abstract：:Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signature...

journal_title：Nature medicine

authors： Potti A,Dressman HK,Bild A,Riedel RF,Chan G,Sayer R,Cragun J,Cottrill H,Kelley MJ,Petersen R,Harpole D,Marks J,Berchuck A,Ginsburg GS,Febbo P,Lancaster J,Nevins JR

更新日期：2006-11-01 00:00:00

abstract：:Smallpox was eradicated without an adequate understanding of how vaccination induced protection. In response to possible bioterrorism with smallpox, the UK government vaccinated approximately 300 health care workers with vaccinia virus (VACV) strain Lister. Antibody responses were analyzed using ELISA for multiple sur...

journal_title：Nature medicine

authors： Pütz MM,Midgley CM,Law M,Smith GL

更新日期：2006-11-01 00:00:00

abstract：:The cycle of gallbladder filling and emptying controls the flow of bile into the intestine for digestion. Here we show that fibroblast growth factor-15, a hormone made by the distal small intestine in response to bile acids, is required for gallbladder filling. These studies demonstrate that gallbladder filling is act...

journal_title：Nature medicine

authors： Choi M,Moschetta A,Bookout AL,Peng L,Umetani M,Holmstrom SR,Suino-Powell K,Xu HE,Richardson JA,Gerard RD,Mangelsdorf DJ,Kliewer SA

更新日期：2006-11-01 00:00:00

abstract：:Clinical use of G-CSF can result in vascular and inflammatory complications. To investigate the molecular basis of these effects, we analyzed the adherence of G-CSF-mobilized human peripheral blood leukocytes (ML) to inflamed (TNF-alpha-stimulated) vascular endothelium. Studies using parallel plate assays under physio...

journal_title：Nature medicine

authors： Dagia NM,Gadhoum SZ,Knoblauch CA,Spencer JA,Zamiri P,Lin CP,Sackstein R

更新日期：2006-10-01 00:00:00

abstract：:Attachment to the plasma membrane by linkage to a glycosylphosphatidylinositol (GPI) anchor is a mode of protein expression highly conserved from protozoa to mammals. As a clinical entity, deficiency of GPI has been recognized as paroxysmal nocturnal hemoglobinuria, an acquired clonal disorder associated with somatic ...

journal_title：Nature medicine

authors： Almeida AM,Murakami Y,Layton DM,Hillmen P,Sellick GS,Maeda Y,Richards S,Patterson S,Kotsianidis I,Mollica L,Crawford DH,Baker A,Ferguson M,Roberts I,Houlston R,Kinoshita T,Karadimitris A

更新日期：2006-07-01 00:00:00

abstract：:Mice carrying mutations in both the dystrophin and utrophin genes die prematurely as a consequence of severe muscular dystrophy. Here, we show that intravascular administration of recombinant adeno-associated viral (rAAV) vectors carrying a microdystrophin gene restores expression of dystrophin in the respiratory, car...

journal_title：Nature medicine

authors： Gregorevic P,Allen JM,Minami E,Blankinship MJ,Haraguchi M,Meuse L,Finn E,Adams ME,Froehner SC,Murry CE,Chamberlain JS

更新日期：2006-07-01 00:00:00

abstract：:Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apopto...

journal_title：Nature medicine

authors： Arumugam TV,Chan SL,Jo DG,Yilmaz G,Tang SC,Cheng A,Gleichmann M,Okun E,Dixit VD,Chigurupati S,Mughal MR,Ouyang X,Miele L,Magnus T,Poosala S,Granger DN,Mattson MP

更新日期：2006-06-01 00:00:00

abstract：:The mechanism underlying the autoimmune polyglandular syndrome type-1 (APS1) has been attributed to defective T-cell negative selection resulting from reduced expression and presentation of autoantigens in thymic medullary epithelial cells (MECs). It has also been postulated that Aire is involved in development of reg...

journal_title：Nature medicine

authors： Mi QS,Deng ZB,Joshi SK,Wang ZZ,Zhou L,Eckenrode S,Joshi R,Ly D,Yi B,Delovitch TL,She JX

