Abstract:
:To improve the efficacy of plasminogen activators, we produced a monoclonal antibody (RWR) that inhibits human alpha 2-antiplasmin (alpha 2AP). In addition to inhibiting alpha 2AP in plasma, RWR binds to and inhibits fibrin cross-linked alpha 2AP and reproduces the "spontaneous" clot lysis that is the hallmark of human alpha 2AP deficiency. By inhibiting the inactivation of plasmin by alpha 2AP, RWR interacts synergistically with plasminogen activators to increase the potency (for 50% clot lysis) of urokinase by 80-fold, tissue plasminogen activator by 27-fold, and streptokinase by 20-fold. Yet, for a given amount of fibrinolysis, the combination of RWR and lower doses of plasminogen activator leads to less fibrinogen consumption than is obtained with higher, equipotent doses of plasminogen activator alone. These results suggest a strategy for increasing the efficacy of plasminogen activators. More generally, this approach to amplifying enzymatic activity by immunoneutralizing an inhibitor may be useful in other biologic processes that are rigidly governed by inhibitors.
journal_name
Proc Natl Acad Sci U S Aauthors
Reed GL 3rd,Matsueda GR,Haber Edoi
10.1073/pnas.87.3.1114subject
Has Abstractpub_date
1990-02-01 00:00:00pages
1114-8issue
3eissn
0027-8424issn
1091-6490journal_volume
87pub_type
杂志文章abstract::In the presence but not in the absence of pokeweed mitogen (PWM), monoclonal antibodies against HLA-DR antigens 147 and 164 helped highly purified B lymphocytes to proliferate and mature to Ig-secreting cells. In contrast, neither anti-DR antibody 231 nor the UCHT1 monoclonal anti-human T cell antibody (both of the sa...
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.80.11.3456
更新日期:1983-06-01 00:00:00
abstract::Ferroelectricity has long been speculated to have important biological functions, although its very existence in biology has never been firmly established. Here, we present compelling evidence that elastin, the key ECM protein found in connective tissues, is ferroelectric, and we elucidate the molecular mechanism of i...
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.1402909111
更新日期:2014-07-08 00:00:00
abstract::High-quality protein crystals meant for structural analysis by X-ray diffraction have been grown by various methods. The observation of dynamical diffraction in protein crystals is an interesting topic because dynamical diffraction generally occurs in perfect crystals such as Si crystals. However, to our knowledge, 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.1720098115
更新日期:2018-04-03 00:00:00
abstract::We propose a motility mechanism that may result in the displacement of objects within the cell. The mechanism, which we call polymer-guided diffusion, involves a microscopic cycle of polymer association and dissociation from a lateral binding site. Reassociation occurs at the polymer subunit adjacent to that which has...
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.84.11.3599
更新日期:1987-06-01 00:00:00
abstract::Disease tolerance, the capacity of tissues to withstand damage caused by a stimulus without a decline in host fitness, varies across tissues, environmental conditions, and physiologic states. While disease tolerance is a known strategy of host defense, its role in noninfectious diseases has been understudied. Here, we...
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.2012003117
更新日期:2020-12-15 00:00:00
abstract::Shell shape and shell thickness of the intertidal snail Littorina obtusata changed markedly between 1871 and 1984 in northern New England. Shells collected prior to 1900 were high-spired with thin walls, whereas shells collected in 1982-84 were low-spired with thick walls. An intertidal crab (Carcinus maenas) which 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.83.18.6897
更新日期:1986-09-01 00:00:00
abstract::Swimming Escherichia coli responds to changes in temperature by modifying its motor behavior. Previous studies using populations of cells have shown that E. coli accumulate in spatial thermal gradients, but these experiments did not cleanly separate thermal responses from chemotactic responses. Here we have isolated 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.0709903105
更新日期:2008-04-08 00:00:00
abstract::Cell-mediated immunity is critical for host resistance to tuberculosis. T lymphocytes recognizing antigens presented by the major histocompatibility complex (MHC) class I and class II molecules have been found to be necessary for control of mycobacterial infection. Mice genetically deficient in the generation of MHC 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.96.26.15190
更新日期:1999-12-21 00:00:00
abstract::We describe an algorithm to compute trisections of orientable four-manifolds using arbitrary triangulations as input. This results in explicit complexity bounds for the trisection genus of a 4-manifold in terms of the number of pentachora (4-simplices) in a triangulation. ...
