Abstract:
:We describe preliminary studies of the pharmacokinetics, biodistribution, and excretion of an oligodeoxy-nucleotide phosphorothioate ([S]oligonucleotide) in mice. After either intravenous or intraperitoneal administration of a single dose (30 mg/kg of body weight), [S]oligonucleotide (35S-labeled at each internucleotide linkage) was found in most of the tissues for up to 48 hr. About 30% of the dose was excreted in urine within 24 hr, irrespective of the mode of administration; the excreted [S]oligonucleotide was found to be extensively degraded. In plasma, stomach, heart, and intestine, the [S]oligonucleotide was degraded by only 15%, whereas in the kidney and liver degradation was about 50% in 48 hr. The surprising observation was made that chain length extension of administered [S]oligonucleotide occurred in kidney, liver, and intestine. These results provide an initial definition of parameters for the pharmaceutical development of antisense oligonucleotides.
journal_name
Proc Natl Acad Sci U S Aauthors
Agrawal S,Temsamani J,Tang JYdoi
10.1073/pnas.88.17.7595subject
Has Abstractpub_date
1991-09-01 00:00:00pages
7595-9issue
17eissn
0027-8424issn
1091-6490journal_volume
88pub_type
杂志文章abstract::The biological roles of estrogen-responsive finger protein (efp) in vivo were evaluated in mice carrying a loss-of-function mutation in efp by gene-targeted mutagenesis. Although efp homozygous mice were viable and fertile in both sexes, the uterus that expressed abundant estrogen receptor alpha exhibited significant ...
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.96.21.12027
更新日期:1999-10-12 00:00:00
abstract::During latent infection of humans with Mycobacterium tuberculosis, bacteria persist in the asymptomatic host within granulomas, organized collections of differentiated macrophages, and other immune cells. The mechanisms for persistence remain poorly understood, as is the metabolic and replicative state of the microbes...
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.002024599
更新日期:2002-03-19 00:00:00
abstract::A neuroethological approach to human and nonhuman primate behavior and cognition predicts biological specializations for social life. Evidence reviewed here indicates that ancestral mechanisms are often duplicated, repurposed, and differentially regulated to support social behavior. Focusing on recent research from no...
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.1301213110
更新日期:2013-06-18 00:00:00
abstract::Lymphocyte homeostasis is the result of a critical balance between cell proliferation and death. Disruption of this subtle equilibrium can lead to the onset of leukemia, an increase in the number of lymphocytes being potentially due to both of these parameters. The relative importance of cell proliferation vs. apoptos...
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.142100999
更新日期:2002-07-23 00:00:00
abstract::The chromophore of photoactive yellow protein (PYP) (i.e., 4-hydroxycinnamic acid) has been replaced by an analogue with a triple bond, rather than a double bond (by using 4-hydroxyphenylpropiolic acid in the reconstitution, yielding hybrid I) and by a "locked" chromophore (through reconstitution with 7-hydroxycoumari...
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.95.13.7396
更新日期:1998-06-23 00:00:00
abstract::By exploiting the ability of Pseudomonas aeruginosa to infect a variety of vertebrate and nonvertebrate hosts, we have developed model systems that use plants and nematodes as adjuncts to mammalian models to help elucidate the molecular basis of P. aeruginosa pathogenesis. Our studies reveal a remarkable degree of con...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.97.16.8815
更新日期:2000-08-01 00:00:00
abstract::Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the ro...
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.1009199108
更新日期:2011-01-04 00:00:00
abstract::Peptides from the three type I repeats of human endothelial cell thrombospondin, containing the consensus sequence-Trp-Ser-Xaa-Trp-, bind to sulfated glycoconjugates including heparin and sulfatide. The peptides are potent inhibitors for the binding of thrombospondin, laminin, or apolipoprotein E to these ligands. The...
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.89.7.3040
更新日期:1992-04-01 00:00:00
abstract::beta1,4-Galactosyltransferase (beta4GalT-I) participates in both glycoconjugate biosynthesis (ubiquitous activity) and lactose biosynthesis (mammary gland-specific activity). In somatic tissues, transcription of the mammalian beta4GalT-I gene results in a 4.1-kb mRNA and a 3.9-kb mRNA as a consequence of initiation at...
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.95.25.14805
更新日期:1998-12-08 00:00:00
abstract::Continuous intravenous infusion of heparin suppresses smooth muscle cell proliferation in rats after endothelial injury but may lead to hemorrhage and other complications. The anticoagulant property has been removed from chemically modified heparin without loss of antiproliferative effect but use of such compounds is ...
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.87.10.3773
更新日期:1990-05-01 00:00:00
abstract::The periaqueductal gray (PAG) and amygdala are known to be important for defensive responses, and many contemporary fear-conditioning models present the PAG as downstream of the amygdala, directing the appropriate behavior (i.e., freezing or fleeing). However, empirical studies of this circuitry are inconsistent and w...
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.1310845110
更新日期:2013-09-03 00:00:00
abstract::A large number of primary petite (rho-) clones were isolated after ethidium bromide mutagenesis of various grande (rho+) strains of S. cerevisiae that contained the mitochondrial genetic markers, CR, ER, OIR (or OIIR), and PR. From the frequency of coretention of markers in the petites, we have deduced a probable circ...
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.73.12.4608
更新日期:1976-12-01 00:00:00
abstract::A 37-kDa glycoprotein has been described recently, whose synthesis is dramatically increased after injury of the rat sciatic and optic nerves. Cells in the nerve sheath, distal to the site of injury, produce and secrete large amounts of this protein, so that by 3 weeks after injury, it represents 2-5% of the total sol...
