Abstract:
:The specific ornithine decarboxylase inhibitor alpha-difluoromethylornithine, when given to adult rats in vivo for 5 wk, resulted in a decrease in peripheral blood cell elements in normal rats and a marked suppression of marrow recovery in rats with chemotherapy-induced marrow hypoplasia. In normal rats, alpha-difluoromethylornithine resulted in a reduction of the leukocyte count to 73% of control, erythrocyte count to 61% of control, and platelet count to 24% of control. The bleeding time was increased to twice normal and 67% of the animals had epistaxis and 42% had melena. In rats treated with the S phase-specific chemotherapeutic agent 1-beta-D-arabinofuranosylcytosine, the simultaneous administration of alpha-difluoromethylornithine prevented the recovery of the bone marrow. The peripheral blood cell counts remained low--leukocyte count was 10% of control, and erythrocyte and platelet counts were 6% of control. All the animals developed epistaxis and melena and there was a 72% mortality. The administration of putrescine (4 mmol/kg, intraperitoneally, daily), the specific polyamine product of ornithine decarboxylase, reversed these hematologic effects in both normal and recovering marrow and resulted in rapid clinical improvement. Thus, the maintenance of normal, adult rat hematologic parameters, as with the proliferation of neoplastic and transformed cells in culture, is critically dependent on continued polyamine biosynthesis.
journal_name
Proc Natl Acad Sci U S Aauthors
Luk GD,Sharkis SJ,Abeloff MD,McCann PP,Sjoerdsma A,Baylin SBdoi
10.1073/pnas.80.16.5090subject
Has Abstractpub_date
1983-08-01 00:00:00pages
5090-3issue
16eissn
0027-8424issn
1091-6490journal_volume
80pub_type
杂志文章abstract::The protooncogene src encodes two proteins, designated pp60c-src+ and pp60c-src.pp60c-src+ is expressed only in neurons, whereas pp60c-src is expressed in neuronal and nonneuronal cells. pp60c-src+ differs from pp60c-src in that it contains an insert of 6 amino acids. To study the evolutionary conservation of the 6-am...
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.86.12.4751
更新日期:1989-06-01 00:00:00
abstract::The transcription factor interferon regulatory factor 5 (IRF5) is essential for the induction of inflammatory cytokines, but the mechanism by which IRF5 is activated is not well understood. Here we present evidence that the kinase IKKβ phosphorylates and activates IRF5 in response to stimulation in several inflammator...
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.1418516111
更新日期:2014-12-09 00:00:00
abstract::The capacity of Shigella to spread within the cytosol of infected epithelial cells and to infect adjacent cells is critical for the development of infection foci, which lead to mucosal abscesses. Shigella is a nonmotile microorganism that appears to utilize host cell microfilaments to generate intra- as well as interc...
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.86.10.3867
更新日期:1989-05-01 00:00:00
abstract::Osedax is a recently discovered group of siboglinid annelids that consume bones on the seafloor and whose evolutionary origins have been linked with Cretaceous marine reptiles or to the post-Cretaceous rise of whales. Here we present whale bones from early Oligocene bathyal sediments exposed in Washington State, which...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1002014107
更新日期:2010-05-11 00:00:00
abstract::A mutation partially suppressing the UV sensitivity caused by recF143 in a uvrA6 background was located at codon 37 of recA where GTG (valine) became ATG (methionine). This mutation, originally named srf-803, was renamed recA803. Little if any suppression of the recF143 defect in UV induction of a lexA regulon 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.85.18.6592
更新日期:1988-09-01 00:00:00
abstract::Mitochondrial DNAs were prepared from maize lines with normal cytoplasm and with the T, C, S, and EP sources of male-sterile cytoplasms. Agarose gel electrophoresis of these preparations revealed a main high-molecular-weight DNA band. In addition, the S cytoplasm was characterized by the presence of two faster migrati...
