian J -- Murphy, Sean D -- Nelson, Keith A -- Nuri, Zubeda -- Parker, Kimberly A -- Prudhomme, Alexandre C -- Puri, Vinita N -- Qureshi, Hina -- Raley, John C -- Reardon, Matthew S -- Regier, Megan A -- Rogers, Yu-Hui C -- Romblad, Deanna L -- Schutz, Jakob -- Scott, John L -- Scott, Richard -- Sitter, Cynthia D -- Smallwood, Michella -- Sprague, Arlan C -- Stewart, Erin -- Strong, Renee V -- Suh, Ellen -- Sylvester, Karena -- Thomas, Reginald -- Tint, Ni Ni -- Tsonis, Christopher -- Wang, Gary -- Wang, George -- Williams, Monica S -- Williams, Sherita M -- Windsor, Sandra M -- Wolfe, Keriellen -- Wu, Mitchell M -- Zaveri, Jayshree -- Chaturvedi, Kabir -- Gabrielian, Andrei E -- Ke, Zhaoxi -- Sun, Jingtao -- Subramanian, Gangadharan -- Venter, J Craig -- Pfannkoch, Cynthia M -- Barnstead, Mary -- Stephenson, Lisa D -- New York, N.Y. -- Science. 2002 May 31;296(5573):1661-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA. richard.mural@celera.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12040188" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Chromosomes/*genetics ; Chromosomes, Human/genetics ; Computational Biology ; Conserved Sequence ; Databases, Nucleic Acid ; Evolution, Molecular ; Genes ; Genetic Markers ; *Genome ; *Genome, Human ; Genomics ; Humans ; Mice ; Mice, Inbred A/genetics ; Mice, Inbred DBA/genetics ; Mice, Inbred Strains/*genetics ; Molecular Sequence Data ; Physical Chromosome Mapping ; Proteins/chemistry/genetics ; Sequence Alignment ; *Sequence Analysis, DNA ; Species Specificity ; *Synteny
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2003-11-01
    Description: Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Changelian, Paul S -- Flanagan, Mark E -- Ball, Douglas J -- Kent, Craig R -- Magnuson, Kelly S -- Martin, William H -- Rizzuti, Bonnie J -- Sawyer, Perry S -- Perry, Bret D -- Brissette, William H -- McCurdy, Sandra P -- Kudlacz, Elizabeth M -- Conklyn, Maryrose J -- Elliott, Eileen A -- Koslov, Erika R -- Fisher, Michael B -- Strelevitz, Timothy J -- Yoon, Kwansik -- Whipple, David A -- Sun, Jianmin -- Munchhof, Michael J -- Doty, John L -- Casavant, Jeffrey M -- Blumenkopf, Todd A -- Hines, Michael -- Brown, Matthew F -- Lillie, Brett M -- Subramanyam, Chakrapani -- Shang-Poa, Chang -- Milici, Anthony J -- Beckius, Gretchen E -- Moyer, James D -- Su, Chunyan -- Woodworth, Thasia G -- Gaweco, Anderson S -- Beals, Chan R -- Littman, Bruce H -- Fisher, Douglas A -- Smith, James F -- Zagouras, Panayiotis -- Magna, Holly A -- Saltarelli, Mary J -- Johnson, Kimberly S -- Nelms, Linda F -- Des Etages, Shelley G -- Hayes, Lisa S -- Kawabata, Thomas T -- Finco-Kent, Deborah -- Baker, Deanna L -- Larson, Michael -- Si, Ming-Sing -- Paniagua, Ricardo -- Higgins, John -- Holm, Bari -- Reitz, Bruce -- Zhou, Yong-Jie -- Morris, Randall E -- O'Shea, John J -- Borie, Dominic C -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):875-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Group, Department of Antibacterials and Immunology, Pfizer Global Researchand Development, Groton, CT 06340, USA. paul_s_changelian@groton.pfizer.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Enzyme Inhibitors/administration & dosage/pharmacology/therapeutic use/toxicity ; Gene Expression Regulation/drug effects ; Graft Rejection/*prevention & control ; Graft Survival/drug effects ; *Heart Transplantation ; Humans ; Immunosuppressive Agents/administration & dosage/*pharmacology/therapeutic ; use/toxicity ; Interleukin-2/immunology ; Janus Kinase 3 ; *Kidney Transplantation ; Lymphocyte Activation/drug effects ; Lymphocyte Count ; Lymphocyte Culture Test, Mixed ; Lymphocyte Subsets/drug effects ; Macaca fascicularis ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Myocardium/metabolism ; Piperidines ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Pyrimidines/administration & dosage/*pharmacology/therapeutic use/toxicity ; Pyrroles/administration & dosage/*pharmacology/therapeutic use/toxicity ; Transplantation, Heterotopic ; Transplantation, Homologous ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2003-04-12
