Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154.

Abstract:

:Reported effects of anti-CD154 treatment on autoimmunity, alloreactivity, and inflammatory events mediated by macrophages and endothelial cells indicated that it might be an ideal agent for the prevention of intrahepatic islet allograft failure. This hypothesis was tested in MHC-mismatched rhesus monkeys. Transplantation of an adequate number of viable islets resulted in engraftment and insulin independence in six of six recipients treated with anti-CD154 (hu5c8) induction plus monthly maintenance therapy (post-operative day >125, >246, >266, >405, >419, >476). Anti-CD154 (hu5c8) displayed no inhibitory effect on islet cell function. For monkeys followed for >100 days, continued improvement in graft function, as determined by first phase insulin release in response to intravenous glucose, was observed after the first 100 days post-transplant. No evidence of toxicity or infectious complications has been observed. All recipients treated with anti-CD154 became specifically nonresponsive to donor cells in mixed lymphocyte reactions. Furthermore, three monkeys are now off therapy (>113, >67, and >54 days off anti-CD154), with continued insulin independence and donor-specific mixed lymphocyte reaction hyporeactivity. In striking contrast to all previously tested strategies, transplantation of an adequate number of functional islets under the cover of anti-CD154 (hu5c8) monotherapy consistently allows for allogeneic islet engraftment and long-term insulin independence in this highly relevant preclinical model.

authors

Kenyon NS,Chatzipetrou M,Masetti M,Ranuncoli A,Oliveira M,Wagner JL,Kirk AD,Harlan DM,Burkly LC,Ricordi C

doi

10.1073/pnas.96.14.8132

keywords:

subject

Has Abstract

pub_date

1999-07-06 00:00:00

pages

8132-7

issue

14

eissn

0027-8424

issn

1091-6490

journal_volume

96

pub_type

杂志文章
  • Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: an indirect feedback pathway.

    abstract::The effect of plasmin-derived fibrinogen fragments on the biosynthesis of fibrinogen was investigated in cultured monolayers of rat hepatocytes. Incubating the cells with several concentrations of either fibrinogen or fibrin fragment D or E had no effect on the synthesis and secretion of fibrinogen by these cells. How...

    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.79.5.1530

    authors: Ritchie DG,Levy BA,Adams MA,Fuller GM

    更新日期:1982-03-01 00:00:00

  • Evolution of behavior by density-dependent natural selection.

    abstract::Theories of density-dependent natural selection predict that evolution should favor those genotypes with the highest per capita rates of population growth under the current density conditions. These theories are silent about the mechanisms that may give rise to these increases in density-dependent growth rates. We hav...

    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.88.23.10905

    authors: Guo PZ,Mueller LD,Ayala FJ

    更新日期:1991-12-01 00:00:00

  • Communicating scientific uncertainty.

    abstract::All science has uncertainty. Unless that uncertainty is communicated effectively, decision makers may put too much or too little faith in it. The information that needs to be communicated depends on the decisions that people face. Are they (i) looking for a signal (e.g., whether to evacuate before a hurricane), (ii) 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.1317504111

    authors: Fischhoff B,Davis AL

    更新日期:2014-09-16 00:00:00

  • Molecular recognition of pathogen attack occurs inside of plant cells in plant disease resistance specified by the Arabidopsis genes RPS2 and RPM1.

    abstract::The Arabidopsis thaliana disease resistance genes RPS2 and RPM1 belong to a class of plant disease resistance genes that encode proteins that contain an N-terminal tripartite nucleotide binding site (NBS) and a C-terminal tandem array of leucine-rich repeats. RPS2 and RPM1 confer resistance to strains of the bacterial...

    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.93.26.15497

    authors: Leister RT,Ausubel FM,Katagiri F

    更新日期:1996-12-24 00:00:00

  • Biosynthesis of the thiazole moiety of thiamin (vitamin B1) in higher plant chloroplasts.

    abstract::The chloroplast stromal proteins from spinach condense the two heterocyclic moieties of vitamin B1--4-methyl-5-(beta-hydroxyethyl)thiazole and 2-methyl-4-amino-5-hydroxymethylpyrimidine--in the presence of MgATP. We have taken advantage of this observation to study thiazole synthesis. We present data indicating that 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.88.6.2042

    authors: Julliard JH,Douce R

    更新日期:1991-03-15 00:00:00

  • Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush.

    abstract::Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen...

