Abstract:
:Previously, recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fabs were generated by antigen selection from random combinatorial libraries displayed at the tip of filamentous phage. Two such Fabs, which exhibited high binding affinity for RSV F glycoprotein (a major protective antigen), were evaluated for therapeutic efficacy in infected mice just before or at the time of peak virus replication in the lungs. Fab 19, which neutralized RSV infectivity with high efficiency in tissue culture, was effective therapeutically when delivered directly into the lungs by intranasal instillation under anesthesia. In contrast, RSV Fab 126, which failed to neutralize virus in cell culture, did not exhibit a therapeutic effect under these conditions. The amount of Fab 19 required to effect a 5000- to 12,000-fold reduction in titer of RSV in the lungs within 24 hr was rather small. In four separate experiments, a single instillation of 12.9-50 micrograms of RSV Fab 19 was sufficient to achieve such a reduction in pulmonary virus in a 25g mouse. The use of Fabs instead of the whole immunoglobulin molecules from which they are derived reduced the protein content of a therapeutic dose. This is important because the protein load that can be delivered effectively into the lungs is limited. The therapeutic effect of a single treatment with Fab 19 was not sustained, so that a rebound in pulmonary virus titer occurred on the 2nd day after treatment. This rebound in pulmonary RSV titer could be prevented by treating infected mice with a single dose of Fab 19 daily for 3 days. These observations suggest that human monoclonal Fabs grown in Escherichia coli may prove useful in the treatment of serious RSV disease as well as diseases caused by other viruses where replication in vivo is limited primarily to the lumenal lining of the respiratory tract.
journal_name
Proc Natl Acad Sci U S Aauthors
Crowe JE Jr,Murphy BR,Chanock RM,Williamson RA,Barbas CF 3rd,Burton DRdoi
10.1073/pnas.91.4.1386subject
Has Abstractpub_date
1994-02-15 00:00:00pages
1386-90issue
4eissn
0027-8424issn
1091-6490journal_volume
91pub_type
杂志文章abstract::We have tested the effect of increased ribosomal fidelity on a modified version of the programmed release factor 2 (RF2) translational frameshift. In the constructs tested, the original UGA codon at the site of the shift was replaced by either of two sense codons, UGG (tryptophan), which allows a frameshift of approxi...
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.90.6.2315
更新日期:1993-03-15 00:00:00
abstract::Through use of a synthetic oligonucleotide probe, human insulin-like growth factor I (IGF-I) cDNA clones were isolated from a liver library. Two types of cDNAs were defined by restriction enzyme analysis and DNA sequencing. Both encode IGF-I precursors of either 195 or 153 amino acids. The two predicted protein precur...
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.83.1.77
更新日期:1986-01-01 00:00:00
abstract::The issue of protein dynamics and its implications in the biological function of proteins are arousing greater and greater interest in different fields of molecular biology. In cryo-electron tomography experiments one may take several snapshots of a given biological macromolecule. In principle, a large enough collecti...
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.0400119101
更新日期:2004-04-27 00:00:00
abstract::Synovial membranes in patients with rheumatoid arthritis as well as other types of chronic destructive inflammatory arthritis contain infiltrates of activated T lymphocytes that probably contribute to the pathogenesis of the disease. In an effort to elucidate the nature of these infiltrates, interleukin 2 (IL-2)-respo...
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.85.4.1179
更新日期:1988-02-01 00:00:00
abstract::Split GFPs have been widely applied for monitoring protein-protein interactions by expressing GFPs as two or more constituent parts linked to separate proteins that only fluoresce on complementing with one another. Although this complementation is typically irreversible, it has been shown previously that light acceler...
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.1618087114
更新日期:2017-03-14 00:00:00
abstract::Despite considerable interest in the forces shaping the relationship between brain size and cognitive abilities, it remains controversial whether larger-brained animals are, indeed, better problem-solvers. Recently, several comparative studies have revealed correlations between brain size and traits thought to require...