    Description: DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scherer, Stephen W -- Cheung, Joseph -- MacDonald, Jeffrey R -- Osborne, Lucy R -- Nakabayashi, Kazuhiko -- Herbrick, Jo-Anne -- Carson, Andrew R -- Parker-Katiraee, Layla -- Skaug, Jennifer -- Khaja, Razi -- Zhang, Junjun -- Hudek, Alexander K -- Li, Martin -- Haddad, May -- Duggan, Gavin E -- Fernandez, Bridget A -- Kanematsu, Emiko -- Gentles, Simone -- Christopoulos, Constantine C -- Choufani, Sanaa -- Kwasnicka, Dorota -- Zheng, Xiangqun H -- Lai, Zhongwu -- Nusskern, Deborah -- Zhang, Qing -- Gu, Zhiping -- Lu, Fu -- Zeesman, Susan -- Nowaczyk, Malgorzata J -- Teshima, Ikuko -- Chitayat, David -- Shuman, Cheryl -- Weksberg, Rosanna -- Zackai, Elaine H -- Grebe, Theresa A -- Cox, Sarah R -- Kirkpatrick, Susan J -- Rahman, Nazneen -- Friedman, Jan M -- Heng, Henry H Q -- Pelicci, Pier Giuseppe -- Lo-Coco, Francesco -- Belloni, Elena -- Shaffer, Lisa G -- Pober, Barbara -- Morton, Cynthia C -- Gusella, James F -- Bruns, Gail A P -- Korf, Bruce R -- Quade, Bradley J -- Ligon, Azra H -- Ferguson, Heather -- Higgins, Anne W -- Leach, Natalia T -- Herrick, Steven R -- Lemyre, Emmanuelle -- Farra, Chantal G -- Kim, Hyung-Goo -- Summers, Anne M -- Gripp, Karen W -- Roberts, Wendy -- Szatmari, Peter -- Winsor, Elizabeth J T -- Grzeschik, Karl-Heinz -- Teebi, Ahmed -- Minassian, Berge A -- Kere, Juha -- Armengol, Lluis -- Pujana, Miguel Angel -- Estivill, Xavier -- Wilson, Michael D -- Koop, Ben F -- Tosi, Sabrina -- Moore, Gudrun E -- Boright, Andrew P -- Zlotorynski, Eitan -- Kerem, Batsheva -- Kroisel, Peter M -- Petek, Erwin -- Oscier, David G -- Mould, Sarah J -- Dohner, Hartmut -- Dohner, Konstanze -- Rommens, Johanna M -- Vincent, John B -- Venter, J Craig -- Li, Peter W -- Mural, Richard J -- Adams, Mark D -- Tsui, Lap-Chee -- 38103/Canadian Institutes of Health Research/Canada -- P01 GM061354/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8. steve@genet.sickkids.on.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690205" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/genetics ; Chromosome Aberrations ; Chromosome Fragile Sites ; Chromosome Fragility ; Chromosome Mapping ; Chromosomes, Human, Pair 7/*genetics ; Computational Biology ; Congenital Abnormalities/genetics ; CpG Islands ; DNA, Complementary ; Databases, Genetic ; Euchromatin/genetics ; Expressed Sequence Tags ; Gene Duplication ; Genes, Overlapping ; Genetic Diseases, Inborn/genetics ; Genomic Imprinting ; Humans ; In Situ Hybridization, Fluorescence ; Limb Deformities, Congenital/genetics ; Mice ; Molecular Sequence Data ; Mutation ; Neoplasms/genetics ; Pseudogenes ; RNA/genetics ; Retroelements ; *Sequence Analysis, DNA ; Williams Syndrome/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2001-01-06
    Description: Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, S T -- Benson, B G -- Bramson, H N -- Chapman, D E -- Dickerson, S H -- Dold, K M -- Eberwein, D J -- Edelstein, M -- Frye, S V -- Gampe Jr, R T -- Griffin, R J -- Harris, P A -- Hassell, A M -- Holmes, W D -- Hunter, R N -- Knick, V B -- Lackey, K -- Lovejoy, B -- Luzzio, M J -- Murray, D -- Parker, P -- Rocque, W J -- Shewchuk, L -- Veal, J M -- Walker, D H -- Kuyper, L F -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):134-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709, USA. std41085@glaxowellcome.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11141566" target="_blank"〉PubMed〈/a〉