更新日期：2006-06-01 00:00:00

abstract：:Despite a more than 20-year experience of therapeutic benefit, the relevant molecular and cellular targets of intravenous immunoglobulin (IVIg) in autoimmune disease remain unclear. Contrary to the prevailing theories of IVIg action in autoimmunity, we show that IVIg drives signaling through activating Fc gamma recept...

journal_title：Nature medicine

authors： Siragam V,Crow AR,Brinc D,Song S,Freedman J,Lazarus AH

更新日期：2006-06-01 00:00:00

abstract：:Defects in major histocompatibility complex (MHC) class I-restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTL...

journal_title：Nature medicine

authors： van Hall T,Wolpert EZ,van Veelen P,Laban S,van der Veer M,Roseboom M,Bres S,Grufman P,de Ru A,Meiring H,de Jong A,Franken K,Teixeira A,Valentijn R,Drijfhout JW,Koning F,Camps M,Ossendorp F,Kärre K,Ljunggren HG,Mel

更新日期：2006-04-01 00:00:00

abstract：:We evaluated the ability of neonatal porcine islets to engraft and restore glucose control in pancreatectomized rhesus macaques. Although porcine islets transplanted into nonimmunosuppressed macaques were rapidly rejected by a process consistent with cellular rejection, recipients treated with a CD28-CD154 costimulati...

journal_title：Nature medicine

authors： Cardona K,Korbutt GS,Milas Z,Lyon J,Cano J,Jiang W,Bello-Laborn H,Hacquoil B,Strobert E,Gangappa S,Weber CJ,Pearson TC,Rajotte RV,Larsen CP

更新日期：2006-03-01 00:00:00

abstract：:We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this ...

journal_title：Nature medicine

authors： Manno CS,Pierce GF,Arruda VR,Glader B,Ragni M,Rasko JJ,Ozelo MC,Hoots K,Blatt P,Konkle B,Dake M,Kaye R,Razavi M,Zajko A,Zehnder J,Rustagi PK,Nakai H,Chew A,Leonard D,Wright JF,Lessard RR,Sommer JM,Tigges M,S

更新日期：2006-03-01 00:00:00

abstract：:Atherosclerosis is an immunoinflammatory disease elicited by accumulation of lipids in the artery wall and leads to myocardial infarction and stroke. Here, we show that naturally arising CD4(+)CD25(+) regulatory T cells, which actively maintain immunological tolerance to self and nonself antigens, are powerful inhibit...

journal_title：Nature medicine

authors： Ait-Oufella H,Salomon BL,Potteaux S,Robertson AK,Gourdy P,Zoll J,Merval R,Esposito B,Cohen JL,Fisson S,Flavell RA,Hansson GK,Klatzmann D,Tedgui A,Mallat Z

更新日期：2006-02-01 00:00:00

abstract：:The structure and function of blood vessels adapt to environmental changes such as physical development and exercise. This phenomenon is based on the ability of the endothelial cells to sense and respond to blood flow; however, the underlying mechanisms remain unclear. Here we show that the ATP-gated P2X4 ion channel,...

journal_title：Nature medicine

authors： Yamamoto K,Sokabe T,Matsumoto T,Yoshimura K,Shibata M,Ohura N,Fukuda T,Sato T,Sekine K,Kato S,Isshiki M,Fujita T,Kobayashi M,Kawamura K,Masuda H,Kamiya A,Ando J

更新日期：2006-01-01 00:00:00

abstract：:An effective acquired immune response to infectious agents mediated by HLA-restricted T-cell recognition can target different stages of disease pathogenesis. We show here that three distinct HLA alleles known to alter the overall rate of AIDS progression act during distinct intervals after HIV-1 infection. The discret...

journal_title：Nature medicine

authors： Gao X,Bashirova A,Iversen AK,Phair J,Goedert JJ,Buchbinder S,Hoots K,Vlahov D,Altfeld M,O'Brien SJ,Carrington M