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.1505913113
更新日期:2016-03-01 00:00:00
abstract::Adjacent paraffin sections of rat hypothalami fixed in Bouin's fluid were treated either with buffer or with luteinizing hormone-releasing hormone (LHRH) before immunocytochemical staining with anti-LHRH. Upon buffer pretreatment, pituitary gonadotrophs were unstained and hypothalamic fibers were stained. Upon LHRH pr...
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.78.8.5216
更新日期:1981-08-01 00:00:00
abstract::The importance of Gly-93 and Gly-94 in transmembrane segment M1 of the Na+,K+-ATPase for interaction with Na+ and K+ was demonstrated by functional analysis of mutants Gly-93-Ala and Gly-94-Ala. In the crystal structures of the Ca2+-ATPase, the corresponding residues, Asp-59 and Leu-60, are located exactly where M1 be...
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.0501201102
更新日期:2005-08-09 00:00:00
abstract::Classical eyeblink conditioning is a well-characterized model paradigm that engages the septohippocampal cholinergic system. This form of associative learning is impaired in normal aging and severely disrupted in Alzheimer's disease (AD). Some nicotinic cholinergic receptor subtypes are lost in AD, making the use of n...
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.031584398
更新日期:2001-02-13 00:00:00
abstract::Dopamine causes a significant retraction of neurites of bull-head catfish horizontal cells maintained in culture. The effects of dopamine are blocked by haloperidol and SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. The dopamine-induced morphological changes were mimicked by SKF 38393, a D1 agonist...
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.87.24.9693
更新日期:1990-12-01 00:00:00
abstract::Angiosperms are the largest and most successful clade of land plants with >250,000 species distributed in nearly every terrestrial habitat. Many phylogenetic studies have been based on DNA sequences of one to several genes, but, despite decades of intensive efforts, relationships among early diverging lineages and sev...
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.0709121104
更新日期:2007-12-04 00:00:00
abstract::The mouse genes encoding the constitutively expressed complement component C4 and its closely related isoform C4-Slp (sex-limited protein), which is expressed only in male animals of several strains, provide a unique model to study sequence elements and trans-acting factors responsible for androgen responsiveness. Our...
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.95.15.8750
更新日期:1998-07-21 00:00:00
abstract::Factor XI (plasma thromboplastin antecedent) deficiency is a blood coagulation abnormality occurring in high frequency in Ashkenazi Jews. Three independent point mutations that result in a blood coagulation abnormality have been identified in the factor XI gene of six unrelated Ashkenazi patients. These mutations eith...
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.86.20.7667
更新日期:1989-10-01 00:00:00
abstract::Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. In the present study, transmission electron microscopy, immunofluorescence stain...
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.1910292116
更新日期:2019-10-29 00:00:00
abstract::Mutation of the p53 gene is one of the most frequent genetic changes found in human cancers. Recent experiments indicated that p53 might contain a transcription-activating domain, which functions when directed to a promoter. This study shows that wild-type p53 suppresses transcription of the retinoblastoma (Rb) gene. ...
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.89.12.5206
更新日期:1992-06-15 00:00:00
abstract::Tropospheric O(3) and sulfate both contribute to air pollution and climate forcing. There is a growing realization that air quality and climate change issues are strongly connected. To date, the importance of the coupling between O(3) and sulfate has not been fully appreciated, and thus regulations treat each pollutan...
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.0508769103
更新日期:2006-03-21 00:00:00
abstract::In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causat...
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.1323279111
更新日期:2014-04-01 00:00:00
abstract::A crucial step in recent theories of human origins is the emergence of strong pair-bonding between males and females accompanied by a dramatic reduction in the male-to-male conflict over mating and an increased investment in offspring. How such a transition from promiscuity to pair-bonding could be achieved is puzzlin...