    Keywords: Alopecia/*chemically induced/*prevention & control ; Animals ; Animals, Newborn ; Antineoplastic Agents/*toxicity ; Antineoplastic Combined Chemotherapy Protocols/toxicity ; Apoptosis/drug effects ; *CDC2-CDC28 Kinases ; Cell Cycle/drug effects ; Cell Line ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinases/*antagonists & inhibitors/metabolism ; Cyclophosphamide/toxicity ; Cytoprotection/drug effects ; DNA/biosynthesis ; Doxorubicin/toxicity ; Drug Design ; Enzyme Inhibitors/chemical synthesis/chemistry/*pharmacology ; Epithelium/drug effects ; Etoposide/toxicity ; Hair Follicle/cytology/*drug effects ; Humans ; Indoles/chemical synthesis/chemistry/*pharmacology ; Mice ; Mice, SCID ; Phosphorylation ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Rats ; Retinoblastoma Protein/metabolism ; Scalp/transplantation ; Sulfonamides/chemical synthesis/chemistry/*pharmacology ; Transplantation, Heterologous
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2002-05-04
    Description: Extracts of the resin of the guggul tree (Commiphora mukul) lower LDL (low-density lipoprotein) cholesterol levels in humans. The plant sterol guggulsterone [4,17(20)-pregnadiene-3,16-dione] is the active agent in this extract. We show that guggulsterone is a highly efficacious antagonist of the farnesoid X receptor (FXR), a nuclear hormone receptor that is activated by bile acids. Guggulsterone treatment decreases hepatic cholesterol in wild-type mice fed a high-cholesterol diet but is not effective in FXR-null mice. Thus, we propose that inhibition of FXR activation is the basis for the cholesterol-lowering activity of guggulsterone. Other natural products with specific biologic effects may modulate the activity of FXR or other relatively promiscuous nuclear hormone receptors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Urizar, Nancy L -- Liverman, Amy B -- Dodds, D'Nette T -- Silva, Frank Valentin -- Ordentlich, Peter -- Yan, Yingzhuo -- Gonzalez, Frank J -- Heyman, Richard A -- Mangelsdorf, David J -- Moore, David D -- New York, N.Y. -- Science. 2002 May 31;296(5573):1703-6. Epub 2002 May 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11988537" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Caco-2 Cells ; Carrier Proteins/genetics/metabolism ; Cells, Cultured ; Chenodeoxycholic Acid/pharmacology ; Cholesterol/*metabolism ; Cholesterol, Dietary/administration & dosage ; DNA/metabolism ; DNA-Binding Proteins/*antagonists & inhibitors/chemistry/genetics/*metabolism ; Hepatocytes/metabolism ; Histone Acetyltransferases ; Humans ; *Hydroxysteroid Dehydrogenases ; Hypolipidemic Agents/metabolism/*pharmacology ; Ligands ; Liver/metabolism ; *Membrane Glycoproteins ; Mice ; Nuclear Receptor Coactivator 1 ; Pregnenediones/metabolism/*pharmacology ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors/genetics/metabolism ; Receptors, Steroid/antagonists & inhibitors/metabolism ; Transcription Factors/*antagonists & inhibitors/chemistry/genetics/*metabolism ; Transcriptional Activation/drug effects ; Transfection ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2002-02-09
