Abstract:
:We have examined the role of cyclooxygenase 2 (COX-2) in a model of inflammation in vivo. Carrageenan administration to the subcutaneous rat air pouch induces a rapid inflammatory response characterized by high levels of prostaglandins (PGs) and leukotrienes in the fluid exudate. The time course of the induction of COX-2 mRNA and protein coincided with the production of PGs in the pouch tissue and cellular infiltrate. Carrageenan-induced COX-2 immunoreactivity was localized to macrophages obtained from the fluid exudate as well as to the inner surface layer of cells within the pouch lining. Dexamethasone inhibited both COX-2 expression and PG synthesis in the fluid exudate but failed to inhibit PG synthesis in the stomach. Furthermore, NS-398, a selective COX-2 inhibitor, and indomethacin, a nonselective COX-1/COX-2 inhibitor, blocked proinflammatory PG synthesis in the air pouch. In contrast, only indomethacin blocked gastric PG and, additionally, produced gastric lesions. These results suggest that inhibitors of COX-2 are potent antiinflammatory agents which do not produce the typical side effects (e.g., gastric ulcers) associated with the nonselective, COX-1-directed antiinflammatory drugs.
journal_name
Proc Natl Acad Sci U S Aauthors
Masferrer JL,Zweifel BS,Manning PT,Hauser SD,Leahy KM,Smith WG,Isakson PC,Seibert Kdoi
10.1073/pnas.91.8.3228subject
Has Abstractpub_date
1994-04-12 00:00:00pages
3228-32issue
8eissn
0027-8424issn
1091-6490journal_volume
91pub_type
杂志文章abstract::The type II cell of the alveolar epithelium of adult rats has been studied by electron microscopy to determine its ability to endocytose electron-dense tracers of differing molecular charge and size. The tracers studied were native (anionic) ferritin, cationic ferritin, 70-kilodalton dextran, and colloidal carbon. Alv...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.19.6054
更新日期:1984-10-01 00:00:00
abstract::In FRTL5 rat thyroid cells, norepinephrine, by interacting with alpha 1-adrenergic receptors, stimulates inositol phosphate formation, through activation of phospholipase C, and arachidonic acid release. Recent studies have shown that GTP-binding proteins couple several types of receptors to phospholipase C activation...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.19.7201
更新日期:1986-10-01 00:00:00
abstract::Utilizing the bicistronic reporter transposon mini-Tn5 lacZ-tet/1, we have identified lacZ fusions to four Escherichia coli genes/operons that are strongly activated by the accumulation of self-produced extracellular signals. These fusions were designated cma9, cma48, cma113, and cma114 for conditioned medium activate...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.8.4610
更新日期:1999-04-13 00:00:00
abstract::We have developed a procedure for purifying highly specific polyclonal antibodies against 5-methylcytosine. These antibodies were used to probe the distribution of 5-methylcytosine among fractionated nucleosomes of mouse cell chromatin. Our results demonstrate that at least 80% of the 5-methylcytosine is localized in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.18.5490
更新日期:1983-09-01 00:00:00
abstract::The neuropeptide oxytocin has been implicated in the mediation of several forms of affiliative behavior including parental care, grooming, and sex behavior. Here we demonstrate that species from the genus Microtus (voles) selected for differences in social affiliation show contrasting patterns of oxytocin receptor exp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.13.5981
更新日期:1992-07-01 00:00:00
abstract::Neurons in the mammalian suprachiasmatic nuclei (SCN) generate daily rhythms in physiology and behavior, but it is unclear how they maintain and synchronize these rhythms in vivo. We hypothesized that parallel signaling pathways in the SCN are required to synchronize rhythms in these neurons for coherent output. We re...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0607466103
更新日期:2006-12-12 00:00:00
abstract::Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic paraparesis is a demyelinating inflammatory neurologic disease associated with HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.13.7568
更新日期:1998-06-23 00:00:00
abstract::Ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid have been attached covalently to the 5' terminus of the deoxynucleotide sequence C-A-C-A-A-T-T-C-C-A-C-A-C-A-A-C (16-mer) via an ethylenediamine linker. In the presence of Fe2+ and dithiothreitol, these reagents bring about the hybridization-depend...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.4.963
更新日期:1985-02-01 00:00:00
abstract::The central limit theorem is applied to group foraging to show an automatic and universal benefit to group living. This may explain the paradoxical inverse correlation between group size and per capita brood production in primitively eusocial insects and why only one of the five major lineages of social insects contai...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.1.36
更新日期:1991-01-01 00:00:00
abstract::We have analyzed ligand-receptor complexes resulting from (i) the incubation of canine hepatic plasma membranes with [125I]iodoglucagon and (ii) subsequent gentle solubilization of receptor-bound ligand with digitonin. The complexes (molecular weight approximately equal to 500,000) retain the radiolabeled ligand durin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.20.6835
更新日期:1985-10-01 00:00:00
abstract::Experimental allergic encephalomyelitis (EAE), an autoimmune model of multiple sclerosis, is a complex disease influenced by genetic, intrinsic, and environmental factors. In this study, we questioned whether parent-of-origin effects influence EAE, using reciprocal F2 intercross progeny generated between EAE-susceptib...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0600536103
更新日期:2006-05-23 00:00:00
abstract::The difficulty of achieving robust functional expression of insect nicotinic acetylcholine receptors (nAChRs) has hampered our understanding of these important molecular targets of globally deployed neonicotinoid insecticides at a time when concerns have grown regarding the toxicity of this chemotype to insect pollina...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2003667117
更新日期:2020-07-14 00:00:00
abstract::In maturing T lineage cells, the helix-loop-helix protein E47 has been shown to enforce a critical proliferation and developmental checkpoint commonly referred to as beta selection. To examine how E47 regulates cellular expansion and developmental progression, we have used an E2A-deficient lymphoma cell line and DNA m...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0603728103
