Abstract:
:Adriamycin (doxorubicin) was encapsulated in human erythrocytes by means of a dialysis technique involving transient hypotonic hemolysis followed by isotonic resealing. Up to 1.6 mg of the drug was entrapped per ml of packed erythrocytes, with the efficiency of encapsulation being 60-80%. In vitro incubation of the Adriamycin-loaded erythrocytes in autologous plasma was accompanied by progressive release of unaltered Adriamycin in the medium. The efflux was still evident after 50 hr. The metabolism of encapsulated Adriamycin was restricted to limited formation of the C-13 hydroxylated metabolite, adriamycinol, in the normal erythrocytes but not in erythrocytes from individuals deficient in glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase, EC 1.1.1.49) activity. Reductive bioactivation of encapsulated Adriamycin to yield the corresponding aglycones was not observed in a variety of conditions. However, when NADPH ferredoxin reductase and ferredoxin, both purified from spinach leaves, were co-entrapped within erythrocytes and allowed to catalyze electron transfer to Adriamycin intracellularly under N2, a quantitative conversion to 7-deoxyadriamycin aglycone was obtained. Adriamycin-loaded erythrocytes did not show any significant oxidative damage, except for a variable increase of methemoglobin, suggesting some redox cycling between native Adriamycin and its semiquinone radical. Encapsulation of Adriamycin in autologous human erythrocytes may represent a therapeutic strategy for the slow release in circulation of this antineoplastic drug in order to reduce or prevent its adverse effects and especially the delayed cardiotoxicity that limits its use in patients with neoplastic disease.
journal_name
Proc Natl Acad Sci U S Aauthors
De Flora A,Benatti U,Guida L,Zocchi Edoi
10.1073/pnas.83.18.7029subject
Has Abstractpub_date
1986-09-01 00:00:00pages
7029-33issue
18eissn
0027-8424issn
1091-6490journal_volume
83pub_type
杂志文章abstract::Chromatophores of Rhodopseudomonas sphaeroides yield the antenna complex B850 in either of two states, depending on the method of isolation. Methods using dodecyl (= lauryl) dimethylamine oxide yield B850 with an absorption spectrum like that in vivo: the bands at 800 and 850 nm, due to the bacteriochlorophyll (Bchl) ...
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.78.9.5583
更新日期:1981-09-01 00:00:00
abstract::A synthetic peptide composed of the first 22 amino acid residues of the Drosophila Shaker K+ channel inhibits a voltage-gated K+ channel in basolateral membrane vesicles from Necturus enterocytes reconstituted in planar phospholipid bilayers when added to the solution bathing the inner surface of this channel but not ...
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.89.5.1770
更新日期:1992-03-01 00:00:00
abstract::The effects of urea and of guanidinium chloride on binding constants in water for 6-(4-tert-butylanilino)-naphthalene-2-sulfonate and of bis(p-tert-butylphenyl) phosphate binding to beta-cyclodextrin and to N,N'-bis(6-beta-cyclo-dextrinyl)imidazolium ion have been determined. Their effects on the water solubility of p...
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.89.15.6916
更新日期:1992-08-01 00:00:00
abstract::Mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) appear and proliferate to form the predominant cell type in rat bone marrow cultures stimulated with factors from antigen- or mitogen-activated lymphocytes. Conditioned media causing a selective proliferation of MMC were derived f...
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.80.14.4499
更新日期:1983-07-01 00:00:00
abstract::Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) a...