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.1200717109
更新日期:2012-06-19 00:00:00
abstract::Extended defects are known to have critical influences in achieving desired material performance. However, the nature of extended defect generation is highly elusive due to the presence of multiple nucleation mechanisms with close energetics. A strategy to design extended defects in a simple and clean way is thus high...
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.1808812115
更新日期:2018-09-18 00:00:00
abstract::On a planet experiencing global environmental change, the governance of natural resources depends on sustained collective action by diverse populations. Engaging in such collective action can only build upon the foundation of human cognition in social-ecological settings. To help understand this foundation, we assess ...
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.1915824117
更新日期:2020-04-07 00:00:00
abstract::The interaction between mutations in the tumor-suppressor genes Apc and p53 was studied in congenic mouse strains to minimize the influence of polymorphic modifiers. The multiplicity and invasiveness of intestinal adenomas of Apc(Min/+) (Min) mice was enhanced by deficiency for p53. In addition, the occurrence of desm...
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.050585597
更新日期:2000-03-28 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::Complementary DNA (cDNA) specific for chick globin mRNA sequences fails to hybridize to total RNA extracted from chicken fibroblasts. After infection by Rous sarcoma virus, RNA complementary to globin cDNA is detectable in 100-500 copies per cell. Infection of fibroblasts with the transformation defective (td) deletio...
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.72.11.4464
更新日期:1975-11-01 00:00:00
abstract::The alternative adaptive immune system of jawless vertebrates is based on different isotypes of variable lymphocyte receptors (VLRs) that are composed of leucine-rich repeats (LRRs) and expressed by distinct B- and T-like lymphocyte lineages. VLRB is expressed by B-like cells, whereas VLRA and VLRC are expressed by tw...
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.1415655111
更新日期:2014-10-14 00:00:00
abstract::Because it is able to produce desalinated water directly using solar energy with minimum carbon footprint, solar steam generation and desalination is considered one of the most important technologies to address the increasingly pressing global water scarcity. Despite tremendous progress in the past few years, efficien...
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.1613031113
更新日期:2016-12-06 00:00:00
abstract::We report here the identification of a pollen-specific gene from Zea mays that contains multiple Ser-(Pro)n repeats, the motif found in the cell wall-associated extensins. Sequence analysis reveals that the encoded protein has a putative globular domain at the N terminus and an extensin-like domain at the C terminus. ...
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.92.8.3086
更新日期:1995-04-11 00:00:00
abstract::3-Methylcholanthrene (MCA) skin painting rapidly induced a 100% incidence of thymic lymphomas in RF/J mice. Tumors developed exclusively in cells of the T-lymphocyte lineage and displayed the surface phenotype: Thy-1+, Lyt-1+, Lyt-2+, Qa-1+, H-2K+, H-2D+, TL-, Ig-, Ia-. This phenotype resembled that of cortisone-resis...
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.81.23.7612
更新日期:1984-12-01 00:00:00
abstract::An in-depth knowledge of the interaction of water with amorphous silica is critical to fundamental studies of interfacial hydration water, as well as to industrial processes such as catalysis, nanofabrication, and chromatography. Silica has a tunable surface comprising hydrophilic silanol groups and moderately hydroph...
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.1722263115
更新日期:2018-03-20 00:00:00
abstract::Reactions of a membrane-bound multienzyme complex (electron-transport chain of rat-liver microsomes) suspended in aqueous-organic solvent used as antifreeze at temperatures below 0 degrees were studied. In the presence of a relatively high concentration of ethylene glycol, electron transfer can still be observed and s...
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.70.9.2633
更新日期:1973-09-01 00:00:00
abstract::Synapsins are abundant synaptic-vesicle phosphoproteins that are known to regulate neurotransmitter release but whose precise function has been difficult to pinpoint. Here, we use knockout mice to analyze the role of synapsins 1 and 2 in the calyx of Held synapse, allowing precise measurements of neurotransmitter rele...
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.0511300103
更新日期:2006-02-21 00:00:00