更新日期：2005-12-01 00:00:00

abstract：:Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a singl...

journal_title：Nature medicine

authors： Rapoport AP,Stadtmauer EA,Aqui N,Badros A,Cotte J,Chrisley L,Veloso E,Zheng Z,Westphal S,Mair R,Chi N,Ratterree B,Pochran MF,Natt S,Hinkle J,Sickles C,Sohal A,Ruehle K,Lynch C,Zhang L,Porter DL,Luger S,Guo C,

更新日期：2005-11-01 00:00:00

abstract：:Neurovascular dysfunction substantially contributes to Alzheimer disease. Here, we show that transcriptional profiling of human brain endothelial cells (BECs) defines a subset of genes whose expression is age-independent but is considerably altered in Alzheimer disease, including the homeobox gene MEOX2 (also known as...

journal_title：Nature medicine

authors： Wu Z,Guo H,Chow N,Sallstrom J,Bell RD,Deane R,Brooks AI,Kanagala S,Rubio A,Sagare A,Liu D,Li F,Armstrong D,Gasiewicz T,Zidovetzki R,Song X,Hofman F,Zlokovic BV

更新日期：2005-09-01 00:00:00

abstract：:To determine the protective potential of the humoral immune response against HIV-1 in vivo we evaluated the potency of three neutralizing antibodies (2G12, 2F5 and 4E10) in suppressing viral rebound in six acutely and eight chronically HIV-1-infected individuals undergoing interruption of antiretroviral treatment (ART...

journal_title：Nature medicine

authors： Trkola A,Kuster H,Rusert P,Joos B,Fischer M,Leemann C,Manrique A,Huber M,Rehr M,Oxenius A,Weber R,Stiegler G,Vcelar B,Katinger H,Aceto L,Günthard HF

更新日期：2005-06-01 00:00:00

abstract：:Systemic inflammation induces various adaptive responses including tachycardia. Although inflammation-associated tachycardia has been thought to result from increased sympathetic discharge caused by inflammatory signals of the immune system, definitive proof has been lacking. Prostanoids, including prostaglandin (PG) ...

journal_title：Nature medicine

authors： Takayama K,Yuhki K,Ono K,Fujino T,Hara A,Yamada T,Kuriyama S,Karibe H,Okada Y,Takahata O,Taniguchi T,Iijima T,Iwasaki H,Narumiya S,Ushikubi F

更新日期：2005-05-01 00:00:00

abstract：:Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthes...

journal_title：Nature medicine

authors： Scaffidi P,Misteli T

更新日期：2005-04-01 00:00:00

abstract：:The vaccines developed over the first two hundred years since Jenner's lifetime have accomplished striking reductions of infection and disease wherever applied. Pasteur's early approaches to vaccine development, attenuation and inactivation, are even now the two poles of vaccine technology. Today, purification of micr...

journal_title：Nature medicine

authors： Plotkin SA

更新日期：2005-04-01 00:00:00

abstract：:Animal allergens are an important cause of asthma and allergic rhinitis. We designed and tested a chimeric human-cat fusion protein composed of a truncated human IgG Fcgamma1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fcgamma-Fel d1 protein induced dose-d...

journal_title：Nature medicine

authors： Zhu D,Kepley CL,Zhang K,Terada T,Yamada T,Saxon A

更新日期：2005-04-01 00:00:00

abstract：:Angiopoietin-related growth factor (AGF), a member of the angiopoietin-like protein (Angptl) family, is secreted predominantly from the liver into the systemic circulation. Here, we show that most (>80%) of the AGF-deficient mice die at about embryonic day 13, whereas the surviving AGF-deficient mice develop marked ob...

journal_title：Nature medicine

authors： Oike Y,Akao M,Yasunaga K,Yamauchi T,Morisada T,Ito Y,Urano T,Kimura Y,Kubota Y,Maekawa H,Miyamoto T,Miyata K,Matsumoto S,Sakai J,Nakagata N,Takeya M,Koseki H,Ogawa Y,Kadowaki T,Suda T