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.1304288110
更新日期:2013-04-23 00:00:00
abstract::Protein phosphorylation is a ubiquitous and one of the most effective means of regulating protein activity. Receptor phosphorylation is a key event in signal transduction. The question, therefore, that arises is whether this modulatory mechanism might produce functional changes in a membrane receptor in the absence 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.88.22.10213
更新日期:1991-11-15 00:00:00
abstract::An Epstein-Barr virus (EBV) deletion mutant, HR-1, cannot immortalize lymphocytes. HR-1 was derived from a virus strain, Jijoye, that is immortalization competent. Using human antiserum from certain patients with chronic active EBV infection, we have identified in Jijoye cells a protein of apparent mass of 78-80 kDa 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.82.21.7429
更新日期:1985-11-01 00:00:00
abstract::Calcium oscillations suppress mitochondrial movements along the microtubules to support on-demand distribution of mitochondria. To activate this mechanism, Ca(2+) targets a yet unidentified cytoplasmic factor that does not seem to be a microtubular motor or a kinase/phosphatase. Here, we have studied the dependence 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.0808953105
更新日期:2008-12-30 00:00:00
abstract::Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid gastrointestinal regulatory peptide that stimulates insulin secretion from pancreatic beta cells in the presence of glucose. Approximately 7.8 x 10(5) recombinant clones of a neonatal rat intestinal cDNA library were screened by using plaque hybridizati...
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.90.5.1992
更新日期:1993-03-01 00:00:00
abstract::Tregs are essential for maintaining peripheral tolerance, and thus targeting these cells may aid in the treatment of autoimmunity and cancer by enhancing or reducing suppressive functions, respectively. Before these cells can be harnessed for therapeutic purposes, it is necessary to understand how they maintain tolera...
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.1605849113
更新日期:2016-08-09 00:00:00
abstract::Current chemotherapeutic approaches for cancer are in part limited by the inability of drugs to destroy neoplastic cells within poorly vascularized compartments of tumors. We have here systematically assessed anaerobic bacteria for their capacity to grow expansively within avascular compartments of transplanted tumors...
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.251543698
更新日期:2001-12-18 00:00:00
abstract::Increased clouds and precipitation normally decrease the diurnal temperature range (DTR) and thus have commonly been offered as explanation for the trend of reduced DTR observed for many land areas over the last several decades. Observations show, however, that the DTR was reduced most in dry regions and especially 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.0700290104
更新日期:2007-11-13 00:00:00
abstract::The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes. Here we report that this gene also encodes at least one HLA-DR4-presented peptide recognized by CD4(+) T cells. The Melan-A/MART-1(51-73) peptide was able to induce the in vitro 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.97.1.400
更新日期:2000-01-04 00:00:00
abstract::Retroviruses evolved from long terminal repeat (LTR) retrotransposons by acquisition of envelope functions, and subsequently reinvaded host genomes. Together, endogenous retroviruses and LTR retrotransposons represent major components of animal, plant, and fungal genomes. Sequences from these elements have been exapte...
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.1900931116
更新日期:2019-05-14 00:00:00
abstract::Recent studies have shown that orthotopic (transurethral) transplantation of human bladder cancer cell lines into nude mice permits tumor growth that accurately reflects their clinical malignant status in the original host. Thus, such a system allows a unique opportunity to analyze the genetic events involved in 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.87.22.9047
更新日期:1990-11-01 00:00:00
abstract::The 32-kDa subunit of replication protein A (RPA) is phosphorylated during the S phase of the cell cycle in vivo and during simian virus 40 DNA replication in vitro. To explore the functional significance of this modification, we purified a HeLa cell protein kinase that phosphorylates RPA in the presence of single-str...
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.91.26.12520
更新日期:1994-12-20 00:00:00
abstract::To test the hypothesis that periodic signals and chemotaxis direct later morphogenesis in Dictyostelium discoideum, we investigated cell behavior and cell movement in slugs. Trails of neutral red-stained prestalk and anterior-like cells were recorded by high-resolution digital image processing. Neutral red-stained ant...
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.89.14.6433
更新日期:1992-07-15 00:00:00
abstract::During reverse transcription of retroviral RNA, synthesis of (-) strand DNA is primed by a cellular tRNA that anneals to an 18-nt primer binding site within the 5' long terminal repeat. For (+) strand synthesis using a (-) strand DNA template linked to the tRNA primer, only the first 18 nt of tRNA are replicated to 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.94.14.7210
更新日期:1997-07-08 00:00:00
abstract::Expansion of polyglutamine repeats in several unrelated proteins causes neurodegenerative diseases with distinct but related pathologies. To provide a model system for investigating common pathogenic features, we have examined the behavior of polyglutamine expansions expressed in Caenorhabditis elegans. The expression...