    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.87.8.2926

    authors: Hantaï D,Rao JS,Festoff BW

    更新日期:1990-04-01 00:00:00

  • Rapid landscape transformation in South Island, New Zealand, following initial Polynesian settlement.

    abstract::Humans have altered natural patterns of fire for millennia, but the impact of human-set fires is thought to have been slight in wet closed-canopy forests. In the South Island of New Zealand, Polynesians (Māori), who arrived 700-800 calibrated years (cal y) ago, and then Europeans, who settled ∼150 cal y ago, used fire...

    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.1011801107

    authors: McWethy DB,Whitlock C,Wilmshurst JM,McGlone MS,Fromont M,Li X,Dieffenbacher-Krall A,Hobbs WO,Fritz SC,Cook ER

    更新日期:2010-12-14 00:00:00

  • An HP1-like protein is missing from transcriptionally silent micronuclei of Tetrahymena.

    abstract::We report the identification and cloning of a 28-kDa polypeptide (p28) in Tetrahymena macronuclei that shares several features with the well studied heterochromatin-associated protein HP1 from Drosophila. Notably, like HP1, p28 contains both a chromodomain and a chromoshadow domain. p28 also shares features with linke...

    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.95.23.13624

    authors: Huang H,Wiley EA,Lending CR,Allis CD

    更新日期:1998-11-10 00:00:00

  • Human XIST yeast artificial chromosome transgenes show partial X inactivation center function in mouse embryonic stem cells.

    abstract::Initiation of X chromosome inactivation requires the presence, in cis, of the X inactivation center (XIC). The Xist gene, which lies within the XIC region in both human and mouse and has the unique property of being expressed only from the inactive X chromosome in female somatic cells, is known to be essential for X 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.96.12.6841

    authors: Heard E,Mongelard F,Arnaud D,Chureau C,Vourc'h C,Avner P

    更新日期:1999-06-08 00:00:00

  • Dichotomy and perceptual distortions in absolute pitch ability.

    abstract::Absolute pitch (AP) is the rare ability to identify the pitch of a tone without the aid of a reference tone. Understanding both the nature and genesis of AP can provide insights into neuroplasticity in the auditory system. We explored factors that may influence the accuracy of pitch perception in AP subjects both duri...

    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.0703868104

    authors: Athos EA,Levinson B,Kistler A,Zemansky J,Bostrom A,Freimer N,Gitschier J

    更新日期:2007-09-11 00:00:00

  • Specification of positional information in retinal ganglion cells of Xenopus: stability of the specified state.

    abstract::In the normal development of retinotectal connections, the site in the tectum at which an optic fiber synapses is related to the position of its ganglion-cell body in the retina. How and when the ganglion cells acquire information about their positions is unknown, but the positional information that each ganglion cell...

    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.69.10.2860

    authors: Hunt RK,Jacobson M

    更新日期:1972-10-01 00:00:00

  • Rate enhancement of reconstitution of glyceraldehyde-3-phosphate dehydrogenase by a covalently bound coenzyme analog.

    abstract::Kinetic analysis of the in vitro reconstitution of glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] from yeast showed that both oxidized and reduced coenzyme enhance the transconformation reaction, which is rate limiting in the sequential foldin...

    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.77.4.1966

    authors: Jaenicke R,Krebs H,Rudolph R,Woenckhaus C

    更新日期:1980-04-01 00:00:00

  • GIGANTEA is a nuclear protein involved in phytochrome signaling in Arabidopsis.

    abstract::In a genetic screen of available T-DNA-mutagenized Arabidopsis populations for loci potentially involved in phytochrome (phy) signaling, we identified a mutant that displayed reduced seedling deetiolation under continuous red light, but little if any change in responsiveness to continuous far-red light. This behavior ...