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.74.7.2904
更新日期:1977-07-01 00:00:00
abstract::Three lines of evidence for abrupt tropical climate change, both past and present, are presented. First, annually and decadally averaged delta(18)O and net mass-balance histories for the last 400 and 2,000 yr, respectively, demonstrate that the current warming at high elevations in the mid- to low latitudes is unprece...
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.0603900103
更新日期:2006-07-11 00:00:00
abstract::The molecular basis of pathogen clone emergence is relatively poorly understood. Acquisition of a bacteriophage encoding a previously unknown secreted phospholipase A(2) (designated SlaA) has been implicated in the rapid emergence in the mid-1980s of a new hypervirulent clone of serotype M3 group A Streptococcus. Alth...
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.0607669103
更新日期:2006-10-24 00:00:00
abstract::The placenta is essential for the success of therian mammalian reproduction. Intense selective pressure has shaped changes in placental anatomy and function during mammalian cladogenesis. Here we challenge the view that the hemochorial placenta is a derived feature in haplorhine primates. Using phylogenetic and statis...
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.0511344103
更新日期:2006-02-28 00:00:00
abstract::We have cloned and identified a DNA sequence complementary to the mRNA of creatine kinase (CK) isozyme M, although the mRNA is a minor species of the total mRNA in developing myoblasts. Poly(A)+RNA from breast and thigh muscle of 5-week-old chicks was enriched for CK mRNA by a novel procedure of sucrose gradient centr...
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.79.16.4997
更新日期:1982-08-01 00:00:00
abstract::Helodermin is a vasoactive intestinal peptide-like peptide in the salivary gland venom of the lizard Heloderma suspectum. Helodermin-like immunofluorescence was observed in the parafollicular (C) cells in several mammals and in the C cell homologues of the chicken ultimobranchial gland. Thus, helodermin-like peptides ...
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.86.4.1357
更新日期:1989-02-01 00:00:00
abstract::Animals treated with potent gamma-glutamyl transpeptidase inhibitors and a patient with severe gamma-glutamyl transpeptidase deficiency excrete much larger than normal amounts of glutathione, gamma-glutamylcysteine, and cysteine in their urine; these compounds were found in disulfide forms. The findings indicate that ...
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.77.6.3384
更新日期:1980-06-01 00:00:00
abstract::Three of the four deoxynucleoside kinases required for growth of Lactobacillus acidophilus R-26 exist as heterodimeric pairs specific for deoxyadenosine (dAK) and deoxycytidine (dCK) or dAK and deoxyguanosine (dGK). However, only two tandem genes, dak/dgk, are found, and are expressed only as dAK/dGK in transformed Es...
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.93.25.14385
更新日期:1996-12-10 00:00:00
abstract::The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a funct...
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.1500107112
更新日期:2015-06-09 00:00:00
abstract::Hydrogen/deuterium exchange followed by trapping of the labeled species in the aprotic solvent DMSO has been used to elucidate structure in both the burst-phase molten globule-folding intermediate of apomyoglobin and in an equilibrium intermediate that models the kinetic intermediate. Precise estimates can be made 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.0409538102
更新日期:2005-03-29 00:00:00
abstract::We describe the use of a series of gradually expanded thymine nucleobase analogs in probing steric effects in DNA polymerase efficiency and fidelity. In these nonpolar compounds, the base size was increased incrementally over a 1.0-A range by use of variably sized atoms (H, F, Cl, Br, and I) to replace the oxygen mole...
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.0505113102
更新日期:2005-11-01 00:00:00
abstract::Intergroup conflict is a persistent feature of many human societies yet little is known about why individuals participate when doing so imposes a mortality risk. To evaluate whether participation in warfare is associated with reproductive benefits, we present data on participation in small-scale livestock raids among ...