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.100107297
更新日期:2000-05-23 00:00:00
abstract::Humans routinely formulate plans in domains so complex that even the most powerful computers are taxed. To do so, they seem to avail themselves of many strategies and heuristics that efficiently simplify, approximate, and hierarchically decompose hard tasks into simpler subtasks. Theoretical and cognitive research 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.1414219112
更新日期:2015-03-10 00:00:00
abstract::The mitotic (or spindle assembly) checkpoint system prevents premature separation of sister chromatids in mitosis. When the checkpoint is turned on, the mitotic checkpoint complex (MCC) inhibits the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C). MCC is composed of the checkpoint proteins BubR1, Bub3, a...
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.1308928110
更新日期:2013-06-25 00:00:00
abstract::Bacteria serve as the central arena for understanding how gene networks and proteins process information and control cellular behaviors. Recently, much effort has been devoted to the investigation of specific bacteria gene circuits as functioning modules. The next challenge is the integrative modeling of complex cellu...
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.0912185106
更新日期:2009-12-15 00:00:00
abstract::Glutamate transporters clear synaptically released glutamate to maintain precise communication between neurons and limit glutamate neurotoxicity. Although much progress has been made on the topology, structure, and function of these carriers, few studies have addressed large-scale structural motions collectively assoc...
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.1112216108
更新日期:2011-09-13 00:00:00
abstract::Glomeruli in the olfactory bulb are anatomically discrete modules receiving input from idiotypic olfactory sensory neurons. To examine the functional organization of sensory inputs to individual glomeruli, we loaded olfactory sensory neurons with a Ca(2+) indicator and measured odorant-evoked presynaptic Ca(2+) signal...
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.0400438101
更新日期:2004-06-15 00:00:00
abstract::A recently determined set of 20 NMR-derived conformations of a 48-residue all-alpha-helical protein, (PDB ID code 2JVD), is validated here by comparing the observed (13)C(alpha) chemical shifts with those computed at the density functional level of theory. In addition, a recently introduced physics-based method, aimed...
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.0807105105
更新日期:2008-09-23 00:00:00
abstract::Acyl-homoserine lactone (acyl-HSL) signaling is thought to mediate quorum sensing in many species of Proteobacteria. The opportunistic human pathogen Pseudomonas aeruginosa uses acyl-HSLs to regulate hundreds of genes, including many that code for extracellular virulence factors. The idea that the P. aeruginosa acyl-H...
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.0503728102
更新日期:2005-06-21 00:00:00
abstract::G-protein metallochaperones ensure fidelity during cofactor assembly for a variety of metalloproteins, including adenosylcobalamin (AdoCbl)-dependent methylmalonyl-CoA mutase and hydrogenase, and thus have both medical and biofuel development applications. Here, we present crystal structures of IcmF, a natural fusion ...
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.1419582112
更新日期:2015-02-24 00:00:00
abstract::The ATM (ataxia telangiectasia mutated) protein plays a central role in sensing and responding to DNA double-strand breaks. Lymphoid cells are unique in undergoing physiologic double-strand breaks in the processes of Ig class switch recombination and T or B cell receptor V(D)J recombination, and a role for ATM in thes...
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.0611222104
更新日期:2007-04-10 00:00:00
abstract::The virB operon of the Agrobacterium tume-faciens pTiA6NC plasmid likely plays a role in directing T-DNA transfer events at the bacterial membrane, as determined previously by mutagenesis and cellular fractionation studies and by DNA sequence analysis of the approximately 12-kilobase-pair operon. The DNA sequence anal...
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.86.24.9677
更新日期:1989-12-01 00:00:00
abstract::Climate change is expected to alter the distribution and abundance of many species. Predictions of climate-induced population extinctions are supported by geographic range shifts that correspond to climatic warming, but few extinctions have been linked mechanistically to climate change. Here we show that extinctions o...
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.052131199
更新日期:2002-04-30 00:00:00