    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.170283997

    authors: Huq E,Tepperman JM,Quail PH

    更新日期:2000-08-15 00:00:00

  • Pregrowth hormone messenger RNA: glucocorticoid induction and identification in rat pituitary cells.

    abstract::We have investigated whether the large (5- to 15-fold) stimulation of synthesis of growth hormone (somatotropin) observed upon exposure of a strain of rat pituitary (GH3) cells to dexamethasone (a synthetic glucocorticoid) arises from a stimulation of pregrowth hormone mRNA. A good agreement was observed between the 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.74.6.2357

    authors: Tushinski RJ,Sussman PM,Yu LY,Bancroft FC

    更新日期:1977-06-01 00:00:00

  • McClintock's challenge in the 21st century.

    abstract::In 1950, Barbara McClintock published a Classic PNAS article, "The origin and behavior of mutable loci in maize," which summarized the evidence leading to her discovery of transposition. The article described a number of genome alterations revealed through her studies of the Dissociation locus, the first mobile geneti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 传,历史文章,杂志文章

    doi:10.1073/pnas.1215482109

    authors: Fedoroff NV

    更新日期:2012-12-11 00:00:00

  • Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig.

    abstract::Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxyste...

    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.0700899104

    authors: Radhakrishnan A,Ikeda Y,Kwon HJ,Brown MS,Goldstein JL

    更新日期:2007-04-17 00:00:00

  • A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin.

    abstract::All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid seque...

    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.93.8.3289

    authors: Berstein RM,Schluter SF,Shen S,Marchalonis JJ

    更新日期:1996-04-16 00:00:00

  • The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics.

    abstract::Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of ph...

    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.1403667112

    authors: Goswami A,Binder WJ,Meachen J,O'Keefe FR

    更新日期:2015-04-21 00:00:00

  • Levinthal's paradox.

    abstract::Levinthal's paradox is that finding the native folded state of a protein by a random search among all possible configurations can take an enormously long time. Yet proteins can fold in seconds or less. Mathematical analysis of a simple model shows that a small and physically reasonable energy bias against locally unfa...

    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.89.1.20

    authors: Zwanzig R,Szabo A,Bagchi B

    更新日期:1992-01-01 00:00:00

  • Parent-independent genotyping for constructing an ultrahigh-density linkage map based on population sequencing.

    abstract::Bar-coded multiplexed sequencing approaches based on new-generation sequencing technologies provide capacity to sequence a mapping population in a single sequencing run. However, such approaches usually generate low-coverage and error-prone sequences for each line in a population. Thus, it is a significant challenge 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.1005931107

    authors: Xie W,Feng Q,Yu H,Huang X,Zhao Q,Xing Y,Yu S,Han B,Zhang Q

    更新日期:2010-06-08 00:00:00

  • Evidence for a biological role in photosynthesis for cytochrome b-559--a component of photosystem II reaction center.

    abstract::Absorbance changes in untreated intact leaf discs, produced upon excitation with high-intensity red light, were shown to be due to the photooxidation of cytochrome b-559. At low intensities (<100 W/m2), photooxidation was almost undetectable. Photooxidation occurred with a half-time of 4.3 sec and an extent of 0.64 mo...

    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.87.23.9295

    authors: Canaani O,Havaux M

    更新日期:1990-12-01 00:00:00

  • Volume-selective magnetic resonance imaging using an adjustable, single-sided, portable sensor.

    abstract::Portable, single-sided NMR sensors can operate under conditions inaccessible to conventional NMR while featuring lower cost, portability, and the ability to analyze arbitrary-sized objects. Such sensors can nondestructively probe the interior of samples by collecting images and measuring relaxation and diffusion const...

    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.0811222106

    authors: Paulsen JL,Bouchard LS,Graziani D,Blümich B,Pines A

    更新日期:2008-12-30 00:00:00

  • Repression of tyrosine hydroxylase is responsible for the sex-linked chocolate mutation of the silkworm, Bombyx mori.

    abstract::Pigmentation patterning has long interested biologists, integrating topics in ecology, development, genetics, and physiology. Wild-type neonatal larvae of the silkworm, Bombyx mori, are completely black. By contrast, the epidermis and head of larvae of the homozygous recessive sex-linked chocolate (sch) mutant are red...