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.1717173115
更新日期:2018-10-23 00:00:00
abstract::Amplitude-modulated phosphorescence/microwave double-resonance (AM-PMDR) spectra are reported for complexes of methylmercury(II) cation, designated CH3Hg(II), with tryptophan and glyceraldehyde-3-phosphate dehydrogenase (GPDHase; from rabbit muscle). Wavelength shifts are observed in the AM-PMDR spectra of CH3Hg(II)-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.79.14.4313
更新日期:1982-07-01 00:00:00
abstract::The kinetics of biomolecular isomerization processes, such as protein folding, is governed by a free-energy surface of high dimensionality and complexity. As an alternative to projections into one or two dimensions, the free-energy surface can be mapped into a weighted network where nodes and links are configurations ...
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.0608099104
更新日期:2007-02-06 00:00:00
abstract::A defect in the yeast GEF1 gene, a CLC chloride channel homolog leads to an iron requirement and cation sensitivity. The iron requirement is due to a failure to load Cu2+ onto a component of the iron uptake system, Fet3. This process, which requires both Gef1 and the Menkes disease Cu2+-ATPase yeast homolog Ccc2, occu...
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.95.7.4046
更新日期:1998-03-31 00:00:00
abstract::HetR is an essential regulator of heterocyst development in cyanobacteria. Many mutations in HetR render Anabaena incapable of nitrogen fixation. The protein binds to a DNA palindrome upstream of hetP and other genes. We have determined the crystal structures of HetR complexed with palindromic DNA targets, 21, 23, and...
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.1305971110
更新日期:2013-05-07 00:00:00
abstract::The traditional morphologically grounded placement of South American guinea pig-like rodents (Caviomorpha) within one of the two rodent suborders, Hystricognathi, has been disputed by recent analysis of protein and nucleic acid sequence data. The Caviomorpha and possibly all Hystricognathi would be considered a separa...
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.90.20.9698
更新日期:1993-10-15 00:00:00
abstract::Melanoma metastases can be categorized by gene expression for the presence of a T-cell-inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differe...
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.1609376113
更新日期:2016-11-29 00:00:00
abstract::The region of the simian virus 40 genome complementary to the 5' end of the most abundant poly(A)-containing 19S and 16S mRNAs was mapped by hybridization of double-labeled RNA ([3H]methyl group and [14C]uridine) to specific DNA fragments. Chemical identification of methylated residues indicated that a common "leader"...
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.74.12.5323
更新日期:1977-12-01 00:00:00
abstract::Recent studies have implicated local inflammation and activation of complement amongst the processes involved in the pathogenesis of age-related macular degeneration (AMD). Several lines of investigation also indicate that bis-retinoid pigments, such as A2E, that accumulate as lipofuscin in retinal pigment epithelial ...
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.0604255103
更新日期:2006-10-31 00:00:00
abstract::Four mouse POU domain genomic DNA clones--Brain-1, Brain-2, Brain-4, and Scip--and Brain-2 cDNA, which are expressed in adult brain, were cloned and the coding and noncoding regions of the genes were sequenced. The amino acid sequences of the four POU domains are highly conserved; sequences in other regions of the pro...
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.89.8.3280
更新日期:1992-04-15 00:00:00
abstract::The prediction of binding sites and the understanding of interfaces associated with protein complexation remains an open problem in molecular biophysics. This work shows that a crucial factor in predicting and rationalizing protein-protein interfaces can be inferred by assessing the extent of intramolecular desolvatio...