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.83.4.1125
更新日期:1986-02-01 00:00:00
abstract::The with-no-lysine (K) (WNK) kinases are an atypical family of protein kinases that regulate ion transport across cell membranes. Mutations that result in their overexpression cause hypertension-related disorders in humans. Of the four mammalian WNKs, only WNK1 is expressed throughout the body. We report that WNK1 inh...
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.1617649113
更新日期:2016-12-13 00:00:00
abstract::Oxidative stress induced in live HeLa cells by menadione (2-methyl-1,4-napthaquinone) was studied in real time by scanning electrochemical microscopy (SECM). The hydrophobic molecule menadione diffuses through a living cell membrane where it is toxic to the cell. However, in the cell it is conjugated with glutathione ...
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.1201555109
更新日期:2012-07-17 00:00:00
abstract::Dimers of bacteriochlorophyll a (Bchla) with optical absorption maximum at 853 nm and a nonconservative circular dichroism spectrum are formed in a solution of formamide/water that contains micelles of Triton X-100. The apparent equilibrium constant and the corresponding Gibbs energy change for the Bchl self-organizat...
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.86.5.1505
更新日期:1989-03-01 00:00:00
abstract::Many current treatments for the reclamation of contaminated water sources are chemical-intensive, energy-intensive, and/or require posttreatment due to unwanted by-product formation. We demonstrate that through the integration of nanostructured materials, enzymatic catalysis, and iron-catalyzed free radical reactions ...
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.1101144108
更新日期:2011-05-24 00:00:00
abstract::A Mr 35,000 calmodulin-binding protein, which also possesses the ability to interact with a number of cytoskeletal elements, was purified from bovine synaptosomal membranes, using hydroxylapatite and phosphocellulose column chromatography. We call this protein "cytosynalin," which is derived from a combination of the ...
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.84.7.1916
更新日期:1987-04-01 00:00:00
abstract::Previous studies have shown that Delta-mediated Notch signaling regulates the number of early differentiating neurons. However, the role of Notch activation and Jagged-mediated signaling during late neurogenesis remains poorly defined. In the developing spinal cord of zebrafish, GABAergic Kolmer-Agduhr (KA'') cells an...
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.0607062104
更新日期:2007-04-03 00:00:00
abstract::Variable regions of Ig chains provide the antigen recognition portion of B-cell receptors and derivative antibodies. Ig heavy-chain variable region exons are assembled developmentally from V, D, J gene segments. Each variable region contains three antigen-contacting complementarity-determining regions (CDRs), with CDR...
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.1709203114
更新日期:2017-08-08 00:00:00
abstract::The high concentration of gonadotropin-releasing hormone (GnRH) in milk of several species implies that the mammary gland is either a site of synthesis for this neuropeptide or that it is efficiently concentrated from plasma by this organ. By PCR amplification of mammary gland cDNA, we have demonstrated expression of ...
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.91.11.4994
更新日期:1994-05-24 00:00:00
abstract::Protein-protein interactions allow the retinoid X receptor (RXR) to bind to cognate DNA as a homo- or a heterodimer and to participate in mediating the effects of a variety of hormones on gene transcription. Here we report a systematic study of the oligomeric state of RXR in the absence of a DNA template. We have used...
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.92.19.8645
更新日期:1995-09-12 00:00:00
abstract::The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We invest...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章
doi:10.1073/pnas.1323342111
更新日期:2014-07-29 00:00:00
abstract::The question was addressed whether the risk of cancer of an individual in a heterogeneous population can be predicted on the basis of measurable biochemical and biological variables postulated to be associated with the process of chemical carcinogenesis. Using the skin tumor model with outbred male NMRI mice, the late...
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.92.13.5900
更新日期:1995-06-20 00:00:00
abstract::The release of catecholamines from adrenal chromaffin cells is known to be blocked by dihydropyridines, such as nitrendipine, and enhanced by others, such as BAY K8644. On the other hand, release from sympathetic neurons is predominantly insensitive to these agents. Release of [3H]norepinephrine from undifferentiated ...
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.83.7.2243
更新日期:1986-04-01 00:00:00
abstract::Recent studies of human disease and transgenic animal experiments have clearly demonstrated the importance of desmosomes in normal tissue architecture. Furthermore, desmosomal components are down-regulated in certain types of carcinomas, suggesting a possible role for desmosomes in suppression of invasion and metastas...
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.95.14.8064
更新日期:1998-07-07 00:00:00
abstract::The expansion of machine learning to high-stakes application domains such as medicine, finance, and criminal justice, where making informed decisions requires clear understanding of the model, has increased the interest in interpretable machine learning. The widely used Classification and Regression Trees (CART) have ...
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.1816748116
更新日期:2019-10-01 00:00:00
abstract::The kidney develops through reciprocal interactions between two precursor tissues: the metanephric mesenchyme and the ureteric bud. We previously demonstrated that the zinc finger protein Sall1 is essential for ureteric bud attraction toward the mesenchyme. Here, we show that Kif26b, a kinesin family gene, is a downst...
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.0913748107
更新日期:2010-05-18 00:00:00
abstract::We have constructed yeast strains that secrete functional mouse-human chimeric antibody and its Fab fragment into the culture medium. For chimeric whole antibody, cDNA copies of the chimeric light-chain and heavy-chain genes of an anti-tumor antibody were inserted into vectors containing the yeast phosphoglycerate kin...
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.85.22.8678
更新日期:1988-11-01 00:00:00
abstract::In both human patients and murine models, the progression from insulitis to diabetes is neither immediate nor inevitable, as illustrated by the innocuous versus destructive infiltrates of BDC2.5 transgenic mice on the nonobese diabetic (NOD) versus C57BL/6.H-2g7 genetic backgrounds. Natural killer (NK)-cell-specific t...
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.0402065101
更新日期:2004-05-25 00:00:00