更新日期：2005-04-01 00:00:00

abstract：:Targeted gene transduction to specific tissues and organs through intravenous injection would be the ultimate preferred method of gene delivery. Here, we report successful targeting in a living animal through intravenous injection of a lentiviral vector pseudotyped with a modified chimeric Sindbis virus envelope (term...

journal_title：Nature medicine

authors： Morizono K,Xie Y,Ringpis GE,Johnson M,Nassanian H,Lee B,Wu L,Chen IS

更新日期：2005-03-01 00:00:00

abstract：:Inflammation may underlie the metabolic disorders of insulin resistance and type 2 diabetes. IkappaB kinase beta (IKK-beta, encoded by Ikbkb) is a central coordinator of inflammatory responses through activation of NF-kappaB. To understand the role of IKK-beta in insulin resistance, we used mice lacking this enzyme in...

journal_title：Nature medicine

authors： Arkan MC,Hevener AL,Greten FR,Maeda S,Li ZW,Long JM,Wynshaw-Boris A,Poli G,Olefsky J,Karin M

更新日期：2005-02-01 00:00:00

abstract：:Modest clinical outcomes of dendritic-cell (DC) vaccine trials call for the refinement of DC vaccine design. Although many potential antigens have been identified, development of methods to enhance antigen presentation by DCs has lagged. We have engineered a potent, drug-inducible CD40 (iCD40) receptor that permits te...

journal_title：Nature medicine

authors： Hanks BA,Jiang J,Singh RA,Song W,Barry M,Huls MH,Slawin KM,Spencer DM

更新日期：2005-02-01 00:00:00

abstract：:Period (Per) genes are involved in regulation of the circadian clock and are thought to modulate several brain functions. We demonstrate that Per2(Brdm1) mutant mice, which have a deletion in the PAS domain of the Per2 protein, show alterations in the glutamatergic system. Lowered expression of the glutamate transport...

journal_title：Nature medicine

authors： Spanagel R,Pendyala G,Abarca C,Zghoul T,Sanchis-Segura C,Magnone MC,Lascorz J,Depner M,Holzberg D,Soyka M,Schreiber S,Matsuda F,Lathrop M,Schumann G,Albrecht U

更新日期：2005-01-01 00:00:00

abstract：:Diabetes, a disease in which the body does not produce or use insulin properly, is a serious global health problem. Gut polypeptides secreted in response to food intake, such as glucagon-like peptide-1 (GLP-1), are potent incretin hormones that enhance the glucose-dependent secretion of insulin from pancreatic beta ce...

journal_title：Nature medicine

authors： Hirasawa A,Tsumaya K,Awaji T,Katsuma S,Adachi T,Yamada M,Sugimoto Y,Miyazaki S,Tsujimoto G

更新日期：2005-01-01 00:00:00

abstract：:The BTB/POZ transcriptional repressor and candidate oncogene BCL6 is frequently misregulated in B-cell lymphomas. The interface through which the BCL6 BTB domain mediates recruitment of the SMRT, NCoR and BCoR corepressors was recently identified. To determine the contribution of this interface to BCL6 transcriptional...

journal_title：Nature medicine

authors： Polo JM,Dell'Oso T,Ranuncolo SM,Cerchietti L,Beck D,Da Silva GF,Prive GG,Licht JD,Melnick A

更新日期：2004-12-01 00:00:00

abstract：:The optimism of the early period of antimicrobial discovery has been tempered by the emergence of bacterial strains with resistance to these therapeutics. Today, clinically important bacteria are characterized not only by single drug resistance but also by multiple antibiotic resistance--the legacy of past decades of ...

journal_title：Nature medicine

authors： Levy SB,Marshall B

更新日期：2004-12-01 00:00:00

abstract：:We studied the effects of Lyn ablation on the survival of drug-resistant chronic myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+)) blasts by 80-95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent ap...