更新日期:2006-06-27 00:00:00
abstract::Single molecule studies, at constant force, of the separation of double-stranded DNA into two separated single strands may provide information relevant to the dynamics of DNA replication. At constant applied force, theory predicts that the unzipped length as a function of time is characterized by jumps during which th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.262789199
更新日期:2003-02-18 00:00:00
abstract::Homologous recombination is an important biological process that occurs in all organisms and facilitates genome rearrangements and repair of DNA double-strand breaks. Eukaryotic Rad51 proteins (Rad51sp or Rhp51 in fission yeast) are functional and structural homologs of bacterial RecA protein, an evolutionarily conser...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2632890100
更新日期:2003-12-23 00:00:00
abstract::Never before have individuals had to adapt to social environments defined by such magnitudes of ethnic diversity and cultural differentiation. However, neurobiological evidence informing about strategies to reduce xenophobic sentiment and foster altruistic cooperation with outsiders is scarce. In a series of experimen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,随机对照试验
doi:10.1073/pnas.1705853114
更新日期:2017-08-29 00:00:00
abstract::Trypanosomosis, or sleeping sickness, is a major disease constraint on livestock productivity in sub-Saharan Africa. To identify quantitative trait loci (QTL) controlling resistance to trypanosomosis in cattle, an experimental cross was made between trypanotolerant African N'Dama (Bos taurus) and trypanosusceptible im...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1232392100
更新日期:2003-06-24 00:00:00
abstract::The translocation of lipids from the inner to the outer membrane of Escherichia coli has been investigated by pulse-chase experiments. After a pulse with [2-3H]glycerol, the specific activity of the newly synthesized [3H]phosphatidylethanolamine was 5 times greater in the inner than in the outer membrane. During the c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.4.1867
更新日期:1980-04-01 00:00:00
abstract::In an fMRI experiment, participants were exposed to narratives based on true stories designed to evoke admiration and compassion in 4 distinct categories: admiration for virtue (AV), admiration for skill (AS), compassion for social/psychological pain (CSP), and compassion for physical pain (CPP). The goal was to test ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0810363106
更新日期:2009-05-12 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2019-02-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.17.6060
更新日期:1987-09-01 00:00:00
abstract::High-valent iron-oxo species are thought to be intermediates in the catalytic cycles of oxygenases and peroxidases. An attractive route to these iron-oxo intermediates involves laser flash-quench oxidation of ferric hemes, as demonstrated by our work on the ferryl (compound II) and ferryl porphyrin radical cation (com...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1012381107
更新日期:2010-11-02 00:00:00
abstract::More than 21 million prescriptions for warfarin are written yearly in the U.S. Despite its importance, warfarin's target, vitamin K epoxide reductase (VKOR), has resisted purification since its identification in 1972. Here, we report its purification and reconstitution. HPC4, a calcium-specific antibody that recognize...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0609401103
更新日期:2006-12-19 00:00:00
abstract::Early events in the action of 17-beta-estradiol can be studied in soluble extracts of rat uterus by exposure of the estradiol-receptor protein to a DNA-cellulose matrix. After complexing with [(3)H]estradiol, the 4S receptor protein binds to the DNA, and it can be eluted with buffer of high ionic strength as a more ti...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.69.8.2105
更新日期:1972-08-01 00:00:00
abstract::The crystal structure of the decanucleotide d(CGCAATTGCG)2 has been solved by a combination of molecular replacement and heavy-atom procedures and has been refined to an R factor of 20.2% at 2.7 A. It is not a fully base-paired duplex but has a central core of eight Watson-Crick base pairs flanked by unpaired terminal...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.23.10767
更新日期:1995-11-07 00:00:00
abstract::The heterogeneous RNA of the HeLa cell nucleus contains short internal poly(A) sequences which, in contrast to the longer poly(A) sequences at the 3' ends, are not found in messenger RNA of the cytoplasm. A distinct origin for each of these homologous sequences is evident when the effects of actinomycin D and 3'-deoxy...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.1.200
更新日期:1974-01-01 00:00:00
abstract::Recent studies have indicated that mammalian cells contain a cytosolic protein disaggregation machinery comprised of Hsc70, DnaJ homologs, and Hsp110 proteins, the last of which acts to accelerate a rate-limiting step of nucleotide exchange of Hsc70. We tested the ability of transgenic overexpression of a Thy1 promote...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1604885113
更新日期:2016-05-10 00:00:00
abstract::Variation between North Korean and Latin American isolates in the circumsporozoite (CS) protein encoding gene of the human malaria parasite Plasmodium vivax was studied. Polymorphic positions are confined to the central tandemly repeated sequences. Nucleotide substitutions in the tandem repeats produce variants; these...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.21.8102
更新日期:1988-11-01 00:00:00
abstract::Tauopathies are a class of neurodegenerative diseases associated with pathological tau. Despite many advances in our understanding of these diseases, the direct mechanism through which tau contributes to neurodegeneration remains poorly understood. Previously, our laboratory implicated the histone demethylase LSD1 in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2013552117
更新日期:2020-11-17 00:00:00
abstract::Serum from bacillus Calmette-Guerin-infected mice injected with endotoxin induces the appearance of surface immunoglobulin, Ia antigen, and complement receptor on the surface of precursor bone-marrow-derived (B) cells. While endotoxin itself causes phenotypic conversion of both thymus-derived (T) cells and B cells in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.3.1200
更新日期:1977-03-01 00:00:00