    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.1001725107

    authors: Liu C,Yamamoto K,Cheng TC,Kadono-Okuda K,Narukawa J,Liu SP,Han Y,Futahashi R,Kidokoro K,Noda H,Kobayashi I,Tamura T,Ohnuma A,Banno Y,Dai FY,Xiang ZH,Goldsmith MR,Mita K,Xia QY

    更新日期:2010-07-20 00:00:00

  • Polyhedra and packings from hyperbolic honeycombs.

    abstract::We derive more than 80 embeddings of 2D hyperbolic honeycombs in Euclidean 3 space, forming 3-periodic infinite polyhedra with cubic symmetry. All embeddings are "minimally frustrated," formed by removing just enough isometries of the (regular, but unphysical) 2D hyperbolic honeycombs [Formula: see text], [Formula: se...

    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.1720307115

    authors: Pedersen MC,Hyde ST

    更新日期:2018-07-03 00:00:00

  • Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks.

    abstract::Signal transduction pathways activated by chemoattractants have been extensively studied, but little is known about the events mediating responses to mechanical stimuli. We discovered that acute mechanical perturbation of cells triggered transient activation of all tested components of the chemotactic signal transduct...

    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.1608767113

    authors: Artemenko Y,Axiotakis L Jr,Borleis J,Iglesias PA,Devreotes PN

    更新日期:2016-11-22 00:00:00

  • Identification of a receptor necessary for Nogo-B stimulated chemotaxis and morphogenesis of endothelial cells.

    abstract::Nogo isoforms (Nogo-A and -B) have been implicated in regulating neural and cardiovascular functions, such as cell spreading and chemotaxis. Unlike the loop domain (Nogo-66) found in all Nogo isoforms that can interact with a neural-specific Nogo-66 receptor, the receptor for the amino terminus of Nogo-B that mediates...

    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.0602427103

    authors: Miao RQ,Gao Y,Harrison KD,Prendergast J,Acevedo LM,Yu J,Hu F,Strittmatter SM,Sessa WC

    更新日期:2006-07-18 00:00:00

  • Transferable anticancer innate immunity in spontaneous regression/complete resistance mice.

    abstract::Spontaneous regression/complete resistance (SR/CR) mice resist very high doses of cancer cells that are lethal to WT mice even at low doses. In this study, we show that this resistance is mediated by rapid infiltration of leukocytes, mostly of innate immunity, in both primary and repeated challenges. Formation of rose...

    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.0602382103

    authors: Hicks AM,Riedlinger G,Willingham MC,Alexander-Miller MA,Von Kap-Herr C,Pettenati MJ,Sanders AM,Weir HM,Du W,Kim J,Simpson AJ,Old LJ,Cui Z

    更新日期:2006-05-16 00:00:00

  • How the Dorsal gradient works: insights from postgenome technologies.

    abstract::Gradients of extracellular signaling molecules and transcription factors are used in a variety of developmental processes, including the patterning of the Drosophila embryo, the establishment of diverse neuronal cell types in the vertebrate neural tube, and the anterior-posterior patterning of vertebrate limbs. Here, ...

    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.0806476105

    authors: Hong JW,Hendrix DA,Papatsenko D,Levine MS

    更新日期:2008-12-23 00:00:00

  • Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome.

    abstract::The nuclear lamina is a network of structural filaments, the A and B type lamins, located at the nuclear envelope and throughout the nucleus. Lamin filaments provide the nucleus with mechanical stability and support many basic activities, including gene regulation. Mutations in LMNA, the gene encoding A type lamins, 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.0601058103

    authors: Dahl KN,Scaffidi P,Islam MF,Yodh AG,Wilson KL,Misteli T

    更新日期:2006-07-05 00:00:00

  • A functional peptide encoded in the Escherichia coli 23S rRNA.

    abstract::A pentapeptide open reading frame equipped with a canonical ribosome-binding site is present in the Escherichia coli 23S rRNA. Overexpression of 23S rRNA fragments containing the mini-gene renders cells resistant to the ribosome-inhibiting antibiotic erythromycin. Mutations that change either the initiator or stop cod...

    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.93.11.5641

    authors: Tenson T,DeBlasio A,Mankin A

    更新日期:1996-05-28 00:00:00