journal_title：Nature medicine

authors： Ptasznik A,Nakata Y,Kalota A,Emerson SG,Gewirtz AM

更新日期：2004-11-01 00:00:00

abstract：:Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enh...

journal_title：Nature medicine

authors： Komazawa N,Matsuda M,Kondoh G,Mizunoya W,Iwaki M,Takagi T,Sumikawa Y,Inoue K,Suzuki A,Mak TW,Nakano T,Fushiki T,Takeda J,Shimomura I

更新日期：2004-11-01 00:00:00

abstract：:The revolution in cancer research can be summed up in a single sentence: cancer is, in essence, a genetic disease. In the last decade, many important genes responsible for the genesis of various cancers have been discovered, their mutations precisely identified, and the pathways through which they act characterized. T...

journal_title：Nature medicine

authors： Vogelstein B,Kinzler KW

更新日期：2004-08-01 00:00:00

abstract：:Recent years have seen an explosion in the rate of discovery of genetic defects linked to Parkinson's disease. These breakthroughs have not provided a direct explanation for the disease process. Nevertheless, they have helped transform Parkinson's disease research by providing tangible clues to the neurobiology of the...

journal_title：Nature medicine

authors： Vila M,Przedborski S

更新日期：2004-07-01 00:00:00

abstract：:We determine here the functional integrity of auxiliary livers in containers fashioned from the small intestine. Liver microfragments from dipeptidyl peptidase 4 (DPP4)-deficient rats were transplanted into syngeneic normal animals with isolated intestinal segments characterized by mucosal denudation but intact vascul...

journal_title：Nature medicine

authors： Joseph B,Berishvili E,Benten D,Kumaran V,Liponava E,Bhargava K,Palestro C,Kakabadze Z,Gupta S

更新日期：2004-07-01 00:00:00

abstract：:Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemic...

journal_title：Nature medicine

authors： Harman FS,Nicol CJ,Marin HE,Ward JM,Gonzalez FJ,Peters JM

更新日期：2004-05-01 00:00:00

abstract：:Although Nogo-A has been identified in the central nervous system as an inhibitor of axonal regeneration, the peripheral roles of Nogo isoforms remain virtually unknown. Here, using a proteomic analysis to identify proteins enriched in caveolae and/or lipid rafts (CEM/LR), we show that Nogo-B is highly expressed in cu...

journal_title：Nature medicine

authors： Acevedo L,Yu J,Erdjument-Bromage H,Miao RQ,Kim JE,Fulton D,Tempst P,Strittmatter SM,Sessa WC

更新日期：2004-04-01 00:00:00

abstract：:Autoimmune T-helper cells drive pathogenic autoantibody production in systemic lupus erythematosus (SLE), but the mechanisms maintaining those T cells are unknown. Autoreactive T cells are normally eliminated by functional inactivation (anergy) and activation-induced cell death (AICD) or apoptosis through death recept...

journal_title：Nature medicine

authors： Xu L,Zhang L,Yi Y,Kang HK,Datta SK

更新日期：2004-04-01 00:00:00

abstract：:Engendering cytotoxic T-lymphocyte (CTL) responses is likely to be an important goal of HIV vaccines. However, CTLs select for viral variants that escape immune detection. Maintenance of such escape variants in human populations could pose an obstacle to HIV vaccine development. We first observed that escape mutations...

journal_title：Nature medicine

authors： Friedrich TC,Dodds EJ,Yant LJ,Vojnov L,Rudersdorf R,Cullen C,Evans DT,Desrosiers RC,Mothé BR,Sidney J,Sette A,Kunstman K,Wolinsky S,Piatak M,Lifson J,Hughes AL,Wilson N,O'Connor DH,Watkins DI

更新日期：2004-03-01 00:00:00

abstract：:Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interfere with PAF-induce...

journal_title：Nature medicine

authors： Göggel R,Winoto-Morbach S,Vielhaber G,Imai Y,Lindner K,Brade L,Brade H,Ehlers S,Slutsky AS,Schütze S,Gulbins E,Uhlig S

更新日期：2004-02-01 00:00:00