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.0136888100
更新日期:2003-01-07 00:00:00
abstract::The regulation of initiation of DNA replication is crucial to ensure that the genome is replicated only once per cell cycle. In the Gram-positive bacterium Bacillus subtilis, the function of the YabA protein in initiation control was assigned based on its interaction with the DnaA initiator and the DnaN sliding clamp ...
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.0506914103
更新日期:2006-02-14 00:00:00
abstract::Nonribosomal peptide synthetases (NRPSs) and polyketide synthases are large, multidomain enzymes that biosynthesize a number of pharmaceutically important natural products. The recognition of biosynthetic intermediates, displayed via covalent attachment to carrier proteins, by catalytic domains is critical for NRPS 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.0601038103
更新日期:2006-04-04 00:00:00
abstract::The M2 protein of influenza A virus forms a transmembrane proton channel important for viral infection and replication. Amantadine blocks this channel, thus inhibiting viral replication. Elucidating the high-resolution structure of the M2 protein and its change upon amantadine binding is crucial for designing antivira...
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.0711500105
更新日期:2008-02-05 00:00:00
abstract::Combined effects of two drugs present simultaneously are usually expressed as summation, synergism or potentiation, and antagonism. When the sum of the effects of each drug present separately equals the combined effect of the two drugs present simultaneously, the action is called additive or summation. However, the ex...
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.73.6.1868
更新日期:1976-06-01 00:00:00
abstract::Prochlorococcus marinus CCMP 1375, a ubiquitous and ecologically important marine prochlorophyte, was bound to possess functional genes coding for the alpha and beta subunits of a phycobiliprotein. The latter is similar to phycoerythrins (PE) from marine Synechococcus cyanobacteria and bind a phycourobilin-like pigmen...
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.93.20.11126
更新日期:1996-10-01 00:00:00
abstract::Oligodeoxyribonucleotides with site-specific modifications have been used as substrates for Escherichia coli DNA polymerase I holoenzyme and Klenow fragment. Modifications included the bulky guanine-8-aminofluorene adduct and a guanine oxidation product resembling the product of photosensitized DNA oxidation. By a 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.82.8.2325
更新日期:1985-04-01 00:00:00
abstract::Defining bacterial species remains a challenging problem even for the model bacterium Escherichia coli and has major practical consequences for reliable diagnosis of infectious disease agents and regulations for transport and possession of organisms of economic importance. E. coli traditionally is thought to live with...
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.1015622108
更新日期:2011-04-26 00:00:00
abstract::The nematode Caenorhabditis elegans exhibits behavioral responses to many volatile odorants. Chemotaxis toward one such odorant, diacetyl (butanedione), requires the function of a seven-transmembrane receptor protein encoded by the odr-10 gene. To determine directly whether ODR-10 protein is an odorant receptor, it 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.94.22.12162
更新日期:1997-10-28 00:00:00
abstract::We have studied the effect of the 3' terminal CCA sequence in precursors of tRNAs on catalysis by the RNase P RNA or the holoenzyme from the cyanobacterium Synechocystis sp. PCC 6803 in a completely homologous system. We have found that the absence of the 3' terminal CCA is not detrimental to activity, which is in sha...
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.96.12.6672
更新日期:1999-06-08 00:00:00
abstract::Myosin IC (myo1c), a widely expressed motor protein that links the actin cytoskeleton to cell membranes, has been associated with numerous cellular processes, including insulin-stimulated transport of GLUT4, mechanosensation in sensory hair cells, endocytosis, transcription of DNA in the nucleus, exocytosis, and membr...
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.1207811109
更新日期:2012-09-11 00:00:00
abstract::The activity of a number of proteins is regulated by self-processing reactions. Elegant examples are the cleavage of the prokaryotic LexA and lambdaCI transcriptional repressors and the UmuD-like mutagenesis proteins. Various studies support the hypothesis that LexA and lambdaCI cleavage reactions are predominantly 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.95.4.1478
更新日期:1998-02-17 00:00:00