    Description: The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gadek, T R -- Burdick, D J -- McDowell, R S -- Stanley, M S -- Marsters, J C Jr -- Paris, K J -- Oare, D A -- Reynolds, M E -- Ladner, C -- Zioncheck, K A -- Lee, W P -- Gribling, P -- Dennis, M S -- Skelton, N J -- Tumas, D B -- Clark, K R -- Keating, S M -- Beresini, M H -- Tilley, J W -- Presta, L G -- Bodary, S C -- New York, N.Y. -- Science. 2002 Feb 8;295(5557):1086-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioorganic Chemistry, Genentech, One DNA Way, South San Francisco, CA 94080, USA. trg@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11834839" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/chemical ; synthesis/chemistry/metabolism/pharmacology ; Cyclosporine/pharmacology ; Dermatitis, Irritant/drug therapy ; Dinitrofluorobenzene ; Drug Design ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Female ; Humans ; Immunoglobulin Fab Fragments/immunology/pharmacology ; Immunosuppressive Agents/chemical synthesis/chemistry/metabolism/*pharmacology ; Intercellular Adhesion Molecule-1/chemistry/*immunology/*metabolism ; Lymphocyte Culture Test, Mixed ; Lymphocyte Function-Associated Antigen-1/immunology/*metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Mimicry ; Mutagenesis ; Protein Structure, Secondary ; Structure-Activity Relationship ; Thiophenes/*chemical synthesis/chemistry/metabolism/*pharmacology ; beta-Alanine/analogs & derivatives/*chemical ; synthesis/chemistry/metabolism/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2000-05-08
    Description: The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tournier, C -- Hess, P -- Yang, D D -- Xu, J -- Turner, T K -- Nimnual, A -- Bar-Sagi, D -- Jones, S N -- Flavell, R A -- Davis, R J -- New York, N.Y. -- Science. 2000 May 5;288(5467):870-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry & Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10797012" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptotic Protease-Activating Factor 1 ; Caspase 3 ; Caspase 9 ; Caspases/metabolism ; Cell Count ; Cell Division ; Cells, Cultured ; Cytochrome c Group/*metabolism ; DNA Fragmentation ; Enzyme Activation ; Fibroblasts ; Gene Targeting ; JNK Mitogen-Activated Protein Kinases ; MAP Kinase Signaling System ; Methyl Methanesulfonate/pharmacology ; Mice ; Mitochondria/metabolism ; Mitogen-Activated Protein Kinases/genetics/*metabolism ; NF-kappa B/metabolism ; *Protein-Serine-Threonine Kinases ; Proteins/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Tumor Suppressor Protein p53/metabolism ; Ultraviolet Rays
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2001-03-17
    Description: The role of NF-kappaB-inducing kinase (NIK) in cytokine signaling remains controversial. To identify the physiologic functions of NIK, we disrupted the NIK locus by gene targeting. Although NIK-/- mice displayed abnormalities in both lymphoid tissue development and antibody responses, NIK-/- cells manifested normal NF-kappaB DNA binding activity when treated with a variety of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and lymphotoxin-beta (LTbeta). However, NIK was selectively required for gene transcription induced through ligation of LTbeta receptor but not TNF receptors. These results reveal that NIK regulates the transcriptional activity of NF-kappaB in a receptor-restricted manner.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yin, L -- Wu, L -- Wesche, H -- Arthur, C D -- White, J M -- Goeddel, D V -- Schreiber, R D -- New York, N.Y. -- Science. 2001 Mar 16;291(5511):2162-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Immunology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11251123" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal ; B-Lymphocytes/metabolism ; Cells, Cultured ; DNA/metabolism ; Fibroblasts/metabolism ; Gene Targeting ; Genes, Reporter ; Interleukin-1/metabolism/pharmacology ; Ligands ; Lymphoid Tissue/abnormalities ; Lymphotoxin beta Receptor ; Mice ; Mice, Inbred C57BL ; NF-kappa B/genetics/*metabolism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Receptors, Tumor Necrosis Factor/immunology/*metabolism ; Signal Transduction ; *Transcription, Genetic ; Tumor Necrosis Factor-alpha/metabolism/pharmacology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2001-11-27