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.1412287112
更新日期:2015-01-13 00:00:00
abstract::Circadian dysfunction is a common attribute of many neurodegenerative diseases, most of which are associated with neuroinflammation. Circadian rhythm dysfunction has been associated with inflammation in the periphery, but the role of the core clock in neuroinflammation remains poorly understood. Here we demonstrate 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.1812405116
更新日期:2019-03-12 00:00:00
abstract::A biomimetic hydrogel platform was designed to signal encapsulated cells using immobilized cell-cell communication cues, with a focus on enhancing the survival and function of encapsulated pancreatic β-cells to treat type 1 diabetes. When MIN6 cells, a pancreatic β-cell line, were encapsulated in poly(ethylene glycol)...
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.1014026108
更新日期:2011-04-19 00:00:00
abstract::A new common cell-surface antigen associated with murine and feline C-type RNA leukemia viruses was demonstrated by the use of rabbit antiserum against feline leukemia virus and the indirect membrane immunofluorescence test. Common cell-surface antigen was found in all leukemias of all strains of mice tested, in norma...
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.70.6.1878
更新日期:1973-06-01 00:00:00
abstract::The genomic RNA of the avian influenza A virus, fowl plague, was fractionated into eight species by electrophoresis in polyacrylamide-agarose gels containing 6 M urea. The separated 32P-labeled RNA species were characterized by digestion with RNase T1 and fractionation of the resulting oligonucleotides by two-dimensio...
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.73.9.3045
更新日期:1976-09-01 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::The role of the renin-angiotensin system in blood pressure control and in the development of hypertension was investigated by generating transgenic mice carrying the rat renin or angiotensinogen gene or both genes under the control of the mouse metallothionein I promoter. The systolic blood pressure was significantly ...
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.87.13.5153
更新日期:1990-07-01 00:00:00
abstract::Embryogenesis requires the precise activation and repression of many transcriptional regulators. The Polycomb group proteins and the associated H3K27me3 histone mark are essential to maintain the inactive state of many of these genes. Mammalian Hox genes are targets of Polycomb proteins and form local 3D clusters cent...
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.1504783112
更新日期:2015-04-14 00:00:00
abstract::The light-harvesting phycobilisome in cyanobacteria and red algae requires the lyase-catalyzed chromophorylation of phycobiliproteins. There are three functionally distinct lyase families known. The heterodimeric E/F type is specific for attaching bilins covalently to α-subunits of phycocyanins and phycoerythrins. Unl...
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.1715495114
更新日期:2017-12-12 00:00:00
abstract::Between 1776 and 1920, the US Congress designed more than 200 distinct securities and stated the maximum amount of each that the Treasury could sell. Between 1917 and 1939, Congress gradually delegated all decisions about designing US debt instruments to the Treasury. In 1939, Congress began imposing a limit on the pa...
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.1719687115
更新日期:2018-03-20 00:00:00
abstract::A model for protein synthesis is proposed in which the donor for the peptide elongation reaction is peptidyl-5S RNA. Space-filling models show that peptide bond formation between peptidyl-5S RNA and aminoacyl-tRNA is eminently feasible from a stereochemical point of view. The peptide is transferred to 5S RNA, while 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.68.10.2357
更新日期:1971-10-01 00:00:00
abstract::The phosphorylation of diacylglycerol (DG), a reaction catalyzed by DG kinase, may be critical in the termination of effector-induced signals mediated by protein kinase C. Synapsin I is a principal target of intracellular protein kinases and is thought to be involved in the release of neurotransmitter from axon termin...
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.88.14.6137
更新日期:1991-07-15 00:00:00
abstract::The influence of speech production on speech perception is well established in adults. However, because adults have a long history of both perceiving and producing speech, the extent to which the perception-production linkage is due to experience is unknown. We addressed this issue by asking whether articulatory confi...
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.1508631112
更新日期:2015-11-03 00:00:00
abstract::Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower molecular weight polypeptide components, as characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. This protein...
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.75.7.3173
更新日期:1978-07-01 00:00:00