    Description: Multiple sclerosis is a demyelinating disease, characterized by inflammation in the brain and spinal cord, possibly due to autoimmunity. Large-scale sequencing of cDNA libraries, derived from plaques dissected from brains of patients with multiple sclerosis (MS), indicated an abundance of transcripts for osteopontin (OPN). Microarray analysis of spinal cords from rats paralyzed by experimental autoimmune encephalomyelitis (EAE), a model of MS, also revealed increased OPN transcripts. Osteopontin-deficient mice were resistant to progressive EAE and had frequent remissions, and myelin-reactive T cells in OPN-/- mice produced more interleukin 10 and less interferon-gamma than in OPN+/+ mice. Osteopontin thus appears to regulate T helper cell-1 (TH1)-mediated demyelinating disease, and it may offer a potential target in blocking development of progressive MS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chabas, D -- Baranzini, S E -- Mitchell, D -- Bernard, C C -- Rittling, S R -- Denhardt, D T -- Sobel, R A -- Lock, C -- Karpuj, M -- Pedotti, R -- Heller, R -- Oksenberg, J R -- Steinman, L -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1731-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, B002, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721059" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Encephalomyelitis, Autoimmune, ; Experimental/genetics/immunology/metabolism/pathology ; Expressed Sequence Tags ; Gene Deletion ; *Gene Expression Profiling ; Gene Library ; Humans ; Inflammation/genetics/immunology/metabolism/pathology ; Interferon-gamma/genetics/metabolism ; Interleukin-10/genetics/metabolism ; Lymphocyte Activation ; Mice ; Mice, Knockout ; Multiple Sclerosis/*genetics/immunology/*metabolism/pathology ; Oligonucleotide Array Sequence Analysis ; Osteopontin ; RNA, Messenger/genetics/metabolism ; Rats ; Sialoglycoproteins/deficiency/genetics/*metabolism ; Spinal Cord/metabolism ; Th1 Cells/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2001-10-27
    Description: Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of muscle atrophy, we performed transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 (MuRF1), and a gene we designate Muscle Atrophy F-box (MAFbx), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bodine, S C -- Latres, E -- Baumhueter, S -- Lai, V K -- Nunez, L -- Clarke, B A -- Poueymirou, W T -- Panaro, F J -- Na, E -- Dharmarajan, K -- Pan, Z Q -- Valenzuela, D M -- DeChiara, T M -- Stitt, T N -- Yancopoulos, G D -- Glass, D J -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1704-8. Epub 2001 Oct 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, 10591-6707, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11679633" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cloning, Molecular ; Creatine Kinase/genetics ; Creatine Kinase, MM Form ; *DNA-Binding Proteins ; Gene Deletion ; *Gene Expression Profiling ; Hindlimb Suspension ; Humans ; Immobilization ; Isoenzymes/genetics ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Muscle Denervation ; Muscle Proteins/genetics ; Muscle, Skeletal/growth & development/*metabolism/pathology/physiopathology ; Muscular Atrophy/*genetics/pathology/physiopathology ; MyoD Protein/genetics ; Myogenic Regulatory Factor 5 ; Myogenin/genetics ; Peptide Synthases/chemistry/deficiency/genetics/*metabolism ; Phenotype ; Protein Binding ; RNA, Messenger/analysis/genetics ; Rats ; Rats, Sprague-Dawley ; SKP Cullin F-Box Protein Ligases ; *Trans-Activators ; Up-Regulation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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